Is catatonia a rare condition that belongs in the history books, or is it more prevalent than we think? If we think we don’t see it often, how will we recognize it? And how do we treat it? This article reviews the evolution of our understanding of the phenomenology and therapy of this interesting and complex condition.

History of the concept

In 1874, Kahlbaum^1,2 was the first to propose a syndrome of motor dysfunction characterized by mutism, immobility, staring gaze, negativism, stereotyped behavior, waxy flexibility, and verbal stereotypies that he called catatonia. Kahlbaum conceptualized catatonia as a distinct disorder,³ but Kraepelin reformulated it as a feature of dementia praecox.⁴ Although Bleuler felt that catatonia could occur in other psychiatric disorders and in normal people,⁴ he also included catatonia as a marker of schizophrenia, where it remained from DSM-I through DSM-IV.³ As was believed to be true of schizophrenia, Kraepelin considered catatonia to be characterized by poor prognosis, whereas Bleuler eliminated poor prognosis as a criterion for catatonia.³

In DSM-IV, catatonia was still a subtype of schizophrenia, but for the first time it was expanded diagnostically to become both a specifier in mood disorders, and a syndrome resulting from a general medical condition.^5,6 In DSM-5, catatonic schizophrenia was deleted, and catatonia became a specifier for 10 disorders, including schizophrenia, mood disorders, and general medical conditions.^3,5-9 In ICD-10, however, catatonia is still associated primarily with schizophrenia.¹⁰

A wide range of presentations

Catatonia is a cyclical syndrome characterized by alterations in motor, behavioral, and vocal signs occurring in the context of medical, neurologic, and psychiatric disorders.⁸ The most common features are immobility, waxy flexibility, stupor, mutism, negativism, echolalia, echopraxia, peculiarities of voluntary movement, and rigidity.^7,11 Features of catatonia that have been repeatedly described through the years are summarized in Table 1.^8,12,13 In general, presentations of catatonia are not specific to any psychiatric or medical etiology.^13,14

Catatonia often is described along a continuum from retarded/stuporous to excited,^14,15 and from benign to malignant.¹³ Examples of these ranges of presentation include^{5,12,13,15-19}:

Stuporous/retarded catatonia (Kahlbaum syndrome) is a primarily negative syndrome in which stupor, mutism, negativism, obsessional slowness, and posturing predominate. Akinetic mutism and coma vigil are sometimes considered to be types of stuporous catatonia, as occasionally are locked-in syndrome and abulia caused by anterior cingulate lesions.

Excited catatonia (hyperkinetic variant, Bell’s mania, oneirophrenia, oneroid state/syndrome, catatonia raptus) is characterized by agitation, combativeness, verbigeration, stereotypies, grimacing, and echo phenomena (echopraxia and echolalia).

Continue to: Malignant (lethal) catatonia

Several specific subtypes of catatonia that may exist anywhere along dimensions of activity and severity also have been described:

Periodic catatonia. In 1908, Kraepelin described a form of periodic catatonia, with rapid shifts from excitement to stupor.⁴ Later, Gjessing described periodic catatonia in schizophrenia and reported success treating it with high doses of thyroid hormone.⁴ Today, periodic catatonia refers to the rapid onset of recurrent, brief hypokinetic or hyperkinetic episodes lasting 4 to 10 days and recurring during the course of weeks to years. Patients often are asymptomatic between episodes except for grimacing, stereotypies, and negativism later in the course.^13,15 At least some forms of periodic catatonia are familial,⁴ with autosomal dominant transmission possibly linked to chromosome 15q15.¹³

A familial form of catatonia has been described that has a poor response to standard therapies (benzodiazepines and electroconvulsive therapy [ECT]), but in view of the high comorbidity of catatonia and bipolar disorder, it is difficult to determine whether this is a separate condition, or a group of patients with bipolar disorder.⁵

Late (ie, late-onset) catatonia is well described in the Japanese literature.¹⁰ Reported primarily in women without a known medical illness or brain disorder, late catatonia begins with prodromal hypochondriacal or depressive symptoms during a stressful situation, followed by unprovoked anxiety and agitation. Some patients develop hallucinations, delusions, and recurrent excitement, along with anxiety and agitation. The next stage involves typical catatonic features (mainly excitement, retardation, negativism, and autonomic disturbance), progressing to stupor, mutism, verbal stereotypies, and negativism, including refusal of food. Most patients have residual symptoms following improvement. A few cases have been noted to remit with ECT, with relapse when treatment was discontinued. Late catatonia has been thought to be associated with late-onset schizophrenia or bipolar disorder, or to be an independent entity.

Continue to: Untreated catatonia can have...

Not as rare as you might think

With the shift from inpatient to outpatient care driven by deinstitutionalization, longitudinal close observation became less common, and clinicians got the impression that the dramatic catatonia that was common in the hospital had become rare.³ The impression that catatonia was unimportant was strengthened by expanding industry promotion of antipsychotic medications while ignoring catatonia, for which the industry had no specific treatment.³ With recent research, however, catatonia has been reported in 7% to 38% of adult psychiatric patients, including 9% to 25% of inpatients, 20% to 25% of patients with mania,^3,5 and 20% of patients with major depressive episodes.⁷ Catatonia has been noted in .6% to 18% of adolescent psychiatric inpatients (especially in communication and social disorders programs),^5,8,22 some children,⁵ and 6% to 18% of adult and juvenile patients with autism spectrum disorder (ASD).²³ In the medical setting, catatonia occurs in 12% to 37% of patients with delirium,^{8,14,17,18,20,24} 7% to 45% of medically ill patients, including those with no psychiatric history,^12,13 and 4% of ICU patients.¹² Several substances have been linked to catatonia; these are discussed later.¹¹ Contrary to earlier impressions, catatonia is more common in mood disorders, particularly mixed bipolar disorder, especially mania,⁵ than in schizophrenia.^7,8,17,25

Pathophysiology/etiology

Conditions associated with catatonia have different features that act through a final common pathway,⁷ possibly related to the neurobiology of an extreme fear response called tonic immobility that has been conserved through evolution.⁸ This mechanism may be mediated by decreased dopamine signaling in basal ganglia, orbitofrontal, and limbic systems, including the hypothalamus and basal forebrain.^3,17,20 Subcortical reduction of dopaminergic neurotransmission appears to be related to reduced GABA_A receptor signaling and dysfunction of N-methyl-d-aspartate (NMDA) receptors with glutaminergic excess in striato-cortical or frontal cortico-cortical systems.^13,20,26,27

Up to one-quarter of cases of catatonia are secondary to medical (mostly neurologic) factors or substances.¹⁵Table 2^5,13,15 lists common medical and neurological causes. Medications and substances known to cause catatonia are noted in Table 3.^5,8,13,16,26

Catatonia can be a specifier, or a separate condition

DSM-5 criteria for catatonia are summarized in Table 4.²⁸ With these features, catatonia can be a specifier for depressive, bipolar, or psychotic disorders; a complication of a medical disorder; or another separate diagnosis.⁸ The diagnosis of catatonia in DSM-5 is made when the clinical picture is dominated by ≥3 of the following core features^8,15:

• motoric immobility as evidenced by catalepsy (including waxy flexibility) or stupor
• excessive purposeless motor activity that is not influenced by external stimuli
• extreme negativism or mutism
• peculiarities of voluntary movement such as posturing, stereotyped movements, prominent mannerisms, or prominent grimacing
• echolalia or echopraxia.

Continue to: DSM-5 criteria for the diagnosis of catatonia are more...

DSM-5 criteria for the diagnosis of catatonia are more restrictive than DSM-IV criteria. As a result, they exclude a significant number of patients who would be considered catatonic in other systems.²⁹ For example, DSM-5 criteria do not include common features noted in Table 1,^8,12,13 such as rigidity and staring.^14,29 If the diagnosis is not obvious, it might be suspected in the presence of >1 of posturing, automatic obedience, or waxy flexibility, or >2 of echopraxia/echolalia, gegenhalten, negativism, mitgehen, or stereotypy/vergiberation.¹² Clues to catatonia that are not included in formal diagnostic systems and are easily confused with features of psychosis include whispered or robotic speech, uncharacteristic foreign accent, tiptoe walking, hopping, rituals, and odd mannerisms.⁵

There are several catatonia rating scales containing between 14 and 40 items that are useful in diagnosing and following treatment response in catatonia (Table 5^8,13,15,29). Of these, the Kanner Scale is primarily applied in neuropsychiatric settings, while the Bush-Francis Catatonia Rating Scale (BFCRS) has had the most widespread use. The BFCRS consists of 23 items, the first 14 of which are used as a screening instrument. It requires 2 of its first 14 items to diagnose catatonia, while DSM-5 requires 3 of 12 signs.²⁹ If the diagnosis remains in doubt, a benzodiazepine agonist test can be instructive.^9,12 The presence of catatonia is suggested by significant improvement, ideally assessed prospectively by improvement of BFCRS scores, shortly after administration of a single dose of 1 to 2 mg lorazepam or 5 mg diazepam IV, or 10 mg zolpidem orally. Further evaluation generally consists of a careful medical and psychiatric histories of patient and family, review of all medications, history of substance use with toxicology as indicated, physical examination focusing on autonomic dysregulation, examination for delirium, and laboratory tests as suggested by the history and examination that may include complete blood count, creatine kinase, serum iron, blood urea nitrogen, electrolytes, creatinine, prolactin, anti-NMDA antibodies, thyroid function tests, serology, metabolic panel, human immunodeficiency virus testing, EEG, and neuroimaging.^8,15,16

A complex differential diagnosis

Manifestations of numerous psychiatric and neurologic disorders can mimic or be identical to those of catatonia. The differential diagnosis is complicated by the fact that some of these disorders can cause catatonia, which is then masked by the primary disorder; some disorders (eg, NMS) are forms of catatonia. Table 6^{5,8,12,19,26,30} lists conditions to consider.

