Q) Some of my CKD patients are malnourished; in fact, some of those on dialysis do not eat well and have low albumin levels. Previously in this column, it was stated that higher albumin levels (> 4 g/dL) confer survival benefits to dialysis patients. Should I consider prescribing megestrol acetate to improve appetite? If I do prescribe it, what dose is safe for CKD and dialysis patients?

Malnutrition affects one-third of dialysis patients,¹ and malnutrition-inflammation complex syn­drome (MICS) is common in those with stage 5 CKD. Albumin is used as an indicator of MICS in dialysis patients; however, since other factors (stress, infection, inflammation, comorbidities) affect nutritional status,² serum albumin alone may not be sufficient to assess it.

In fact, a recent consensus statement on malnutrition from the Academy of Nutrition and Dietetics and the American Society for Parenteral and Enteral Nutrition excluded serum albumin as a diagnostic characteristic; the criteria included percentage of energy requirement, percentage of weight loss and time frame, loss of body fat and muscle mass, presence of edema, and reduced grip strength.³ These may be better measures of malnutrition in dialysis patients and could be used as criteria for determining when to prescribe an appetite stimulant, such as megestrol acetate.

In recent years, megestrol acetate (an antineoplastic drug) has been used to improve appetite, weight, albumin levels, and MICS in patients receiving maintenance dialysis.^1,4-6 Rammohan et al found significant increases in weight, BMI, body fat, triceps skinfold thickness, protein/energy intake, and serum albumin in 10 dialysis patients who took megestrol acetate (400 mg/d) for 16 weeks.⁴

Continue for megestrol acetate's effects >>

In a 20-week randomized, double-blind, placebo-controlled trial, Yeh et al found significant increases in weight, body fat, and fat-free mass in elderly hemodialysis patients receiving megestrol acetate (800 mg/d). The treatment group also demonstrated greater improvement in ability to exercise.⁵

Monfared and colleagues looked specifically at megestrol acetate’s effect on serum albumin levels in dialysis patients.¹ Using a much lower dose (40 mg bid for two months), they found a significant increase in serum albumin in the treatment group. Although an increase in appetite was noted, the researchers did not observe any significant change in total weight following treatment.¹

In a letter to the editor of the Journal of Renal Nutrition, Golebiewska et al reported their use of megestrol acetate in maintenance hemodialysis and peritoneal dialysis patients.⁶ Hypoalbuminemic patients were given megestrol acetate (160 mg/d). Significant increases in weight, BMI, subjective global assessment scores (a measure of nutritional status based on clinical indices such as weight, appetite, muscle, and fat mass), and serum albumin levels were seen. Only 12 of the 32 patients completed the study; the others dropped out due to adverse effects, including high intradialytic weight gain (the amount of fluid gained between dialysis sessions), dyspnea, diarrhea, and nausea.⁶

Currently, there is no consensus in the literature regarding the most effective dosage of megestrol acetate. Furthermore, evidence is lacking as to whether megestrol acetate–induced increases in appetite, oral intake, weight, and serum albumin level bestow any survival benefit or affect outcomes in dialysis patients.⁴ However, the increased sense of well-being a patient experiences when appetite returns and weight is restored may be worth the effort.

Luanne DiGuglielmo, MS, RD, CSR
DaVita Summit Renal Center
Mountainside, New Jersey

REFERENCES
1. Monfared A, Heidarzadeh A, Ghaffari M, Akbarpour M. Effect of megestrol acetate on serum albumin level in malnourished dialysis patients. J Renal Nutr. 2009;19(2):167-171.
2. Byham-Gray L, Stover J, Wiesen K. A clinical guide to nutrition care in kidney disease. Acad Nutr Diet. 2013.
3. White JV, Guenter P, Jensen G, Malone A, Schofield M; Academy of Nutrition and Dietetics Malnutrition Work Group; ASPEN Malnutrition Task Force; ASPEN Board of Directors. Consensus statement of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition)  [erratum appears in J Acad Nutr Diet. 2012 Nov;112(11):1899].
J Acad Nutr Diet. 2012;112(5):730-738.
4. Rammohan M, Kalantar-Zedeh K, Liang A, Ghossein C. Megestrol acetate in a moderate dose for the treatment of malnutrition-inflammation complex in maintenance dialysis patients. J Ren Nutr. 2005;15(3):345-355.
5. Yeh S, Marandi M, Thode H Jr, et al. Report of a pilot, double blind, placebo-controlled study of megestrol acetate in elderly dialysis patients with cachexia. J Ren Nutr. 2010; 20(1):52-62.
6. Golebiewska JE, Lichodziejewska-Niemierko M, Aleksandrowicz-Wrona E, et al. Megestrol acetate use in hypoalbuminemic dialysis patients [comment]. J Ren Nutr. 2011;21(2): 200-202.
7. Bendik I, Friedel A, Roos FF, et al. Vitamin D: a critical and necessary micronutrient for human health. Front Physiol. 2014;5:248.
8. Cabone F, Mach F, Vuilleumier N, Montecucco F. Potential pathophysiological role for the vitamin D deficiency in essential hypertension. World J Cardiol. 2014;6(5):260-276. 
9. Sypniewska G, Pollak J, Strozecki P, et al. 25-hydroxyvitamin D, biomarkers of endothelial dysfunction and subclinical organ damage in adults with hypertension. Am J Hypertens. 2014;27(1):114-121. 
10. Vimaleswaran KS, Cavadino A, Berry DJ, et al. Association of vitamin D status with arterial blood pressure and hypertension risk:  a mendelian randomisation study. Lancet Diabetes Endocrinol. 2014;2(9):719-729.

Q) Some of my CKD patients are malnourished; in fact, some of those on dialysis do not eat well and have low albumin levels. Previously in this column, it was stated that higher albumin levels (> 4 g/dL) confer survival benefits to dialysis patients. Should I consider prescribing megestrol acetate to improve appetite? If I do prescribe it, what dose is safe for CKD and dialysis patients?

Malnutrition affects one-third of dialysis patients,¹ and malnutrition-inflammation complex syn­drome (MICS) is common in those with stage 5 CKD. Albumin is used as an indicator of MICS in dialysis patients; however, since other factors (stress, infection, inflammation, comorbidities) affect nutritional status,² serum albumin alone may not be sufficient to assess it.

In fact, a recent consensus statement on malnutrition from the Academy of Nutrition and Dietetics and the American Society for Parenteral and Enteral Nutrition excluded serum albumin as a diagnostic characteristic; the criteria included percentage of energy requirement, percentage of weight loss and time frame, loss of body fat and muscle mass, presence of edema, and reduced grip strength.³ These may be better measures of malnutrition in dialysis patients and could be used as criteria for determining when to prescribe an appetite stimulant, such as megestrol acetate.

In recent years, megestrol acetate (an antineoplastic drug) has been used to improve appetite, weight, albumin levels, and MICS in patients receiving maintenance dialysis.^1,4-6 Rammohan et al found significant increases in weight, BMI, body fat, triceps skinfold thickness, protein/energy intake, and serum albumin in 10 dialysis patients who took megestrol acetate (400 mg/d) for 16 weeks.⁴

Continue for megestrol acetate's effects >>

In a 20-week randomized, double-blind, placebo-controlled trial, Yeh et al found significant increases in weight, body fat, and fat-free mass in elderly hemodialysis patients receiving megestrol acetate (800 mg/d). The treatment group also demonstrated greater improvement in ability to exercise.⁵

Monfared and colleagues looked specifically at megestrol acetate’s effect on serum albumin levels in dialysis patients.¹ Using a much lower dose (40 mg bid for two months), they found a significant increase in serum albumin in the treatment group. Although an increase in appetite was noted, the researchers did not observe any significant change in total weight following treatment.¹

In a letter to the editor of the Journal of Renal Nutrition, Golebiewska et al reported their use of megestrol acetate in maintenance hemodialysis and peritoneal dialysis patients.⁶ Hypoalbuminemic patients were given megestrol acetate (160 mg/d). Significant increases in weight, BMI, subjective global assessment scores (a measure of nutritional status based on clinical indices such as weight, appetite, muscle, and fat mass), and serum albumin levels were seen. Only 12 of the 32 patients completed the study; the others dropped out due to adverse effects, including high intradialytic weight gain (the amount of fluid gained between dialysis sessions), dyspnea, diarrhea, and nausea.⁶

Currently, there is no consensus in the literature regarding the most effective dosage of megestrol acetate. Furthermore, evidence is lacking as to whether megestrol acetate–induced increases in appetite, oral intake, weight, and serum albumin level bestow any survival benefit or affect outcomes in dialysis patients.⁴ However, the increased sense of well-being a patient experiences when appetite returns and weight is restored may be worth the effort.

Luanne DiGuglielmo, MS, RD, CSR
DaVita Summit Renal Center
Mountainside, New Jersey

REFERENCES
1. Monfared A, Heidarzadeh A, Ghaffari M, Akbarpour M. Effect of megestrol acetate on serum albumin level in malnourished dialysis patients. J Renal Nutr. 2009;19(2):167-171.
2. Byham-Gray L, Stover J, Wiesen K. A clinical guide to nutrition care in kidney disease. Acad Nutr Diet. 2013.
3. White JV, Guenter P, Jensen G, Malone A, Schofield M; Academy of Nutrition and Dietetics Malnutrition Work Group; ASPEN Malnutrition Task Force; ASPEN Board of Directors. Consensus statement of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition)  [erratum appears in J Acad Nutr Diet. 2012 Nov;112(11):1899].
J Acad Nutr Diet. 2012;112(5):730-738.
4. Rammohan M, Kalantar-Zedeh K, Liang A, Ghossein C. Megestrol acetate in a moderate dose for the treatment of malnutrition-inflammation complex in maintenance dialysis patients. J Ren Nutr. 2005;15(3):345-355.
5. Yeh S, Marandi M, Thode H Jr, et al. Report of a pilot, double blind, placebo-controlled study of megestrol acetate in elderly dialysis patients with cachexia. J Ren Nutr. 2010; 20(1):52-62.
6. Golebiewska JE, Lichodziejewska-Niemierko M, Aleksandrowicz-Wrona E, et al. Megestrol acetate use in hypoalbuminemic dialysis patients [comment]. J Ren Nutr. 2011;21(2): 200-202.
7. Bendik I, Friedel A, Roos FF, et al. Vitamin D: a critical and necessary micronutrient for human health. Front Physiol. 2014;5:248.
8. Cabone F, Mach F, Vuilleumier N, Montecucco F. Potential pathophysiological role for the vitamin D deficiency in essential hypertension. World J Cardiol. 2014;6(5):260-276. 
9. Sypniewska G, Pollak J, Strozecki P, et al. 25-hydroxyvitamin D, biomarkers of endothelial dysfunction and subclinical organ damage in adults with hypertension. Am J Hypertens. 2014;27(1):114-121. 
10. Vimaleswaran KS, Cavadino A, Berry DJ, et al. Association of vitamin D status with arterial blood pressure and hypertension risk:  a mendelian randomisation study. Lancet Diabetes Endocrinol. 2014;2(9):719-729.

Q) Some of my CKD patients are malnourished; in fact, some of those on dialysis do not eat well and have low albumin levels. Previously in this column, it was stated that higher albumin levels (> 4 g/dL) confer survival benefits to dialysis patients. Should I consider prescribing megestrol acetate to improve appetite? If I do prescribe it, what dose is safe for CKD and dialysis patients?

Malnutrition affects one-third of dialysis patients,¹ and malnutrition-inflammation complex syn­drome (MICS) is common in those with stage 5 CKD. Albumin is used as an indicator of MICS in dialysis patients; however, since other factors (stress, infection, inflammation, comorbidities) affect nutritional status,² serum albumin alone may not be sufficient to assess it.

In fact, a recent consensus statement on malnutrition from the Academy of Nutrition and Dietetics and the American Society for Parenteral and Enteral Nutrition excluded serum albumin as a diagnostic characteristic; the criteria included percentage of energy requirement, percentage of weight loss and time frame, loss of body fat and muscle mass, presence of edema, and reduced grip strength.³ These may be better measures of malnutrition in dialysis patients and could be used as criteria for determining when to prescribe an appetite stimulant, such as megestrol acetate.

In recent years, megestrol acetate (an antineoplastic drug) has been used to improve appetite, weight, albumin levels, and MICS in patients receiving maintenance dialysis.^1,4-6 Rammohan et al found significant increases in weight, BMI, body fat, triceps skinfold thickness, protein/energy intake, and serum albumin in 10 dialysis patients who took megestrol acetate (400 mg/d) for 16 weeks.⁴

Continue for megestrol acetate's effects >>

In a 20-week randomized, double-blind, placebo-controlled trial, Yeh et al found significant increases in weight, body fat, and fat-free mass in elderly hemodialysis patients receiving megestrol acetate (800 mg/d). The treatment group also demonstrated greater improvement in ability to exercise.⁵

Monfared and colleagues looked specifically at megestrol acetate’s effect on serum albumin levels in dialysis patients.¹ Using a much lower dose (40 mg bid for two months), they found a significant increase in serum albumin in the treatment group. Although an increase in appetite was noted, the researchers did not observe any significant change in total weight following treatment.¹

In a letter to the editor of the Journal of Renal Nutrition, Golebiewska et al reported their use of megestrol acetate in maintenance hemodialysis and peritoneal dialysis patients.⁶ Hypoalbuminemic patients were given megestrol acetate (160 mg/d). Significant increases in weight, BMI, subjective global assessment scores (a measure of nutritional status based on clinical indices such as weight, appetite, muscle, and fat mass), and serum albumin levels were seen. Only 12 of the 32 patients completed the study; the others dropped out due to adverse effects, including high intradialytic weight gain (the amount of fluid gained between dialysis sessions), dyspnea, diarrhea, and nausea.⁶

Currently, there is no consensus in the literature regarding the most effective dosage of megestrol acetate. Furthermore, evidence is lacking as to whether megestrol acetate–induced increases in appetite, oral intake, weight, and serum albumin level bestow any survival benefit or affect outcomes in dialysis patients.⁴ However, the increased sense of well-being a patient experiences when appetite returns and weight is restored may be worth the effort.

Luanne DiGuglielmo, MS, RD, CSR
DaVita Summit Renal Center
Mountainside, New Jersey

REFERENCES
1. Monfared A, Heidarzadeh A, Ghaffari M, Akbarpour M. Effect of megestrol acetate on serum albumin level in malnourished dialysis patients. J Renal Nutr. 2009;19(2):167-171.
2. Byham-Gray L, Stover J, Wiesen K. A clinical guide to nutrition care in kidney disease. Acad Nutr Diet. 2013.
3. White JV, Guenter P, Jensen G, Malone A, Schofield M; Academy of Nutrition and Dietetics Malnutrition Work Group; ASPEN Malnutrition Task Force; ASPEN Board of Directors. Consensus statement of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition)  [erratum appears in J Acad Nutr Diet. 2012 Nov;112(11):1899].
J Acad Nutr Diet. 2012;112(5):730-738.
4. Rammohan M, Kalantar-Zedeh K, Liang A, Ghossein C. Megestrol acetate in a moderate dose for the treatment of malnutrition-inflammation complex in maintenance dialysis patients. J Ren Nutr. 2005;15(3):345-355.
5. Yeh S, Marandi M, Thode H Jr, et al. Report of a pilot, double blind, placebo-controlled study of megestrol acetate in elderly dialysis patients with cachexia. J Ren Nutr. 2010; 20(1):52-62.
6. Golebiewska JE, Lichodziejewska-Niemierko M, Aleksandrowicz-Wrona E, et al. Megestrol acetate use in hypoalbuminemic dialysis patients [comment]. J Ren Nutr. 2011;21(2): 200-202.
7. Bendik I, Friedel A, Roos FF, et al. Vitamin D: a critical and necessary micronutrient for human health. Front Physiol. 2014;5:248.
8. Cabone F, Mach F, Vuilleumier N, Montecucco F. Potential pathophysiological role for the vitamin D deficiency in essential hypertension. World J Cardiol. 2014;6(5):260-276. 
9. Sypniewska G, Pollak J, Strozecki P, et al. 25-hydroxyvitamin D, biomarkers of endothelial dysfunction and subclinical organ damage in adults with hypertension. Am J Hypertens. 2014;27(1):114-121. 
10. Vimaleswaran KS, Cavadino A, Berry DJ, et al. Association of vitamin D status with arterial blood pressure and hypertension risk:  a mendelian randomisation study. Lancet Diabetes Endocrinol. 2014;2(9):719-729.

CASE Seizures, amnesia
Ms. A, age 13, who has a history of seizures, presents to the emergency department (ED) with sudden onset of memory loss. Her family reports that she had been spend­ing a normal evening at home with family and friends. After going to the bathroom, Ms. A became acutely confused and extremely upset, had slurred speech, and did not recognize anyone in the room except her mother.

Initial neurologic examination in the ED reports that Ms. A does not remember recent or remote past events. Her family denies any recent stressors.

Vital signs are within normal range. She has mild muscle soreness and gait instability, which is attributed to a presumed postictal phase. Her medication regimen includes: leve­tiracetam, 500 mg, 3 times a day; valproic acid, 1,000 mg/d; and oxcarbazepine, 2,400 mg/d, for seizure management.

Complete blood count and comprehen­sive metabolic panel are within normal limits. Pregnancy test is negative. Urine toxicology report is negative. Serum valproic acid level is 71 μg/mL; oxcarbazepine level, <2 μg/mL; ammonia level, 71 μg/dL (reference range, 15 to 45 μg/dL). Other than the aforementioned deficits, she is neurologically intact. The team thinks that her symptoms are part of a postic­tal phase of an unwitnessed seizure.

Ms. A is admitted to the inpatient medi­cal unit for further work up. Along with the memory loss and seizures, she reports visual hallucinations.

What could be causing Ms. A’s amnesia?
   a) a seizure disorder
   b) malingering
   c) posttraumatic stress disorder
   d) traumatic brain injury

HISTORY Repeat ED visits
Ms. A’s mother reports that 3 years ago her daughter was treated for tics with quetiapine and aripiprazole, prescribed by a primary care physician. She received a short course of coun­seling 6 years ago after her sister was sexually abused by her grandfather. Approximately 6 months ago, Ms. A engaged in self-injurious behavior by cutting herself, and she briefly received counseling. There is no history of sui­cide attempts, psychiatric hospitalization, or a psychiatric diagnosis.

Medical and surgical history include viral meningitis at age 6 months. Medical records show a visit to the ED for abdominal pain after a classmate punched her in the abdomen, which resolved with supportive care. She was given a diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections 6 years ago.

Ms. A developed multiple recurrent methicillin-resistant Staphylococcus aureus abscesses a year ago, which lasted for 4 months; it was noted that she was self-inoculating by scratching eczema. She had a possible syncopal episode 5 months ago, but the medical work-up was normal. The pediat­ric neurology service diagnosed and treated seizures 4 months ago.

Levetiracetam was prescribed after a pos­sible syncopal episode followed by a tonic-clonic seizure. Because she was still having seizure-like episodes with a single antiepilep­tic drug (AED), oxcarbazepine, then valproic acid were added. Whether her seizures were generalized or partial was inconclusive. The seizures were followed by a postictal phase lasting 3 minutes to 1 hour. Her last general­ized tonic-clonic seizure was 1 month before admission.

Ms. A had 3 MRI studies of the brain over the past 3 years, which showed consistent and unchanged multifocal punctate white matter lesions. The findings represented gliosis from an old perivascular inflammation, trauma, or ischemic damage. There is no history of trau­matic brain injury.

Her perinatal history is unremarkable, with normal vaginal delivery at 36 weeks (pre-term birth). All developmental milestones were on target.

Ms. A lives at home with her mother, 6-year-old brother, and stepfather. Her par­ents are divorced, but her biological father has been involved in her upbringing. She is in seventh grade, but is home schooled after she withdrew from school because of mul­tiple seizure episodes. Ms. A denied bullying at school although she had been punched by a peer. It was unclear if it was a single incident or bullying continued and she was hesitant to disclose it.

The authors’ observations
We focus on the amnesia because it has an acute onset and it seems this is the first time Ms. A presented with this symptom. There is no need to wait for neurology consultation, even though organic causes of amnesia need to be ruled out. Our plan is to develop rapport with Ms. A, and then administer a mental status examina­tion focusing on memory assessment. We understand that, because Ms. A’s chief concern is amnesia, she might not be able to provide many details. We start the initial interview with the family in the patient’s room to understand family dynamics, and then interview Ms. A alone.

EVALUATION Memory problems
On initial psychiatric interview, Ms. A can rec­ognize some of her family members. She is seen in clean attire, with short hair, lying in the bed with good eye contact and a calm demeanor. She seems to be difficult to engage because of her reserved nature.

Ms. A displays some psychomotor retarda­tion. She reports her mood as tired, and her affect is flat and mood incongruent. She is alert and oriented to person only; not to place, time, or situation. She can do a simple spell­ing task, perform 5-minute recall of 3 words, complete serial 3 subtractions, repeat phrases, read aloud, focus on a coin task, and name simple objects. She does not compare similar objects or answer simple historical or factual questions.

Ms. A replies “I don’t know” to most his­torical questions, such as her birthday, favor­ite color, and family members; she does not answer when asked how many legs a dog has, who is the current or past president, what month the Fourth of July is in, or when Christmas is. She can complete some memory tasks on the Mini-Mental State Examination, but does not attempt many others. Ms. A says she is upset about her memory deficit, but her affect was flat. Her mood and her affect were incongruent. She describes a vision of a “girl with black holes [for eyes]” in the corner of her hospital room telling her not to believe any­one and that the interviewers are lying to her. Also, she reports that “the girl” tells her to hurt herself and others, but she is not going to act on the commands because she knows it is not the right thing to do. When we ask Ms. A about a history of substance abuse, she says she has never heard of drugs or alcohol.

Overall, she displays multiple apparent deficits in declarative memory, both episodic and semantic. Regarding non-declarative or procedural memory, she can dress herself, use the bathroom independently, order meals off the menu, and feed herself, among other rou­tine tasks, without difficulty.

According to Ms. A’s mother, Ms. A has shown a decline in overall functioning and personality changes during the past 5 months. She started to cut herself superficially on her forearms 6 months ago and also tried to change her appearance with a new hairstyle when school started. She displayed noticeably intense and disturbing writings, artwork, and conversations with others over 3 to 4 months.

She started experiencing seizures, with 3 to 4 seizures a day; however, she could attend sleepovers seizure-free. She had prolonged periods of seizures lasting up to an hour, much longer than would be expected clinically. She also had requested to go to the cemetery for unclear reasons (because the spirit wanted her to visit), and was observed mumbling under her breath.

Six years ago, Ms. A’s 6-year-old sister tried to suffocate her infant brother. Child protec­tive services was involved and the sister was hospitalized in a psychiatric facility, where she was given a diagnosis of bipolar disorder; she was then transferred to foster care, and later placed in residential treatment. Her mother relinquished her parental rights and gave cus­tody of Ms. A’s sister to the state.

Ms. A’s mother has a history of depression, but her younger brother is healthy. There is no history of autism, attention problems, tics, substance abuse, brain tumor, or intellectual disabilities in the family.

Which diagnosis does Ms. A’s presentation and history suggest?
   a) dissociative amnesia
   b) factitious disorder imposed on self
   c) conversion disorder (neurological symp­tom disorder)
   d) psychosis not otherwise specified
   e) malingering

The authors’ observations
The history of unwitnessed seizures, sud­den onset of visual hallucinations, and transient amnesia points to a possible post­ictal cause. Selective amnesia brings up the question of whether psychological compo­nents are driving the symptoms.

Her psychotic symptoms appear to be mediated by anxiety and possibly related to the trauma of losing her only sister when her mother relinquished custody to the state; the circumstances might have aroused feelings of insecurity or fear of abandonment and raised questions about her mother’s love toward her. Her sis­ter’s abuse by a family member might have created reticence to trust others. These background experiences could be intensely conflicting at this age when the second separation individuation process commences, especially in an emotionally immature adolescent.

OUTCOME Medication change
The neurology team recommends discontinuing levetiracetam because the visual hallucinations, mood disturbance, and personality change could be adverse effects of the drug. Because of generalized uncontrolled body movements with staring episodes and unresponsiveness, an EEG is ordered to rule out ongoing seizures.

Ms. A recognizes the psychosomatic medi­cine team members when they interview her again. The team employs consistent reassur­ance and a non-confrontational approach. She spends 3 days in the medical unit during which she reports that the frequency of visual and auditory hallucinations decreases and her memory symptoms resolve. Her 24-hour EEG is negative for seizure activity, and the 24-hour video EEG does not show any signs of epilepto­genic foci. Ms. A’s family declines inpatient psy­chiatric hospitalization.

Because of gradual improvement in Ms. A’s symptoms and no imminent safety concerns, she is discharged home with valproic acid, 1,000 mg/d, and oxcarbazepine, 1,200 mg/d, and follow-up appointments with her primary care physician, a neurologist, and a psychiatrist.

The authors’ observations
Dissociative amnesia
Generalized dissociative amnesia is dif­ficult to differentiate from factitious disorder or malingering. According to DSM-5, there is loss of episodic memory in dissociative amnesia, in which the person is unable to recall the stressful event after trauma (Table 1).¹ Although there have been case reports of dissocia­tive amnesia with loss of semantic and procedural memory, episodic memory is the last to return.² In Ms. A’s case, there was no immediate basis to explain amne­sia onset, although she had experienced the trauma of losing her sister. She had episodic and mostly semantic memory loss.