Some of these conditions warrant discussion. ASD may have catatonia-like features such as echolalia, echopraxia, excitement, combativeness, grimacing, mutism, logorrhea, verbigeration, catalepsy, mannerisms, rigidity, staring and withdrawal.⁸ Catatonia may also be a stage of deterioration of autism, in which case it is characterized by increases in slowness of movement and speech, reliance on physical or verbal prompting from others, passivity, and lack of motivation.²³ At the same time, catatonic features such as mutism, stereotypic speech, repetitive behavior, echolalia, posturing, mannerisms, purposeless agitation, and rigidity in catatonia can be misinterpreted as signs of ASD.⁸ Catatonia should be suspected as a complication of longstanding ASD in the presence of a consistent, marked change in motor behavior, such as immobility, decreased speech, stupor, excitement, or mixtures or alternations of stupor and excitement.⁸ Freezing while doing something, difficulty crossing lines, or uncharacteristic persistence of a particular behavior may also herald the presence of catatonia with ASD.⁸

Catatonia caused by a neurologic or metabolic factor or a substance can be difficult to distinguish from delirium complicated by catatonia. Delirium may be identified in patients with catatonia by the presence of a waxing and waning level of consciousness (vs fluctuating behavior in catatonia) and slowing of the EEG.^12,15 Antipsychotic medications can improve delirium but worsen catatonia, while benzodiazepines can improve catatonia but worsen delirium.

Continue to: Among other neurologic syndromes...

Benzodiazepines, ECT are the usual treatments

Experience dictates that the general principles of treatment noted in Table 7^12,15,23,31 apply to all patients with catatonia. Since the first reported improvement of catatonia with amobarbital in 1930,⁶ there have been no controlled studies of specific treatments of catatonia.¹³ Meaningful treatment trials are either naturalistic, or have been performed only for NMS and malignant catatonia.⁵ However, multiple case reports and case series suggest that treatments with agents that have anticonvulsant properties (benzodiazepines, barbiturates) and ECT are effective.⁵

Benzodiazepines and related compounds. Case series have suggested a 60% to 80% remission rate of catatonia with benzodiazepines, the most commonly utilized of which has been lorazepam.^7,13,32 Treatment begins with a lorazepam challenge test of 1 to 2 mg in adults and 0.5 to 1 mg in children and geriatric patients,^9,15 administered orally (including via nasogastric tube), IM, or IV. Following a response (≥50% improvement), the dose is increased to 2 mg 3 times per day. The dose is further increased to 6 to 16 mg/d, and sometimes up to 30 mg/d.^9,11 Oral is less effective than sublingual or IM administration.¹¹ Diazepam can be helpful at doses 5 times the lorazepam dose.^9,17 A zolpidem challenge test of 10 mg orally or via nasogastric tube has also been utilized.¹⁵ Response is brief and is usually followed by lorazepam, although zolpidem up to 40 mg/d has been used for ongoing treatment.⁹

One alternative benzodiazepine protocol utilizes an initial IV dose of 2 mg lorazepam, repeated 3 to 5 times per day; the dose is increased to 10 to 12 mg/d if the first doses are partially effective.¹⁶ A lorazepam/diazepam approach involves a combination of IM lorazepam and IV diazepam.¹¹ The protocol begins with 2 mg of IM lorazepam. If there is no effect within 2 hours, a second 2 mg dose is administered, followed by an IV infusion of 10 mg diazepam in 500 ml of normal saline at 1.25 mg/hour until catatonia remits.

An Indian study of 107 patients (mean age 26) receiving relatively low doses of lorazepam (3 to 6 mg/d for at least 3 days) found that factors suggesting a robust response include a shorter duration of catatonia and waxy flexibility, while passivity, mutism, and auditory hallucinations describing the patient in the third person were associated with a poorer acute response.³¹ Catatonia with marked retardation and mutism complicating schizophrenia, especially with chronic negative symptoms, may be associated with a lower response rate to benzodiazepines.^20,33 Maintenance lorazepam has been effective in reducing relapse and recurrence.¹¹ There are no controlled studies of maintenance treatment with benzodiazepines, but clinical reports suggest that doses in the range of 4 to 10 mg/d are effective.³²

Continue to: ECT was used for catatonia in 1934...

ECT was first used for catatonia in 1934, when Laszlo Meduna used chemically induced seizures in catatonic patients who had been on tube feeding for months and no longer needed it after treatment.^6,7 As was true for other disorders, this approach was replaced by ECT.⁷ In various case series, the effectiveness of ECT in catatonia has been 53% to 100%.^7,13,15 Right unilateral ECT has been reported to be effective with 1 treatment.²¹ However, the best-established approach is with bitemporal ECT with a suprathreshold stimulus,⁹ usually with an acute course of 6 to 20 treatments.²⁰ ECT has been reported to be equally safe and effective in adolescents and adults.³⁴ Continued ECT is usually necessary until the patient has returned to baseline.⁹

ECT usually is recommended within 24 hours for treatment-resistant malignant catatonia or refusal to eat or drink, and within 2 to 3 days if medications are not sufficiently effective in other forms of catatonia.^12,15,20 If ECT is initiated after a benzodiazepine trial, the benzodiazepine antagonist flumazenil is administered first to reverse the anticonvulsant effect.⁹ Some experts recommend using a muscle relaxant other than succinylcholine in the presence of evidence of muscle damage.⁷

Alternatives to benzodiazepines and ECT. Based on case reports, the treatments described in Table 8^{13,15,17,20,25} have been used for patients with catatonia who do not tolerate or respond to standard treatments. The largest number of case reports have been with NMDA antagonists, while the presumed involvement of reduced dopamine signaling suggests that dopaminergic medications should be helpful. Dantrolene, which blocks release of calcium from intracellular stores and has been used to treat malignant hyperthermia, is sometimes used for NMS, often with disappointing results.

Whereas first-generation antipsychotics definitely increase the risk of catatonia and second-generation antipsychotics (SGAs) probably do so, SGAs are sometimes necessary to treat persistent psychosis in patients with schizophrenia who develop catatonia. Of these medications, clozapine may be most desirable because of low potency for dopamine receptor blockade and modulation of glutamatergic signaling. Partial dopamine agonism by aripiprazole, and the potential for increased subcortical prefrontal dopamine release resulting from serotonin 5HT2A antagonism and 5HT1A agonism by other SGAs, could also be helpful or at least not harmful in catatonia. Lorazepam is usually administered along with these medications to ameliorate treatment-emergent exacerbation of catatonia.

There are no controlled studies of any of these treatments. Based on case reports, most experts would recommend initiating treatment of catatonia with lorazepam, followed by ECT if necessary or in the presence of life-threatening catatonia. If ECT is not available, ineffective, or not tolerated, the first alternatives to be considered would be an NMDA antagonist or an anticonvulsant.²⁰

Continue to: Course varies by patient, underlying cause

Course varies by patient, underlying cause

The response to benzodiazepines or ECT can vary from episode to episode¹¹ and is similar in adults and younger patients.²² Many patients recover completely after a single episode, while relapse after remission occurs repeatedly in periodic catatonia, which involves chronic alternating stupor and excitement waxing and waning over years.¹¹ Relapses may occur frequently, or every few years.¹¹ Some cases of catatonia initially have an episodic course and become chronic and deteriorating, possibly paralleling the original descriptions of the natural history of untreated catatonia, while malignant catatonia can be complicated by medical morbidity or death.⁴ The long-term prognosis generally depends on the underlying cause of catatonia.⁵

Bottom Line

Much more common than many clinicians realize, catatonia can be overlooked because symptoms can mimic or overlap with features of an underlying medical or neurologic disorder. Suspect catatonia when one of these illnesses has an unexpected course or an inadequate treatment response. Be alert to characteristic changes in behavior and speech. A benzodiazepine challenge can be used to diagnose and begin treatment of catatonia. Consider electroconvulsive therapy sooner rather than later, especially for severely ill patients.

Related Resources

• Gibson RC, Walcott G. Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses. Cochrane Database Syst Rev. 2008;(4):CD006570. 
• Newcastle University. Catatonia. https://youtu.be/_s1lzxHRO4U.

Drug Brand Names

Amantadine • Symmetrel
Amobarbital • Amytal
Aripiprazole • Abilify
Azithromycin • Zithromax
Baclofen • Lioresal
Benztropine • Cogentin
Carbamazepine • Carbatrol, Tegretol
Carbidopa/levodopa • Sinemet
Ciprofloxacin • Cipro
Clozapine • Clozaril
Dantrolene • Dantrium
Dexamethasone • Decadron
Dextromethorphan/quinidine • Neudexta
Diazepam • Valium
Disulfiram • Antabuse
Flumazenil • Romazicon
Fluoxetine • Prozac
Fluvoxamine • Luvox
Levetiracetam • Keppra
Lithium • Eskalith, Lithobid
Lorazepam • Ativan
Memantine • Namenda
Methylphenidate • Ritalin
Minocycline • Minocin
Olanzapine • Zyprexa
Risperidone • Risperdal
Succinylcholine • Anectine
Topiramate • Topamax
Trihexyphenidyl • Artane
Valproate • Depakote
Ziprasidone • Geodon
Zolpidem • Ambien

Is catatonia a rare condition that belongs in the history books, or is it more prevalent than we think? If we think we don’t see it often, how will we recognize it? And how do we treat it? This article reviews the evolution of our understanding of the phenomenology and therapy of this interesting and complex condition.

History of the concept

In 1874, Kahlbaum^1,2 was the first to propose a syndrome of motor dysfunction characterized by mutism, immobility, staring gaze, negativism, stereotyped behavior, waxy flexibility, and verbal stereotypies that he called catatonia. Kahlbaum conceptualized catatonia as a distinct disorder,³ but Kraepelin reformulated it as a feature of dementia praecox.⁴ Although Bleuler felt that catatonia could occur in other psychiatric disorders and in normal people,⁴ he also included catatonia as a marker of schizophrenia, where it remained from DSM-I through DSM-IV.³ As was believed to be true of schizophrenia, Kraepelin considered catatonia to be characterized by poor prognosis, whereas Bleuler eliminated poor prognosis as a criterion for catatonia.³

In DSM-IV, catatonia was still a subtype of schizophrenia, but for the first time it was expanded diagnostically to become both a specifier in mood disorders, and a syndrome resulting from a general medical condition.^5,6 In DSM-5, catatonic schizophrenia was deleted, and catatonia became a specifier for 10 disorders, including schizophrenia, mood disorders, and general medical conditions.^3,5-9 In ICD-10, however, catatonia is still associated primarily with schizophrenia.¹⁰

A wide range of presentations

Catatonia is a cyclical syndrome characterized by alterations in motor, behavioral, and vocal signs occurring in the context of medical, neurologic, and psychiatric disorders.⁸ The most common features are immobility, waxy flexibility, stupor, mutism, negativism, echolalia, echopraxia, peculiarities of voluntary movement, and rigidity.^7,11 Features of catatonia that have been repeatedly described through the years are summarized in Table 1.^8,12,13 In general, presentations of catatonia are not specific to any psychiatric or medical etiology.^13,14

Catatonia often is described along a continuum from retarded/stuporous to excited,^14,15 and from benign to malignant.¹³ Examples of these ranges of presentation include^{5,12,13,15-19}:

Stuporous/retarded catatonia (Kahlbaum syndrome) is a primarily negative syndrome in which stupor, mutism, negativism, obsessional slowness, and posturing predominate. Akinetic mutism and coma vigil are sometimes considered to be types of stuporous catatonia, as occasionally are locked-in syndrome and abulia caused by anterior cingulate lesions.

Excited catatonia (hyperkinetic variant, Bell’s mania, oneirophrenia, oneroid state/syndrome, catatonia raptus) is characterized by agitation, combativeness, verbigeration, stereotypies, grimacing, and echo phenomena (echopraxia and echolalia).

Continue to: Malignant (lethal) catatonia

Several specific subtypes of catatonia that may exist anywhere along dimensions of activity and severity also have been described:

Periodic catatonia. In 1908, Kraepelin described a form of periodic catatonia, with rapid shifts from excitement to stupor.⁴ Later, Gjessing described periodic catatonia in schizophrenia and reported success treating it with high doses of thyroid hormone.⁴ Today, periodic catatonia refers to the rapid onset of recurrent, brief hypokinetic or hyperkinetic episodes lasting 4 to 10 days and recurring during the course of weeks to years. Patients often are asymptomatic between episodes except for grimacing, stereotypies, and negativism later in the course.^13,15 At least some forms of periodic catatonia are familial,⁴ with autosomal dominant transmission possibly linked to chromosome 15q15.¹³

A familial form of catatonia has been described that has a poor response to standard therapies (benzodiazepines and electroconvulsive therapy [ECT]), but in view of the high comorbidity of catatonia and bipolar disorder, it is difficult to determine whether this is a separate condition, or a group of patients with bipolar disorder.⁵

Late (ie, late-onset) catatonia is well described in the Japanese literature.¹⁰ Reported primarily in women without a known medical illness or brain disorder, late catatonia begins with prodromal hypochondriacal or depressive symptoms during a stressful situation, followed by unprovoked anxiety and agitation. Some patients develop hallucinations, delusions, and recurrent excitement, along with anxiety and agitation. The next stage involves typical catatonic features (mainly excitement, retardation, negativism, and autonomic disturbance), progressing to stupor, mutism, verbal stereotypies, and negativism, including refusal of food. Most patients have residual symptoms following improvement. A few cases have been noted to remit with ECT, with relapse when treatment was discontinued. Late catatonia has been thought to be associated with late-onset schizophrenia or bipolar disorder, or to be an independent entity.

Continue to: Untreated catatonia can have...

Not as rare as you might think

With the shift from inpatient to outpatient care driven by deinstitutionalization, longitudinal close observation became less common, and clinicians got the impression that the dramatic catatonia that was common in the hospital had become rare.³ The impression that catatonia was unimportant was strengthened by expanding industry promotion of antipsychotic medications while ignoring catatonia, for which the industry had no specific treatment.³ With recent research, however, catatonia has been reported in 7% to 38% of adult psychiatric patients, including 9% to 25% of inpatients, 20% to 25% of patients with mania,^3,5 and 20% of patients with major depressive episodes.⁷ Catatonia has been noted in .6% to 18% of adolescent psychiatric inpatients (especially in communication and social disorders programs),^5,8,22 some children,⁵ and 6% to 18% of adult and juvenile patients with autism spectrum disorder (ASD).²³ In the medical setting, catatonia occurs in 12% to 37% of patients with delirium,^{8,14,17,18,20,24} 7% to 45% of medically ill patients, including those with no psychiatric history,^12,13 and 4% of ICU patients.¹² Several substances have been linked to catatonia; these are discussed later.¹¹ Contrary to earlier impressions, catatonia is more common in mood disorders, particularly mixed bipolar disorder, especially mania,⁵ than in schizophrenia.^7,8,17,25

Pathophysiology/etiology

Conditions associated with catatonia have different features that act through a final common pathway,⁷ possibly related to the neurobiology of an extreme fear response called tonic immobility that has been conserved through evolution.⁸ This mechanism may be mediated by decreased dopamine signaling in basal ganglia, orbitofrontal, and limbic systems, including the hypothalamus and basal forebrain.^3,17,20 Subcortical reduction of dopaminergic neurotransmission appears to be related to reduced GABA_A receptor signaling and dysfunction of N-methyl-d-aspartate (NMDA) receptors with glutaminergic excess in striato-cortical or frontal cortico-cortical systems.^13,20,26,27

Up to one-quarter of cases of catatonia are secondary to medical (mostly neurologic) factors or substances.¹⁵Table 2^5,13,15 lists common medical and neurological causes. Medications and substances known to cause catatonia are noted in Table 3.^5,8,13,16,26

Catatonia can be a specifier, or a separate condition

DSM-5 criteria for catatonia are summarized in Table 4.²⁸ With these features, catatonia can be a specifier for depressive, bipolar, or psychotic disorders; a complication of a medical disorder; or another separate diagnosis.⁸ The diagnosis of catatonia in DSM-5 is made when the clinical picture is dominated by ≥3 of the following core features^8,15:

• motoric immobility as evidenced by catalepsy (including waxy flexibility) or stupor
• excessive purposeless motor activity that is not influenced by external stimuli
• extreme negativism or mutism
• peculiarities of voluntary movement such as posturing, stereotyped movements, prominent mannerisms, or prominent grimacing
• echolalia or echopraxia.

Continue to: DSM-5 criteria for the diagnosis of catatonia are more...

DSM-5 criteria for the diagnosis of catatonia are more restrictive than DSM-IV criteria. As a result, they exclude a significant number of patients who would be considered catatonic in other systems.²⁹ For example, DSM-5 criteria do not include common features noted in Table 1,^8,12,13 such as rigidity and staring.^14,29 If the diagnosis is not obvious, it might be suspected in the presence of >1 of posturing, automatic obedience, or waxy flexibility, or >2 of echopraxia/echolalia, gegenhalten, negativism, mitgehen, or stereotypy/vergiberation.¹² Clues to catatonia that are not included in formal diagnostic systems and are easily confused with features of psychosis include whispered or robotic speech, uncharacteristic foreign accent, tiptoe walking, hopping, rituals, and odd mannerisms.⁵

There are several catatonia rating scales containing between 14 and 40 items that are useful in diagnosing and following treatment response in catatonia (Table 5^8,13,15,29). Of these, the Kanner Scale is primarily applied in neuropsychiatric settings, while the Bush-Francis Catatonia Rating Scale (BFCRS) has had the most widespread use. The BFCRS consists of 23 items, the first 14 of which are used as a screening instrument. It requires 2 of its first 14 items to diagnose catatonia, while DSM-5 requires 3 of 12 signs.²⁹ If the diagnosis remains in doubt, a benzodiazepine agonist test can be instructive.^9,12 The presence of catatonia is suggested by significant improvement, ideally assessed prospectively by improvement of BFCRS scores, shortly after administration of a single dose of 1 to 2 mg lorazepam or 5 mg diazepam IV, or 10 mg zolpidem orally. Further evaluation generally consists of a careful medical and psychiatric histories of patient and family, review of all medications, history of substance use with toxicology as indicated, physical examination focusing on autonomic dysregulation, examination for delirium, and laboratory tests as suggested by the history and examination that may include complete blood count, creatine kinase, serum iron, blood urea nitrogen, electrolytes, creatinine, prolactin, anti-NMDA antibodies, thyroid function tests, serology, metabolic panel, human immunodeficiency virus testing, EEG, and neuroimaging.^8,15,16

A complex differential diagnosis

Manifestations of numerous psychiatric and neurologic disorders can mimic or be identical to those of catatonia. The differential diagnosis is complicated by the fact that some of these disorders can cause catatonia, which is then masked by the primary disorder; some disorders (eg, NMS) are forms of catatonia. Table 6^{5,8,12,19,26,30} lists conditions to consider.

Some of these conditions warrant discussion. ASD may have catatonia-like features such as echolalia, echopraxia, excitement, combativeness, grimacing, mutism, logorrhea, verbigeration, catalepsy, mannerisms, rigidity, staring and withdrawal.⁸ Catatonia may also be a stage of deterioration of autism, in which case it is characterized by increases in slowness of movement and speech, reliance on physical or verbal prompting from others, passivity, and lack of motivation.²³ At the same time, catatonic features such as mutism, stereotypic speech, repetitive behavior, echolalia, posturing, mannerisms, purposeless agitation, and rigidity in catatonia can be misinterpreted as signs of ASD.⁸ Catatonia should be suspected as a complication of longstanding ASD in the presence of a consistent, marked change in motor behavior, such as immobility, decreased speech, stupor, excitement, or mixtures or alternations of stupor and excitement.⁸ Freezing while doing something, difficulty crossing lines, or uncharacteristic persistence of a particular behavior may also herald the presence of catatonia with ASD.⁸

Catatonia caused by a neurologic or metabolic factor or a substance can be difficult to distinguish from delirium complicated by catatonia. Delirium may be identified in patients with catatonia by the presence of a waxing and waning level of consciousness (vs fluctuating behavior in catatonia) and slowing of the EEG.^12,15 Antipsychotic medications can improve delirium but worsen catatonia, while benzodiazepines can improve catatonia but worsen delirium.

Continue to: Among other neurologic syndromes...