Although organic causes can pre­cipitate amnesia,³ Ms. A’s EEG and MRI results did not reflect that. Patients with a dissociative disorder often report some physical, sexual, or emotional abuse.⁴ Although Ms. A did not report any abuse, it cannot be completely ruled out because of her sister’s history of abuse.

Suicidality or self-injurious behavior is common among adults with dissociative amnesia, although it is not well studied in children.^4,5 Generally, the constella­tion of primary dissociative symptoms that patients develop are forgetfulness, fragmentation, and emotional numbing. Ms. A presented with some of these fea­tures; did she, in fact, have dissociative amnesia?

Factitious amnesia
Factious amnesia (Table 2)⁶ is a symptom of factious disorder in which amnesia appears with the motivation to assume a sick role.³ Ms. A’s amnesia garnered sig­nificant attention from her mother and other family members; this may have been related to insecurity in her family relationships because her sister was given up to the state. She also could be afraid of entering adolescence and leaving her sister behind. Did she want more time to bond with her mother? Did she experi­ence emotional benefit from being cared for by medical professionals?⁷ Her affect during interviews was blunted and her attitude was nonchalant, and her multiple visits to the hospital since childhood for abdominal pain, abscesses (it isn’t clear whether the abscesses were related to self-injury and scratching), tics, seizures, and, recently, amnesia and hallucinations indi­cated some desire to occupy a sick role. Furthermore, the severity of her symp­toms seemed to be increasing over time, from somatic to neurologic (seizure-like episodes) to significant and less frequent psychiatric symptoms (amnesia and hal­lucinations). One could speculate that her symptoms were escalating because she was not receiving the attention she needed.

Malingered amnesia
Although malingering is not a psychi­atric diagnosis, it can be a focus of clini­cal attention. It is challenging to identify malingered cognitive impairments.⁸ Children often have difficulty malinger­ing symptoms because they have limited understanding of the illness they are try­ing to simulate.⁹ Many malingerers do not want to participate in their medical work up and might exhibit a hostile attitude toward examiners (Table 2⁶). Clinicians could rely on family to provide informa­tion regarding history and inconsistencies in clinical deficits.⁹ The clinical interview, mental status examination, and collateral information are crucial for identifying malingering.

Most of Ms. A’s seizure-like episodes happened in specific contexts, such as in school, but not at friends’ houses, raising the question of whether she is aware of her episodes. Ms. A’s grades are consis­tently good; because she is being home schooled, there is no secondary gain from not going to school. There is no other reason to speculate that she was malingering.

The inconsistency of Ms. A’s symptoms and her compliance with assessment and treatment did not reflect malingering. Interestingly, Ms. A’s amnesia was retrograde in nature. There have been more studies on malingered anterograde amne­sia⁸ than on retrograde amnesia, making her presentation even more unusual.

Amnesia presenting as conversion disorder
Amnesia as a symptom of conversion disorder is referred as psychogenic amne­sia; the memory loss mostly is isolated retrograde amnesia.¹⁰ Ms. A likely had unconsciously produced symptoms of non-epileptic seizures, followed by audi­tory and visual hallucinations not related to her seizures, and then later developed selective transient amnesia. Conversion disorder seemed to be the diagnosis most consistent with her indifference (“la belle indifference”) and the significant atten­tion she gained from the acute memory loss (Table 3).¹ It seemed that she devel­oped multiple symptoms in progression leading toward a conversion disorder diagnosis. The question arises whether Ms. A’s presentation is a gradually increasing cry for help or reflects depres­sive or anxiety symptoms, which often are comorbid with conversion disorder.

FOLLOW-UP Suicide attempt
Ms. A has frequent visits to the ED with symp­toms of syncope and seizures and undergoes medical work-up and multiple EEGs. A pro­longed 5-day video EEG is performed to assess seizure episodes after AEDs were withdrawn, but no seizure activity is elicited. She also has an ED visit for recurrent tic emergence.

The last visit in the ED is for a suicide attempt with overdose of an unknown quantity of unspecified pills. Ms. A talks to a social worker, who reports that Ms. A needed answers to such questions as why her grandfather abused her sister? Could she have stopped them and made a difference for the family?

The authors’ observations
Conversion disorder arises from uncon­scious psychological conflicts, needs, or responses to trauma. Ms. A’s consistent conflict about her sister and grandfather’s relationship was evident from occasions when she tried to confide in hospital staff. During an ED visit, she reported her sis­ter’s abuse to a staff member. Another time, while recovering from sedation, she spontaneously spoke about her sister’s abuse. When asked again, she said she did not remember saying it.

Freud said that patients develop conver­sion disorder to avoid unacceptable conflict­ing thoughts and feelings.¹⁰ It appeared that Ms. A was struggling with these questions because she brought them up again when she visited the ED after the suicide attempt.

Dissociative symptoms arise from unsta­ble parenting and disciplining styles with variable family dynamics. Patients show extreme detachment and emotional unre­sponsiveness akin to attachment disorder.¹¹ Ms. A had inconsistent parenting because both her stepfather and biological father were involved with her care. Her mother had relinquished her parental rights to her sister, which indicated some attachment issues.

Ms. A’s idea that her mother was indifferent stemmed from her uncaring approach toward her sister and not able to understand her emotionally. Her amnesia could be thought of as “I don’t know you because I don’t remember that I am related to you.” The traumas of infancy (referred to as hidden traumas) that were a result of par­ent-child mismatch of needs and availabil­ity at times of distress might not be obvious to the examiner.¹¹

Although Ms. A’s infancy was reported to be unremarkable, there always is a question, especially in a consultation-liaison setting, of whether conversion disorder might be mask­ing an attachment problem. Perhaps with long-term psychotherapy, an attachment issue would be revealed.

Excluding an organic cause or a neuro­logic disorder is important when diagnosing conversion disorder¹⁰; Ms. A’s negative neu­rologic tests favored a diagnosis of amnesia due to conversion disorder. It appears that, although Ms. A presented with “transient amnesia,” she had underlying psychiatric symptoms, likely depression or anxiety. We were concerned about possible psychiatric comorbidity and recommended inpatient hospitalization to clarify the diagnosis and provide intensive therapy, but her family declined. She may have received outpatient services, but that was not documented.


Bottom Line
Psychogenic amnesia can be a form of conversion disorder or a symptom of
malingering; can occur in dissociative disorder; and can be factitious in nature.
Regardless of the cause, the condition requires continuous close follow up. Although organic causes of amnesia should be ruled out, mental health care can help address comorbid psychiatric symptoms and might change the course of the illness.

Related Resources
• Byatt N, Toor R. Young, pregnant, ataxic—and jilted. Current Psychiatry. 2015;14(1):44-49.
• Leipsic J. A teen who is wasting away. Current Psychiatry. 2013;12(6):40-45.

Drug Brand Names
Aripiprazole • Abilify              Quetiapine • Seroquel
Levetiracetam • Keppra         Valproic acid • Depakote
Oxcarbazepine • Trileptal

 Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE Seizures, amnesia
Ms. A, age 13, who has a history of seizures, presents to the emergency department (ED) with sudden onset of memory loss. Her family reports that she had been spend­ing a normal evening at home with family and friends. After going to the bathroom, Ms. A became acutely confused and extremely upset, had slurred speech, and did not recognize anyone in the room except her mother.

Initial neurologic examination in the ED reports that Ms. A does not remember recent or remote past events. Her family denies any recent stressors.

Vital signs are within normal range. She has mild muscle soreness and gait instability, which is attributed to a presumed postictal phase. Her medication regimen includes: leve­tiracetam, 500 mg, 3 times a day; valproic acid, 1,000 mg/d; and oxcarbazepine, 2,400 mg/d, for seizure management.

Complete blood count and comprehen­sive metabolic panel are within normal limits. Pregnancy test is negative. Urine toxicology report is negative. Serum valproic acid level is 71 μg/mL; oxcarbazepine level, <2 μg/mL; ammonia level, 71 μg/dL (reference range, 15 to 45 μg/dL). Other than the aforementioned deficits, she is neurologically intact. The team thinks that her symptoms are part of a postic­tal phase of an unwitnessed seizure.

Ms. A is admitted to the inpatient medi­cal unit for further work up. Along with the memory loss and seizures, she reports visual hallucinations.

What could be causing Ms. A’s amnesia?
   a) a seizure disorder
   b) malingering
   c) posttraumatic stress disorder
   d) traumatic brain injury

HISTORY Repeat ED visits
Ms. A’s mother reports that 3 years ago her daughter was treated for tics with quetiapine and aripiprazole, prescribed by a primary care physician. She received a short course of coun­seling 6 years ago after her sister was sexually abused by her grandfather. Approximately 6 months ago, Ms. A engaged in self-injurious behavior by cutting herself, and she briefly received counseling. There is no history of sui­cide attempts, psychiatric hospitalization, or a psychiatric diagnosis.

Medical and surgical history include viral meningitis at age 6 months. Medical records show a visit to the ED for abdominal pain after a classmate punched her in the abdomen, which resolved with supportive care. She was given a diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections 6 years ago.

Ms. A developed multiple recurrent methicillin-resistant Staphylococcus aureus abscesses a year ago, which lasted for 4 months; it was noted that she was self-inoculating by scratching eczema. She had a possible syncopal episode 5 months ago, but the medical work-up was normal. The pediat­ric neurology service diagnosed and treated seizures 4 months ago.

Levetiracetam was prescribed after a pos­sible syncopal episode followed by a tonic-clonic seizure. Because she was still having seizure-like episodes with a single antiepilep­tic drug (AED), oxcarbazepine, then valproic acid were added. Whether her seizures were generalized or partial was inconclusive. The seizures were followed by a postictal phase lasting 3 minutes to 1 hour. Her last general­ized tonic-clonic seizure was 1 month before admission.

Ms. A had 3 MRI studies of the brain over the past 3 years, which showed consistent and unchanged multifocal punctate white matter lesions. The findings represented gliosis from an old perivascular inflammation, trauma, or ischemic damage. There is no history of trau­matic brain injury.

Her perinatal history is unremarkable, with normal vaginal delivery at 36 weeks (pre-term birth). All developmental milestones were on target.

Ms. A lives at home with her mother, 6-year-old brother, and stepfather. Her par­ents are divorced, but her biological father has been involved in her upbringing. She is in seventh grade, but is home schooled after she withdrew from school because of mul­tiple seizure episodes. Ms. A denied bullying at school although she had been punched by a peer. It was unclear if it was a single incident or bullying continued and she was hesitant to disclose it.

The authors’ observations
We focus on the amnesia because it has an acute onset and it seems this is the first time Ms. A presented with this symptom. There is no need to wait for neurology consultation, even though organic causes of amnesia need to be ruled out. Our plan is to develop rapport with Ms. A, and then administer a mental status examina­tion focusing on memory assessment. We understand that, because Ms. A’s chief concern is amnesia, she might not be able to provide many details. We start the initial interview with the family in the patient’s room to understand family dynamics, and then interview Ms. A alone.

EVALUATION Memory problems
On initial psychiatric interview, Ms. A can rec­ognize some of her family members. She is seen in clean attire, with short hair, lying in the bed with good eye contact and a calm demeanor. She seems to be difficult to engage because of her reserved nature.

Ms. A displays some psychomotor retarda­tion. She reports her mood as tired, and her affect is flat and mood incongruent. She is alert and oriented to person only; not to place, time, or situation. She can do a simple spell­ing task, perform 5-minute recall of 3 words, complete serial 3 subtractions, repeat phrases, read aloud, focus on a coin task, and name simple objects. She does not compare similar objects or answer simple historical or factual questions.

Ms. A replies “I don’t know” to most his­torical questions, such as her birthday, favor­ite color, and family members; she does not answer when asked how many legs a dog has, who is the current or past president, what month the Fourth of July is in, or when Christmas is. She can complete some memory tasks on the Mini-Mental State Examination, but does not attempt many others. Ms. A says she is upset about her memory deficit, but her affect was flat. Her mood and her affect were incongruent. She describes a vision of a “girl with black holes [for eyes]” in the corner of her hospital room telling her not to believe any­one and that the interviewers are lying to her. Also, she reports that “the girl” tells her to hurt herself and others, but she is not going to act on the commands because she knows it is not the right thing to do. When we ask Ms. A about a history of substance abuse, she says she has never heard of drugs or alcohol.

Overall, she displays multiple apparent deficits in declarative memory, both episodic and semantic. Regarding non-declarative or procedural memory, she can dress herself, use the bathroom independently, order meals off the menu, and feed herself, among other rou­tine tasks, without difficulty.

According to Ms. A’s mother, Ms. A has shown a decline in overall functioning and personality changes during the past 5 months. She started to cut herself superficially on her forearms 6 months ago and also tried to change her appearance with a new hairstyle when school started. She displayed noticeably intense and disturbing writings, artwork, and conversations with others over 3 to 4 months.

She started experiencing seizures, with 3 to 4 seizures a day; however, she could attend sleepovers seizure-free. She had prolonged periods of seizures lasting up to an hour, much longer than would be expected clinically. She also had requested to go to the cemetery for unclear reasons (because the spirit wanted her to visit), and was observed mumbling under her breath.

Six years ago, Ms. A’s 6-year-old sister tried to suffocate her infant brother. Child protec­tive services was involved and the sister was hospitalized in a psychiatric facility, where she was given a diagnosis of bipolar disorder; she was then transferred to foster care, and later placed in residential treatment. Her mother relinquished her parental rights and gave cus­tody of Ms. A’s sister to the state.

Ms. A’s mother has a history of depression, but her younger brother is healthy. There is no history of autism, attention problems, tics, substance abuse, brain tumor, or intellectual disabilities in the family.

Which diagnosis does Ms. A’s presentation and history suggest?
   a) dissociative amnesia
   b) factitious disorder imposed on self
   c) conversion disorder (neurological symp­tom disorder)
   d) psychosis not otherwise specified
   e) malingering

The authors’ observations
The history of unwitnessed seizures, sud­den onset of visual hallucinations, and transient amnesia points to a possible post­ictal cause. Selective amnesia brings up the question of whether psychological compo­nents are driving the symptoms.

Her psychotic symptoms appear to be mediated by anxiety and possibly related to the trauma of losing her only sister when her mother relinquished custody to the state; the circumstances might have aroused feelings of insecurity or fear of abandonment and raised questions about her mother’s love toward her. Her sis­ter’s abuse by a family member might have created reticence to trust others. These background experiences could be intensely conflicting at this age when the second separation individuation process commences, especially in an emotionally immature adolescent.

OUTCOME Medication change
The neurology team recommends discontinuing levetiracetam because the visual hallucinations, mood disturbance, and personality change could be adverse effects of the drug. Because of generalized uncontrolled body movements with staring episodes and unresponsiveness, an EEG is ordered to rule out ongoing seizures.

Ms. A recognizes the psychosomatic medi­cine team members when they interview her again. The team employs consistent reassur­ance and a non-confrontational approach. She spends 3 days in the medical unit during which she reports that the frequency of visual and auditory hallucinations decreases and her memory symptoms resolve. Her 24-hour EEG is negative for seizure activity, and the 24-hour video EEG does not show any signs of epilepto­genic foci. Ms. A’s family declines inpatient psy­chiatric hospitalization.

Because of gradual improvement in Ms. A’s symptoms and no imminent safety concerns, she is discharged home with valproic acid, 1,000 mg/d, and oxcarbazepine, 1,200 mg/d, and follow-up appointments with her primary care physician, a neurologist, and a psychiatrist.

The authors’ observations
Dissociative amnesia
Generalized dissociative amnesia is dif­ficult to differentiate from factitious disorder or malingering. According to DSM-5, there is loss of episodic memory in dissociative amnesia, in which the person is unable to recall the stressful event after trauma (Table 1).¹ Although there have been case reports of dissocia­tive amnesia with loss of semantic and procedural memory, episodic memory is the last to return.² In Ms. A’s case, there was no immediate basis to explain amne­sia onset, although she had experienced the trauma of losing her sister. She had episodic and mostly semantic memory loss.

Although organic causes can pre­cipitate amnesia,³ Ms. A’s EEG and MRI results did not reflect that. Patients with a dissociative disorder often report some physical, sexual, or emotional abuse.⁴ Although Ms. A did not report any abuse, it cannot be completely ruled out because of her sister’s history of abuse.

Suicidality or self-injurious behavior is common among adults with dissociative amnesia, although it is not well studied in children.^4,5 Generally, the constella­tion of primary dissociative symptoms that patients develop are forgetfulness, fragmentation, and emotional numbing. Ms. A presented with some of these fea­tures; did she, in fact, have dissociative amnesia?

Factitious amnesia
Factious amnesia (Table 2)⁶ is a symptom of factious disorder in which amnesia appears with the motivation to assume a sick role.³ Ms. A’s amnesia garnered sig­nificant attention from her mother and other family members; this may have been related to insecurity in her family relationships because her sister was given up to the state. She also could be afraid of entering adolescence and leaving her sister behind. Did she want more time to bond with her mother? Did she experi­ence emotional benefit from being cared for by medical professionals?⁷ Her affect during interviews was blunted and her attitude was nonchalant, and her multiple visits to the hospital since childhood for abdominal pain, abscesses (it isn’t clear whether the abscesses were related to self-injury and scratching), tics, seizures, and, recently, amnesia and hallucinations indi­cated some desire to occupy a sick role. Furthermore, the severity of her symp­toms seemed to be increasing over time, from somatic to neurologic (seizure-like episodes) to significant and less frequent psychiatric symptoms (amnesia and hal­lucinations). One could speculate that her symptoms were escalating because she was not receiving the attention she needed.

Malingered amnesia
Although malingering is not a psychi­atric diagnosis, it can be a focus of clini­cal attention. It is challenging to identify malingered cognitive impairments.⁸ Children often have difficulty malinger­ing symptoms because they have limited understanding of the illness they are try­ing to simulate.⁹ Many malingerers do not want to participate in their medical work up and might exhibit a hostile attitude toward examiners (Table 2⁶). Clinicians could rely on family to provide informa­tion regarding history and inconsistencies in clinical deficits.⁹ The clinical interview, mental status examination, and collateral information are crucial for identifying malingering.

Most of Ms. A’s seizure-like episodes happened in specific contexts, such as in school, but not at friends’ houses, raising the question of whether she is aware of her episodes. Ms. A’s grades are consis­tently good; because she is being home schooled, there is no secondary gain from not going to school. There is no other reason to speculate that she was malingering.

The inconsistency of Ms. A’s symptoms and her compliance with assessment and treatment did not reflect malingering. Interestingly, Ms. A’s amnesia was retrograde in nature. There have been more studies on malingered anterograde amne­sia⁸ than on retrograde amnesia, making her presentation even more unusual.

Amnesia presenting as conversion disorder
Amnesia as a symptom of conversion disorder is referred as psychogenic amne­sia; the memory loss mostly is isolated retrograde amnesia.¹⁰ Ms. A likely had unconsciously produced symptoms of non-epileptic seizures, followed by audi­tory and visual hallucinations not related to her seizures, and then later developed selective transient amnesia. Conversion disorder seemed to be the diagnosis most consistent with her indifference (“la belle indifference”) and the significant atten­tion she gained from the acute memory loss (Table 3).¹ It seemed that she devel­oped multiple symptoms in progression leading toward a conversion disorder diagnosis. The question arises whether Ms. A’s presentation is a gradually increasing cry for help or reflects depres­sive or anxiety symptoms, which often are comorbid with conversion disorder.

FOLLOW-UP Suicide attempt
Ms. A has frequent visits to the ED with symp­toms of syncope and seizures and undergoes medical work-up and multiple EEGs. A pro­longed 5-day video EEG is performed to assess seizure episodes after AEDs were withdrawn, but no seizure activity is elicited. She also has an ED visit for recurrent tic emergence.

The last visit in the ED is for a suicide attempt with overdose of an unknown quantity of unspecified pills. Ms. A talks to a social worker, who reports that Ms. A needed answers to such questions as why her grandfather abused her sister? Could she have stopped them and made a difference for the family?

The authors’ observations
Conversion disorder arises from uncon­scious psychological conflicts, needs, or responses to trauma. Ms. A’s consistent conflict about her sister and grandfather’s relationship was evident from occasions when she tried to confide in hospital staff. During an ED visit, she reported her sis­ter’s abuse to a staff member. Another time, while recovering from sedation, she spontaneously spoke about her sister’s abuse. When asked again, she said she did not remember saying it.

Freud said that patients develop conver­sion disorder to avoid unacceptable conflict­ing thoughts and feelings.¹⁰ It appeared that Ms. A was struggling with these questions because she brought them up again when she visited the ED after the suicide attempt.

Dissociative symptoms arise from unsta­ble parenting and disciplining styles with variable family dynamics. Patients show extreme detachment and emotional unre­sponsiveness akin to attachment disorder.¹¹ Ms. A had inconsistent parenting because both her stepfather and biological father were involved with her care. Her mother had relinquished her parental rights to her sister, which indicated some attachment issues.

Ms. A’s idea that her mother was indifferent stemmed from her uncaring approach toward her sister and not able to understand her emotionally. Her amnesia could be thought of as “I don’t know you because I don’t remember that I am related to you.” The traumas of infancy (referred to as hidden traumas) that were a result of par­ent-child mismatch of needs and availabil­ity at times of distress might not be obvious to the examiner.¹¹

Although Ms. A’s infancy was reported to be unremarkable, there always is a question, especially in a consultation-liaison setting, of whether conversion disorder might be mask­ing an attachment problem. Perhaps with long-term psychotherapy, an attachment issue would be revealed.

Excluding an organic cause or a neuro­logic disorder is important when diagnosing conversion disorder¹⁰; Ms. A’s negative neu­rologic tests favored a diagnosis of amnesia due to conversion disorder. It appears that, although Ms. A presented with “transient amnesia,” she had underlying psychiatric symptoms, likely depression or anxiety. We were concerned about possible psychiatric comorbidity and recommended inpatient hospitalization to clarify the diagnosis and provide intensive therapy, but her family declined. She may have received outpatient services, but that was not documented.


Bottom Line
Psychogenic amnesia can be a form of conversion disorder or a symptom of
malingering; can occur in dissociative disorder; and can be factitious in nature.
Regardless of the cause, the condition requires continuous close follow up. Although organic causes of amnesia should be ruled out, mental health care can help address comorbid psychiatric symptoms and might change the course of the illness.

Related Resources
• Byatt N, Toor R. Young, pregnant, ataxic—and jilted. Current Psychiatry. 2015;14(1):44-49.
• Leipsic J. A teen who is wasting away. Current Psychiatry. 2013;12(6):40-45.

Drug Brand Names
Aripiprazole • Abilify              Quetiapine • Seroquel
Levetiracetam • Keppra         Valproic acid • Depakote
Oxcarbazepine • Trileptal

 Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE Seizures, amnesia
Ms. A, age 13, who has a history of seizures, presents to the emergency department (ED) with sudden onset of memory loss. Her family reports that she had been spend­ing a normal evening at home with family and friends. After going to the bathroom, Ms. A became acutely confused and extremely upset, had slurred speech, and did not recognize anyone in the room except her mother.

Initial neurologic examination in the ED reports that Ms. A does not remember recent or remote past events. Her family denies any recent stressors.

Vital signs are within normal range. She has mild muscle soreness and gait instability, which is attributed to a presumed postictal phase. Her medication regimen includes: leve­tiracetam, 500 mg, 3 times a day; valproic acid, 1,000 mg/d; and oxcarbazepine, 2,400 mg/d, for seizure management.

Complete blood count and comprehen­sive metabolic panel are within normal limits. Pregnancy test is negative. Urine toxicology report is negative. Serum valproic acid level is 71 μg/mL; oxcarbazepine level, <2 μg/mL; ammonia level, 71 μg/dL (reference range, 15 to 45 μg/dL). Other than the aforementioned deficits, she is neurologically intact. The team thinks that her symptoms are part of a postic­tal phase of an unwitnessed seizure.

Ms. A is admitted to the inpatient medi­cal unit for further work up. Along with the memory loss and seizures, she reports visual hallucinations.

What could be causing Ms. A’s amnesia?
   a) a seizure disorder
   b) malingering
   c) posttraumatic stress disorder
   d) traumatic brain injury

HISTORY Repeat ED visits
Ms. A’s mother reports that 3 years ago her daughter was treated for tics with quetiapine and aripiprazole, prescribed by a primary care physician. She received a short course of coun­seling 6 years ago after her sister was sexually abused by her grandfather. Approximately 6 months ago, Ms. A engaged in self-injurious behavior by cutting herself, and she briefly received counseling. There is no history of sui­cide attempts, psychiatric hospitalization, or a psychiatric diagnosis.

Medical and surgical history include viral meningitis at age 6 months. Medical records show a visit to the ED for abdominal pain after a classmate punched her in the abdomen, which resolved with supportive care. She was given a diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections 6 years ago.

Ms. A developed multiple recurrent methicillin-resistant Staphylococcus aureus abscesses a year ago, which lasted for 4 months; it was noted that she was self-inoculating by scratching eczema. She had a possible syncopal episode 5 months ago, but the medical work-up was normal. The pediat­ric neurology service diagnosed and treated seizures 4 months ago.

Levetiracetam was prescribed after a pos­sible syncopal episode followed by a tonic-clonic seizure. Because she was still having seizure-like episodes with a single antiepilep­tic drug (AED), oxcarbazepine, then valproic acid were added. Whether her seizures were generalized or partial was inconclusive. The seizures were followed by a postictal phase lasting 3 minutes to 1 hour. Her last general­ized tonic-clonic seizure was 1 month before admission.