Benzodiazepines, ECT are the usual treatments

Experience dictates that the general principles of treatment noted in Table 7^12,15,23,31 apply to all patients with catatonia. Since the first reported improvement of catatonia with amobarbital in 1930,⁶ there have been no controlled studies of specific treatments of catatonia.¹³ Meaningful treatment trials are either naturalistic, or have been performed only for NMS and malignant catatonia.⁵ However, multiple case reports and case series suggest that treatments with agents that have anticonvulsant properties (benzodiazepines, barbiturates) and ECT are effective.⁵

Benzodiazepines and related compounds. Case series have suggested a 60% to 80% remission rate of catatonia with benzodiazepines, the most commonly utilized of which has been lorazepam.^7,13,32 Treatment begins with a lorazepam challenge test of 1 to 2 mg in adults and 0.5 to 1 mg in children and geriatric patients,^9,15 administered orally (including via nasogastric tube), IM, or IV. Following a response (≥50% improvement), the dose is increased to 2 mg 3 times per day. The dose is further increased to 6 to 16 mg/d, and sometimes up to 30 mg/d.^9,11 Oral is less effective than sublingual or IM administration.¹¹ Diazepam can be helpful at doses 5 times the lorazepam dose.^9,17 A zolpidem challenge test of 10 mg orally or via nasogastric tube has also been utilized.¹⁵ Response is brief and is usually followed by lorazepam, although zolpidem up to 40 mg/d has been used for ongoing treatment.⁹

One alternative benzodiazepine protocol utilizes an initial IV dose of 2 mg lorazepam, repeated 3 to 5 times per day; the dose is increased to 10 to 12 mg/d if the first doses are partially effective.¹⁶ A lorazepam/diazepam approach involves a combination of IM lorazepam and IV diazepam.¹¹ The protocol begins with 2 mg of IM lorazepam. If there is no effect within 2 hours, a second 2 mg dose is administered, followed by an IV infusion of 10 mg diazepam in 500 ml of normal saline at 1.25 mg/hour until catatonia remits.

An Indian study of 107 patients (mean age 26) receiving relatively low doses of lorazepam (3 to 6 mg/d for at least 3 days) found that factors suggesting a robust response include a shorter duration of catatonia and waxy flexibility, while passivity, mutism, and auditory hallucinations describing the patient in the third person were associated with a poorer acute response.³¹ Catatonia with marked retardation and mutism complicating schizophrenia, especially with chronic negative symptoms, may be associated with a lower response rate to benzodiazepines.^20,33 Maintenance lorazepam has been effective in reducing relapse and recurrence.¹¹ There are no controlled studies of maintenance treatment with benzodiazepines, but clinical reports suggest that doses in the range of 4 to 10 mg/d are effective.³²

Continue to: ECT was used for catatonia in 1934...

ECT was first used for catatonia in 1934, when Laszlo Meduna used chemically induced seizures in catatonic patients who had been on tube feeding for months and no longer needed it after treatment.^6,7 As was true for other disorders, this approach was replaced by ECT.⁷ In various case series, the effectiveness of ECT in catatonia has been 53% to 100%.^7,13,15 Right unilateral ECT has been reported to be effective with 1 treatment.²¹ However, the best-established approach is with bitemporal ECT with a suprathreshold stimulus,⁹ usually with an acute course of 6 to 20 treatments.²⁰ ECT has been reported to be equally safe and effective in adolescents and adults.³⁴ Continued ECT is usually necessary until the patient has returned to baseline.⁹

ECT usually is recommended within 24 hours for treatment-resistant malignant catatonia or refusal to eat or drink, and within 2 to 3 days if medications are not sufficiently effective in other forms of catatonia.^12,15,20 If ECT is initiated after a benzodiazepine trial, the benzodiazepine antagonist flumazenil is administered first to reverse the anticonvulsant effect.⁹ Some experts recommend using a muscle relaxant other than succinylcholine in the presence of evidence of muscle damage.⁷

Alternatives to benzodiazepines and ECT. Based on case reports, the treatments described in Table 8^{13,15,17,20,25} have been used for patients with catatonia who do not tolerate or respond to standard treatments. The largest number of case reports have been with NMDA antagonists, while the presumed involvement of reduced dopamine signaling suggests that dopaminergic medications should be helpful. Dantrolene, which blocks release of calcium from intracellular stores and has been used to treat malignant hyperthermia, is sometimes used for NMS, often with disappointing results.

Whereas first-generation antipsychotics definitely increase the risk of catatonia and second-generation antipsychotics (SGAs) probably do so, SGAs are sometimes necessary to treat persistent psychosis in patients with schizophrenia who develop catatonia. Of these medications, clozapine may be most desirable because of low potency for dopamine receptor blockade and modulation of glutamatergic signaling. Partial dopamine agonism by aripiprazole, and the potential for increased subcortical prefrontal dopamine release resulting from serotonin 5HT2A antagonism and 5HT1A agonism by other SGAs, could also be helpful or at least not harmful in catatonia. Lorazepam is usually administered along with these medications to ameliorate treatment-emergent exacerbation of catatonia.

There are no controlled studies of any of these treatments. Based on case reports, most experts would recommend initiating treatment of catatonia with lorazepam, followed by ECT if necessary or in the presence of life-threatening catatonia. If ECT is not available, ineffective, or not tolerated, the first alternatives to be considered would be an NMDA antagonist or an anticonvulsant.²⁰

Continue to: Course varies by patient, underlying cause

Course varies by patient, underlying cause

The response to benzodiazepines or ECT can vary from episode to episode¹¹ and is similar in adults and younger patients.²² Many patients recover completely after a single episode, while relapse after remission occurs repeatedly in periodic catatonia, which involves chronic alternating stupor and excitement waxing and waning over years.¹¹ Relapses may occur frequently, or every few years.¹¹ Some cases of catatonia initially have an episodic course and become chronic and deteriorating, possibly paralleling the original descriptions of the natural history of untreated catatonia, while malignant catatonia can be complicated by medical morbidity or death.⁴ The long-term prognosis generally depends on the underlying cause of catatonia.⁵

Bottom Line

Much more common than many clinicians realize, catatonia can be overlooked because symptoms can mimic or overlap with features of an underlying medical or neurologic disorder. Suspect catatonia when one of these illnesses has an unexpected course or an inadequate treatment response. Be alert to characteristic changes in behavior and speech. A benzodiazepine challenge can be used to diagnose and begin treatment of catatonia. Consider electroconvulsive therapy sooner rather than later, especially for severely ill patients.

Related Resources

• Gibson RC, Walcott G. Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses. Cochrane Database Syst Rev. 2008;(4):CD006570. 
• Newcastle University. Catatonia. https://youtu.be/_s1lzxHRO4U.

Drug Brand Names

Amantadine • Symmetrel
Amobarbital • Amytal
Aripiprazole • Abilify
Azithromycin • Zithromax
Baclofen • Lioresal
Benztropine • Cogentin
Carbamazepine • Carbatrol, Tegretol
Carbidopa/levodopa • Sinemet
Ciprofloxacin • Cipro
Clozapine • Clozaril
Dantrolene • Dantrium
Dexamethasone • Decadron
Dextromethorphan/quinidine • Neudexta
Diazepam • Valium
Disulfiram • Antabuse
Flumazenil • Romazicon
Fluoxetine • Prozac
Fluvoxamine • Luvox
Levetiracetam • Keppra
Lithium • Eskalith, Lithobid
Lorazepam • Ativan
Memantine • Namenda
Methylphenidate • Ritalin
Minocycline • Minocin
Olanzapine • Zyprexa
Risperidone • Risperdal
Succinylcholine • Anectine
Topiramate • Topamax
Trihexyphenidyl • Artane
Valproate • Depakote
Ziprasidone • Geodon
Zolpidem • Ambien

Is catatonia a rare condition that belongs in the history books, or is it more prevalent than we think? If we think we don’t see it often, how will we recognize it? And how do we treat it? This article reviews the evolution of our understanding of the phenomenology and therapy of this interesting and complex condition.

History of the concept

In 1874, Kahlbaum^1,2 was the first to propose a syndrome of motor dysfunction characterized by mutism, immobility, staring gaze, negativism, stereotyped behavior, waxy flexibility, and verbal stereotypies that he called catatonia. Kahlbaum conceptualized catatonia as a distinct disorder,³ but Kraepelin reformulated it as a feature of dementia praecox.⁴ Although Bleuler felt that catatonia could occur in other psychiatric disorders and in normal people,⁴ he also included catatonia as a marker of schizophrenia, where it remained from DSM-I through DSM-IV.³ As was believed to be true of schizophrenia, Kraepelin considered catatonia to be characterized by poor prognosis, whereas Bleuler eliminated poor prognosis as a criterion for catatonia.³

In DSM-IV, catatonia was still a subtype of schizophrenia, but for the first time it was expanded diagnostically to become both a specifier in mood disorders, and a syndrome resulting from a general medical condition.^5,6 In DSM-5, catatonic schizophrenia was deleted, and catatonia became a specifier for 10 disorders, including schizophrenia, mood disorders, and general medical conditions.^3,5-9 In ICD-10, however, catatonia is still associated primarily with schizophrenia.¹⁰

A wide range of presentations

Catatonia is a cyclical syndrome characterized by alterations in motor, behavioral, and vocal signs occurring in the context of medical, neurologic, and psychiatric disorders.⁸ The most common features are immobility, waxy flexibility, stupor, mutism, negativism, echolalia, echopraxia, peculiarities of voluntary movement, and rigidity.^7,11 Features of catatonia that have been repeatedly described through the years are summarized in Table 1.^8,12,13 In general, presentations of catatonia are not specific to any psychiatric or medical etiology.^13,14

Catatonia often is described along a continuum from retarded/stuporous to excited,^14,15 and from benign to malignant.¹³ Examples of these ranges of presentation include^{5,12,13,15-19}:

Stuporous/retarded catatonia (Kahlbaum syndrome) is a primarily negative syndrome in which stupor, mutism, negativism, obsessional slowness, and posturing predominate. Akinetic mutism and coma vigil are sometimes considered to be types of stuporous catatonia, as occasionally are locked-in syndrome and abulia caused by anterior cingulate lesions.

Excited catatonia (hyperkinetic variant, Bell’s mania, oneirophrenia, oneroid state/syndrome, catatonia raptus) is characterized by agitation, combativeness, verbigeration, stereotypies, grimacing, and echo phenomena (echopraxia and echolalia).

Continue to: Malignant (lethal) catatonia

Several specific subtypes of catatonia that may exist anywhere along dimensions of activity and severity also have been described:

Periodic catatonia. In 1908, Kraepelin described a form of periodic catatonia, with rapid shifts from excitement to stupor.⁴ Later, Gjessing described periodic catatonia in schizophrenia and reported success treating it with high doses of thyroid hormone.⁴ Today, periodic catatonia refers to the rapid onset of recurrent, brief hypokinetic or hyperkinetic episodes lasting 4 to 10 days and recurring during the course of weeks to years. Patients often are asymptomatic between episodes except for grimacing, stereotypies, and negativism later in the course.^13,15 At least some forms of periodic catatonia are familial,⁴ with autosomal dominant transmission possibly linked to chromosome 15q15.¹³

A familial form of catatonia has been described that has a poor response to standard therapies (benzodiazepines and electroconvulsive therapy [ECT]), but in view of the high comorbidity of catatonia and bipolar disorder, it is difficult to determine whether this is a separate condition, or a group of patients with bipolar disorder.⁵

Late (ie, late-onset) catatonia is well described in the Japanese literature.¹⁰ Reported primarily in women without a known medical illness or brain disorder, late catatonia begins with prodromal hypochondriacal or depressive symptoms during a stressful situation, followed by unprovoked anxiety and agitation. Some patients develop hallucinations, delusions, and recurrent excitement, along with anxiety and agitation. The next stage involves typical catatonic features (mainly excitement, retardation, negativism, and autonomic disturbance), progressing to stupor, mutism, verbal stereotypies, and negativism, including refusal of food. Most patients have residual symptoms following improvement. A few cases have been noted to remit with ECT, with relapse when treatment was discontinued. Late catatonia has been thought to be associated with late-onset schizophrenia or bipolar disorder, or to be an independent entity.

Continue to: Untreated catatonia can have...

Not as rare as you might think

With the shift from inpatient to outpatient care driven by deinstitutionalization, longitudinal close observation became less common, and clinicians got the impression that the dramatic catatonia that was common in the hospital had become rare.³ The impression that catatonia was unimportant was strengthened by expanding industry promotion of antipsychotic medications while ignoring catatonia, for which the industry had no specific treatment.³ With recent research, however, catatonia has been reported in 7% to 38% of adult psychiatric patients, including 9% to 25% of inpatients, 20% to 25% of patients with mania,^3,5 and 20% of patients with major depressive episodes.⁷ Catatonia has been noted in .6% to 18% of adolescent psychiatric inpatients (especially in communication and social disorders programs),^5,8,22 some children,⁵ and 6% to 18% of adult and juvenile patients with autism spectrum disorder (ASD).²³ In the medical setting, catatonia occurs in 12% to 37% of patients with delirium,^{8,14,17,18,20,24} 7% to 45% of medically ill patients, including those with no psychiatric history,^12,13 and 4% of ICU patients.¹² Several substances have been linked to catatonia; these are discussed later.¹¹ Contrary to earlier impressions, catatonia is more common in mood disorders, particularly mixed bipolar disorder, especially mania,⁵ than in schizophrenia.^7,8,17,25

Pathophysiology/etiology

Conditions associated with catatonia have different features that act through a final common pathway,⁷ possibly related to the neurobiology of an extreme fear response called tonic immobility that has been conserved through evolution.⁸ This mechanism may be mediated by decreased dopamine signaling in basal ganglia, orbitofrontal, and limbic systems, including the hypothalamus and basal forebrain.^3,17,20 Subcortical reduction of dopaminergic neurotransmission appears to be related to reduced GABA_A receptor signaling and dysfunction of N-methyl-d-aspartate (NMDA) receptors with glutaminergic excess in striato-cortical or frontal cortico-cortical systems.^13,20,26,27

Up to one-quarter of cases of catatonia are secondary to medical (mostly neurologic) factors or substances.¹⁵Table 2^5,13,15 lists common medical and neurological causes. Medications and substances known to cause catatonia are noted in Table 3.^5,8,13,16,26

Catatonia can be a specifier, or a separate condition

DSM-5 criteria for catatonia are summarized in Table 4.²⁸ With these features, catatonia can be a specifier for depressive, bipolar, or psychotic disorders; a complication of a medical disorder; or another separate diagnosis.⁸ The diagnosis of catatonia in DSM-5 is made when the clinical picture is dominated by ≥3 of the following core features^8,15:

• motoric immobility as evidenced by catalepsy (including waxy flexibility) or stupor
• excessive purposeless motor activity that is not influenced by external stimuli
• extreme negativism or mutism
• peculiarities of voluntary movement such as posturing, stereotyped movements, prominent mannerisms, or prominent grimacing
• echolalia or echopraxia.

Continue to: DSM-5 criteria for the diagnosis of catatonia are more...

DSM-5 criteria for the diagnosis of catatonia are more restrictive than DSM-IV criteria. As a result, they exclude a significant number of patients who would be considered catatonic in other systems.²⁹ For example, DSM-5 criteria do not include common features noted in Table 1,^8,12,13 such as rigidity and staring.^14,29 If the diagnosis is not obvious, it might be suspected in the presence of >1 of posturing, automatic obedience, or waxy flexibility, or >2 of echopraxia/echolalia, gegenhalten, negativism, mitgehen, or stereotypy/vergiberation.¹² Clues to catatonia that are not included in formal diagnostic systems and are easily confused with features of psychosis include whispered or robotic speech, uncharacteristic foreign accent, tiptoe walking, hopping, rituals, and odd mannerisms.⁵

There are several catatonia rating scales containing between 14 and 40 items that are useful in diagnosing and following treatment response in catatonia (Table 5^8,13,15,29). Of these, the Kanner Scale is primarily applied in neuropsychiatric settings, while the Bush-Francis Catatonia Rating Scale (BFCRS) has had the most widespread use. The BFCRS consists of 23 items, the first 14 of which are used as a screening instrument. It requires 2 of its first 14 items to diagnose catatonia, while DSM-5 requires 3 of 12 signs.²⁹ If the diagnosis remains in doubt, a benzodiazepine agonist test can be instructive.^9,12 The presence of catatonia is suggested by significant improvement, ideally assessed prospectively by improvement of BFCRS scores, shortly after administration of a single dose of 1 to 2 mg lorazepam or 5 mg diazepam IV, or 10 mg zolpidem orally. Further evaluation generally consists of a careful medical and psychiatric histories of patient and family, review of all medications, history of substance use with toxicology as indicated, physical examination focusing on autonomic dysregulation, examination for delirium, and laboratory tests as suggested by the history and examination that may include complete blood count, creatine kinase, serum iron, blood urea nitrogen, electrolytes, creatinine, prolactin, anti-NMDA antibodies, thyroid function tests, serology, metabolic panel, human immunodeficiency virus testing, EEG, and neuroimaging.^8,15,16

A complex differential diagnosis

Manifestations of numerous psychiatric and neurologic disorders can mimic or be identical to those of catatonia. The differential diagnosis is complicated by the fact that some of these disorders can cause catatonia, which is then masked by the primary disorder; some disorders (eg, NMS) are forms of catatonia. Table 6^{5,8,12,19,26,30} lists conditions to consider.

Some of these conditions warrant discussion. ASD may have catatonia-like features such as echolalia, echopraxia, excitement, combativeness, grimacing, mutism, logorrhea, verbigeration, catalepsy, mannerisms, rigidity, staring and withdrawal.⁸ Catatonia may also be a stage of deterioration of autism, in which case it is characterized by increases in slowness of movement and speech, reliance on physical or verbal prompting from others, passivity, and lack of motivation.²³ At the same time, catatonic features such as mutism, stereotypic speech, repetitive behavior, echolalia, posturing, mannerisms, purposeless agitation, and rigidity in catatonia can be misinterpreted as signs of ASD.⁸ Catatonia should be suspected as a complication of longstanding ASD in the presence of a consistent, marked change in motor behavior, such as immobility, decreased speech, stupor, excitement, or mixtures or alternations of stupor and excitement.⁸ Freezing while doing something, difficulty crossing lines, or uncharacteristic persistence of a particular behavior may also herald the presence of catatonia with ASD.⁸

Catatonia caused by a neurologic or metabolic factor or a substance can be difficult to distinguish from delirium complicated by catatonia. Delirium may be identified in patients with catatonia by the presence of a waxing and waning level of consciousness (vs fluctuating behavior in catatonia) and slowing of the EEG.^12,15 Antipsychotic medications can improve delirium but worsen catatonia, while benzodiazepines can improve catatonia but worsen delirium.

Continue to: Among other neurologic syndromes...

Benzodiazepines, ECT are the usual treatments

Experience dictates that the general principles of treatment noted in Table 7^12,15,23,31 apply to all patients with catatonia. Since the first reported improvement of catatonia with amobarbital in 1930,⁶ there have been no controlled studies of specific treatments of catatonia.¹³ Meaningful treatment trials are either naturalistic, or have been performed only for NMS and malignant catatonia.⁵ However, multiple case reports and case series suggest that treatments with agents that have anticonvulsant properties (benzodiazepines, barbiturates) and ECT are effective.⁵

Benzodiazepines and related compounds. Case series have suggested a 60% to 80% remission rate of catatonia with benzodiazepines, the most commonly utilized of which has been lorazepam.^7,13,32 Treatment begins with a lorazepam challenge test of 1 to 2 mg in adults and 0.5 to 1 mg in children and geriatric patients,^9,15 administered orally (including via nasogastric tube), IM, or IV. Following a response (≥50% improvement), the dose is increased to 2 mg 3 times per day. The dose is further increased to 6 to 16 mg/d, and sometimes up to 30 mg/d.^9,11 Oral is less effective than sublingual or IM administration.¹¹ Diazepam can be helpful at doses 5 times the lorazepam dose.^9,17 A zolpidem challenge test of 10 mg orally or via nasogastric tube has also been utilized.¹⁵ Response is brief and is usually followed by lorazepam, although zolpidem up to 40 mg/d has been used for ongoing treatment.⁹

One alternative benzodiazepine protocol utilizes an initial IV dose of 2 mg lorazepam, repeated 3 to 5 times per day; the dose is increased to 10 to 12 mg/d if the first doses are partially effective.¹⁶ A lorazepam/diazepam approach involves a combination of IM lorazepam and IV diazepam.¹¹ The protocol begins with 2 mg of IM lorazepam. If there is no effect within 2 hours, a second 2 mg dose is administered, followed by an IV infusion of 10 mg diazepam in 500 ml of normal saline at 1.25 mg/hour until catatonia remits.