Ms. A had 3 MRI studies of the brain over the past 3 years, which showed consistent and unchanged multifocal punctate white matter lesions. The findings represented gliosis from an old perivascular inflammation, trauma, or ischemic damage. There is no history of trau­matic brain injury.

Her perinatal history is unremarkable, with normal vaginal delivery at 36 weeks (pre-term birth). All developmental milestones were on target.

Ms. A lives at home with her mother, 6-year-old brother, and stepfather. Her par­ents are divorced, but her biological father has been involved in her upbringing. She is in seventh grade, but is home schooled after she withdrew from school because of mul­tiple seizure episodes. Ms. A denied bullying at school although she had been punched by a peer. It was unclear if it was a single incident or bullying continued and she was hesitant to disclose it.

The authors’ observations
We focus on the amnesia because it has an acute onset and it seems this is the first time Ms. A presented with this symptom. There is no need to wait for neurology consultation, even though organic causes of amnesia need to be ruled out. Our plan is to develop rapport with Ms. A, and then administer a mental status examina­tion focusing on memory assessment. We understand that, because Ms. A’s chief concern is amnesia, she might not be able to provide many details. We start the initial interview with the family in the patient’s room to understand family dynamics, and then interview Ms. A alone.

EVALUATION Memory problems
On initial psychiatric interview, Ms. A can rec­ognize some of her family members. She is seen in clean attire, with short hair, lying in the bed with good eye contact and a calm demeanor. She seems to be difficult to engage because of her reserved nature.

Ms. A displays some psychomotor retarda­tion. She reports her mood as tired, and her affect is flat and mood incongruent. She is alert and oriented to person only; not to place, time, or situation. She can do a simple spell­ing task, perform 5-minute recall of 3 words, complete serial 3 subtractions, repeat phrases, read aloud, focus on a coin task, and name simple objects. She does not compare similar objects or answer simple historical or factual questions.

Ms. A replies “I don’t know” to most his­torical questions, such as her birthday, favor­ite color, and family members; she does not answer when asked how many legs a dog has, who is the current or past president, what month the Fourth of July is in, or when Christmas is. She can complete some memory tasks on the Mini-Mental State Examination, but does not attempt many others. Ms. A says she is upset about her memory deficit, but her affect was flat. Her mood and her affect were incongruent. She describes a vision of a “girl with black holes [for eyes]” in the corner of her hospital room telling her not to believe any­one and that the interviewers are lying to her. Also, she reports that “the girl” tells her to hurt herself and others, but she is not going to act on the commands because she knows it is not the right thing to do. When we ask Ms. A about a history of substance abuse, she says she has never heard of drugs or alcohol.

Overall, she displays multiple apparent deficits in declarative memory, both episodic and semantic. Regarding non-declarative or procedural memory, she can dress herself, use the bathroom independently, order meals off the menu, and feed herself, among other rou­tine tasks, without difficulty.

According to Ms. A’s mother, Ms. A has shown a decline in overall functioning and personality changes during the past 5 months. She started to cut herself superficially on her forearms 6 months ago and also tried to change her appearance with a new hairstyle when school started. She displayed noticeably intense and disturbing writings, artwork, and conversations with others over 3 to 4 months.

She started experiencing seizures, with 3 to 4 seizures a day; however, she could attend sleepovers seizure-free. She had prolonged periods of seizures lasting up to an hour, much longer than would be expected clinically. She also had requested to go to the cemetery for unclear reasons (because the spirit wanted her to visit), and was observed mumbling under her breath.

Six years ago, Ms. A’s 6-year-old sister tried to suffocate her infant brother. Child protec­tive services was involved and the sister was hospitalized in a psychiatric facility, where she was given a diagnosis of bipolar disorder; she was then transferred to foster care, and later placed in residential treatment. Her mother relinquished her parental rights and gave cus­tody of Ms. A’s sister to the state.

Ms. A’s mother has a history of depression, but her younger brother is healthy. There is no history of autism, attention problems, tics, substance abuse, brain tumor, or intellectual disabilities in the family.

Which diagnosis does Ms. A’s presentation and history suggest?
   a) dissociative amnesia
   b) factitious disorder imposed on self
   c) conversion disorder (neurological symp­tom disorder)
   d) psychosis not otherwise specified
   e) malingering

The authors’ observations
The history of unwitnessed seizures, sud­den onset of visual hallucinations, and transient amnesia points to a possible post­ictal cause. Selective amnesia brings up the question of whether psychological compo­nents are driving the symptoms.

Her psychotic symptoms appear to be mediated by anxiety and possibly related to the trauma of losing her only sister when her mother relinquished custody to the state; the circumstances might have aroused feelings of insecurity or fear of abandonment and raised questions about her mother’s love toward her. Her sis­ter’s abuse by a family member might have created reticence to trust others. These background experiences could be intensely conflicting at this age when the second separation individuation process commences, especially in an emotionally immature adolescent.

OUTCOME Medication change
The neurology team recommends discontinuing levetiracetam because the visual hallucinations, mood disturbance, and personality change could be adverse effects of the drug. Because of generalized uncontrolled body movements with staring episodes and unresponsiveness, an EEG is ordered to rule out ongoing seizures.

Ms. A recognizes the psychosomatic medi­cine team members when they interview her again. The team employs consistent reassur­ance and a non-confrontational approach. She spends 3 days in the medical unit during which she reports that the frequency of visual and auditory hallucinations decreases and her memory symptoms resolve. Her 24-hour EEG is negative for seizure activity, and the 24-hour video EEG does not show any signs of epilepto­genic foci. Ms. A’s family declines inpatient psy­chiatric hospitalization.

Because of gradual improvement in Ms. A’s symptoms and no imminent safety concerns, she is discharged home with valproic acid, 1,000 mg/d, and oxcarbazepine, 1,200 mg/d, and follow-up appointments with her primary care physician, a neurologist, and a psychiatrist.

The authors’ observations
Dissociative amnesia
Generalized dissociative amnesia is dif­ficult to differentiate from factitious disorder or malingering. According to DSM-5, there is loss of episodic memory in dissociative amnesia, in which the person is unable to recall the stressful event after trauma (Table 1).¹ Although there have been case reports of dissocia­tive amnesia with loss of semantic and procedural memory, episodic memory is the last to return.² In Ms. A’s case, there was no immediate basis to explain amne­sia onset, although she had experienced the trauma of losing her sister. She had episodic and mostly semantic memory loss.

Although organic causes can pre­cipitate amnesia,³ Ms. A’s EEG and MRI results did not reflect that. Patients with a dissociative disorder often report some physical, sexual, or emotional abuse.⁴ Although Ms. A did not report any abuse, it cannot be completely ruled out because of her sister’s history of abuse.

Suicidality or self-injurious behavior is common among adults with dissociative amnesia, although it is not well studied in children.^4,5 Generally, the constella­tion of primary dissociative symptoms that patients develop are forgetfulness, fragmentation, and emotional numbing. Ms. A presented with some of these fea­tures; did she, in fact, have dissociative amnesia?

Factitious amnesia
Factious amnesia (Table 2)⁶ is a symptom of factious disorder in which amnesia appears with the motivation to assume a sick role.³ Ms. A’s amnesia garnered sig­nificant attention from her mother and other family members; this may have been related to insecurity in her family relationships because her sister was given up to the state. She also could be afraid of entering adolescence and leaving her sister behind. Did she want more time to bond with her mother? Did she experi­ence emotional benefit from being cared for by medical professionals?⁷ Her affect during interviews was blunted and her attitude was nonchalant, and her multiple visits to the hospital since childhood for abdominal pain, abscesses (it isn’t clear whether the abscesses were related to self-injury and scratching), tics, seizures, and, recently, amnesia and hallucinations indi­cated some desire to occupy a sick role. Furthermore, the severity of her symp­toms seemed to be increasing over time, from somatic to neurologic (seizure-like episodes) to significant and less frequent psychiatric symptoms (amnesia and hal­lucinations). One could speculate that her symptoms were escalating because she was not receiving the attention she needed.

Malingered amnesia
Although malingering is not a psychi­atric diagnosis, it can be a focus of clini­cal attention. It is challenging to identify malingered cognitive impairments.⁸ Children often have difficulty malinger­ing symptoms because they have limited understanding of the illness they are try­ing to simulate.⁹ Many malingerers do not want to participate in their medical work up and might exhibit a hostile attitude toward examiners (Table 2⁶). Clinicians could rely on family to provide informa­tion regarding history and inconsistencies in clinical deficits.⁹ The clinical interview, mental status examination, and collateral information are crucial for identifying malingering.

Most of Ms. A’s seizure-like episodes happened in specific contexts, such as in school, but not at friends’ houses, raising the question of whether she is aware of her episodes. Ms. A’s grades are consis­tently good; because she is being home schooled, there is no secondary gain from not going to school. There is no other reason to speculate that she was malingering.

The inconsistency of Ms. A’s symptoms and her compliance with assessment and treatment did not reflect malingering. Interestingly, Ms. A’s amnesia was retrograde in nature. There have been more studies on malingered anterograde amne­sia⁸ than on retrograde amnesia, making her presentation even more unusual.

Amnesia presenting as conversion disorder
Amnesia as a symptom of conversion disorder is referred as psychogenic amne­sia; the memory loss mostly is isolated retrograde amnesia.¹⁰ Ms. A likely had unconsciously produced symptoms of non-epileptic seizures, followed by audi­tory and visual hallucinations not related to her seizures, and then later developed selective transient amnesia. Conversion disorder seemed to be the diagnosis most consistent with her indifference (“la belle indifference”) and the significant atten­tion she gained from the acute memory loss (Table 3).¹ It seemed that she devel­oped multiple symptoms in progression leading toward a conversion disorder diagnosis. The question arises whether Ms. A’s presentation is a gradually increasing cry for help or reflects depres­sive or anxiety symptoms, which often are comorbid with conversion disorder.

FOLLOW-UP Suicide attempt
Ms. A has frequent visits to the ED with symp­toms of syncope and seizures and undergoes medical work-up and multiple EEGs. A pro­longed 5-day video EEG is performed to assess seizure episodes after AEDs were withdrawn, but no seizure activity is elicited. She also has an ED visit for recurrent tic emergence.

The last visit in the ED is for a suicide attempt with overdose of an unknown quantity of unspecified pills. Ms. A talks to a social worker, who reports that Ms. A needed answers to such questions as why her grandfather abused her sister? Could she have stopped them and made a difference for the family?

The authors’ observations
Conversion disorder arises from uncon­scious psychological conflicts, needs, or responses to trauma. Ms. A’s consistent conflict about her sister and grandfather’s relationship was evident from occasions when she tried to confide in hospital staff. During an ED visit, she reported her sis­ter’s abuse to a staff member. Another time, while recovering from sedation, she spontaneously spoke about her sister’s abuse. When asked again, she said she did not remember saying it.

Freud said that patients develop conver­sion disorder to avoid unacceptable conflict­ing thoughts and feelings.¹⁰ It appeared that Ms. A was struggling with these questions because she brought them up again when she visited the ED after the suicide attempt.

Dissociative symptoms arise from unsta­ble parenting and disciplining styles with variable family dynamics. Patients show extreme detachment and emotional unre­sponsiveness akin to attachment disorder.¹¹ Ms. A had inconsistent parenting because both her stepfather and biological father were involved with her care. Her mother had relinquished her parental rights to her sister, which indicated some attachment issues.

Ms. A’s idea that her mother was indifferent stemmed from her uncaring approach toward her sister and not able to understand her emotionally. Her amnesia could be thought of as “I don’t know you because I don’t remember that I am related to you.” The traumas of infancy (referred to as hidden traumas) that were a result of par­ent-child mismatch of needs and availabil­ity at times of distress might not be obvious to the examiner.¹¹

Although Ms. A’s infancy was reported to be unremarkable, there always is a question, especially in a consultation-liaison setting, of whether conversion disorder might be mask­ing an attachment problem. Perhaps with long-term psychotherapy, an attachment issue would be revealed.

Excluding an organic cause or a neuro­logic disorder is important when diagnosing conversion disorder¹⁰; Ms. A’s negative neu­rologic tests favored a diagnosis of amnesia due to conversion disorder. It appears that, although Ms. A presented with “transient amnesia,” she had underlying psychiatric symptoms, likely depression or anxiety. We were concerned about possible psychiatric comorbidity and recommended inpatient hospitalization to clarify the diagnosis and provide intensive therapy, but her family declined. She may have received outpatient services, but that was not documented.


Bottom Line
Psychogenic amnesia can be a form of conversion disorder or a symptom of
malingering; can occur in dissociative disorder; and can be factitious in nature.
Regardless of the cause, the condition requires continuous close follow up. Although organic causes of amnesia should be ruled out, mental health care can help address comorbid psychiatric symptoms and might change the course of the illness.

Related Resources
• Byatt N, Toor R. Young, pregnant, ataxic—and jilted. Current Psychiatry. 2015;14(1):44-49.
• Leipsic J. A teen who is wasting away. Current Psychiatry. 2013;12(6):40-45.

Drug Brand Names
Aripiprazole • Abilify              Quetiapine • Seroquel
Levetiracetam • Keppra         Valproic acid • Depakote
Oxcarbazepine • Trileptal

 Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Lisdexamfetamine, approved by the FDA in 2007 for attention-deficit/hyperactivity disorder (ADHD), has a new indication: binge eating disorder (BED) (Table 1). BED is characterized by recurrent episodes of consuming a large amount of food in a short time. A prodrug of amphet­amine, lisdexamfetamine is a Schedule-II controlled substance, with a high potential for abuse and the risk of severe psychologi­cal or physical dependence.

Lisdexamfetamine is not indicated for weight loss or obesity.

Dosage
For BED, the initial dosage of lisdexamfet­amine is 30 mg/d in the morning, titrated by 20 mg/d per week to the target dos­age of 50 to 70 mg/d. Maximum dosage is 70 mg/d. Morning dosing is recommended to avoid sleep disturbance.

Efficacy
The clinical efficacy of lisdexamfetamine was assessed in two 12-week parallel group, flexible-dose, placebo-controlled trials in adults with BED (age 18 to 55). Primary efficacy measure was the num­ber of binge days per week. Both studies had a 4-week dose-optimization period and an 8-week dose-maintenance period and followed the same dosage protocol. Patients began treatment at 30 mg/d and after 1 week were titrated to 50 mg/d; increases to 70 mg/d were made if clini­cally necessary and well tolerated. Patients were maintained on the optimized dos­age during the 8-week dose-maintenance period. A dosage of 30 mg/d did not produce a statistically significant effect, but 50 mg/d and 70 mg/d dosages were statistically superior to placebo. Patients taking lisdexamfetamine also had greater improvement on the Clinical Global Impression—Improvement scores, 4-week binge cessation, and greater reduction in the Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating score.

The prescribing information does not state if lisdexamfetamine should be con­tinued long-term for treating BED.

Adverse reactions
In controlled trials, 5.1% of patients receiv­ing lisdexamfetamine for BED discontin­ued the drug because of an adverse event, compared with 2.4% of patients receiv­ing placebo. The most common adverse reactions in BED studies were dry mouth (36%), insomnia (20%), decreased appetite (8%), increased heart rate (8%), constipation (6%), and feeling jittery (6%). In trials of children, adolescents, and adults with ADHD, decreased appetite was more com­mon (39%, 34%, and 27%, respectively) than in BED trials (Table 2). Anaphylactic reac­tions, Stevens-Johnson syndrome, angio­edema, and urticaria have been described in postmarketing reports.

The safety of lisdexamfetamine for BED has not been studied in patients age <18, but has been studied in patients with ADHD.

Contraindications
Do not give lisdexamfetamine to patients who have a known hypersensitivity to amphetamine products or other ingredi­ents in lisdexamfetamine capsules.

Lisdexamfetamine is contraindicated in patients who are taking a monoamine oxi­dase inhibitor, because of a risk of hyper­tensive crisis.
 

Related Resources
• Wilens TE. Lisdexamfetamine for ADHD. Current Psychiatry. 2007;6(6):96-98,105.
• Peat CM, Brownley KA, Berkman ND, et al. Binge eating dis­order: evidence-based treatments. Current Psychiatry. 2012; 11(5):32-39.

Lisdexamfetamine, approved by the FDA in 2007 for attention-deficit/hyperactivity disorder (ADHD), has a new indication: binge eating disorder (BED) (Table 1). BED is characterized by recurrent episodes of consuming a large amount of food in a short time. A prodrug of amphet­amine, lisdexamfetamine is a Schedule-II controlled substance, with a high potential for abuse and the risk of severe psychologi­cal or physical dependence.

Lisdexamfetamine is not indicated for weight loss or obesity.

Dosage
For BED, the initial dosage of lisdexamfet­amine is 30 mg/d in the morning, titrated by 20 mg/d per week to the target dos­age of 50 to 70 mg/d. Maximum dosage is 70 mg/d. Morning dosing is recommended to avoid sleep disturbance.

Efficacy
The clinical efficacy of lisdexamfetamine was assessed in two 12-week parallel group, flexible-dose, placebo-controlled trials in adults with BED (age 18 to 55). Primary efficacy measure was the num­ber of binge days per week. Both studies had a 4-week dose-optimization period and an 8-week dose-maintenance period and followed the same dosage protocol. Patients began treatment at 30 mg/d and after 1 week were titrated to 50 mg/d; increases to 70 mg/d were made if clini­cally necessary and well tolerated. Patients were maintained on the optimized dos­age during the 8-week dose-maintenance period. A dosage of 30 mg/d did not produce a statistically significant effect, but 50 mg/d and 70 mg/d dosages were statistically superior to placebo. Patients taking lisdexamfetamine also had greater improvement on the Clinical Global Impression—Improvement scores, 4-week binge cessation, and greater reduction in the Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating score.

The prescribing information does not state if lisdexamfetamine should be con­tinued long-term for treating BED.

Adverse reactions
In controlled trials, 5.1% of patients receiv­ing lisdexamfetamine for BED discontin­ued the drug because of an adverse event, compared with 2.4% of patients receiv­ing placebo. The most common adverse reactions in BED studies were dry mouth (36%), insomnia (20%), decreased appetite (8%), increased heart rate (8%), constipation (6%), and feeling jittery (6%). In trials of children, adolescents, and adults with ADHD, decreased appetite was more com­mon (39%, 34%, and 27%, respectively) than in BED trials (Table 2). Anaphylactic reac­tions, Stevens-Johnson syndrome, angio­edema, and urticaria have been described in postmarketing reports.

The safety of lisdexamfetamine for BED has not been studied in patients age <18, but has been studied in patients with ADHD.

Contraindications
Do not give lisdexamfetamine to patients who have a known hypersensitivity to amphetamine products or other ingredi­ents in lisdexamfetamine capsules.

Lisdexamfetamine is contraindicated in patients who are taking a monoamine oxi­dase inhibitor, because of a risk of hyper­tensive crisis.
 

Related Resources
• Wilens TE. Lisdexamfetamine for ADHD. Current Psychiatry. 2007;6(6):96-98,105.
• Peat CM, Brownley KA, Berkman ND, et al. Binge eating dis­order: evidence-based treatments. Current Psychiatry. 2012; 11(5):32-39.

Lisdexamfetamine, approved by the FDA in 2007 for attention-deficit/hyperactivity disorder (ADHD), has a new indication: binge eating disorder (BED) (Table 1). BED is characterized by recurrent episodes of consuming a large amount of food in a short time. A prodrug of amphet­amine, lisdexamfetamine is a Schedule-II controlled substance, with a high potential for abuse and the risk of severe psychologi­cal or physical dependence.

Lisdexamfetamine is not indicated for weight loss or obesity.

Dosage
For BED, the initial dosage of lisdexamfet­amine is 30 mg/d in the morning, titrated by 20 mg/d per week to the target dos­age of 50 to 70 mg/d. Maximum dosage is 70 mg/d. Morning dosing is recommended to avoid sleep disturbance.

Efficacy
The clinical efficacy of lisdexamfetamine was assessed in two 12-week parallel group, flexible-dose, placebo-controlled trials in adults with BED (age 18 to 55). Primary efficacy measure was the num­ber of binge days per week. Both studies had a 4-week dose-optimization period and an 8-week dose-maintenance period and followed the same dosage protocol. Patients began treatment at 30 mg/d and after 1 week were titrated to 50 mg/d; increases to 70 mg/d were made if clini­cally necessary and well tolerated. Patients were maintained on the optimized dos­age during the 8-week dose-maintenance period. A dosage of 30 mg/d did not produce a statistically significant effect, but 50 mg/d and 70 mg/d dosages were statistically superior to placebo. Patients taking lisdexamfetamine also had greater improvement on the Clinical Global Impression—Improvement scores, 4-week binge cessation, and greater reduction in the Yale-Brown Obsessive Compulsive Scale Modified for Binge Eating score.

The prescribing information does not state if lisdexamfetamine should be con­tinued long-term for treating BED.

Adverse reactions
In controlled trials, 5.1% of patients receiv­ing lisdexamfetamine for BED discontin­ued the drug because of an adverse event, compared with 2.4% of patients receiv­ing placebo. The most common adverse reactions in BED studies were dry mouth (36%), insomnia (20%), decreased appetite (8%), increased heart rate (8%), constipation (6%), and feeling jittery (6%). In trials of children, adolescents, and adults with ADHD, decreased appetite was more com­mon (39%, 34%, and 27%, respectively) than in BED trials (Table 2). Anaphylactic reac­tions, Stevens-Johnson syndrome, angio­edema, and urticaria have been described in postmarketing reports.

The safety of lisdexamfetamine for BED has not been studied in patients age <18, but has been studied in patients with ADHD.

Contraindications
Do not give lisdexamfetamine to patients who have a known hypersensitivity to amphetamine products or other ingredi­ents in lisdexamfetamine capsules.

Lisdexamfetamine is contraindicated in patients who are taking a monoamine oxi­dase inhibitor, because of a risk of hyper­tensive crisis.
 

Related Resources
• Wilens TE. Lisdexamfetamine for ADHD. Current Psychiatry. 2007;6(6):96-98,105.
• Peat CM, Brownley KA, Berkman ND, et al. Binge eating dis­order: evidence-based treatments. Current Psychiatry. 2012; 11(5):32-39.

A 28-year-old man presented to a Maryland hospital emergency department (ED) with a two-day history of low-grade fever, nonproductive cough, and dizziness. He was also tachycardic and significantly hypoxic. After an hour’s wait, the patient saw an emergency physician, who noted complaints of weakness, shortness of breath, and lightheadedness. The differential diagnosis included pneumonia, congestive heart failure, and pulmonary embolism (PE).

After an ECG, chest x-ray, and blood work, the emergency physician diagnosed pneumonia and renal insufficiency. The patient was admitted but within eight hours of arrival at the ED was transferred to another hospital. The admitting physician at the second hospital did not evaluate the patient on admission.

Almost five hours later, the patient got out of bed and collapsed in the presence of his wife. A code was called, but the man never regained consciousness and was pronounced dead about 90 minutes later. An autopsy confirmed a PE as the cause of death.

Plaintiff for the decedent alleged negligence in the clinicians’ failure to diagnose and treat the PE. The plaintiff claimed that with proper treatment, the patient would have ­survived.

The defendants argued that there was no negligence involved and that heparin therapy would not have prevented the patient’s death.

What was the outcome? >>

OUTCOME
According to a published account, a $6.1 million verdict was returned.

COMMENT
This is a substantial verdict, reflecting the jury’s revulsion at the loss of a 28-year-old patient. His initial presentation of low-grade fever, nonproductive cough, and dizziness with tachycardia and hypoxia could be consistent with either pneumonia or PE. The facts as presented render the chest x-ray findings and the magnitude of hypoxia unclear. We also are not told whether any specific risk factors existed to make PE more likely, nor whether there was evidence of deep vein thrombosis (DVT) during presentation or at autopsy.

Diagnosing PE can be difficult. However, jurors confronted with a case involving a fatal PE may be led to believe that the diagnosis is straightforward and should never be missed. Plaintiff’s counsel will argue that the patient “would be standing here today” in a fully functional status if the diagnosis had been made.

Here, presumptively, the chest films and chest auscultation were suggestive of pneumonia and led the clinician, who actively considered PE, to ultimately exclude the possibility. It is not clear why the patient was transferred and not formally evaluated upon arrival at the second hospital, but the facts indicate that the patient was “significantly hypoxic.” This should have entailed close monitoring by the receiving clinician, irrespective of the diagnosis.

The pathophysiology of PE is straightforward—but the presentation is often variable and nonspecific and the diagnosis tricky. Thus, for the clinician confronted with a hypoxic patient, it is important to consider this diagnosis early and thoroughly. Evaluate for risk factors: hypercoagulability, as in cases of malignancy, estrogen use, pregnancy, antiphospholipid syndrome (Hughes syndrome), or genomic mutations (eg, factor V Leiden mutation, prothrombin mutation, factor VIII mutations, protein C and protein S deficiency); venous stasis; and vascular endothelial damage, as possibly occasioned by hypertension or atherosclerotic disease.