An Indian study of 107 patients (mean age 26) receiving relatively low doses of lorazepam (3 to 6 mg/d for at least 3 days) found that factors suggesting a robust response include a shorter duration of catatonia and waxy flexibility, while passivity, mutism, and auditory hallucinations describing the patient in the third person were associated with a poorer acute response.³¹ Catatonia with marked retardation and mutism complicating schizophrenia, especially with chronic negative symptoms, may be associated with a lower response rate to benzodiazepines.^20,33 Maintenance lorazepam has been effective in reducing relapse and recurrence.¹¹ There are no controlled studies of maintenance treatment with benzodiazepines, but clinical reports suggest that doses in the range of 4 to 10 mg/d are effective.³²

Continue to: ECT was used for catatonia in 1934...

ECT was first used for catatonia in 1934, when Laszlo Meduna used chemically induced seizures in catatonic patients who had been on tube feeding for months and no longer needed it after treatment.^6,7 As was true for other disorders, this approach was replaced by ECT.⁷ In various case series, the effectiveness of ECT in catatonia has been 53% to 100%.^7,13,15 Right unilateral ECT has been reported to be effective with 1 treatment.²¹ However, the best-established approach is with bitemporal ECT with a suprathreshold stimulus,⁹ usually with an acute course of 6 to 20 treatments.²⁰ ECT has been reported to be equally safe and effective in adolescents and adults.³⁴ Continued ECT is usually necessary until the patient has returned to baseline.⁹

ECT usually is recommended within 24 hours for treatment-resistant malignant catatonia or refusal to eat or drink, and within 2 to 3 days if medications are not sufficiently effective in other forms of catatonia.^12,15,20 If ECT is initiated after a benzodiazepine trial, the benzodiazepine antagonist flumazenil is administered first to reverse the anticonvulsant effect.⁹ Some experts recommend using a muscle relaxant other than succinylcholine in the presence of evidence of muscle damage.⁷

Alternatives to benzodiazepines and ECT. Based on case reports, the treatments described in Table 8^{13,15,17,20,25} have been used for patients with catatonia who do not tolerate or respond to standard treatments. The largest number of case reports have been with NMDA antagonists, while the presumed involvement of reduced dopamine signaling suggests that dopaminergic medications should be helpful. Dantrolene, which blocks release of calcium from intracellular stores and has been used to treat malignant hyperthermia, is sometimes used for NMS, often with disappointing results.

Whereas first-generation antipsychotics definitely increase the risk of catatonia and second-generation antipsychotics (SGAs) probably do so, SGAs are sometimes necessary to treat persistent psychosis in patients with schizophrenia who develop catatonia. Of these medications, clozapine may be most desirable because of low potency for dopamine receptor blockade and modulation of glutamatergic signaling. Partial dopamine agonism by aripiprazole, and the potential for increased subcortical prefrontal dopamine release resulting from serotonin 5HT2A antagonism and 5HT1A agonism by other SGAs, could also be helpful or at least not harmful in catatonia. Lorazepam is usually administered along with these medications to ameliorate treatment-emergent exacerbation of catatonia.

There are no controlled studies of any of these treatments. Based on case reports, most experts would recommend initiating treatment of catatonia with lorazepam, followed by ECT if necessary or in the presence of life-threatening catatonia. If ECT is not available, ineffective, or not tolerated, the first alternatives to be considered would be an NMDA antagonist or an anticonvulsant.²⁰

Continue to: Course varies by patient, underlying cause

Course varies by patient, underlying cause

The response to benzodiazepines or ECT can vary from episode to episode¹¹ and is similar in adults and younger patients.²² Many patients recover completely after a single episode, while relapse after remission occurs repeatedly in periodic catatonia, which involves chronic alternating stupor and excitement waxing and waning over years.¹¹ Relapses may occur frequently, or every few years.¹¹ Some cases of catatonia initially have an episodic course and become chronic and deteriorating, possibly paralleling the original descriptions of the natural history of untreated catatonia, while malignant catatonia can be complicated by medical morbidity or death.⁴ The long-term prognosis generally depends on the underlying cause of catatonia.⁵

Bottom Line

Much more common than many clinicians realize, catatonia can be overlooked because symptoms can mimic or overlap with features of an underlying medical or neurologic disorder. Suspect catatonia when one of these illnesses has an unexpected course or an inadequate treatment response. Be alert to characteristic changes in behavior and speech. A benzodiazepine challenge can be used to diagnose and begin treatment of catatonia. Consider electroconvulsive therapy sooner rather than later, especially for severely ill patients.

Related Resources

• Gibson RC, Walcott G. Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses. Cochrane Database Syst Rev. 2008;(4):CD006570. 
• Newcastle University. Catatonia. https://youtu.be/_s1lzxHRO4U.

Drug Brand Names

Amantadine • Symmetrel
Amobarbital • Amytal
Aripiprazole • Abilify
Azithromycin • Zithromax
Baclofen • Lioresal
Benztropine • Cogentin
Carbamazepine • Carbatrol, Tegretol
Carbidopa/levodopa • Sinemet
Ciprofloxacin • Cipro
Clozapine • Clozaril
Dantrolene • Dantrium
Dexamethasone • Decadron
Dextromethorphan/quinidine • Neudexta
Diazepam • Valium
Disulfiram • Antabuse
Flumazenil • Romazicon
Fluoxetine • Prozac
Fluvoxamine • Luvox
Levetiracetam • Keppra
Lithium • Eskalith, Lithobid
Lorazepam • Ativan
Memantine • Namenda
Methylphenidate • Ritalin
Minocycline • Minocin
Olanzapine • Zyprexa
Risperidone • Risperdal
Succinylcholine • Anectine
Topiramate • Topamax
Trihexyphenidyl • Artane
Valproate • Depakote
Ziprasidone • Geodon
Zolpidem • Ambien

Resources

Liang JL, Tiwari T, Moro P, et al. Prevention of pertussis, tetanus, and diphtheria with vaccines in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2018;67:1-44.

Centers for Disease Control and Prevention. Pertussis (whooping cough). Available at: https://www.cdc.gov/pertussis/index.html. Accessed July 6, 2018.

Resources

Liang JL, Tiwari T, Moro P, et al. Prevention of pertussis, tetanus, and diphtheria with vaccines in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2018;67:1-44.

Centers for Disease Control and Prevention. Pertussis (whooping cough). Available at: https://www.cdc.gov/pertussis/index.html. Accessed July 6, 2018.

Resources

Liang JL, Tiwari T, Moro P, et al. Prevention of pertussis, tetanus, and diphtheria with vaccines in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2018;67:1-44.

Centers for Disease Control and Prevention. Pertussis (whooping cough). Available at: https://www.cdc.gov/pertussis/index.html. Accessed July 6, 2018.

Recently, a medical consulting group published, “The disruption of primary care: How customer-obsessed companies are changing everything.”¹ The essay paints a not-too-rosy picture for the future of traditional family medicine in our Internet-dominated, immediate-gratification-seeking society. They contend:

“The future of primary care extends far beyond the physician’s office to pharmacies, supermarkets and retail clinics including CVS, Walgreens, Target and CityMD, as well as virtual care companies such as MDLive and Amwell. Increasingly, Internet and technology companies like Amazon, Google and Apple are showing signs of getting into the healthcare services and information arena. … These formidable customer-centric companies are primed to become preferred alternative providers of health information and low-acuity services, while lowering the price point of primary care services.”

I remain bullish on family medicine and believe the future remains bright for those who practice high-quality primary care.

While it is an interesting piece, I remain bullish on family medicine and believe the future remains bright for those who practice high-quality primary care. Why?

1. Cost efficacy. For common medical conditions, family physicians (FPs) are much more cost-effective than specialty or emergency department care. For example, a young man recently hit his thumb and had a subungual hematoma. He visited an orthopedic physician’s office, where the physician ordered an unnecessary x-ray and sent him home without draining the hematoma. The cost was more than $300. The patient was referred to our office where, later that day, we drained the hematoma with a hypodermic needle at a cost of $90. We all have similar stories of expensive but ineffective care.

2. Immediate care. Many family medicine groups have responded to the demand for immediate care with extended hours, assigning a doctor of the day, and/or having an open-access schedule that allows for a sufficient number of same-day appointments. Many FPs are now available for “virtual visits,” since Web portals for electronic medical records have been become easy to use for secure communication. In addition, many FPs have developed e-consult services to streamline specialist consultations. At the Cleveland Clinic, an FP leads the primary care telemedicine program.

3. A future that is not mutually exclusive. The authors contend that the future will be a matrix of health care services available via the Internet like the Amazon model. I see that model as fully compatible with excellent family medicine. In such a model, a skilled FP and staff provide timely acute care and chronic disease management; they connect patients to other health-related services and high-quality health care information; and they guide patients through our increasingly complex medical system. Isn’t that what we’re already doing?

Recently, a medical consulting group published, “The disruption of primary care: How customer-obsessed companies are changing everything.”¹ The essay paints a not-too-rosy picture for the future of traditional family medicine in our Internet-dominated, immediate-gratification-seeking society. They contend:

“The future of primary care extends far beyond the physician’s office to pharmacies, supermarkets and retail clinics including CVS, Walgreens, Target and CityMD, as well as virtual care companies such as MDLive and Amwell. Increasingly, Internet and technology companies like Amazon, Google and Apple are showing signs of getting into the healthcare services and information arena. … These formidable customer-centric companies are primed to become preferred alternative providers of health information and low-acuity services, while lowering the price point of primary care services.”

I remain bullish on family medicine and believe the future remains bright for those who practice high-quality primary care.

While it is an interesting piece, I remain bullish on family medicine and believe the future remains bright for those who practice high-quality primary care. Why?

1. Cost efficacy. For common medical conditions, family physicians (FPs) are much more cost-effective than specialty or emergency department care. For example, a young man recently hit his thumb and had a subungual hematoma. He visited an orthopedic physician’s office, where the physician ordered an unnecessary x-ray and sent him home without draining the hematoma. The cost was more than $300. The patient was referred to our office where, later that day, we drained the hematoma with a hypodermic needle at a cost of $90. We all have similar stories of expensive but ineffective care.

2. Immediate care. Many family medicine groups have responded to the demand for immediate care with extended hours, assigning a doctor of the day, and/or having an open-access schedule that allows for a sufficient number of same-day appointments. Many FPs are now available for “virtual visits,” since Web portals for electronic medical records have been become easy to use for secure communication. In addition, many FPs have developed e-consult services to streamline specialist consultations. At the Cleveland Clinic, an FP leads the primary care telemedicine program.

3. A future that is not mutually exclusive. The authors contend that the future will be a matrix of health care services available via the Internet like the Amazon model. I see that model as fully compatible with excellent family medicine. In such a model, a skilled FP and staff provide timely acute care and chronic disease management; they connect patients to other health-related services and high-quality health care information; and they guide patients through our increasingly complex medical system. Isn’t that what we’re already doing?

Recently, a medical consulting group published, “The disruption of primary care: How customer-obsessed companies are changing everything.”¹ The essay paints a not-too-rosy picture for the future of traditional family medicine in our Internet-dominated, immediate-gratification-seeking society. They contend:

“The future of primary care extends far beyond the physician’s office to pharmacies, supermarkets and retail clinics including CVS, Walgreens, Target and CityMD, as well as virtual care companies such as MDLive and Amwell. Increasingly, Internet and technology companies like Amazon, Google and Apple are showing signs of getting into the healthcare services and information arena. … These formidable customer-centric companies are primed to become preferred alternative providers of health information and low-acuity services, while lowering the price point of primary care services.”

I remain bullish on family medicine and believe the future remains bright for those who practice high-quality primary care.

While it is an interesting piece, I remain bullish on family medicine and believe the future remains bright for those who practice high-quality primary care. Why?

1. Cost efficacy. For common medical conditions, family physicians (FPs) are much more cost-effective than specialty or emergency department care. For example, a young man recently hit his thumb and had a subungual hematoma. He visited an orthopedic physician’s office, where the physician ordered an unnecessary x-ray and sent him home without draining the hematoma. The cost was more than $300. The patient was referred to our office where, later that day, we drained the hematoma with a hypodermic needle at a cost of $90. We all have similar stories of expensive but ineffective care.

2. Immediate care. Many family medicine groups have responded to the demand for immediate care with extended hours, assigning a doctor of the day, and/or having an open-access schedule that allows for a sufficient number of same-day appointments. Many FPs are now available for “virtual visits,” since Web portals for electronic medical records have been become easy to use for secure communication. In addition, many FPs have developed e-consult services to streamline specialist consultations. At the Cleveland Clinic, an FP leads the primary care telemedicine program.

3. A future that is not mutually exclusive. The authors contend that the future will be a matrix of health care services available via the Internet like the Amazon model. I see that model as fully compatible with excellent family medicine. In such a model, a skilled FP and staff provide timely acute care and chronic disease management; they connect patients to other health-related services and high-quality health care information; and they guide patients through our increasingly complex medical system. Isn’t that what we’re already doing?

EVIDENCE SUMMARY

A meta-analysis of RCTs evaluating levofloxacin-based triple therapy as a secondary treatment regimen for patients with H pylori infection who had failed initial clarithromycin-based triple therapy found cure rates averaging 76% (TABLE).¹ Most of the regimens comprised levofloxacin (500 mg), amoxicillin (1 g), and a PPI (40 mg), all twice daily for 7 to 10 days. Ten-day regimens produced better cure rates than 7-day regimens (84% vs 69%; comparison statistic not supplied).

The meta-analysis also included RCTs evaluating bismuth-based quadruple therapy as secondary treatment, which found cure rates averaging 78%.¹ The regimens varied, comprising bismuth salts (120-600 mg, 2-4 times daily), metronidazole (250-500 mg, 2-4 times daily), tetracycline (250-500 mg, 2-4 times daily), and a PPI (40 mg twice daily). Longer duration of therapy produced higher cure rates (7 days=76%; 95% confidence interval [CI], 0.72-0.80 in 29 RCTs with 2097 patients; 10 days=77%; 95% CI, 0.60-0.93 in 2 RCTs with 142 patients; 14 days=82%; 95% CI, 0.76-0.88 in 12 RCTs with 831 patients).

Repeating the original clarithromycin-based triple therapy (8 RCTs, 265 patients) produced low cure rates (46%).¹

Metronidazole-based therapy has high cure rate in a homogeneous population

A meta-analysis of 24 RCTs (1611 patients) that evaluated metronidazole-based triple therapy (mostly composed of amoxicillin 750 mg, metronidazole 250 mg, and any of a number of PPIs, all dosed at 40 mg) twice daily for 7 days found cure rates averaging 87% in an exclusively Japanese study population.¹

Comparable cure rates for levofloxacin- and bismuth-based therapy

Six RCTs with a total of 1057 patients compared cure rates for levofloxacin-based triple therapy with bismuth-based quadruple therapy and found no difference.¹

Two earlier meta-analyses not included in the previously described study, comprising 8 RCTs with a total of 613 patients, produced conflicting results. The larger study (15 RCTs, 1462 patients) found no difference in cure rates.² The smaller study (7 RCTs, 787 patients) favored quadruple therapy.³

Continue to: Two secondary antibiotic regimens show similar cure rates

A meta-analysis of 4 RCTs (total 460 patients) that compared susceptibility-guided antibiotic secondary treatment (SGT) with empiric antibiotic secondary treatment found no difference in cure rates, although the largest single RCT (172 patients) favored SGT.⁴

RECOMMENDATIONS

The Maastricht IV/Florence Consensus Report (a periodically updated European study group evaluating Helicobacter management) includes expert opinion-based guidelines for H pylori treatment that recommend using antibiotic susceptibility to select treatment regimens in the event of 2 treatment failures.⁵ The report also notes that bismuth-based quadruple therapy may not be available in all countries and has a more complex dosing regimen, and that local resistance to levofloxacin must be taken into account when prescribing levofloxacin-based triple therapy.

EVIDENCE SUMMARY

A meta-analysis of RCTs evaluating levofloxacin-based triple therapy as a secondary treatment regimen for patients with H pylori infection who had failed initial clarithromycin-based triple therapy found cure rates averaging 76% (TABLE).¹ Most of the regimens comprised levofloxacin (500 mg), amoxicillin (1 g), and a PPI (40 mg), all twice daily for 7 to 10 days. Ten-day regimens produced better cure rates than 7-day regimens (84% vs 69%; comparison statistic not supplied).

The meta-analysis also included RCTs evaluating bismuth-based quadruple therapy as secondary treatment, which found cure rates averaging 78%.¹ The regimens varied, comprising bismuth salts (120-600 mg, 2-4 times daily), metronidazole (250-500 mg, 2-4 times daily), tetracycline (250-500 mg, 2-4 times daily), and a PPI (40 mg twice daily). Longer duration of therapy produced higher cure rates (7 days=76%; 95% confidence interval [CI], 0.72-0.80 in 29 RCTs with 2097 patients; 10 days=77%; 95% CI, 0.60-0.93 in 2 RCTs with 142 patients; 14 days=82%; 95% CI, 0.76-0.88 in 12 RCTs with 831 patients).

Repeating the original clarithromycin-based triple therapy (8 RCTs, 265 patients) produced low cure rates (46%).¹

Metronidazole-based therapy has high cure rate in a homogeneous population

A meta-analysis of 24 RCTs (1611 patients) that evaluated metronidazole-based triple therapy (mostly composed of amoxicillin 750 mg, metronidazole 250 mg, and any of a number of PPIs, all dosed at 40 mg) twice daily for 7 days found cure rates averaging 87% in an exclusively Japanese study population.¹

Comparable cure rates for levofloxacin- and bismuth-based therapy

Six RCTs with a total of 1057 patients compared cure rates for levofloxacin-based triple therapy with bismuth-based quadruple therapy and found no difference.¹

Two earlier meta-analyses not included in the previously described study, comprising 8 RCTs with a total of 613 patients, produced conflicting results. The larger study (15 RCTs, 1462 patients) found no difference in cure rates.² The smaller study (7 RCTs, 787 patients) favored quadruple therapy.³

Continue to: Two secondary antibiotic regimens show similar cure rates

A meta-analysis of 4 RCTs (total 460 patients) that compared susceptibility-guided antibiotic secondary treatment (SGT) with empiric antibiotic secondary treatment found no difference in cure rates, although the largest single RCT (172 patients) favored SGT.⁴

RECOMMENDATIONS

The Maastricht IV/Florence Consensus Report (a periodically updated European study group evaluating Helicobacter management) includes expert opinion-based guidelines for H pylori treatment that recommend using antibiotic susceptibility to select treatment regimens in the event of 2 treatment failures.⁵ The report also notes that bismuth-based quadruple therapy may not be available in all countries and has a more complex dosing regimen, and that local resistance to levofloxacin must be taken into account when prescribing levofloxacin-based triple therapy.

EVIDENCE SUMMARY

A meta-analysis of RCTs evaluating levofloxacin-based triple therapy as a secondary treatment regimen for patients with H pylori infection who had failed initial clarithromycin-based triple therapy found cure rates averaging 76% (TABLE).¹ Most of the regimens comprised levofloxacin (500 mg), amoxicillin (1 g), and a PPI (40 mg), all twice daily for 7 to 10 days. Ten-day regimens produced better cure rates than 7-day regimens (84% vs 69%; comparison statistic not supplied).

The meta-analysis also included RCTs evaluating bismuth-based quadruple therapy as secondary treatment, which found cure rates averaging 78%.¹ The regimens varied, comprising bismuth salts (120-600 mg, 2-4 times daily), metronidazole (250-500 mg, 2-4 times daily), tetracycline (250-500 mg, 2-4 times daily), and a PPI (40 mg twice daily). Longer duration of therapy produced higher cure rates (7 days=76%; 95% confidence interval [CI], 0.72-0.80 in 29 RCTs with 2097 patients; 10 days=77%; 95% CI, 0.60-0.93 in 2 RCTs with 142 patients; 14 days=82%; 95% CI, 0.76-0.88 in 12 RCTs with 831 patients).