In addition, it is important to confirm the presence or absence of a DVT. Follow evidence-based rules, such as the Wells score, to guide decision making. In Wells scoring, points are assigned for each of seven criteria, allowing the patient to be categorized by high, moderate, or low probability for PE. The Wells scoring criteria comprise
• Suspected DVT (3 points)
• PE the most likely diagnosis, or equally likely as a second diagnosis (3 points)
• Tachycardia (heart rate > 100 beats/min; 1.5 points)
• Immobilization for at least three days or surgery within the previous four weeks (1.5 points)
• History of DVT or PE (1.5 points)
• Hemoptysis (1 point)
• Malignancy with treatment within previous six months (1 point)

Patients with a total score exceeding 6 points are considered high-probability for PE and should undergo multidetector CT. Those with a score of 2 to 6 have moderate probability and should undergo high-sensitivity d-dimer testing; negative d-dimer results exclude PE and positive results warrant multidetector CT and lower-extremity ultrasound. In low-probability patients (Wells score below 2) with negative d-dimer results, PE is excluded; if d-dimer results are positive, multidetector CT should be ordered.

IN SUM
Extensive discussion of clinical predictive rules, diagnostic modalities, and treatment is beyond the scope of this comment. But clinicians should apply evidence-based decision-making rules to establish a diagnosis. And it should be apparent that hypoxic patients warrant close monitoring—particularly when a change of provider, service, or institution occurs. —DML

A 28-year-old man presented to a Maryland hospital emergency department (ED) with a two-day history of low-grade fever, nonproductive cough, and dizziness. He was also tachycardic and significantly hypoxic. After an hour’s wait, the patient saw an emergency physician, who noted complaints of weakness, shortness of breath, and lightheadedness. The differential diagnosis included pneumonia, congestive heart failure, and pulmonary embolism (PE).

After an ECG, chest x-ray, and blood work, the emergency physician diagnosed pneumonia and renal insufficiency. The patient was admitted but within eight hours of arrival at the ED was transferred to another hospital. The admitting physician at the second hospital did not evaluate the patient on admission.

Almost five hours later, the patient got out of bed and collapsed in the presence of his wife. A code was called, but the man never regained consciousness and was pronounced dead about 90 minutes later. An autopsy confirmed a PE as the cause of death.

Plaintiff for the decedent alleged negligence in the clinicians’ failure to diagnose and treat the PE. The plaintiff claimed that with proper treatment, the patient would have ­survived.

The defendants argued that there was no negligence involved and that heparin therapy would not have prevented the patient’s death.

What was the outcome? >>

OUTCOME
According to a published account, a $6.1 million verdict was returned.

COMMENT
This is a substantial verdict, reflecting the jury’s revulsion at the loss of a 28-year-old patient. His initial presentation of low-grade fever, nonproductive cough, and dizziness with tachycardia and hypoxia could be consistent with either pneumonia or PE. The facts as presented render the chest x-ray findings and the magnitude of hypoxia unclear. We also are not told whether any specific risk factors existed to make PE more likely, nor whether there was evidence of deep vein thrombosis (DVT) during presentation or at autopsy.

Diagnosing PE can be difficult. However, jurors confronted with a case involving a fatal PE may be led to believe that the diagnosis is straightforward and should never be missed. Plaintiff’s counsel will argue that the patient “would be standing here today” in a fully functional status if the diagnosis had been made.

Here, presumptively, the chest films and chest auscultation were suggestive of pneumonia and led the clinician, who actively considered PE, to ultimately exclude the possibility. It is not clear why the patient was transferred and not formally evaluated upon arrival at the second hospital, but the facts indicate that the patient was “significantly hypoxic.” This should have entailed close monitoring by the receiving clinician, irrespective of the diagnosis.

The pathophysiology of PE is straightforward—but the presentation is often variable and nonspecific and the diagnosis tricky. Thus, for the clinician confronted with a hypoxic patient, it is important to consider this diagnosis early and thoroughly. Evaluate for risk factors: hypercoagulability, as in cases of malignancy, estrogen use, pregnancy, antiphospholipid syndrome (Hughes syndrome), or genomic mutations (eg, factor V Leiden mutation, prothrombin mutation, factor VIII mutations, protein C and protein S deficiency); venous stasis; and vascular endothelial damage, as possibly occasioned by hypertension or atherosclerotic disease.

In addition, it is important to confirm the presence or absence of a DVT. Follow evidence-based rules, such as the Wells score, to guide decision making. In Wells scoring, points are assigned for each of seven criteria, allowing the patient to be categorized by high, moderate, or low probability for PE. The Wells scoring criteria comprise
• Suspected DVT (3 points)
• PE the most likely diagnosis, or equally likely as a second diagnosis (3 points)
• Tachycardia (heart rate > 100 beats/min; 1.5 points)
• Immobilization for at least three days or surgery within the previous four weeks (1.5 points)
• History of DVT or PE (1.5 points)
• Hemoptysis (1 point)
• Malignancy with treatment within previous six months (1 point)

Patients with a total score exceeding 6 points are considered high-probability for PE and should undergo multidetector CT. Those with a score of 2 to 6 have moderate probability and should undergo high-sensitivity d-dimer testing; negative d-dimer results exclude PE and positive results warrant multidetector CT and lower-extremity ultrasound. In low-probability patients (Wells score below 2) with negative d-dimer results, PE is excluded; if d-dimer results are positive, multidetector CT should be ordered.

IN SUM
Extensive discussion of clinical predictive rules, diagnostic modalities, and treatment is beyond the scope of this comment. But clinicians should apply evidence-based decision-making rules to establish a diagnosis. And it should be apparent that hypoxic patients warrant close monitoring—particularly when a change of provider, service, or institution occurs. —DML

A 28-year-old man presented to a Maryland hospital emergency department (ED) with a two-day history of low-grade fever, nonproductive cough, and dizziness. He was also tachycardic and significantly hypoxic. After an hour’s wait, the patient saw an emergency physician, who noted complaints of weakness, shortness of breath, and lightheadedness. The differential diagnosis included pneumonia, congestive heart failure, and pulmonary embolism (PE).

After an ECG, chest x-ray, and blood work, the emergency physician diagnosed pneumonia and renal insufficiency. The patient was admitted but within eight hours of arrival at the ED was transferred to another hospital. The admitting physician at the second hospital did not evaluate the patient on admission.

Almost five hours later, the patient got out of bed and collapsed in the presence of his wife. A code was called, but the man never regained consciousness and was pronounced dead about 90 minutes later. An autopsy confirmed a PE as the cause of death.

Plaintiff for the decedent alleged negligence in the clinicians’ failure to diagnose and treat the PE. The plaintiff claimed that with proper treatment, the patient would have ­survived.

The defendants argued that there was no negligence involved and that heparin therapy would not have prevented the patient’s death.

What was the outcome? >>

OUTCOME
According to a published account, a $6.1 million verdict was returned.

COMMENT
This is a substantial verdict, reflecting the jury’s revulsion at the loss of a 28-year-old patient. His initial presentation of low-grade fever, nonproductive cough, and dizziness with tachycardia and hypoxia could be consistent with either pneumonia or PE. The facts as presented render the chest x-ray findings and the magnitude of hypoxia unclear. We also are not told whether any specific risk factors existed to make PE more likely, nor whether there was evidence of deep vein thrombosis (DVT) during presentation or at autopsy.

Diagnosing PE can be difficult. However, jurors confronted with a case involving a fatal PE may be led to believe that the diagnosis is straightforward and should never be missed. Plaintiff’s counsel will argue that the patient “would be standing here today” in a fully functional status if the diagnosis had been made.

Here, presumptively, the chest films and chest auscultation were suggestive of pneumonia and led the clinician, who actively considered PE, to ultimately exclude the possibility. It is not clear why the patient was transferred and not formally evaluated upon arrival at the second hospital, but the facts indicate that the patient was “significantly hypoxic.” This should have entailed close monitoring by the receiving clinician, irrespective of the diagnosis.

The pathophysiology of PE is straightforward—but the presentation is often variable and nonspecific and the diagnosis tricky. Thus, for the clinician confronted with a hypoxic patient, it is important to consider this diagnosis early and thoroughly. Evaluate for risk factors: hypercoagulability, as in cases of malignancy, estrogen use, pregnancy, antiphospholipid syndrome (Hughes syndrome), or genomic mutations (eg, factor V Leiden mutation, prothrombin mutation, factor VIII mutations, protein C and protein S deficiency); venous stasis; and vascular endothelial damage, as possibly occasioned by hypertension or atherosclerotic disease.

In addition, it is important to confirm the presence or absence of a DVT. Follow evidence-based rules, such as the Wells score, to guide decision making. In Wells scoring, points are assigned for each of seven criteria, allowing the patient to be categorized by high, moderate, or low probability for PE. The Wells scoring criteria comprise
• Suspected DVT (3 points)
• PE the most likely diagnosis, or equally likely as a second diagnosis (3 points)
• Tachycardia (heart rate > 100 beats/min; 1.5 points)
• Immobilization for at least three days or surgery within the previous four weeks (1.5 points)
• History of DVT or PE (1.5 points)
• Hemoptysis (1 point)
• Malignancy with treatment within previous six months (1 point)

Patients with a total score exceeding 6 points are considered high-probability for PE and should undergo multidetector CT. Those with a score of 2 to 6 have moderate probability and should undergo high-sensitivity d-dimer testing; negative d-dimer results exclude PE and positive results warrant multidetector CT and lower-extremity ultrasound. In low-probability patients (Wells score below 2) with negative d-dimer results, PE is excluded; if d-dimer results are positive, multidetector CT should be ordered.

IN SUM
Extensive discussion of clinical predictive rules, diagnostic modalities, and treatment is beyond the scope of this comment. But clinicians should apply evidence-based decision-making rules to establish a diagnosis. And it should be apparent that hypoxic patients warrant close monitoring—particularly when a change of provider, service, or institution occurs. —DML

Dear Dr. Mossman,

At the hospital where I serve as the psychi­atric consultant, a medical team asked me to evaluate a patient’s capacity to designate a new power of attorney (POA) for health care. The patient’s relatives want the change because they think the current POA—also a relative—is stealing the patient’s funds. The contentious family situation made me wonder: What legal risks might I face after I assess the patient’s capacity to choose a new POA?

Submitted by “Dr. P”

As America’s population ages, situa­tions like the one Dr. P has encoun­tered will become more common. Many variables—time constraints, patients’ cognitive impairments, lack of prior rela­tionships with patients, complex medical situations, and strained family dynamics— can make these clinical situations complex and daunting.

Dr. P realizes that feuding relatives can redirect their anger toward a well-meaning physician who might appear to take sides in a dispute. Yet staying silent isn’t a good option, either: If the patient is being mis­treated or abused, Dr. P may have a duty to initiate appropriate protective action.

In this article, we’ll respond to Dr. P’s question by examining these topics:
   • what a POA is and the rationale for having one
   • standards for capacity to choose a POA
   • characteristics and dynamics of poten­tial surrogates
   • responding to possible elder abuse.

Surrogate decision-makers
People can lose their decision-making capacity because of dementia, acute or chronic illness, or sudden injury. Although autonomy and respecting decisions of mentally capable people are paramount American values, our legal system has several mechanisms that can be activated on behalf of people who have lost their decision-making capabilities.

When a careful evaluation suggests that a patient cannot make informed medical decisions, one solution is to turn to a sur­rogate decision-maker whom the patient previously has designated to act on his (her) behalf, should he (she) become inca­pacitated. A surrogate can make decisions based on the incapacitated person’s cur­rent utterances (eg, expressions of pain), previously expressed wishes about what should happen under certain circum­stances, or the surrogate’s judgment of the person’s best interest.¹

States have varied legal frameworks for establishing surrogacy and refer to a sur­rogate using terms such as proxy, agent, attorney-in-fact, and power of attorney.² POA responsibilities can encompass a broad array of decision-making tasks or can be limited, for example, to handling banking transactions or managing estate planning.^3,4 A POA can be “durable” and grant lasting power regardless of disability, or “spring­ing” and operational only when the desig­nator has lost capacity.

A health care POA designates a substi­tute decision-maker for medical care. The Patient Self-Determination Act and the Joint Commission obligate health care pro­fessionals to follow the decisions made by a legally valid POA. Generally, providers who follow a surrogate’s decision in good faith have legal immunity, but they must challenge a surrogate’s decision if it devi­ates widely from usual protocol.²

Legal standards
Dr. P received a consultation request that asked whether a patient with compro­mised medical decision-making powers nonetheless had the current capacity to choose a new POA.

To evaluate the patient’s capacity to des­ignate a new POA, Dr. P must know what having this capacity means. What deter­mines if someone has the capacity to des­ignate a POA is a legal matter, and unless Dr. P is sure what the laws in her state say about this, she should consult a lawyer who can explain the jurisdiction’s applicable legal standards to her.⁵

The law generally presumes that adults are competent to make health care decisions, including decisions about appointing a POA.⁵ The law also recognizes that people with cog­nitive impairments or mental illnesses still can be competent to appoint POAs.⁴

Most states don’t have statutes that define the capacity to appoint a health care POA. In these jurisdictions, courts may apply standards similar to those concerning competence to enter into a contract.⁶Table 1 describes criteria in 4 states that do have statutory provisions concerning compe­tence to designate a health care POA.

Approaching the evaluation
Before evaluating a person’s capacity to designate a POA, you should first under­stand the person’s medical condition and learn what powers the surrogate would have. A detailed description of the evalu­ation process lies beyond the scope of this article. For more information, please con­sult the structured interviews described by Moye et al⁴ and Soliman’s guide to the evaluation process.⁷

In addition to examining the patient’s psychological status and cognitive capacity, you also might have to consider contextual variables, such as:
   • potential risks of not allowing the appointment of POA, including a delay in needed care
   • the person’s relationship to the pro­posed POA
   • possible power imbalances or evi­dence of coercion
   • how the person would benefit from having the POA.⁸

People who have good marital or parent-child relationships are more likely to select loved ones as their POAs.⁹ Family mem­bers who have not previously served as surrogates or have not had talked with their loved ones about their preferences feel less confident exercising the duties of a POA.¹⁰ An evaluation, therefore, should consider the prior relationship between the designator and proposed surrogate, and particularly whether these parties have dis­cussed the designator’s health care prefer­ences. Table 2 lists potential pitfalls in POA evaluations.^{2,4,5,8,11-13,16}

Many variables—the stress of the situation,⁸ pre-existing relationship dynamics,¹⁸ and caregiver psychopathology¹¹—lead POAs to exploit their designator. Sometimes, family members believe that they are enti­tled to a relative’s money because of real or imagined transgressions¹⁹ or because they regard themselves as eventual heirs to their relative’s estate.¹⁶ Some desig­nated POAs use designators’ funds sim­ply because they need money. Kemp and Mosqueda²⁰ have developed an evaluation framework for assessing possible financial abuse (Table 3).

Although reporting financial abuse can strain alliances between patients and their families, psychiatrists bear a responsibil­ity to look out for the welfare of their older patients.⁸ Indeed, all 50 states have elder abuse statutes, most of which mandate reporting by physicians.²¹

Suspicion of financial abuse could indi­cate the need to evaluate the susceptible person’s capacity to make financial deci­sions.¹² Depending on the patient’s circum­stances and medical problems, further steps might include:
   • contacting proper authorities, such as Adult Protective Services or the Department of Human Services
   • contacting local law enforcement
   • instituting procedures for emergency guardianship
   • arranging for more in-home services for the patient or recommending a higher level of care
   • developing a treatment plan for the patient’s medical and psychiatric problems
   • communicating with other trusted family members.^12,18

Bottom Line
Evaluating the capacity to appoint a power of attorney (POA) often requires awareness of social systems, family dynamics, and legal requirements, combined with the psychiatric data from a systematic individual assessment. Evaluating psychiatrists should understand what type of POA is being considered and the applicable legal standards in the jurisdictions where they work.

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Dear Dr. Mossman,

At the hospital where I serve as the psychi­atric consultant, a medical team asked me to evaluate a patient’s capacity to designate a new power of attorney (POA) for health care. The patient’s relatives want the change because they think the current POA—also a relative—is stealing the patient’s funds. The contentious family situation made me wonder: What legal risks might I face after I assess the patient’s capacity to choose a new POA?

Submitted by “Dr. P”

As America’s population ages, situa­tions like the one Dr. P has encoun­tered will become more common. Many variables—time constraints, patients’ cognitive impairments, lack of prior rela­tionships with patients, complex medical situations, and strained family dynamics— can make these clinical situations complex and daunting.

Dr. P realizes that feuding relatives can redirect their anger toward a well-meaning physician who might appear to take sides in a dispute. Yet staying silent isn’t a good option, either: If the patient is being mis­treated or abused, Dr. P may have a duty to initiate appropriate protective action.

In this article, we’ll respond to Dr. P’s question by examining these topics:
   • what a POA is and the rationale for having one
   • standards for capacity to choose a POA
   • characteristics and dynamics of poten­tial surrogates
   • responding to possible elder abuse.

Surrogate decision-makers
People can lose their decision-making capacity because of dementia, acute or chronic illness, or sudden injury. Although autonomy and respecting decisions of mentally capable people are paramount American values, our legal system has several mechanisms that can be activated on behalf of people who have lost their decision-making capabilities.

When a careful evaluation suggests that a patient cannot make informed medical decisions, one solution is to turn to a sur­rogate decision-maker whom the patient previously has designated to act on his (her) behalf, should he (she) become inca­pacitated. A surrogate can make decisions based on the incapacitated person’s cur­rent utterances (eg, expressions of pain), previously expressed wishes about what should happen under certain circum­stances, or the surrogate’s judgment of the person’s best interest.¹

States have varied legal frameworks for establishing surrogacy and refer to a sur­rogate using terms such as proxy, agent, attorney-in-fact, and power of attorney.² POA responsibilities can encompass a broad array of decision-making tasks or can be limited, for example, to handling banking transactions or managing estate planning.^3,4 A POA can be “durable” and grant lasting power regardless of disability, or “spring­ing” and operational only when the desig­nator has lost capacity.

A health care POA designates a substi­tute decision-maker for medical care. The Patient Self-Determination Act and the Joint Commission obligate health care pro­fessionals to follow the decisions made by a legally valid POA. Generally, providers who follow a surrogate’s decision in good faith have legal immunity, but they must challenge a surrogate’s decision if it devi­ates widely from usual protocol.²

Legal standards
Dr. P received a consultation request that asked whether a patient with compro­mised medical decision-making powers nonetheless had the current capacity to choose a new POA.

To evaluate the patient’s capacity to des­ignate a new POA, Dr. P must know what having this capacity means. What deter­mines if someone has the capacity to des­ignate a POA is a legal matter, and unless Dr. P is sure what the laws in her state say about this, she should consult a lawyer who can explain the jurisdiction’s applicable legal standards to her.⁵

The law generally presumes that adults are competent to make health care decisions, including decisions about appointing a POA.⁵ The law also recognizes that people with cog­nitive impairments or mental illnesses still can be competent to appoint POAs.⁴

Most states don’t have statutes that define the capacity to appoint a health care POA. In these jurisdictions, courts may apply standards similar to those concerning competence to enter into a contract.⁶Table 1 describes criteria in 4 states that do have statutory provisions concerning compe­tence to designate a health care POA.

Approaching the evaluation
Before evaluating a person’s capacity to designate a POA, you should first under­stand the person’s medical condition and learn what powers the surrogate would have. A detailed description of the evalu­ation process lies beyond the scope of this article. For more information, please con­sult the structured interviews described by Moye et al⁴ and Soliman’s guide to the evaluation process.⁷

In addition to examining the patient’s psychological status and cognitive capacity, you also might have to consider contextual variables, such as:
   • potential risks of not allowing the appointment of POA, including a delay in needed care
   • the person’s relationship to the pro­posed POA
   • possible power imbalances or evi­dence of coercion
   • how the person would benefit from having the POA.⁸

People who have good marital or parent-child relationships are more likely to select loved ones as their POAs.⁹ Family mem­bers who have not previously served as surrogates or have not had talked with their loved ones about their preferences feel less confident exercising the duties of a POA.¹⁰ An evaluation, therefore, should consider the prior relationship between the designator and proposed surrogate, and particularly whether these parties have dis­cussed the designator’s health care prefer­ences. Table 2 lists potential pitfalls in POA evaluations.^{2,4,5,8,11-13,16}

Many variables—the stress of the situation,⁸ pre-existing relationship dynamics,¹⁸ and caregiver psychopathology¹¹—lead POAs to exploit their designator. Sometimes, family members believe that they are enti­tled to a relative’s money because of real or imagined transgressions¹⁹ or because they regard themselves as eventual heirs to their relative’s estate.¹⁶ Some desig­nated POAs use designators’ funds sim­ply because they need money. Kemp and Mosqueda²⁰ have developed an evaluation framework for assessing possible financial abuse (Table 3).

Although reporting financial abuse can strain alliances between patients and their families, psychiatrists bear a responsibil­ity to look out for the welfare of their older patients.⁸ Indeed, all 50 states have elder abuse statutes, most of which mandate reporting by physicians.²¹

Suspicion of financial abuse could indi­cate the need to evaluate the susceptible person’s capacity to make financial deci­sions.¹² Depending on the patient’s circum­stances and medical problems, further steps might include:
   • contacting proper authorities, such as Adult Protective Services or the Department of Human Services
   • contacting local law enforcement
   • instituting procedures for emergency guardianship
   • arranging for more in-home services for the patient or recommending a higher level of care
   • developing a treatment plan for the patient’s medical and psychiatric problems
   • communicating with other trusted family members.^12,18

Bottom Line
Evaluating the capacity to appoint a power of attorney (POA) often requires awareness of social systems, family dynamics, and legal requirements, combined with the psychiatric data from a systematic individual assessment. Evaluating psychiatrists should understand what type of POA is being considered and the applicable legal standards in the jurisdictions where they work.

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Dear Dr. Mossman,

At the hospital where I serve as the psychi­atric consultant, a medical team asked me to evaluate a patient’s capacity to designate a new power of attorney (POA) for health care. The patient’s relatives want the change because they think the current POA—also a relative—is stealing the patient’s funds. The contentious family situation made me wonder: What legal risks might I face after I assess the patient’s capacity to choose a new POA?

Submitted by “Dr. P”

As America’s population ages, situa­tions like the one Dr. P has encoun­tered will become more common. Many variables—time constraints, patients’ cognitive impairments, lack of prior rela­tionships with patients, complex medical situations, and strained family dynamics— can make these clinical situations complex and daunting.

Dr. P realizes that feuding relatives can redirect their anger toward a well-meaning physician who might appear to take sides in a dispute. Yet staying silent isn’t a good option, either: If the patient is being mis­treated or abused, Dr. P may have a duty to initiate appropriate protective action.

In this article, we’ll respond to Dr. P’s question by examining these topics:
   • what a POA is and the rationale for having one
   • standards for capacity to choose a POA
   • characteristics and dynamics of poten­tial surrogates
   • responding to possible elder abuse.

Surrogate decision-makers
People can lose their decision-making capacity because of dementia, acute or chronic illness, or sudden injury. Although autonomy and respecting decisions of mentally capable people are paramount American values, our legal system has several mechanisms that can be activated on behalf of people who have lost their decision-making capabilities.

When a careful evaluation suggests that a patient cannot make informed medical decisions, one solution is to turn to a sur­rogate decision-maker whom the patient previously has designated to act on his (her) behalf, should he (she) become inca­pacitated. A surrogate can make decisions based on the incapacitated person’s cur­rent utterances (eg, expressions of pain), previously expressed wishes about what should happen under certain circum­stances, or the surrogate’s judgment of the person’s best interest.¹

States have varied legal frameworks for establishing surrogacy and refer to a sur­rogate using terms such as proxy, agent, attorney-in-fact, and power of attorney.² POA responsibilities can encompass a broad array of decision-making tasks or can be limited, for example, to handling banking transactions or managing estate planning.^3,4 A POA can be “durable” and grant lasting power regardless of disability, or “spring­ing” and operational only when the desig­nator has lost capacity.

A health care POA designates a substi­tute decision-maker for medical care. The Patient Self-Determination Act and the Joint Commission obligate health care pro­fessionals to follow the decisions made by a legally valid POA. Generally, providers who follow a surrogate’s decision in good faith have legal immunity, but they must challenge a surrogate’s decision if it devi­ates widely from usual protocol.²

Legal standards
Dr. P received a consultation request that asked whether a patient with compro­mised medical decision-making powers nonetheless had the current capacity to choose a new POA.

To evaluate the patient’s capacity to des­ignate a new POA, Dr. P must know what having this capacity means. What deter­mines if someone has the capacity to des­ignate a POA is a legal matter, and unless Dr. P is sure what the laws in her state say about this, she should consult a lawyer who can explain the jurisdiction’s applicable legal standards to her.⁵

The law generally presumes that adults are competent to make health care decisions, including decisions about appointing a POA.⁵ The law also recognizes that people with cog­nitive impairments or mental illnesses still can be competent to appoint POAs.⁴

Most states don’t have statutes that define the capacity to appoint a health care POA. In these jurisdictions, courts may apply standards similar to those concerning competence to enter into a contract.⁶Table 1 describes criteria in 4 states that do have statutory provisions concerning compe­tence to designate a health care POA.

Approaching the evaluation
Before evaluating a person’s capacity to designate a POA, you should first under­stand the person’s medical condition and learn what powers the surrogate would have. A detailed description of the evalu­ation process lies beyond the scope of this article. For more information, please con­sult the structured interviews described by Moye et al⁴ and Soliman’s guide to the evaluation process.⁷

In addition to examining the patient’s psychological status and cognitive capacity, you also might have to consider contextual variables, such as:
   • potential risks of not allowing the appointment of POA, including a delay in needed care
   • the person’s relationship to the pro­posed POA
   • possible power imbalances or evi­dence of coercion
   • how the person would benefit from having the POA.⁸

People who have good marital or parent-child relationships are more likely to select loved ones as their POAs.⁹ Family mem­bers who have not previously served as surrogates or have not had talked with their loved ones about their preferences feel less confident exercising the duties of a POA.¹⁰ An evaluation, therefore, should consider the prior relationship between the designator and proposed surrogate, and particularly whether these parties have dis­cussed the designator’s health care prefer­ences. Table 2 lists potential pitfalls in POA evaluations.^{2,4,5,8,11-13,16}

Many variables—the stress of the situation,⁸ pre-existing relationship dynamics,¹⁸ and caregiver psychopathology¹¹—lead POAs to exploit their designator. Sometimes, family members believe that they are enti­tled to a relative’s money because of real or imagined transgressions¹⁹ or because they regard themselves as eventual heirs to their relative’s estate.¹⁶ Some desig­nated POAs use designators’ funds sim­ply because they need money. Kemp and Mosqueda²⁰ have developed an evaluation framework for assessing possible financial abuse (Table 3).

Although reporting financial abuse can strain alliances between patients and their families, psychiatrists bear a responsibil­ity to look out for the welfare of their older patients.⁸ Indeed, all 50 states have elder abuse statutes, most of which mandate reporting by physicians.²¹

Suspicion of financial abuse could indi­cate the need to evaluate the susceptible person’s capacity to make financial deci­sions.¹² Depending on the patient’s circum­stances and medical problems, further steps might include:
   • contacting proper authorities, such as Adult Protective Services or the Department of Human Services
   • contacting local law enforcement
   • instituting procedures for emergency guardianship
   • arranging for more in-home services for the patient or recommending a higher level of care
   • developing a treatment plan for the patient’s medical and psychiatric problems
   • communicating with other trusted family members.^12,18

Bottom Line
Evaluating the capacity to appoint a power of attorney (POA) often requires awareness of social systems, family dynamics, and legal requirements, combined with the psychiatric data from a systematic individual assessment. Evaluating psychiatrists should understand what type of POA is being considered and the applicable legal standards in the jurisdictions where they work.

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Too few psychiatrists. A growing number of patients. A new federal law, technological advances, and a genera­tional shift in the way people communicate. Add them together and you have the perfect environment for telepsy­chiatry—the remote practice of psychiatry by means of tele­medicine—to take root (Box 1). Although telepsychiatry has, in various forms, been around since the 1950s,¹ only recently has it expanded into almost all areas of psychiatric practice.

Here are some observations from my daily work on why I see this method of delivering mental health care is poised to expand in 2015 and beyond. Does telepsychiatry make sense for you?

Lack of supply is a big driver
There are simply not enough psychiatrists where they are needed, which is the primary driver of the expansion of telepsychiatry. With 77% of counties in the United States reporting a shortage of psychiatrists² and the “graying” of the psychiatric workforce,³ a more efficient way to make use of a psychiatrist’s time is needed. Telepsychiatry elimi­nates travel time and allows psychiatrists to visit distant sites virtually.

The shortage of psychiatric practitioners that we see today is only going to become worse. The Patient Protection and Affordable Care Act of 2010 includes mental health care and substance abuse treatment among its 10 essential benefits; just as important, new rules arising from the Mental Health Parity and Addiction Equity Act of 2008 limit restrictions on access to mental health care when insurance provides such cover­age.⁴ These legislative initiatives likely will lead to increased demand for psychiatrists in all care settings—from outpatient consults to acute inpatient admissions.


Why so attractive an option?
The shortage of psychiatrists creates limita­tions on access to care. Fortunately, telemed­icine has entered a new age, ushered in by widely available teleconferencing technol­ogy. Specialists from dermatology to surgery currently are using telemedicine; psychia­try is a good fit for telemedicine because of (1) the limited amount of “touch” required to make a psychiatric assessment, (2) signifi­cant improvements in video quality in recent years, and (3) a decrease in the stigma associ­ated with visiting a psychiatrist.

A generation raised on the Internet is entering the health care marketplace. These consumers and clinicians are accustomed to using video for many daily activities, and they seek health information from the Web. Visiting a psychiatrist through teleconferenc­ing isn’t strange or alienating to this genera­tion; their comfort with technology allows them to have intimate exchanges on video.

Subspecialty particulars
The earliest adopters, not surprisingly, are in areas where the strain of shortage has been felt most, with pediatric, geriatric, and correctional psychiatrists leading the way. In these fields, a substantial literature supports the use of telepsychiatry from a number of practice perspectives.

Pediatric psychiatry. The literature shows that children, families, and clinicians are, on the whole, satisfied with telepsychia­try.⁵ Children and adolescents who have been shown to benefit from telepsychia­try include those with depression,⁶ post­traumatic stress disorder, and eating disorders.⁷ Based on a case series, some authors have asserted that telepsychiatry might be preferable to in-person treatment (Box 2).⁸

Correctional psychiatry. Clinicians work­ing in correctional psychiatry have been at the forefront of experimentation with tele­psychiatry. The technology is a natural fit for this setting:  
   • Prisons often are located in remote locations.  
   • Psychiatrists can be reluctant to pro­vide on-site services because of safety concerns.

With correctional telepsychiatry, not only are patient outcomes comparable with in-person psychiatry, but the cost of delivering care can be significantly lower.¹¹ With the U.S. Department of Justice reporting that 50% of inmates have a diagnosable mental disorder, including substance abuse,¹² the need for access to a psychiatrist in the cor­rectional system is acute.

Telepsychiatry can confidently be pro­vided in a number of settings:  
   • emergency rooms  
   • nursing homes  
   • offices of primary care physicians  
   • in-home care.

Clinical services in these settings have been offered, studied, and reviewed.¹³

Can confidentiality and security be assured?
As with any new medical tool, the risk and benefits must be weighed care­ fully. The most obvious risk is to privacy. Telepsychiatry visits, like all patient encounters, must be secure and confiden­tial. Given the growing suspicion among the public and professionals who use com­puters that all data are at risk, clinicians must take appropriate cautions and, at the same time, warn patients of the risks. Readily available videoconferencing soft­ware, such as Skype, does not provide the level of security that patients expect from health care providers.¹⁴

Other common concerns about telepsy­chiatry are stable access to videoconferenc­ing and the safety from hackers of necessary hardware. Medical device companies have created hardware and software for use in telepsychiatry that provide a Health Insurance Portability and Accountability Act-compliant high-quality, stable, video­conferencing visit.

Do patients benefit?
Clinically, patients have fared well when they receive care through telepsychiatry. In some studies, however, clinicians have expressed some dissatisfaction with the technology¹³— understandable, given the value that psychi­atry traditionally has put on sitting with the patient. As Knoedler¹⁵ described it, making the switch to telepsychiatry from in-person contact can engender loneliness in some phy­sicians; not only is patient contact shifted to videoconferencing, but the psychiatrist loses the supportive environment of a busy clinical practice. Knoedler also pointed out that, on the other hand, telepsychiatry offers practi­tioners the opportunity to evaluate and treat people who otherwise would not have men­tal health care.

Obstacles—practical, knotty ones
Reimbursement and licensing. These are 2 pressing problems of telepsychiatry, although recent policy developments will help expand telepsychiatry and make it more appealing to physicians:
   • Medicare reimburses for telepsychiatry in non-metropolitan areas.
   • In 41 states, Medicaid has included tele­psychiatry as a benefit.¹⁶
   • Nine states offer a specific medical license for practicing telepsychiatry¹⁷ (in the remaining states, a full medical license must be obtained before one can provide telemedi­cine services).
   • The Joint Commission has included lan­guage in its regulations that could expedite privileging of telepsychiatrists.¹⁸

Even with such advancements, problems with licensure, credentialing, privacy, secu­rity, confidentiality, informed consent, and professional liability remain.¹⁹ I urge you to do your research on these key areas before plunging in.

Changes to models of care. The risk that telepsychiatry poses to various models of care has to be considered. Telepsychiatry is a dramatic innovation, but it should be used to support only high-quality, evidence-based care to which patients are entitled.²⁰ With new technology—as with new medi­cations—use must be carefully monitored and scrutinized.

Although evidence of the value of telepsy­chiatry is growing, many methods of long-distance practice are still in their infancy. Data must be collected and poor outcomes assessed honestly to ensure that the “more-good-than-harm” mandate is met.
 

Good reasons to call this shift ‘inevitable’
The future of telepsychiatry includes expansion into new areas of practice. The move to providing services to patients where they happen to be—at work or home— seems inevitable:
   • In rural areas, practitioners can com­municate with patients so that they are cared for in their homes, without the expense of transportation.
   • Employers can invest in workplace health clinics that use telemedicine ser­vices to reduce absenteeism.
   • For psychiatrists, the ability to provide services to patients across a wide region, from a single convenient location, and at lower cost is an attractive prospect.

To conclude: telepsychiatry holds potential to provide greater reimburse­ment and improved quality of life for psy­chiatrists and patients: It allows physicians to choose where they live and work, and limits the number of unreimbursed com­mutes, and gives patients access to psychi­atric care locally, without disruptive travel and delays.

Bottom Line
The exchange of medical information from 1 site to another by means of electronic communication has great potential to improve the health of patients and to alleviate the shortage of psychiatric practitioners across regions and settings. Pediatric, geriatric, and correctional psychiatry stand to benefit because of the nature of the patients and locations.

Related Resources
• American Telemedicine Association. Practice guidelines for video-based online mental health services. http://www. americantelemed.org/docs/default-source/standards/practice-guidelines-for-video-based-online-mental-health-services. pdf?sfvrsn=6. Published May 2013. Accessed February 10, 2015.
• Freudenberg N, Yellowlees PM. Telepsychiatry as part of a com­prehensive care plan. Virtual Mentor. 2014;16(12):964-968.
• Kornbluh R. Telepsychiatry is a tool that we must exploit. Clinical Psychiatry News. August 7, 2014. http://www. clinicalpsychiatrynews.com/home/article/telepsychiatry-is-a-tool-that-we-must-exploit/28c87bec298e0aa208309fa 9bc48dedc.html.
• University of Colorado Denver. Telemental Health Guide. http:// www.tmhguide.org.

Disclosure
Dr. Kornbluh reports no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Too few psychiatrists. A growing number of patients. A new federal law, technological advances, and a genera­tional shift in the way people communicate. Add them together and you have the perfect environment for telepsy­chiatry—the remote practice of psychiatry by means of tele­medicine—to take root (Box 1). Although telepsychiatry has, in various forms, been around since the 1950s,¹ only recently has it expanded into almost all areas of psychiatric practice.

Here are some observations from my daily work on why I see this method of delivering mental health care is poised to expand in 2015 and beyond. Does telepsychiatry make sense for you?

Lack of supply is a big driver
There are simply not enough psychiatrists where they are needed, which is the primary driver of the expansion of telepsychiatry. With 77% of counties in the United States reporting a shortage of psychiatrists² and the “graying” of the psychiatric workforce,³ a more efficient way to make use of a psychiatrist’s time is needed. Telepsychiatry elimi­nates travel time and allows psychiatrists to visit distant sites virtually.

The shortage of psychiatric practitioners that we see today is only going to become worse. The Patient Protection and Affordable Care Act of 2010 includes mental health care and substance abuse treatment among its 10 essential benefits; just as important, new rules arising from the Mental Health Parity and Addiction Equity Act of 2008 limit restrictions on access to mental health care when insurance provides such cover­age.⁴ These legislative initiatives likely will lead to increased demand for psychiatrists in all care settings—from outpatient consults to acute inpatient admissions.


Why so attractive an option?
The shortage of psychiatrists creates limita­tions on access to care. Fortunately, telemed­icine has entered a new age, ushered in by widely available teleconferencing technol­ogy. Specialists from dermatology to surgery currently are using telemedicine; psychia­try is a good fit for telemedicine because of (1) the limited amount of “touch” required to make a psychiatric assessment, (2) signifi­cant improvements in video quality in recent years, and (3) a decrease in the stigma associ­ated with visiting a psychiatrist.

A generation raised on the Internet is entering the health care marketplace. These consumers and clinicians are accustomed to using video for many daily activities, and they seek health information from the Web. Visiting a psychiatrist through teleconferenc­ing isn’t strange or alienating to this genera­tion; their comfort with technology allows them to have intimate exchanges on video.

Subspecialty particulars
The earliest adopters, not surprisingly, are in areas where the strain of shortage has been felt most, with pediatric, geriatric, and correctional psychiatrists leading the way. In these fields, a substantial literature supports the use of telepsychiatry from a number of practice perspectives.

Pediatric psychiatry. The literature shows that children, families, and clinicians are, on the whole, satisfied with telepsychia­try.⁵ Children and adolescents who have been shown to benefit from telepsychia­try include those with depression,⁶ post­traumatic stress disorder, and eating disorders.⁷ Based on a case series, some authors have asserted that telepsychiatry might be preferable to in-person treatment (Box 2).⁸

Correctional psychiatry. Clinicians work­ing in correctional psychiatry have been at the forefront of experimentation with tele­psychiatry. The technology is a natural fit for this setting:  
   • Prisons often are located in remote locations.  
   • Psychiatrists can be reluctant to pro­vide on-site services because of safety concerns.

With correctional telepsychiatry, not only are patient outcomes comparable with in-person psychiatry, but the cost of delivering care can be significantly lower.¹¹ With the U.S. Department of Justice reporting that 50% of inmates have a diagnosable mental disorder, including substance abuse,¹² the need for access to a psychiatrist in the cor­rectional system is acute.

Telepsychiatry can confidently be pro­vided in a number of settings:  
   • emergency rooms  
   • nursing homes  
   • offices of primary care physicians  
   • in-home care.

Clinical services in these settings have been offered, studied, and reviewed.¹³

Can confidentiality and security be assured?
As with any new medical tool, the risk and benefits must be weighed care­ fully. The most obvious risk is to privacy. Telepsychiatry visits, like all patient encounters, must be secure and confiden­tial. Given the growing suspicion among the public and professionals who use com­puters that all data are at risk, clinicians must take appropriate cautions and, at the same time, warn patients of the risks. Readily available videoconferencing soft­ware, such as Skype, does not provide the level of security that patients expect from health care providers.¹⁴

Other common concerns about telepsy­chiatry are stable access to videoconferenc­ing and the safety from hackers of necessary hardware. Medical device companies have created hardware and software for use in telepsychiatry that provide a Health Insurance Portability and Accountability Act-compliant high-quality, stable, video­conferencing visit.

Do patients benefit?
Clinically, patients have fared well when they receive care through telepsychiatry. In some studies, however, clinicians have expressed some dissatisfaction with the technology¹³— understandable, given the value that psychi­atry traditionally has put on sitting with the patient. As Knoedler¹⁵ described it, making the switch to telepsychiatry from in-person contact can engender loneliness in some phy­sicians; not only is patient contact shifted to videoconferencing, but the psychiatrist loses the supportive environment of a busy clinical practice. Knoedler also pointed out that, on the other hand, telepsychiatry offers practi­tioners the opportunity to evaluate and treat people who otherwise would not have men­tal health care.

Obstacles—practical, knotty ones
Reimbursement and licensing. These are 2 pressing problems of telepsychiatry, although recent policy developments will help expand telepsychiatry and make it more appealing to physicians:
   • Medicare reimburses for telepsychiatry in non-metropolitan areas.
   • In 41 states, Medicaid has included tele­psychiatry as a benefit.¹⁶
   • Nine states offer a specific medical license for practicing telepsychiatry¹⁷ (in the remaining states, a full medical license must be obtained before one can provide telemedi­cine services).
   • The Joint Commission has included lan­guage in its regulations that could expedite privileging of telepsychiatrists.¹⁸

Even with such advancements, problems with licensure, credentialing, privacy, secu­rity, confidentiality, informed consent, and professional liability remain.¹⁹ I urge you to do your research on these key areas before plunging in.

Changes to models of care. The risk that telepsychiatry poses to various models of care has to be considered. Telepsychiatry is a dramatic innovation, but it should be used to support only high-quality, evidence-based care to which patients are entitled.²⁰ With new technology—as with new medi­cations—use must be carefully monitored and scrutinized.

Although evidence of the value of telepsy­chiatry is growing, many methods of long-distance practice are still in their infancy. Data must be collected and poor outcomes assessed honestly to ensure that the “more-good-than-harm” mandate is met.
 

Good reasons to call this shift ‘inevitable’
The future of telepsychiatry includes expansion into new areas of practice. The move to providing services to patients where they happen to be—at work or home— seems inevitable:
   • In rural areas, practitioners can com­municate with patients so that they are cared for in their homes, without the expense of transportation.
   • Employers can invest in workplace health clinics that use telemedicine ser­vices to reduce absenteeism.
   • For psychiatrists, the ability to provide services to patients across a wide region, from a single convenient location, and at lower cost is an attractive prospect.

To conclude: telepsychiatry holds potential to provide greater reimburse­ment and improved quality of life for psy­chiatrists and patients: It allows physicians to choose where they live and work, and limits the number of unreimbursed com­mutes, and gives patients access to psychi­atric care locally, without disruptive travel and delays.

Bottom Line
The exchange of medical information from 1 site to another by means of electronic communication has great potential to improve the health of patients and to alleviate the shortage of psychiatric practitioners across regions and settings. Pediatric, geriatric, and correctional psychiatry stand to benefit because of the nature of the patients and locations.

Related Resources
• American Telemedicine Association. Practice guidelines for video-based online mental health services. http://www. americantelemed.org/docs/default-source/standards/practice-guidelines-for-video-based-online-mental-health-services. pdf?sfvrsn=6. Published May 2013. Accessed February 10, 2015.
• Freudenberg N, Yellowlees PM. Telepsychiatry as part of a com­prehensive care plan. Virtual Mentor. 2014;16(12):964-968.
• Kornbluh R. Telepsychiatry is a tool that we must exploit. Clinical Psychiatry News. August 7, 2014. http://www. clinicalpsychiatrynews.com/home/article/telepsychiatry-is-a-tool-that-we-must-exploit/28c87bec298e0aa208309fa 9bc48dedc.html.
• University of Colorado Denver. Telemental Health Guide. http:// www.tmhguide.org.

Disclosure
Dr. Kornbluh reports no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Too few psychiatrists. A growing number of patients. A new federal law, technological advances, and a genera­tional shift in the way people communicate. Add them together and you have the perfect environment for telepsy­chiatry—the remote practice of psychiatry by means of tele­medicine—to take root (Box 1). Although telepsychiatry has, in various forms, been around since the 1950s,¹ only recently has it expanded into almost all areas of psychiatric practice.

Here are some observations from my daily work on why I see this method of delivering mental health care is poised to expand in 2015 and beyond. Does telepsychiatry make sense for you?

Lack of supply is a big driver
There are simply not enough psychiatrists where they are needed, which is the primary driver of the expansion of telepsychiatry. With 77% of counties in the United States reporting a shortage of psychiatrists² and the “graying” of the psychiatric workforce,³ a more efficient way to make use of a psychiatrist’s time is needed. Telepsychiatry elimi­nates travel time and allows psychiatrists to visit distant sites virtually.

The shortage of psychiatric practitioners that we see today is only going to become worse. The Patient Protection and Affordable Care Act of 2010 includes mental health care and substance abuse treatment among its 10 essential benefits; just as important, new rules arising from the Mental Health Parity and Addiction Equity Act of 2008 limit restrictions on access to mental health care when insurance provides such cover­age.⁴ These legislative initiatives likely will lead to increased demand for psychiatrists in all care settings—from outpatient consults to acute inpatient admissions.


Why so attractive an option?
The shortage of psychiatrists creates limita­tions on access to care. Fortunately, telemed­icine has entered a new age, ushered in by widely available teleconferencing technol­ogy. Specialists from dermatology to surgery currently are using telemedicine; psychia­try is a good fit for telemedicine because of (1) the limited amount of “touch” required to make a psychiatric assessment, (2) signifi­cant improvements in video quality in recent years, and (3) a decrease in the stigma associ­ated with visiting a psychiatrist.

A generation raised on the Internet is entering the health care marketplace. These consumers and clinicians are accustomed to using video for many daily activities, and they seek health information from the Web. Visiting a psychiatrist through teleconferenc­ing isn’t strange or alienating to this genera­tion; their comfort with technology allows them to have intimate exchanges on video.

Subspecialty particulars
The earliest adopters, not surprisingly, are in areas where the strain of shortage has been felt most, with pediatric, geriatric, and correctional psychiatrists leading the way. In these fields, a substantial literature supports the use of telepsychiatry from a number of practice perspectives.

Pediatric psychiatry. The literature shows that children, families, and clinicians are, on the whole, satisfied with telepsychia­try.⁵ Children and adolescents who have been shown to benefit from telepsychia­try include those with depression,⁶ post­traumatic stress disorder, and eating disorders.⁷ Based on a case series, some authors have asserted that telepsychiatry might be preferable to in-person treatment (Box 2).⁸

Correctional psychiatry. Clinicians work­ing in correctional psychiatry have been at the forefront of experimentation with tele­psychiatry. The technology is a natural fit for this setting:  
   • Prisons often are located in remote locations.  
   • Psychiatrists can be reluctant to pro­vide on-site services because of safety concerns.

With correctional telepsychiatry, not only are patient outcomes comparable with in-person psychiatry, but the cost of delivering care can be significantly lower.¹¹ With the U.S. Department of Justice reporting that 50% of inmates have a diagnosable mental disorder, including substance abuse,¹² the need for access to a psychiatrist in the cor­rectional system is acute.

Telepsychiatry can confidently be pro­vided in a number of settings:  
   • emergency rooms  
   • nursing homes  
   • offices of primary care physicians  
   • in-home care.

Clinical services in these settings have been offered, studied, and reviewed.¹³

Can confidentiality and security be assured?
As with any new medical tool, the risk and benefits must be weighed care­ fully. The most obvious risk is to privacy. Telepsychiatry visits, like all patient encounters, must be secure and confiden­tial. Given the growing suspicion among the public and professionals who use com­puters that all data are at risk, clinicians must take appropriate cautions and, at the same time, warn patients of the risks. Readily available videoconferencing soft­ware, such as Skype, does not provide the level of security that patients expect from health care providers.¹⁴

Other common concerns about telepsy­chiatry are stable access to videoconferenc­ing and the safety from hackers of necessary hardware. Medical device companies have created hardware and software for use in telepsychiatry that provide a Health Insurance Portability and Accountability Act-compliant high-quality, stable, video­conferencing visit.

Do patients benefit?
Clinically, patients have fared well when they receive care through telepsychiatry. In some studies, however, clinicians have expressed some dissatisfaction with the technology¹³— understandable, given the value that psychi­atry traditionally has put on sitting with the patient. As Knoedler¹⁵ described it, making the switch to telepsychiatry from in-person contact can engender loneliness in some phy­sicians; not only is patient contact shifted to videoconferencing, but the psychiatrist loses the supportive environment of a busy clinical practice. Knoedler also pointed out that, on the other hand, telepsychiatry offers practi­tioners the opportunity to evaluate and treat people who otherwise would not have men­tal health care.

Obstacles—practical, knotty ones
Reimbursement and licensing. These are 2 pressing problems of telepsychiatry, although recent policy developments will help expand telepsychiatry and make it more appealing to physicians:
   • Medicare reimburses for telepsychiatry in non-metropolitan areas.
   • In 41 states, Medicaid has included tele­psychiatry as a benefit.¹⁶
   • Nine states offer a specific medical license for practicing telepsychiatry¹⁷ (in the remaining states, a full medical license must be obtained before one can provide telemedi­cine services).
   • The Joint Commission has included lan­guage in its regulations that could expedite privileging of telepsychiatrists.¹⁸

Even with such advancements, problems with licensure, credentialing, privacy, secu­rity, confidentiality, informed consent, and professional liability remain.¹⁹ I urge you to do your research on these key areas before plunging in.

Changes to models of care. The risk that telepsychiatry poses to various models of care has to be considered. Telepsychiatry is a dramatic innovation, but it should be used to support only high-quality, evidence-based care to which patients are entitled.²⁰ With new technology—as with new medi­cations—use must be carefully monitored and scrutinized.

Although evidence of the value of telepsy­chiatry is growing, many methods of long-distance practice are still in their infancy. Data must be collected and poor outcomes assessed honestly to ensure that the “more-good-than-harm” mandate is met.
 

Good reasons to call this shift ‘inevitable’
The future of telepsychiatry includes expansion into new areas of practice. The move to providing services to patients where they happen to be—at work or home— seems inevitable:
   • In rural areas, practitioners can com­municate with patients so that they are cared for in their homes, without the expense of transportation.
   • Employers can invest in workplace health clinics that use telemedicine ser­vices to reduce absenteeism.
   • For psychiatrists, the ability to provide services to patients across a wide region, from a single convenient location, and at lower cost is an attractive prospect.

To conclude: telepsychiatry holds potential to provide greater reimburse­ment and improved quality of life for psy­chiatrists and patients: It allows physicians to choose where they live and work, and limits the number of unreimbursed com­mutes, and gives patients access to psychi­atric care locally, without disruptive travel and delays.

Bottom Line
The exchange of medical information from 1 site to another by means of electronic communication has great potential to improve the health of patients and to alleviate the shortage of psychiatric practitioners across regions and settings. Pediatric, geriatric, and correctional psychiatry stand to benefit because of the nature of the patients and locations.

Related Resources
• American Telemedicine Association. Practice guidelines for video-based online mental health services. http://www. americantelemed.org/docs/default-source/standards/practice-guidelines-for-video-based-online-mental-health-services. pdf?sfvrsn=6. Published May 2013. Accessed February 10, 2015.
• Freudenberg N, Yellowlees PM. Telepsychiatry as part of a com­prehensive care plan. Virtual Mentor. 2014;16(12):964-968.
• Kornbluh R. Telepsychiatry is a tool that we must exploit. Clinical Psychiatry News. August 7, 2014. http://www. clinicalpsychiatrynews.com/home/article/telepsychiatry-is-a-tool-that-we-must-exploit/28c87bec298e0aa208309fa 9bc48dedc.html.
• University of Colorado Denver. Telemental Health Guide. http:// www.tmhguide.org.

Disclosure
Dr. Kornbluh reports no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

PRACTICE CHANGER
Stop requiring your patients to fast before undergoing lipid testing. Nonfasting total cholesterol (TC), HDL cholesterol, and LDL cholesterol levels are equally predictive of cardiovascular mortality and all-cause mortality.¹

STRENGTH OF RECOMMENDATION
B: Based on a large, cross-sectional cohort study of adults followed for a mean of 14 years with patient-oriented outcomes.¹

ILLUSTRATIVE CASE
A 57-year-old man with diabetes refuses to fast before coming to the clinic for lipid testing because he’s afraid he’ll become hypoglycemic. You have not been able to obtain a lipid panel on him for more than a year, and you want to determine his LDL level. Will a nonfasting lipid panel be useful?

Approximately 71 million adults in the United States have high LDL.² The 2013 American College of Cardiology/American Heart Association guidelines recommend fasting cholesterol checks for all adults ages 21 and older for primary prevention of cardiovascular disease.³ The US Preventive Services Task Force (USPSTF) has long recommended screening cholesterol in adults to prevent atherosclerotic vascular disease.

In 2008, the USPSTF recommended lipid screening for all men ages 35 and older, for all men ages 20 to 35 who are at increased risk for coronary heart disease, and for all women ages 20 and older who are at increased risk for coronary heart disease.⁴ The ­USPSTF recommends TC and HDL as the preferred screening tests and states that these can be performed on fasting or nonfasting samples; however, if LDL is added, a fasting sample is recommended.⁴ Other national and international guidelines on cholesterol management also recommend a fasting lipid panel to stratify patients’ risk and determine treatment options.^5-7

LDL usually is reported as a calculated value using the Friedewald equation (LDL equals TC minus HDL minus [triglycerides divided by 5]).⁸ This calculation is not accurate for patients with triglyceride levels > 400 mg/dL, which has prompted most authorities to recommend a fasting sample. That’s because while TC and HDL are not affected by food (and LDL may vary by only 10% or less), triglycerides can fluctuate by 20% to 30%, which would influence the calculation of a nonfasting LDL.^9,10 LDL can be measured directly, but the process is generally expensive and not commonly used.¹¹

The CDC estimates that more than 20% of US adults (48 million people) have not had a screening lipid panel in the previous five years.¹² One barrier to screening is that both clinicians and patients often believe that a fasting specimen is required. Yet fasting specimens are difficult to obtain because they often require a separate visit to the clinic, which can result in lost time from work and additional transportation costs.

Continue for study summary >>

STUDY SUMMARY
There’s no difference between fasting and nonfasting LDL
Doran et al¹ used data from the NHANES III survey to compare the prognostic value of fasting versus nonfasting LDL for all-cause mortality and cardiovascular mortality. NHANES III is a nationally representative cross-sectional survey that was conducted from 1988 to 1994.¹³ Doran et al¹ included 16,161 US adults ages 18 and older for whom data on fasting time were available. Participants for whom LDL calculations were not possible (due to missing HDL, TC, or triglyceride levels) were excluded. Those with triglycerides ≥ 400 mg/dL were excluded from the primary analysis.

Participants were stratified based on fasting status (≥ 8 hours or < 8 hours) and followed for a mean of 14 years. To control for possible confounders, the researchers used propensity score matching to identify 4,299 pairs of fasting and nonfasting individuals with similar cardiovascular risk factors, including race, smoking history, prior cardiovascular disease, cholesterol medication use, diabetes, elevated TC, low HDL, hypertension, enlarged waist circumference, and low socioeconomic status. After matching, the baseline characteristics of the fasting and nonfasting groups were similar.

The primary outcome was all-cause mortality, and the secondary outcome was cardiovascular mortality. The prognostic value of fasting and nonfasting LDL for these outcomes was evaluated as the area under the receiver operator characteristic (ROC) curve using the Hosmer-Lemeshow C-statistic.¹⁴ (In this case, similar C-statistics indicate that the tests have similar prognostic values.*) Kaplan-Meier curves were used to assess survival. The association of LDL with mortality, after adjustment for potential confounders, was evaluated using Cox proportional hazard models. The groups were divided into tertiles based on LDL levels (< 100 mg/dL, 100-130 mg/dL, and > 130 mg/dL).

As expected, compared to individuals in the first LDL tertile (< 100 mg/dL), those with a higher LDL had an increased risk for all-cause mortality (hazard ratios [HR], 1.61 for the second tertile and 2.10 for the third tertile). The prognostic value of fasting versus nonfasting status for predicting all-cause mortality was similar, as suggested by the C-statistics (0.59 vs 0.58; P = .73).

The risk for cardiovascular mortality also increased with increasing LDL tertiles. As was the case with all-cause mortality, the prognostic value of fasting versus nonfasting status was similar for predicting cardiovascular mortality as observed by similar C-statistics (0.64 vs 0.63; P = .49). In addition, fasting versus nonfasting C-statistics were similar for both diabetic and nondiabetic patients.

WHAT’S NEW
Results suggest fasting may no longer be necessary
While obtaining a fasting lipid panel is recommended by multiple guidelines and has become traditional practice, the need for fasting originated primarily out of concern for the effect of postprandial triglycerides on calculating LDL. This is the first study that compared the prognostic value of fasting and nonfasting LDL levels for predicting mortality; it demonstrated that they are essentially the same.

Next page: Caveats and challenges >>

CAVEATS
Fasting and nonfasting ­measurements were taken from different patients
The fasting and nonfasting lipids were not collected from the same individuals. However, to decrease confounding, Doran et al¹ factored in multiple cardiovascular risk factors as covariables.

Another caveat is that individuals with triglyceride levels > 400 mg/dL were excluded. However, investigators ran a sensitivity analysis that included individuals with triglycerides > 400 mg/dL and found no significant difference in C-statistics between the fasting and nonfasting groups.

CHALLENGES TO IMPLEMENTATION
Dropping the requirement to fast goes against established practice
It may be difficult for clinicians to change a longstanding practice of checking fasting lipid profiles, but we see no other barriers to adopting this recommendation.

REFERENCES
1. Doran B, Guo Y, Xu J, et al. Prognostic value of fasting versus nonfasting low-density lipoprotein cholesterol levels on long-term mortality: insight from the National Health and Nutrition Examination Survey III (NHANES-III). Circulation. 2014;130:546-553.
2. CDC. Vital signs: prevalence, treatment, and control of high levels of low-density lipoprotein cholesterol—United States, 1999-2002 and 2005-2008. MMWR Morb Mortal Wkly Rep. 2011;60:109-114.
3. Stone NJ, Robinson JG, Lichtenstein AH, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25 pt B):2889-2934.
4. US Preventive Services Task Force. Clinical summary: lipid disorders in adults (cholesterol, dyslipidemia)—screening. www.uspreventiveservicestaskforce.org/Page/Docu ment/ClinicalSummaryFinal/lipid-disorders-in-adults-cholesterol-dyslipidemia-screening. Accessed February 13, 2015.
5. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106: 3143-3421.
6. De Backer G, Ambrosioni E, Borch-Johnsen K, et al; European Society of Cardiology, American Heart Association. American College of Cardiology. European guidelines on cardiovascular disease prevention in clinical practice: third Joint Task Force of European and other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of eight societies and by invited experts). Atherosclerosis. 2004;173:381-391.
7. Genest J, McPherson R, Frohlich J, et al. 2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult—2009 recommendations. Can J Cardiol. 2009;25:567-579.
8. Friedewald WT, Levy RI, Fredrickson DS. ­Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;8:499-502.
9. Sidhu D, Naugler C. Fasting time and lipid levels in a community-based population: a cross-sectional study. Arch Intern Med. 2012;172:1707-1710.
10. Langsted A, Nordestgaard BG. Nonfasting lipids, lipoproteins, and apolipoproteins in individuals with and without diabetes: 58,434 individuals from the Copenhagen General Population Study. Clin Chem. 2001;57:482-489.
11. Mora S, Rifai N, Buring JE, et al. Comparison of LDL cholesterol concentrations by Friedewald calculation and direct measurement in relation to cardiovascular events in 27,331 women. Clin Chem. 2009;55:888-894.
12. Gillespie CD, Keenan NL, Miner JB, et al; CDC. Screening for lipid disorders among adults—National Health and Nutrition Examination Survey, United States, 2005-2008. MMWR Morb Mortal Wkly Rep. 2012;61 suppl:26-31.
13.  CDC. National Health and Nutrition Examination Survey. www.cdc.gov/nchs/nhanes/nh3data.htm. Accessed February 13, 2015.
14.  Hosmer DW, Lemeshow S. Applied Logistic Regression. 2nd ed. New York, NY: John Wiley & Sons; 2000.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2015. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2015;64(2):113-115.

PRACTICE CHANGER
Stop requiring your patients to fast before undergoing lipid testing. Nonfasting total cholesterol (TC), HDL cholesterol, and LDL cholesterol levels are equally predictive of cardiovascular mortality and all-cause mortality.¹

STRENGTH OF RECOMMENDATION
B: Based on a large, cross-sectional cohort study of adults followed for a mean of 14 years with patient-oriented outcomes.¹

ILLUSTRATIVE CASE
A 57-year-old man with diabetes refuses to fast before coming to the clinic for lipid testing because he’s afraid he’ll become hypoglycemic. You have not been able to obtain a lipid panel on him for more than a year, and you want to determine his LDL level. Will a nonfasting lipid panel be useful?

Approximately 71 million adults in the United States have high LDL.² The 2013 American College of Cardiology/American Heart Association guidelines recommend fasting cholesterol checks for all adults ages 21 and older for primary prevention of cardiovascular disease.³ The US Preventive Services Task Force (USPSTF) has long recommended screening cholesterol in adults to prevent atherosclerotic vascular disease.

In 2008, the USPSTF recommended lipid screening for all men ages 35 and older, for all men ages 20 to 35 who are at increased risk for coronary heart disease, and for all women ages 20 and older who are at increased risk for coronary heart disease.⁴ The ­USPSTF recommends TC and HDL as the preferred screening tests and states that these can be performed on fasting or nonfasting samples; however, if LDL is added, a fasting sample is recommended.⁴ Other national and international guidelines on cholesterol management also recommend a fasting lipid panel to stratify patients’ risk and determine treatment options.^5-7

LDL usually is reported as a calculated value using the Friedewald equation (LDL equals TC minus HDL minus [triglycerides divided by 5]).⁸ This calculation is not accurate for patients with triglyceride levels > 400 mg/dL, which has prompted most authorities to recommend a fasting sample. That’s because while TC and HDL are not affected by food (and LDL may vary by only 10% or less), triglycerides can fluctuate by 20% to 30%, which would influence the calculation of a nonfasting LDL.^9,10 LDL can be measured directly, but the process is generally expensive and not commonly used.¹¹

The CDC estimates that more than 20% of US adults (48 million people) have not had a screening lipid panel in the previous five years.¹² One barrier to screening is that both clinicians and patients often believe that a fasting specimen is required. Yet fasting specimens are difficult to obtain because they often require a separate visit to the clinic, which can result in lost time from work and additional transportation costs.

Continue for study summary >>

STUDY SUMMARY
There’s no difference between fasting and nonfasting LDL
Doran et al¹ used data from the NHANES III survey to compare the prognostic value of fasting versus nonfasting LDL for all-cause mortality and cardiovascular mortality. NHANES III is a nationally representative cross-sectional survey that was conducted from 1988 to 1994.¹³ Doran et al¹ included 16,161 US adults ages 18 and older for whom data on fasting time were available. Participants for whom LDL calculations were not possible (due to missing HDL, TC, or triglyceride levels) were excluded. Those with triglycerides ≥ 400 mg/dL were excluded from the primary analysis.

Participants were stratified based on fasting status (≥ 8 hours or < 8 hours) and followed for a mean of 14 years. To control for possible confounders, the researchers used propensity score matching to identify 4,299 pairs of fasting and nonfasting individuals with similar cardiovascular risk factors, including race, smoking history, prior cardiovascular disease, cholesterol medication use, diabetes, elevated TC, low HDL, hypertension, enlarged waist circumference, and low socioeconomic status. After matching, the baseline characteristics of the fasting and nonfasting groups were similar.

The primary outcome was all-cause mortality, and the secondary outcome was cardiovascular mortality. The prognostic value of fasting and nonfasting LDL for these outcomes was evaluated as the area under the receiver operator characteristic (ROC) curve using the Hosmer-Lemeshow C-statistic.¹⁴ (In this case, similar C-statistics indicate that the tests have similar prognostic values.*) Kaplan-Meier curves were used to assess survival. The association of LDL with mortality, after adjustment for potential confounders, was evaluated using Cox proportional hazard models. The groups were divided into tertiles based on LDL levels (< 100 mg/dL, 100-130 mg/dL, and > 130 mg/dL).

As expected, compared to individuals in the first LDL tertile (< 100 mg/dL), those with a higher LDL had an increased risk for all-cause mortality (hazard ratios [HR], 1.61 for the second tertile and 2.10 for the third tertile). The prognostic value of fasting versus nonfasting status for predicting all-cause mortality was similar, as suggested by the C-statistics (0.59 vs 0.58; P = .73).

The risk for cardiovascular mortality also increased with increasing LDL tertiles. As was the case with all-cause mortality, the prognostic value of fasting versus nonfasting status was similar for predicting cardiovascular mortality as observed by similar C-statistics (0.64 vs 0.63; P = .49). In addition, fasting versus nonfasting C-statistics were similar for both diabetic and nondiabetic patients.

WHAT’S NEW
Results suggest fasting may no longer be necessary
While obtaining a fasting lipid panel is recommended by multiple guidelines and has become traditional practice, the need for fasting originated primarily out of concern for the effect of postprandial triglycerides on calculating LDL. This is the first study that compared the prognostic value of fasting and nonfasting LDL levels for predicting mortality; it demonstrated that they are essentially the same.

Next page: Caveats and challenges >>

CAVEATS
Fasting and nonfasting ­measurements were taken from different patients
The fasting and nonfasting lipids were not collected from the same individuals. However, to decrease confounding, Doran et al¹ factored in multiple cardiovascular risk factors as covariables.

Another caveat is that individuals with triglyceride levels > 400 mg/dL were excluded. However, investigators ran a sensitivity analysis that included individuals with triglycerides > 400 mg/dL and found no significant difference in C-statistics between the fasting and nonfasting groups.

CHALLENGES TO IMPLEMENTATION
Dropping the requirement to fast goes against established practice
It may be difficult for clinicians to change a longstanding practice of checking fasting lipid profiles, but we see no other barriers to adopting this recommendation.

REFERENCES
1. Doran B, Guo Y, Xu J, et al. Prognostic value of fasting versus nonfasting low-density lipoprotein cholesterol levels on long-term mortality: insight from the National Health and Nutrition Examination Survey III (NHANES-III). Circulation. 2014;130:546-553.
2. CDC. Vital signs: prevalence, treatment, and control of high levels of low-density lipoprotein cholesterol—United States, 1999-2002 and 2005-2008. MMWR Morb Mortal Wkly Rep. 2011;60:109-114.
3. Stone NJ, Robinson JG, Lichtenstein AH, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25 pt B):2889-2934.
4. US Preventive Services Task Force. Clinical summary: lipid disorders in adults (cholesterol, dyslipidemia)—screening. www.uspreventiveservicestaskforce.org/Page/Docu ment/ClinicalSummaryFinal/lipid-disorders-in-adults-cholesterol-dyslipidemia-screening. Accessed February 13, 2015.
5. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106: 3143-3421.
6. De Backer G, Ambrosioni E, Borch-Johnsen K, et al; European Society of Cardiology, American Heart Association. American College of Cardiology. European guidelines on cardiovascular disease prevention in clinical practice: third Joint Task Force of European and other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of eight societies and by invited experts). Atherosclerosis. 2004;173:381-391.
7. Genest J, McPherson R, Frohlich J, et al. 2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult—2009 recommendations. Can J Cardiol. 2009;25:567-579.
8. Friedewald WT, Levy RI, Fredrickson DS. ­Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;8:499-502.
9. Sidhu D, Naugler C. Fasting time and lipid levels in a community-based population: a cross-sectional study. Arch Intern Med. 2012;172:1707-1710.
10. Langsted A, Nordestgaard BG. Nonfasting lipids, lipoproteins, and apolipoproteins in individuals with and without diabetes: 58,434 individuals from the Copenhagen General Population Study. Clin Chem. 2001;57:482-489.
11. Mora S, Rifai N, Buring JE, et al. Comparison of LDL cholesterol concentrations by Friedewald calculation and direct measurement in relation to cardiovascular events in 27,331 women. Clin Chem. 2009;55:888-894.
12. Gillespie CD, Keenan NL, Miner JB, et al; CDC. Screening for lipid disorders among adults—National Health and Nutrition Examination Survey, United States, 2005-2008. MMWR Morb Mortal Wkly Rep. 2012;61 suppl:26-31.
13.  CDC. National Health and Nutrition Examination Survey. www.cdc.gov/nchs/nhanes/nh3data.htm. Accessed February 13, 2015.
14.  Hosmer DW, Lemeshow S. Applied Logistic Regression. 2nd ed. New York, NY: John Wiley & Sons; 2000.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2015. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2015;64(2):113-115.

PRACTICE CHANGER
Stop requiring your patients to fast before undergoing lipid testing. Nonfasting total cholesterol (TC), HDL cholesterol, and LDL cholesterol levels are equally predictive of cardiovascular mortality and all-cause mortality.¹

STRENGTH OF RECOMMENDATION
B: Based on a large, cross-sectional cohort study of adults followed for a mean of 14 years with patient-oriented outcomes.¹

ILLUSTRATIVE CASE
A 57-year-old man with diabetes refuses to fast before coming to the clinic for lipid testing because he’s afraid he’ll become hypoglycemic. You have not been able to obtain a lipid panel on him for more than a year, and you want to determine his LDL level. Will a nonfasting lipid panel be useful?

Approximately 71 million adults in the United States have high LDL.² The 2013 American College of Cardiology/American Heart Association guidelines recommend fasting cholesterol checks for all adults ages 21 and older for primary prevention of cardiovascular disease.³ The US Preventive Services Task Force (USPSTF) has long recommended screening cholesterol in adults to prevent atherosclerotic vascular disease.

In 2008, the USPSTF recommended lipid screening for all men ages 35 and older, for all men ages 20 to 35 who are at increased risk for coronary heart disease, and for all women ages 20 and older who are at increased risk for coronary heart disease.⁴ The ­USPSTF recommends TC and HDL as the preferred screening tests and states that these can be performed on fasting or nonfasting samples; however, if LDL is added, a fasting sample is recommended.⁴ Other national and international guidelines on cholesterol management also recommend a fasting lipid panel to stratify patients’ risk and determine treatment options.^5-7

LDL usually is reported as a calculated value using the Friedewald equation (LDL equals TC minus HDL minus [triglycerides divided by 5]).⁸ This calculation is not accurate for patients with triglyceride levels > 400 mg/dL, which has prompted most authorities to recommend a fasting sample. That’s because while TC and HDL are not affected by food (and LDL may vary by only 10% or less), triglycerides can fluctuate by 20% to 30%, which would influence the calculation of a nonfasting LDL.^9,10 LDL can be measured directly, but the process is generally expensive and not commonly used.¹¹

The CDC estimates that more than 20% of US adults (48 million people) have not had a screening lipid panel in the previous five years.¹² One barrier to screening is that both clinicians and patients often believe that a fasting specimen is required. Yet fasting specimens are difficult to obtain because they often require a separate visit to the clinic, which can result in lost time from work and additional transportation costs.

Continue for study summary >>

STUDY SUMMARY
There’s no difference between fasting and nonfasting LDL
Doran et al¹ used data from the NHANES III survey to compare the prognostic value of fasting versus nonfasting LDL for all-cause mortality and cardiovascular mortality. NHANES III is a nationally representative cross-sectional survey that was conducted from 1988 to 1994.¹³ Doran et al¹ included 16,161 US adults ages 18 and older for whom data on fasting time were available. Participants for whom LDL calculations were not possible (due to missing HDL, TC, or triglyceride levels) were excluded. Those with triglycerides ≥ 400 mg/dL were excluded from the primary analysis.

Participants were stratified based on fasting status (≥ 8 hours or < 8 hours) and followed for a mean of 14 years. To control for possible confounders, the researchers used propensity score matching to identify 4,299 pairs of fasting and nonfasting individuals with similar cardiovascular risk factors, including race, smoking history, prior cardiovascular disease, cholesterol medication use, diabetes, elevated TC, low HDL, hypertension, enlarged waist circumference, and low socioeconomic status. After matching, the baseline characteristics of the fasting and nonfasting groups were similar.

The primary outcome was all-cause mortality, and the secondary outcome was cardiovascular mortality. The prognostic value of fasting and nonfasting LDL for these outcomes was evaluated as the area under the receiver operator characteristic (ROC) curve using the Hosmer-Lemeshow C-statistic.¹⁴ (In this case, similar C-statistics indicate that the tests have similar prognostic values.*) Kaplan-Meier curves were used to assess survival. The association of LDL with mortality, after adjustment for potential confounders, was evaluated using Cox proportional hazard models. The groups were divided into tertiles based on LDL levels (< 100 mg/dL, 100-130 mg/dL, and > 130 mg/dL).

As expected, compared to individuals in the first LDL tertile (< 100 mg/dL), those with a higher LDL had an increased risk for all-cause mortality (hazard ratios [HR], 1.61 for the second tertile and 2.10 for the third tertile). The prognostic value of fasting versus nonfasting status for predicting all-cause mortality was similar, as suggested by the C-statistics (0.59 vs 0.58; P = .73).

The risk for cardiovascular mortality also increased with increasing LDL tertiles. As was the case with all-cause mortality, the prognostic value of fasting versus nonfasting status was similar for predicting cardiovascular mortality as observed by similar C-statistics (0.64 vs 0.63; P = .49). In addition, fasting versus nonfasting C-statistics were similar for both diabetic and nondiabetic patients.

WHAT’S NEW
Results suggest fasting may no longer be necessary
While obtaining a fasting lipid panel is recommended by multiple guidelines and has become traditional practice, the need for fasting originated primarily out of concern for the effect of postprandial triglycerides on calculating LDL. This is the first study that compared the prognostic value of fasting and nonfasting LDL levels for predicting mortality; it demonstrated that they are essentially the same.

Next page: Caveats and challenges >>

CAVEATS
Fasting and nonfasting ­measurements were taken from different patients
The fasting and nonfasting lipids were not collected from the same individuals. However, to decrease confounding, Doran et al¹ factored in multiple cardiovascular risk factors as covariables.

Another caveat is that individuals with triglyceride levels > 400 mg/dL were excluded. However, investigators ran a sensitivity analysis that included individuals with triglycerides > 400 mg/dL and found no significant difference in C-statistics between the fasting and nonfasting groups.

CHALLENGES TO IMPLEMENTATION
Dropping the requirement to fast goes against established practice
It may be difficult for clinicians to change a longstanding practice of checking fasting lipid profiles, but we see no other barriers to adopting this recommendation.

REFERENCES
1. Doran B, Guo Y, Xu J, et al. Prognostic value of fasting versus nonfasting low-density lipoprotein cholesterol levels on long-term mortality: insight from the National Health and Nutrition Examination Survey III (NHANES-III). Circulation. 2014;130:546-553.
2. CDC. Vital signs: prevalence, treatment, and control of high levels of low-density lipoprotein cholesterol—United States, 1999-2002 and 2005-2008. MMWR Morb Mortal Wkly Rep. 2011;60:109-114.
3. Stone NJ, Robinson JG, Lichtenstein AH, et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25 pt B):2889-2934.
4. US Preventive Services Task Force. Clinical summary: lipid disorders in adults (cholesterol, dyslipidemia)—screening. www.uspreventiveservicestaskforce.org/Page/Docu ment/ClinicalSummaryFinal/lipid-disorders-in-adults-cholesterol-dyslipidemia-screening. Accessed February 13, 2015.
5. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106: 3143-3421.
6. De Backer G, Ambrosioni E, Borch-Johnsen K, et al; European Society of Cardiology, American Heart Association. American College of Cardiology. European guidelines on cardiovascular disease prevention in clinical practice: third Joint Task Force of European and other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of eight societies and by invited experts). Atherosclerosis. 2004;173:381-391.
7. Genest J, McPherson R, Frohlich J, et al. 2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult—2009 recommendations. Can J Cardiol. 2009;25:567-579.
8. Friedewald WT, Levy RI, Fredrickson DS. ­Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;8:499-502.
9. Sidhu D, Naugler C. Fasting time and lipid levels in a community-based population: a cross-sectional study. Arch Intern Med. 2012;172:1707-1710.
10. Langsted A, Nordestgaard BG. Nonfasting lipids, lipoproteins, and apolipoproteins in individuals with and without diabetes: 58,434 individuals from the Copenhagen General Population Study. Clin Chem. 2001;57:482-489.
11. Mora S, Rifai N, Buring JE, et al. Comparison of LDL cholesterol concentrations by Friedewald calculation and direct measurement in relation to cardiovascular events in 27,331 women. Clin Chem. 2009;55:888-894.
12. Gillespie CD, Keenan NL, Miner JB, et al; CDC. Screening for lipid disorders among adults—National Health and Nutrition Examination Survey, United States, 2005-2008. MMWR Morb Mortal Wkly Rep. 2012;61 suppl:26-31.
13.  CDC. National Health and Nutrition Examination Survey. www.cdc.gov/nchs/nhanes/nh3data.htm. Accessed February 13, 2015.
14.  Hosmer DW, Lemeshow S. Applied Logistic Regression. 2nd ed. New York, NY: John Wiley & Sons; 2000.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2015. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2015;64(2):113-115.

Muscle flaps have come to play an invaluable role in the management of complex groin wounds (Figure 1). We have found that the gracilis muscle offers significant advantages over other local muscle flaps. In comparison to the segmental blood supply of the sartorius muscle which can be disrupted during mobilization, the gracilis muscle has a single vascular pedicle that arises reliably from the medial femoral circumflex vessels. Unlike the sartorius muscle which may be damaged by the infectious/inflammatory process in the groin, the gracilis muscle is remote from the groin wound itself. In addition, the procedure is relatively simple and can be completed in less than thirty minutes.

The procedure is performed with the patient in the supine position with the knee slightly flexed. The gracilis muscle can be palpated along the medial aspect of the thigh and the longitudinal incision is placed directly over the muscle . After the deep fascia is divided, the muscle can be easily freed from surrounding attachments (Figure 2). We completely mobilize the distal two-thirds of the muscle and divide it at the musculotendinous insertion on the femur. We do not mobilize the proximal one-third of the muscle to avoid injury to the vascular pedicle). The muscle is retroflexed into the groin wound using a ringed-forceps. The muscle provides excellent coverage of the femoral triangle. A vacuum dressing may be applied without concern for injury to the femoral vessels.

We used the gracilis flap to treat complex groin wounds in 68 limbs in 64 patients at the University of Arkansas for Medical Sciences, Little Rock. Complete healing was achieved in 91%. In six patients (9%), recurrent or persistent infection led to bleeding that required surgical management. Limb salvage was achieved in 86%.

The presence of autogenous vascular reconstruction was associated with a reduced risk of persistent/recurrent infection in comparison to synthetic grafts (2.3% vs 23.8%, P = .006). Age greater than 75 years was associated with worse outcomes overall. Wound problems (infection, hematoma, seroma) at the harvest site were rare.

We prefer the gracilis flap to the sartorius or other groin muscle flaps in the management of complex groin wounds. The procedure is simple enough for a vascular surgeon, the muscle is reliable in location and blood supply, and the results are satisfactory given the complexity of the problem.

Dr. Eidt is at Greenville Health System, University of South Carolina School of Medicine Greenville, and Dr. Ali is at University of Arkansas for Medical Sciences, Little Rock.

Muscle flaps have come to play an invaluable role in the management of complex groin wounds (Figure 1). We have found that the gracilis muscle offers significant advantages over other local muscle flaps. In comparison to the segmental blood supply of the sartorius muscle which can be disrupted during mobilization, the gracilis muscle has a single vascular pedicle that arises reliably from the medial femoral circumflex vessels. Unlike the sartorius muscle which may be damaged by the infectious/inflammatory process in the groin, the gracilis muscle is remote from the groin wound itself. In addition, the procedure is relatively simple and can be completed in less than thirty minutes.

The procedure is performed with the patient in the supine position with the knee slightly flexed. The gracilis muscle can be palpated along the medial aspect of the thigh and the longitudinal incision is placed directly over the muscle . After the deep fascia is divided, the muscle can be easily freed from surrounding attachments (Figure 2). We completely mobilize the distal two-thirds of the muscle and divide it at the musculotendinous insertion on the femur. We do not mobilize the proximal one-third of the muscle to avoid injury to the vascular pedicle). The muscle is retroflexed into the groin wound using a ringed-forceps. The muscle provides excellent coverage of the femoral triangle. A vacuum dressing may be applied without concern for injury to the femoral vessels.

We used the gracilis flap to treat complex groin wounds in 68 limbs in 64 patients at the University of Arkansas for Medical Sciences, Little Rock. Complete healing was achieved in 91%. In six patients (9%), recurrent or persistent infection led to bleeding that required surgical management. Limb salvage was achieved in 86%.

The presence of autogenous vascular reconstruction was associated with a reduced risk of persistent/recurrent infection in comparison to synthetic grafts (2.3% vs 23.8%, P = .006). Age greater than 75 years was associated with worse outcomes overall. Wound problems (infection, hematoma, seroma) at the harvest site were rare.

We prefer the gracilis flap to the sartorius or other groin muscle flaps in the management of complex groin wounds. The procedure is simple enough for a vascular surgeon, the muscle is reliable in location and blood supply, and the results are satisfactory given the complexity of the problem.

Dr. Eidt is at Greenville Health System, University of South Carolina School of Medicine Greenville, and Dr. Ali is at University of Arkansas for Medical Sciences, Little Rock.

Muscle flaps have come to play an invaluable role in the management of complex groin wounds (Figure 1). We have found that the gracilis muscle offers significant advantages over other local muscle flaps. In comparison to the segmental blood supply of the sartorius muscle which can be disrupted during mobilization, the gracilis muscle has a single vascular pedicle that arises reliably from the medial femoral circumflex vessels. Unlike the sartorius muscle which may be damaged by the infectious/inflammatory process in the groin, the gracilis muscle is remote from the groin wound itself. In addition, the procedure is relatively simple and can be completed in less than thirty minutes.

The procedure is performed with the patient in the supine position with the knee slightly flexed. The gracilis muscle can be palpated along the medial aspect of the thigh and the longitudinal incision is placed directly over the muscle . After the deep fascia is divided, the muscle can be easily freed from surrounding attachments (Figure 2). We completely mobilize the distal two-thirds of the muscle and divide it at the musculotendinous insertion on the femur. We do not mobilize the proximal one-third of the muscle to avoid injury to the vascular pedicle). The muscle is retroflexed into the groin wound using a ringed-forceps. The muscle provides excellent coverage of the femoral triangle. A vacuum dressing may be applied without concern for injury to the femoral vessels.

We used the gracilis flap to treat complex groin wounds in 68 limbs in 64 patients at the University of Arkansas for Medical Sciences, Little Rock. Complete healing was achieved in 91%. In six patients (9%), recurrent or persistent infection led to bleeding that required surgical management. Limb salvage was achieved in 86%.

The presence of autogenous vascular reconstruction was associated with a reduced risk of persistent/recurrent infection in comparison to synthetic grafts (2.3% vs 23.8%, P = .006). Age greater than 75 years was associated with worse outcomes overall. Wound problems (infection, hematoma, seroma) at the harvest site were rare.

We prefer the gracilis flap to the sartorius or other groin muscle flaps in the management of complex groin wounds. The procedure is simple enough for a vascular surgeon, the muscle is reliable in location and blood supply, and the results are satisfactory given the complexity of the problem.

Dr. Eidt is at Greenville Health System, University of South Carolina School of Medicine Greenville, and Dr. Ali is at University of Arkansas for Medical Sciences, Little Rock.

“Mr. Smith seems somewhat confused today” is one of the most serious and concerning pre-visit reports you can receive from your staff or the patient’s family. Such a descriptor can be confusing—pardon the pun—not only for the patient, but to even seasoned mental health providers.

The term confusion can be code for diagnoses ranging from delirium^a to a progressive neurocognitive disorder (NCD) such as major NCD due to Alzheimer’s disease (AD), or even a more challenging prob­lem such as beclouded dementia (delirium superimposed on demen­tia/NCD). It is essential for all mental health professionals to have an evidence-based approach when encountering signs or symptoms of confusion.

^aICD-10 code R41.0 encompasses Confusion, Other Specified Delirium, or Unspecified Delirium.

CASE REPORT
Ms. T, age 62, has hypothyroidism and bipolar I disorder, most recently depressed, with comorbid generalized anxiety disorder. She has been tak­ing lithium, 600 mg/d, to control her mood symptoms. Her daughter-in-law reports that Ms. T has been exhibiting increasing signs of confusion. During the office evaluation, Ms. T minimizes her symptoms, only describ­ing mild issues with forgetfulness while cooking and concern over increas­ing anxiety. Her daughter-in-law plays a voicemail message from earlier in the week, in which Ms. T’s speech is halting, disorganized, and in a word, confused. I decide to use the mnemonic decision chart MR. MIND (Table 1) to get to the bottom of her recent confusion.

Measure cognition
It is nice to receive advanced warning about a cognitive change or a change in activities of daily living; however, many patients present with subtle, sub-acute changes that are more difficult to assess. When encountering a broad symptom such as “confusion”—which has an equally broad differential diagnosis—systematic assess­ment of the current cognitive state com­pared with the patient’s baseline becomes the first order of business. However, this requires that the patient has had a baseline cognitive assessment.

In my practice, I often administer one of the validated neurocognitive screening instruments when a patient first begins care—even a brief test such as the Mini- Cog (3-item recall plus clock drawing test), which is comparable to longer screening tests at least for NCD/dementia.¹ During a presentation for confusion, a more detailed neurocognitive assessment instrument would be recommended, allowing one to marry the clinical impression with a validated, objective measure. Formal neu­ropsychological testing by a clinical neuro­psychologist is the gold standard, but such testing is time-consuming and expensive and often not readily available. The screen­ing instrument I use for a more thorough evaluation depends on the clinical scenario.

The Six-Item Screener is used in some emergency settings because it is short but boasts a higher sensitivity than the Mini- Cog (94% vs 75%) with similar specificity when screening for cognitive impairment.² The Mini-Mental State Examination (MMSE) is a valuable instrument, although, recently, the Saint Louis University Mental Status Examination has been thought to be better at detecting mild NCD than the MMSE; more data are needed to substan­tiate this claim.³ The Montreal Cognitive Assessment is another validated screening tool that has been shown to be superior to the MMSE in terms of screening for mild cognitive impairment.⁴ The best delirium-specific assessment tool is the Confusion Assessment Method (Table 2).⁵

Review medications
A review of the medication list is not just a Joint Commission mandate (medication reconciliation during each encounter) but is important whenever confusion is noted. Polypharmacy can be a concern, but is not as concerning as the class of medication prescribed, particularly anticholinergic and sedative medications in patients age >65. The Drug Burden Index can be helpful in assessing this risk.⁶ Medications such as the benzodiazepine-receptor agonists, tri­cyclic antidepressants, and antipsychotics should be discontinued if possible, keeping in mind that the addition or subtraction of medications must be done prudently and only after reviewing the evidence and in consultation with the patient. A detailed medication review is as important for confused outpatients as it is for an inpatient case (steps 2 and 3 of the inpatient algo­rithm outlined in Table 3).⁷

In Ms. T’s case, the primary concern on her medication list was that her medical team was prescribing levothyroxine, 112 mcg/d, and desiccated thyroid (combination thy­roxine and triiodothyronine in the form of 20 mg Armour Thyroid), despite a lack of data for such combination therapy. Earlier, I had discontinued lorazepam, leaving lithium, 600 mg/d, quetiapine, 400 mg/d, and escitalopram, 10 mg/d, as her remain­ing psychotropics. Her other medications included atorvastatin, 40 mg/d, for hyper-lipidemia and metformin, 750 mg/d, for type 2 diabetes mellitus.

Medical illness
An organic basis must rank high in the dif­ferential diagnosis if medications are not the culprit. There are myriad medical disorders that can lead to confusion (Table 4).⁸ In an outpatient psychiatric setting, labo­ratory and radiology testing might not be readily available. It then becomes impor­tant to collaborate with a patient’s medical team if any of the following are met:
   •there is high suspicion of a medical cause
   •there could be delays in performing a medical workup
   •a physical examination is needed.

Other laboratory testing could be valu­able depending on the clinical scenario. These include tests such as:
   •drug level monitoring (lithium, val­proic acid, etc.) to assess for toxicity
   •HIV and rapid plasma reagin for sus­pected sexually transmitted infections
   •vitamin levels in patients with poor nutrition or post bariatric surgery
   •erythrocyte sedimentation rate or C-reactive protein, or both, if there are signs of inflammation
   •bacterial culture if blood or tissue infec­tion is a concern.

Esoteric tests include ceruloplasmin (Wilson’s disease), heavy metals screen, and even tests such as anti-gliadin anti­bodies because the prevalence of gluten sensitivity and celiac disease appear to be on the rise and have been associated with neuropsychiatric problems including encephalopathy.¹⁰

Brain imaging is an important consider­ation when a medical differential diagnosis for confusion is formulated. Unfortunately, there is little evidence-based guidance as to when brain imaging should be performed, often leading to overuse of tests such as CT, especially in emergency settings when con­fusion is noted. From a clinical standpoint, a head CT scan often is best ordered for patients who demonstrate an acute change in mental status, are age >70, are receiving anticoagulation, or have sustained trauma to the head. The key concern would be intracranial hemorrhage. However, some data suggest that the best use of head CT is for patients who have an impaired level of consciousness or a new focal neurologic deficit.¹¹

Apart from more acute changes, a brain MRI study is more helpful than a head CT when evaluating the brain parenchyma for more sub-acute diagnoses such as multiple sclerosis or a brain tumor. T2-weighted hyperintensities seen on an MRI are thought to predict an increased risk of stroke, dementia, and death.

Their discov­ery should prompt a detailed evaluation for risk factors of stroke and dementia/NCD.¹²

In Ms. T’s case, she was taking lithium, so it was logical to obtain a trough lith­ium level 12 hours after the last dose and to check kidney function (serum creati­nine to estimate the glomerular filtration rate), which were in the therapeutic/nor­mal range. Her serum lithium level was 0.7 mEq/L. Brain imaging was not ordered, but several other labs (CMP, CBC, hemoglo­bin A1c [HgbA1c], and TSH) were drawn. These labs were notable for HgbA1c of 5.1% (normal <5.7%) and TSH of 0.5 mIU/L (normal level, 1.5 mIU/L), which is low for someone taking thyroid replacement.

I requested that Ms. T stop Armour Thyroid to address the suppressed TSH. I also requested that she stop metfor­min because, although hypoglycemia from metformin monotherapy is uncom­mon, it can happen in older patients. Hypoglycemia associated with metformin also can occur in situations when caloric intake is deficient or when metformin is used in combination with other drugs such as sulfonylureas (ie, glipizide), beta-adrenergic blocking drugs, angiotensin-converting enzyme inhibitors, or even nonsteroidal anti-inflammatory drugs.¹³

Identifying overlapping psychiatric (or psychological) illness
Symptoms of depression, anxiety, psycho­sis, and even dissociation can present as con­fusion. The term pseudodementia describes patients who exhibit cognitive symptoms consistent with NCD but could improve once the underlying mood, thought, anxi­ety, or personality disorder is treated.

For example, a patient with depression typically exhibits neurovegetative symp­toms—such as poor sleep or appetite— amotivation, and low energy. All of these can lead to abrupt-onset cognitive changes, which are a hallmark of pseudodementia rather than the more insidious pattern of mild NCD. In cases of pseudodementia, neurocognitive testing will show impair­ment that often rapidly improves after the primary psychiatric (or psychological) issue is rectified. Making a diagnosis of pseu­dodementia at the initial presentation is difficult because neurocognitive tests such as the MMSE often fail to separate depres­sion from true cognitive changes.¹⁴ Such a diagnosis typically requires hindsight. Yet, one must also keep in mind that pseudode­mentia may be part of a NCD prodrome.¹⁵

Conversion disorder as well as the disso­ciative disorders and substance-related dis­orders are notorious for causing confusion. In Ms. T’s case, pseudodementia stemming from her underlying bipolar disorder and anxiety figured prominently in the differ­ential diagnosis, but she did not have any other overt psychopathology, personality disorder, or signs of malingering to further complicate her picture.

Notebook. I recommend that my patients keep a small notebook to record medical data ranging from blood pressure and gly­cemic measurements to details about sleep and dietary intake. Such data comprise the necessary metrics to properly assess target conditions and then track changes once treatment is initiated. This exercise not only yields much-needed detail about the patient’s condition for the clinician; the act of journaling also can be therapeutic for the writer through a process known as experi­mental disclosure, in which writing down one’s thoughts and observations has a posi­tive impact on the writer’s physical health and psychology.¹⁶

Diagnosis. The first rule in medicine (perhaps the second, behind primum non nocere) is to determine what you are treat­ing before beginning treatment (decernite quid tractemus, prius cura ministrandi, for Latin buffs). This means trying to fash­ion the best diagnostic label, even if it is merely a place-holder, while assessment of the confused state continues. DSM-5 has attempted to remove stigma from several neuropsychiatric disorders. On the cog­nition front, the new name for dementia is “neurocognitive disorder (NCD),” the umbrella term that focuses on the decline from a previous level of cognitive func­tioning. NCD has been divided into mild or major cognitive impairment headings either “with” or “without behavioral dis­turbance” subspecifiers.¹⁷

Aside from NCD, there are several other diagnoses in the differential for confusion. Delirium remains the most prominent and focuses on disturbances in attention and orientation that develops over a short period of time, with a change seen in an additional cognitive domain, such as memory, but not in the context of a severely reduced level of arousal such as coma. Subjective cognitive impairment (SCI) is when subjective complaints of cog­nitive impairment are hallmark compared with objective findings—with evidence suggesting that the presence of SCI could predict a 4.5 times higher rate of develop­ing mild cognitive impairment (MCI) over 7 years.¹⁸ MCI was originally used to describe the early prodrome of AD, minus functional decline.


Treatment
After even a provisional diagnosis comes the final, all-important challenge: treating the neuropsychiatric symptoms (NPS) of the confused patient. NPS are nearly universal in NCD/delirium throughout the course of illness. There are no FDA-approved treat­ments for the NPS associated with these conditions. In terms of treating delirium, the best approach is to treat the underlying medical condition. For control of behavior, which can range from agitated to psychotic to hypoactive, nonpharmacotherapeutic interventions are paramount; they include making sure that the patient is at the appro­priate level of care, which, for the confused outpatient, could mean hospitalization. Ensuring proper nutrition, hydration, sen­sory care (hearing aids, glasses, etc.), and stability in ambulation must be done before considering pharmacotherapy.

Antipsychotic use has been the mainstay of drug treatment of behavioral dyscontrol. Haloperidol has been the traditional go-to medication because there is no evidence that low-dose haloperidol (<3 mg/d) has any different efficacy compared with the atypical antipsychotics or has a greater fre­quency of adverse drug effects. However, high-dose haloperidol (>4.5 mg/d) was associated with a greater incidence of adverse effects, mainly parkinsonism, than atypical antipsychotics.¹⁹ Neither the typi­cal nor atypical antipsychotics have shown mortality benefit—the real outcome mea­sure of interest.

In terms of treating major (or minor) NCD, there are only 2 FDA-approved medication classes: cholinesterase inhibi­tors (donepezil, galantamine, rivastig­mine, etc.) and memantine. However, these medication classes—even when combined together—have only shown marginal benefit in terms of improving cognition. Worse, even when given early in the course of illness they do not reduce the rate of NCD. For pseudodementia, selec­tive serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors tend to form the mainstay of treating underlying depression or anxiety leading to cognitive changes. Preliminary data suggest that some SSRIs might improve cognition in terms of process­ing speed, verbal learning, and memory.²⁰ More studies are needed before definitive conclusions can be drawn.

For the confused patient, a personalized therapeutic program, in which multiple interventions are considered at once (tar­geting all areas of the patient’s life) is gain­ing research traction. For example, a novel, comprehensive program involving mul­tiple modalities designed to achieve meta­bolic enhancement for neurodegeneration (MEND) recently has shown robust benefit for patients with AD, MCI, and SCI.²¹ Using an individual approach to improve diet, activity, sleep, metabolic status including body mass index, and several other mark­ers that affect neural plasticity, researchers demonstrated symptom improvement in 9 of 10 study patients.

Yet, some of the interventions, such as the use of statins for hyperlipidemia, remain controversial, with some studies suggesting that they help cognition,^22,23 and others showing no association.²⁴ The researchers caution that further research is warranted before costly dementia pre­vention trials with statins are undertaken. It does not appear that there are current MEND-type research projects in delirium but it’s to be hoped that we will see these in the future.

In the case of Ms. T, the cause of delir­ium vs mild NCD was thought to be mul­tifactorial. Discontinuing Armour Thyroid and metformin—symptoms of hypoglyce­mia emerged as a leading concern—were simple adjustments that led to resolution of the most concerning elements of her confusion. She continued her other psy­chotropics, although there might be mild residual cognitive issues that warrant close observation.

Related Resources
• Lin JS, O’Connor E, Rossum RC, et al. Screening for cognitive impairment in older adults: an evidence update for the U.S. Preventive Services Task Force. Rockville, MD: Agency for Healthcare Research and Quality (US); 2013.
• Grover S, Kate N. Assessment scales for delirium: a review. World J Psychiatry. 2012;2(4):58-70.

Drug Brand Names
Atorvastatin • Lipitor                           Lithium • Eskalith, Lithobid
Donepezil • Aricept                              Lorazepam • Ativan
Escitalopram • Lexapro                        Memantine • Namenda
Flumazenil • Romazicon                       Metformin • Glucophage
Galantamine • Razadyne                      Naloxone • Narcan
Glipizide • Glucotrol                             Physostigmine • Antilirium
Haloperidol • Haldol                             Quetiapine • Seroquel
Levothyroxine • Levoxyl, Synthroid       Rivastigmine • Exelon
Lithium • Eskalith, Lithobid                   Valproic acid • Depakene

Disclosure
Dr. Raj is a speaker for Actavis Pharmaceuticals, AstraZeneca, and Merck.

“Mr. Smith seems somewhat confused today” is one of the most serious and concerning pre-visit reports you can receive from your staff or the patient’s family. Such a descriptor can be confusing—pardon the pun—not only for the patient, but to even seasoned mental health providers.

The term confusion can be code for diagnoses ranging from delirium^a to a progressive neurocognitive disorder (NCD) such as major NCD due to Alzheimer’s disease (AD), or even a more challenging prob­lem such as beclouded dementia (delirium superimposed on demen­tia/NCD). It is essential for all mental health professionals to have an evidence-based approach when encountering signs or symptoms of confusion.

^aICD-10 code R41.0 encompasses Confusion, Other Specified Delirium, or Unspecified Delirium.

CASE REPORT
Ms. T, age 62, has hypothyroidism and bipolar I disorder, most recently depressed, with comorbid generalized anxiety disorder. She has been tak­ing lithium, 600 mg/d, to control her mood symptoms. Her daughter-in-law reports that Ms. T has been exhibiting increasing signs of confusion. During the office evaluation, Ms. T minimizes her symptoms, only describ­ing mild issues with forgetfulness while cooking and concern over increas­ing anxiety. Her daughter-in-law plays a voicemail message from earlier in the week, in which Ms. T’s speech is halting, disorganized, and in a word, confused. I decide to use the mnemonic decision chart MR. MIND (Table 1) to get to the bottom of her recent confusion.

Measure cognition
It is nice to receive advanced warning about a cognitive change or a change in activities of daily living; however, many patients present with subtle, sub-acute changes that are more difficult to assess. When encountering a broad symptom such as “confusion”—which has an equally broad differential diagnosis—systematic assess­ment of the current cognitive state com­pared with the patient’s baseline becomes the first order of business. However, this requires that the patient has had a baseline cognitive assessment.

In my practice, I often administer one of the validated neurocognitive screening instruments when a patient first begins care—even a brief test such as the Mini- Cog (3-item recall plus clock drawing test), which is comparable to longer screening tests at least for NCD/dementia.¹ During a presentation for confusion, a more detailed neurocognitive assessment instrument would be recommended, allowing one to marry the clinical impression with a validated, objective measure. Formal neu­ropsychological testing by a clinical neuro­psychologist is the gold standard, but such testing is time-consuming and expensive and often not readily available. The screen­ing instrument I use for a more thorough evaluation depends on the clinical scenario.

The Six-Item Screener is used in some emergency settings because it is short but boasts a higher sensitivity than the Mini- Cog (94% vs 75%) with similar specificity when screening for cognitive impairment.² The Mini-Mental State Examination (MMSE) is a valuable instrument, although, recently, the Saint Louis University Mental Status Examination has been thought to be better at detecting mild NCD than the MMSE; more data are needed to substan­tiate this claim.³ The Montreal Cognitive Assessment is another validated screening tool that has been shown to be superior to the MMSE in terms of screening for mild cognitive impairment.⁴ The best delirium-specific assessment tool is the Confusion Assessment Method (Table 2).⁵

Review medications
A review of the medication list is not just a Joint Commission mandate (medication reconciliation during each encounter) but is important whenever confusion is noted. Polypharmacy can be a concern, but is not as concerning as the class of medication prescribed, particularly anticholinergic and sedative medications in patients age >65. The Drug Burden Index can be helpful in assessing this risk.⁶ Medications such as the benzodiazepine-receptor agonists, tri­cyclic antidepressants, and antipsychotics should be discontinued if possible, keeping in mind that the addition or subtraction of medications must be done prudently and only after reviewing the evidence and in consultation with the patient. A detailed medication review is as important for confused outpatients as it is for an inpatient case (steps 2 and 3 of the inpatient algo­rithm outlined in Table 3).⁷

In Ms. T’s case, the primary concern on her medication list was that her medical team was prescribing levothyroxine, 112 mcg/d, and desiccated thyroid (combination thy­roxine and triiodothyronine in the form of 20 mg Armour Thyroid), despite a lack of data for such combination therapy. Earlier, I had discontinued lorazepam, leaving lithium, 600 mg/d, quetiapine, 400 mg/d, and escitalopram, 10 mg/d, as her remain­ing psychotropics. Her other medications included atorvastatin, 40 mg/d, for hyper-lipidemia and metformin, 750 mg/d, for type 2 diabetes mellitus.

Medical illness
An organic basis must rank high in the dif­ferential diagnosis if medications are not the culprit. There are myriad medical disorders that can lead to confusion (Table 4).⁸ In an outpatient psychiatric setting, labo­ratory and radiology testing might not be readily available. It then becomes impor­tant to collaborate with a patient’s medical team if any of the following are met:
   •there is high suspicion of a medical cause
   •there could be delays in performing a medical workup
   •a physical examination is needed.

Other laboratory testing could be valu­able depending on the clinical scenario. These include tests such as:
   •drug level monitoring (lithium, val­proic acid, etc.) to assess for toxicity
   •HIV and rapid plasma reagin for sus­pected sexually transmitted infections
   •vitamin levels in patients with poor nutrition or post bariatric surgery
   •erythrocyte sedimentation rate or C-reactive protein, or both, if there are signs of inflammation
   •bacterial culture if blood or tissue infec­tion is a concern.

Esoteric tests include ceruloplasmin (Wilson’s disease), heavy metals screen, and even tests such as anti-gliadin anti­bodies because the prevalence of gluten sensitivity and celiac disease appear to be on the rise and have been associated with neuropsychiatric problems including encephalopathy.¹⁰

Brain imaging is an important consider­ation when a medical differential diagnosis for confusion is formulated. Unfortunately, there is little evidence-based guidance as to when brain imaging should be performed, often leading to overuse of tests such as CT, especially in emergency settings when con­fusion is noted. From a clinical standpoint, a head CT scan often is best ordered for patients who demonstrate an acute change in mental status, are age >70, are receiving anticoagulation, or have sustained trauma to the head. The key concern would be intracranial hemorrhage. However, some data suggest that the best use of head CT is for patients who have an impaired level of consciousness or a new focal neurologic deficit.¹¹

Apart from more acute changes, a brain MRI study is more helpful than a head CT when evaluating the brain parenchyma for more sub-acute diagnoses such as multiple sclerosis or a brain tumor. T2-weighted hyperintensities seen on an MRI are thought to predict an increased risk of stroke, dementia, and death.

Their discov­ery should prompt a detailed evaluation for risk factors of stroke and dementia/NCD.¹²

In Ms. T’s case, she was taking lithium, so it was logical to obtain a trough lith­ium level 12 hours after the last dose and to check kidney function (serum creati­nine to estimate the glomerular filtration rate), which were in the therapeutic/nor­mal range. Her serum lithium level was 0.7 mEq/L. Brain imaging was not ordered, but several other labs (CMP, CBC, hemoglo­bin A1c [HgbA1c], and TSH) were drawn. These labs were notable for HgbA1c of 5.1% (normal <5.7%) and TSH of 0.5 mIU/L (normal level, 1.5 mIU/L), which is low for someone taking thyroid replacement.

I requested that Ms. T stop Armour Thyroid to address the suppressed TSH. I also requested that she stop metfor­min because, although hypoglycemia from metformin monotherapy is uncom­mon, it can happen in older patients. Hypoglycemia associated with metformin also can occur in situations when caloric intake is deficient or when metformin is used in combination with other drugs such as sulfonylureas (ie, glipizide), beta-adrenergic blocking drugs, angiotensin-converting enzyme inhibitors, or even nonsteroidal anti-inflammatory drugs.¹³

Identifying overlapping psychiatric (or psychological) illness
Symptoms of depression, anxiety, psycho­sis, and even dissociation can present as con­fusion. The term pseudodementia describes patients who exhibit cognitive symptoms consistent with NCD but could improve once the underlying mood, thought, anxi­ety, or personality disorder is treated.

For example, a patient with depression typically exhibits neurovegetative symp­toms—such as poor sleep or appetite— amotivation, and low energy. All of these can lead to abrupt-onset cognitive changes, which are a hallmark of pseudodementia rather than the more insidious pattern of mild NCD. In cases of pseudodementia, neurocognitive testing will show impair­ment that often rapidly improves after the primary psychiatric (or psychological) issue is rectified. Making a diagnosis of pseu­dodementia at the initial presentation is difficult because neurocognitive tests such as the MMSE often fail to separate depres­sion from true cognitive changes.¹⁴ Such a diagnosis typically requires hindsight. Yet, one must also keep in mind that pseudode­mentia may be part of a NCD prodrome.¹⁵

Conversion disorder as well as the disso­ciative disorders and substance-related dis­orders are notorious for causing confusion. In Ms. T’s case, pseudodementia stemming from her underlying bipolar disorder and anxiety figured prominently in the differ­ential diagnosis, but she did not have any other overt psychopathology, personality disorder, or signs of malingering to further complicate her picture.

Notebook. I recommend that my patients keep a small notebook to record medical data ranging from blood pressure and gly­cemic measurements to details about sleep and dietary intake. Such data comprise the necessary metrics to properly assess target conditions and then track changes once treatment is initiated. This exercise not only yields much-needed detail about the patient’s condition for the clinician; the act of journaling also can be therapeutic for the writer through a process known as experi­mental disclosure, in which writing down one’s thoughts and observations has a posi­tive impact on the writer’s physical health and psychology.¹⁶

Diagnosis. The first rule in medicine (perhaps the second, behind primum non nocere) is to determine what you are treat­ing before beginning treatment (decernite quid tractemus, prius cura ministrandi, for Latin buffs). This means trying to fash­ion the best diagnostic label, even if it is merely a place-holder, while assessment of the confused state continues. DSM-5 has attempted to remove stigma from several neuropsychiatric disorders. On the cog­nition front, the new name for dementia is “neurocognitive disorder (NCD),” the umbrella term that focuses on the decline from a previous level of cognitive func­tioning. NCD has been divided into mild or major cognitive impairment headings either “with” or “without behavioral dis­turbance” subspecifiers.¹⁷

Aside from NCD, there are several other diagnoses in the differential for confusion. Delirium remains the most prominent and focuses on disturbances in attention and orientation that develops over a short period of time, with a change seen in an additional cognitive domain, such as memory, but not in the context of a severely reduced level of arousal such as coma. Subjective cognitive impairment (SCI) is when subjective complaints of cog­nitive impairment are hallmark compared with objective findings—with evidence suggesting that the presence of SCI could predict a 4.5 times higher rate of develop­ing mild cognitive impairment (MCI) over 7 years.¹⁸ MCI was originally used to describe the early prodrome of AD, minus functional decline.


Treatment
After even a provisional diagnosis comes the final, all-important challenge: treating the neuropsychiatric symptoms (NPS) of the confused patient. NPS are nearly universal in NCD/delirium throughout the course of illness. There are no FDA-approved treat­ments for the NPS associated with these conditions. In terms of treating delirium, the best approach is to treat the underlying medical condition. For control of behavior, which can range from agitated to psychotic to hypoactive, nonpharmacotherapeutic interventions are paramount; they include making sure that the patient is at the appro­priate level of care, which, for the confused outpatient, could mean hospitalization. Ensuring proper nutrition, hydration, sen­sory care (hearing aids, glasses, etc.), and stability in ambulation must be done before considering pharmacotherapy.

Antipsychotic use has been the mainstay of drug treatment of behavioral dyscontrol. Haloperidol has been the traditional go-to medication because there is no evidence that low-dose haloperidol (<3 mg/d) has any different efficacy compared with the atypical antipsychotics or has a greater fre­quency of adverse drug effects. However, high-dose haloperidol (>4.5 mg/d) was associated with a greater incidence of adverse effects, mainly parkinsonism, than atypical antipsychotics.¹⁹ Neither the typi­cal nor atypical antipsychotics have shown mortality benefit—the real outcome mea­sure of interest.

In terms of treating major (or minor) NCD, there are only 2 FDA-approved medication classes: cholinesterase inhibi­tors (donepezil, galantamine, rivastig­mine, etc.) and memantine. However, these medication classes—even when combined together—have only shown marginal benefit in terms of improving cognition. Worse, even when given early in the course of illness they do not reduce the rate of NCD. For pseudodementia, selec­tive serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors tend to form the mainstay of treating underlying depression or anxiety leading to cognitive changes. Preliminary data suggest that some SSRIs might improve cognition in terms of process­ing speed, verbal learning, and memory.²⁰ More studies are needed before definitive conclusions can be drawn.

For the confused patient, a personalized therapeutic program, in which multiple interventions are considered at once (tar­geting all areas of the patient’s life) is gain­ing research traction. For example, a novel, comprehensive program involving mul­tiple modalities designed to achieve meta­bolic enhancement for neurodegeneration (MEND) recently has shown robust benefit for patients with AD, MCI, and SCI.²¹ Using an individual approach to improve diet, activity, sleep, metabolic status including body mass index, and several other mark­ers that affect neural plasticity, researchers demonstrated symptom improvement in 9 of 10 study patients.

Yet, some of the interventions, such as the use of statins for hyperlipidemia, remain controversial, with some studies suggesting that they help cognition,^22,23 and others showing no association.²⁴ The researchers caution that further research is warranted before costly dementia pre­vention trials with statins are undertaken. It does not appear that there are current MEND-type research projects in delirium but it’s to be hoped that we will see these in the future.

In the case of Ms. T, the cause of delir­ium vs mild NCD was thought to be mul­tifactorial. Discontinuing Armour Thyroid and metformin—symptoms of hypoglyce­mia emerged as a leading concern—were simple adjustments that led to resolution of the most concerning elements of her confusion. She continued her other psy­chotropics, although there might be mild residual cognitive issues that warrant close observation.

Related Resources
• Lin JS, O’Connor E, Rossum RC, et al. Screening for cognitive impairment in older adults: an evidence update for the U.S. Preventive Services Task Force. Rockville, MD: Agency for Healthcare Research and Quality (US); 2013.
• Grover S, Kate N. Assessment scales for delirium: a review. World J Psychiatry. 2012;2(4):58-70.

Drug Brand Names
Atorvastatin • Lipitor                           Lithium • Eskalith, Lithobid
Donepezil • Aricept                              Lorazepam • Ativan
Escitalopram • Lexapro                        Memantine • Namenda
Flumazenil • Romazicon                       Metformin • Glucophage
Galantamine • Razadyne                      Naloxone • Narcan
Glipizide • Glucotrol                             Physostigmine • Antilirium
Haloperidol • Haldol                             Quetiapine • Seroquel
Levothyroxine • Levoxyl, Synthroid       Rivastigmine • Exelon
Lithium • Eskalith, Lithobid                   Valproic acid • Depakene

Disclosure
Dr. Raj is a speaker for Actavis Pharmaceuticals, AstraZeneca, and Merck.

“Mr. Smith seems somewhat confused today” is one of the most serious and concerning pre-visit reports you can receive from your staff or the patient’s family. Such a descriptor can be confusing—pardon the pun—not only for the patient, but to even seasoned mental health providers.

The term confusion can be code for diagnoses ranging from delirium^a to a progressive neurocognitive disorder (NCD) such as major NCD due to Alzheimer’s disease (AD), or even a more challenging prob­lem such as beclouded dementia (delirium superimposed on demen­tia/NCD). It is essential for all mental health professionals to have an evidence-based approach when encountering signs or symptoms of confusion.

^aICD-10 code R41.0 encompasses Confusion, Other Specified Delirium, or Unspecified Delirium.

CASE REPORT
Ms. T, age 62, has hypothyroidism and bipolar I disorder, most recently depressed, with comorbid generalized anxiety disorder. She has been tak­ing lithium, 600 mg/d, to control her mood symptoms. Her daughter-in-law reports that Ms. T has been exhibiting increasing signs of confusion. During the office evaluation, Ms. T minimizes her symptoms, only describ­ing mild issues with forgetfulness while cooking and concern over increas­ing anxiety. Her daughter-in-law plays a voicemail message from earlier in the week, in which Ms. T’s speech is halting, disorganized, and in a word, confused. I decide to use the mnemonic decision chart MR. MIND (Table 1) to get to the bottom of her recent confusion.

Measure cognition
It is nice to receive advanced warning about a cognitive change or a change in activities of daily living; however, many patients present with subtle, sub-acute changes that are more difficult to assess. When encountering a broad symptom such as “confusion”—which has an equally broad differential diagnosis—systematic assess­ment of the current cognitive state com­pared with the patient’s baseline becomes the first order of business. However, this requires that the patient has had a baseline cognitive assessment.

In my practice, I often administer one of the validated neurocognitive screening instruments when a patient first begins care—even a brief test such as the Mini- Cog (3-item recall plus clock drawing test), which is comparable to longer screening tests at least for NCD/dementia.¹ During a presentation for confusion, a more detailed neurocognitive assessment instrument would be recommended, allowing one to marry the clinical impression with a validated, objective measure. Formal neu­ropsychological testing by a clinical neuro­psychologist is the gold standard, but such testing is time-consuming and expensive and often not readily available. The screen­ing instrument I use for a more thorough evaluation depends on the clinical scenario.

The Six-Item Screener is used in some emergency settings because it is short but boasts a higher sensitivity than the Mini- Cog (94% vs 75%) with similar specificity when screening for cognitive impairment.² The Mini-Mental State Examination (MMSE) is a valuable instrument, although, recently, the Saint Louis University Mental Status Examination has been thought to be better at detecting mild NCD than the MMSE; more data are needed to substan­tiate this claim.³ The Montreal Cognitive Assessment is another validated screening tool that has been shown to be superior to the MMSE in terms of screening for mild cognitive impairment.⁴ The best delirium-specific assessment tool is the Confusion Assessment Method (Table 2).⁵

Review medications
A review of the medication list is not just a Joint Commission mandate (medication reconciliation during each encounter) but is important whenever confusion is noted. Polypharmacy can be a concern, but is not as concerning as the class of medication prescribed, particularly anticholinergic and sedative medications in patients age >65. The Drug Burden Index can be helpful in assessing this risk.⁶ Medications such as the benzodiazepine-receptor agonists, tri­cyclic antidepressants, and antipsychotics should be discontinued if possible, keeping in mind that the addition or subtraction of medications must be done prudently and only after reviewing the evidence and in consultation with the patient. A detailed medication review is as important for confused outpatients as it is for an inpatient case (steps 2 and 3 of the inpatient algo­rithm outlined in Table 3).⁷

In Ms. T’s case, the primary concern on her medication list was that her medical team was prescribing levothyroxine, 112 mcg/d, and desiccated thyroid (combination thy­roxine and triiodothyronine in the form of 20 mg Armour Thyroid), despite a lack of data for such combination therapy. Earlier, I had discontinued lorazepam, leaving lithium, 600 mg/d, quetiapine, 400 mg/d, and escitalopram, 10 mg/d, as her remain­ing psychotropics. Her other medications included atorvastatin, 40 mg/d, for hyper-lipidemia and metformin, 750 mg/d, for type 2 diabetes mellitus.

Medical illness
An organic basis must rank high in the dif­ferential diagnosis if medications are not the culprit. There are myriad medical disorders that can lead to confusion (Table 4).⁸ In an outpatient psychiatric setting, labo­ratory and radiology testing might not be readily available. It then becomes impor­tant to collaborate with a patient’s medical team if any of the following are met:
   •there is high suspicion of a medical cause
   •there could be delays in performing a medical workup
   •a physical examination is needed.

Other laboratory testing could be valu­able depending on the clinical scenario. These include tests such as:
   •drug level monitoring (lithium, val­proic acid, etc.) to assess for toxicity
   •HIV and rapid plasma reagin for sus­pected sexually transmitted infections
   •vitamin levels in patients with poor nutrition or post bariatric surgery
   •erythrocyte sedimentation rate or C-reactive protein, or both, if there are signs of inflammation
   •bacterial culture if blood or tissue infec­tion is a concern.

Esoteric tests include ceruloplasmin (Wilson’s disease), heavy metals screen, and even tests such as anti-gliadin anti­bodies because the prevalence of gluten sensitivity and celiac disease appear to be on the rise and have been associated with neuropsychiatric problems including encephalopathy.¹⁰

Brain imaging is an important consider­ation when a medical differential diagnosis for confusion is formulated. Unfortunately, there is little evidence-based guidance as to when brain imaging should be performed, often leading to overuse of tests such as CT, especially in emergency settings when con­fusion is noted. From a clinical standpoint, a head CT scan often is best ordered for patients who demonstrate an acute change in mental status, are age >70, are receiving anticoagulation, or have sustained trauma to the head. The key concern would be intracranial hemorrhage. However, some data suggest that the best use of head CT is for patients who have an impaired level of consciousness or a new focal neurologic deficit.¹¹

Apart from more acute changes, a brain MRI study is more helpful than a head CT when evaluating the brain parenchyma for more sub-acute diagnoses such as multiple sclerosis or a brain tumor. T2-weighted hyperintensities seen on an MRI are thought to predict an increased risk of stroke, dementia, and death.

Their discov­ery should prompt a detailed evaluation for risk factors of stroke and dementia/NCD.¹²

In Ms. T’s case, she was taking lithium, so it was logical to obtain a trough lith­ium level 12 hours after the last dose and to check kidney function (serum creati­nine to estimate the glomerular filtration rate), which were in the therapeutic/nor­mal range. Her serum lithium level was 0.7 mEq/L. Brain imaging was not ordered, but several other labs (CMP, CBC, hemoglo­bin A1c [HgbA1c], and TSH) were drawn. These labs were notable for HgbA1c of 5.1% (normal <5.7%) and TSH of 0.5 mIU/L (normal level, 1.5 mIU/L), which is low for someone taking thyroid replacement.

I requested that Ms. T stop Armour Thyroid to address the suppressed TSH. I also requested that she stop metfor­min because, although hypoglycemia from metformin monotherapy is uncom­mon, it can happen in older patients. Hypoglycemia associated with metformin also can occur in situations when caloric intake is deficient or when metformin is used in combination with other drugs such as sulfonylureas (ie, glipizide), beta-adrenergic blocking drugs, angiotensin-converting enzyme inhibitors, or even nonsteroidal anti-inflammatory drugs.¹³

Identifying overlapping psychiatric (or psychological) illness
Symptoms of depression, anxiety, psycho­sis, and even dissociation can present as con­fusion. The term pseudodementia describes patients who exhibit cognitive symptoms consistent with NCD but could improve once the underlying mood, thought, anxi­ety, or personality disorder is treated.

For example, a patient with depression typically exhibits neurovegetative symp­toms—such as poor sleep or appetite— amotivation, and low energy. All of these can lead to abrupt-onset cognitive changes, which are a hallmark of pseudodementia rather than the more insidious pattern of mild NCD. In cases of pseudodementia, neurocognitive testing will show impair­ment that often rapidly improves after the primary psychiatric (or psychological) issue is rectified. Making a diagnosis of pseu­dodementia at the initial presentation is difficult because neurocognitive tests such as the MMSE often fail to separate depres­sion from true cognitive changes.¹⁴ Such a diagnosis typically requires hindsight. Yet, one must also keep in mind that pseudode­mentia may be part of a NCD prodrome.¹⁵

Conversion disorder as well as the disso­ciative disorders and substance-related dis­orders are notorious for causing confusion. In Ms. T’s case, pseudodementia stemming from her underlying bipolar disorder and anxiety figured prominently in the differ­ential diagnosis, but she did not have any other overt psychopathology, personality disorder, or signs of malingering to further complicate her picture.

Notebook. I recommend that my patients keep a small notebook to record medical data ranging from blood pressure and gly­cemic measurements to details about sleep and dietary intake. Such data comprise the necessary metrics to properly assess target conditions and then track changes once treatment is initiated. This exercise not only yields much-needed detail about the patient’s condition for the clinician; the act of journaling also can be therapeutic for the writer through a process known as experi­mental disclosure, in which writing down one’s thoughts and observations has a posi­tive impact on the writer’s physical health and psychology.¹⁶

Diagnosis. The first rule in medicine (perhaps the second, behind primum non nocere) is to determine what you are treat­ing before beginning treatment (decernite quid tractemus, prius cura ministrandi, for Latin buffs). This means trying to fash­ion the best diagnostic label, even if it is merely a place-holder, while assessment of the confused state continues. DSM-5 has attempted to remove stigma from several neuropsychiatric disorders. On the cog­nition front, the new name for dementia is “neurocognitive disorder (NCD),” the umbrella term that focuses on the decline from a previous level of cognitive func­tioning. NCD has been divided into mild or major cognitive impairment headings either “with” or “without behavioral dis­turbance” subspecifiers.¹⁷

Aside from NCD, there are several other diagnoses in the differential for confusion. Delirium remains the most prominent and focuses on disturbances in attention and orientation that develops over a short period of time, with a change seen in an additional cognitive domain, such as memory, but not in the context of a severely reduced level of arousal such as coma. Subjective cognitive impairment (SCI) is when subjective complaints of cog­nitive impairment are hallmark compared with objective findings—with evidence suggesting that the presence of SCI could predict a 4.5 times higher rate of develop­ing mild cognitive impairment (MCI) over 7 years.¹⁸ MCI was originally used to describe the early prodrome of AD, minus functional decline.


Treatment
After even a provisional diagnosis comes the final, all-important challenge: treating the neuropsychiatric symptoms (NPS) of the confused patient. NPS are nearly universal in NCD/delirium throughout the course of illness. There are no FDA-approved treat­ments for the NPS associated with these conditions. In terms of treating delirium, the best approach is to treat the underlying medical condition. For control of behavior, which can range from agitated to psychotic to hypoactive, nonpharmacotherapeutic interventions are paramount; they include making sure that the patient is at the appro­priate level of care, which, for the confused outpatient, could mean hospitalization. Ensuring proper nutrition, hydration, sen­sory care (hearing aids, glasses, etc.), and stability in ambulation must be done before considering pharmacotherapy.

Antipsychotic use has been the mainstay of drug treatment of behavioral dyscontrol. Haloperidol has been the traditional go-to medication because there is no evidence that low-dose haloperidol (<3 mg/d) has any different efficacy compared with the atypical antipsychotics or has a greater fre­quency of adverse drug effects. However, high-dose haloperidol (>4.5 mg/d) was associated with a greater incidence of adverse effects, mainly parkinsonism, than atypical antipsychotics.¹⁹ Neither the typi­cal nor atypical antipsychotics have shown mortality benefit—the real outcome mea­sure of interest.

In terms of treating major (or minor) NCD, there are only 2 FDA-approved medication classes: cholinesterase inhibi­tors (donepezil, galantamine, rivastig­mine, etc.) and memantine. However, these medication classes—even when combined together—have only shown marginal benefit in terms of improving cognition. Worse, even when given early in the course of illness they do not reduce the rate of NCD. For pseudodementia, selec­tive serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors tend to form the mainstay of treating underlying depression or anxiety leading to cognitive changes. Preliminary data suggest that some SSRIs might improve cognition in terms of process­ing speed, verbal learning, and memory.²⁰ More studies are needed before definitive conclusions can be drawn.

For the confused patient, a personalized therapeutic program, in which multiple interventions are considered at once (tar­geting all areas of the patient’s life) is gain­ing research traction. For example, a novel, comprehensive program involving mul­tiple modalities designed to achieve meta­bolic enhancement for neurodegeneration (MEND) recently has shown robust benefit for patients with AD, MCI, and SCI.²¹ Using an individual approach to improve diet, activity, sleep, metabolic status including body mass index, and several other mark­ers that affect neural plasticity, researchers demonstrated symptom improvement in 9 of 10 study patients.

Yet, some of the interventions, such as the use of statins for hyperlipidemia, remain controversial, with some studies suggesting that they help cognition,^22,23 and others showing no association.²⁴ The researchers caution that further research is warranted before costly dementia pre­vention trials with statins are undertaken. It does not appear that there are current MEND-type research projects in delirium but it’s to be hoped that we will see these in the future.

In the case of Ms. T, the cause of delir­ium vs mild NCD was thought to be mul­tifactorial. Discontinuing Armour Thyroid and metformin—symptoms of hypoglyce­mia emerged as a leading concern—were simple adjustments that led to resolution of the most concerning elements of her confusion. She continued her other psy­chotropics, although there might be mild residual cognitive issues that warrant close observation.

Related Resources
• Lin JS, O’Connor E, Rossum RC, et al. Screening for cognitive impairment in older adults: an evidence update for the U.S. Preventive Services Task Force. Rockville, MD: Agency for Healthcare Research and Quality (US); 2013.
• Grover S, Kate N. Assessment scales for delirium: a review. World J Psychiatry. 2012;2(4):58-70.

Drug Brand Names
Atorvastatin • Lipitor                           Lithium • Eskalith, Lithobid
Donepezil • Aricept                              Lorazepam • Ativan
Escitalopram • Lexapro                        Memantine • Namenda
Flumazenil • Romazicon                       Metformin • Glucophage
Galantamine • Razadyne                      Naloxone • Narcan
Glipizide • Glucotrol                             Physostigmine • Antilirium
Haloperidol • Haldol                             Quetiapine • Seroquel
Levothyroxine • Levoxyl, Synthroid       Rivastigmine • Exelon
Lithium • Eskalith, Lithobid                   Valproic acid • Depakene

Disclosure
Dr. Raj is a speaker for Actavis Pharmaceuticals, AstraZeneca, and Merck.