Repeating the original clarithromycin-based triple therapy (8 RCTs, 265 patients) produced low cure rates (46%).¹

Metronidazole-based therapy has high cure rate in a homogeneous population

A meta-analysis of 24 RCTs (1611 patients) that evaluated metronidazole-based triple therapy (mostly composed of amoxicillin 750 mg, metronidazole 250 mg, and any of a number of PPIs, all dosed at 40 mg) twice daily for 7 days found cure rates averaging 87% in an exclusively Japanese study population.¹

Comparable cure rates for levofloxacin- and bismuth-based therapy

Six RCTs with a total of 1057 patients compared cure rates for levofloxacin-based triple therapy with bismuth-based quadruple therapy and found no difference.¹

Two earlier meta-analyses not included in the previously described study, comprising 8 RCTs with a total of 613 patients, produced conflicting results. The larger study (15 RCTs, 1462 patients) found no difference in cure rates.² The smaller study (7 RCTs, 787 patients) favored quadruple therapy.³

Continue to: Two secondary antibiotic regimens show similar cure rates

A meta-analysis of 4 RCTs (total 460 patients) that compared susceptibility-guided antibiotic secondary treatment (SGT) with empiric antibiotic secondary treatment found no difference in cure rates, although the largest single RCT (172 patients) favored SGT.⁴

RECOMMENDATIONS

The Maastricht IV/Florence Consensus Report (a periodically updated European study group evaluating Helicobacter management) includes expert opinion-based guidelines for H pylori treatment that recommend using antibiotic susceptibility to select treatment regimens in the event of 2 treatment failures.⁵ The report also notes that bismuth-based quadruple therapy may not be available in all countries and has a more complex dosing regimen, and that local resistance to levofloxacin must be taken into account when prescribing levofloxacin-based triple therapy.

THE CASE

A 29-year-old G1P0 woman at 13 weeks’ gestation came in for a routine prenatal visit complaining of sudden-onset heart palpitations that were occurring about once a week. Each episode lasted between 15 and 60 minutes and was accompanied by chest tightness, with no identifiable cause. The patient could inconsistently terminate the episodes with Valsalva maneuvers. She reported having had 2 similar incidents of palpitations within the past year. Her family history was significant for sudden cardiac death of her father and paternal grandfather in their fifth decades of life.

A cardiovascular exam was normal; heart auscultation revealed a regular rate and rhythm without murmurs, rubs, or gallops, and the peripheral pulses were normal. A thyroid-stimulating hormone (TSH) level, basic metabolic panel (BMP), and complete blood count (CBC) were within normal limits. A transthoracic echocardiogram was negative for structural heart disease.

THE DIAGNOSIS

An initial Holter monitor study failed to capture an episode of her palpitations. The frequency of her palpitations increased as her pregnancy progressed, occurring almost daily by the second half of the third trimester, and a repeat Holter monitor study in the third trimester was significant for a 3-minute episode of supraventricular tachycardia (SVT) that correlated with patient-recorded symptoms (FIGURE).

Based on these results, we diagnosed the patient with an atrioventricular nodal reentry tachycardia (AVNRT). Although atrioventricular reciprocating tachycardia (AVRT) remained a remote possibility, it is far less common, and a 12-lead electrocardiogram (EKG) showed no evidence of pre-excitation.

DISCUSSION

AVNRT is the most common form of paroxysmal supraventricular tachycardia (PSVT). It occurs more frequently in women and typically manifests in the second to fourth decades of life.¹ AVNRT is a narrow complex tachycardia characterized by a heart rate of 120 to >200 beats/min.

Hemodynamic changes in pregnancy can trigger arrhythmias

During pregnancy, hemodynamic changes (including increased blood volume and cardiac output) are thought to stimulate stretch-activated ion channels within the walls of the heart.^2-4 Such changes may exacerbate previously existing cardiac arrhythmias or (less commonly) cause new-onset arrhythmias.^3,4 A family history positive for arrhythmias or sudden cardiac death increases the likelihood of developing tachyarrhythmia during pregnancy.³ Women with a known history of PSVT might experience symptom exacerbation despite being on prophylactic therapy.⁴

Detection and diagnosis

While AVNRT is relatively benign in pregnancy, other cardiac arrhythmias (eg, atrial fibrillation/flutter, ventricular tachycardia) carry a greater risk for fetal and maternal complications, underscoring the need to correctly identify the type of arrhythmia.^2,3

Continue to: Physical exam findings

Physical exam findings are often unremarkable unless the patient is actively experiencing SVT in the office, in which case prominent jugular pulsations may be seen due to simultaneous contraction of the atria and ventricles.

The initial evaluation of a pregnant patient presenting with tachycardia should include a BMP, TSH, 12-lead EKG, and transthoracic echocardiography.^3,5 In most patients with AVNRT, the results of these tests will be normal. A Holter monitor can be used to document an arrhythmia if the episodes are relatively frequent or an event monitor can be used if the episodes are infrequent.⁵

EKG findings. When patients are actively experiencing SVT, EKG findings include a P wave obscured by the QRS complex, sometimes manifesting as a pseudo-R wave in the V1 lead and a pseudo-S wave in leads II, III, and AVF. The QRS complex is narrow and the R-R interval is regular.⁶

Types of treatment

Valsalva maneuvers. Treatment of AVNRT in pregnancy should first involve addressing any precipitating causes, including metabolic and endocrine abnormalities.³ As virtually all antiarrhythmic drugs cross the placenta and are traceable in breast milk,^2,3 patients should be counseled to try to stop episodes using Valsalva maneuvers before moving to pharmacologic treatment.

Antiarrhythmics. First-line pharmacologic treatment for the prevention of AVNRT in pregnancy is metoprolol or verapamil.^2,5 Neither drug has been associated with adverse outcomes in infants, although there is a large body of evidence suggesting that low levels of metoprolol are present in breast milk.⁷

Continue to: Acute episodes of SVT that are refractory to...

Acute episodes of SVT that are refractory to vagal maneuvers or occur despite medical management can be treated acutely in pregnancy with adenosine, which effectively stops episodes about 90% of the time.² (See the TABLE^8,9 for a list of antiarrhythmics that may be used to treat AVNRT.)

Catheter ablation is first-line treatment for AVNRT in nonpregnant patients.^1,5 The risks of undergoing ablation during pregnancy include fetal exposure to radiation and anesthetic drugs.^2,3 Therefore, this treatment should be used only when pharmacologic treatment is unsuccessful and risks to the mother and fetus due to the arrhythmia outweigh the risks of the procedure. Ablation can be offered postpartum as more definitive therapy.

Our patient was started on metoprolol tartrate 12.5 mg bid at 35 weeks’ gestation due to increasingly common and persistent palpitations. This helped control the episodes for 2 weeks, at which point they increased again in frequency. These were terminated using Valsalva maneuvers; increasing the metoprolol dosage was prohibitive due to patient intolerance.

Tachyarrhythmias such as atrioventricular nodal reentry tachycardia may worsen or manifest with physiologic changes that occur during pregnancy.

Following an uncomplicated delivery, and discontinuation of metoprolol, the patient reported a decrease in both the number of episodes and the duration of SVT. Ultimately, she opted for a catheter ablation to prevent SVT exacerbation during subsequent pregnancies.

THE TAKEAWAY

AVNRT (and other tachyarrhythmias) may worsen or manifest with physiologic changes that occur during pregnancy. After establishing the diagnosis, effort should be made to manage the condition conservatively with Valsalva maneuvers and medication. Catheter ablation should be offered postpartum as a more definitive treatment option.

CORRESPONDENCE
Joseph Lane Wilson, MD, ECU Brody School of Medicine, Department of Family Medicine Medical Director, 101 Heart Drive, Greenville, NC 27834; [email protected].

THE CASE

A 29-year-old G1P0 woman at 13 weeks’ gestation came in for a routine prenatal visit complaining of sudden-onset heart palpitations that were occurring about once a week. Each episode lasted between 15 and 60 minutes and was accompanied by chest tightness, with no identifiable cause. The patient could inconsistently terminate the episodes with Valsalva maneuvers. She reported having had 2 similar incidents of palpitations within the past year. Her family history was significant for sudden cardiac death of her father and paternal grandfather in their fifth decades of life.

A cardiovascular exam was normal; heart auscultation revealed a regular rate and rhythm without murmurs, rubs, or gallops, and the peripheral pulses were normal. A thyroid-stimulating hormone (TSH) level, basic metabolic panel (BMP), and complete blood count (CBC) were within normal limits. A transthoracic echocardiogram was negative for structural heart disease.

THE DIAGNOSIS

An initial Holter monitor study failed to capture an episode of her palpitations. The frequency of her palpitations increased as her pregnancy progressed, occurring almost daily by the second half of the third trimester, and a repeat Holter monitor study in the third trimester was significant for a 3-minute episode of supraventricular tachycardia (SVT) that correlated with patient-recorded symptoms (FIGURE).

Based on these results, we diagnosed the patient with an atrioventricular nodal reentry tachycardia (AVNRT). Although atrioventricular reciprocating tachycardia (AVRT) remained a remote possibility, it is far less common, and a 12-lead electrocardiogram (EKG) showed no evidence of pre-excitation.

DISCUSSION

AVNRT is the most common form of paroxysmal supraventricular tachycardia (PSVT). It occurs more frequently in women and typically manifests in the second to fourth decades of life.¹ AVNRT is a narrow complex tachycardia characterized by a heart rate of 120 to >200 beats/min.

Hemodynamic changes in pregnancy can trigger arrhythmias

During pregnancy, hemodynamic changes (including increased blood volume and cardiac output) are thought to stimulate stretch-activated ion channels within the walls of the heart.^2-4 Such changes may exacerbate previously existing cardiac arrhythmias or (less commonly) cause new-onset arrhythmias.^3,4 A family history positive for arrhythmias or sudden cardiac death increases the likelihood of developing tachyarrhythmia during pregnancy.³ Women with a known history of PSVT might experience symptom exacerbation despite being on prophylactic therapy.⁴

Detection and diagnosis

While AVNRT is relatively benign in pregnancy, other cardiac arrhythmias (eg, atrial fibrillation/flutter, ventricular tachycardia) carry a greater risk for fetal and maternal complications, underscoring the need to correctly identify the type of arrhythmia.^2,3

Continue to: Physical exam findings

Physical exam findings are often unremarkable unless the patient is actively experiencing SVT in the office, in which case prominent jugular pulsations may be seen due to simultaneous contraction of the atria and ventricles.

The initial evaluation of a pregnant patient presenting with tachycardia should include a BMP, TSH, 12-lead EKG, and transthoracic echocardiography.^3,5 In most patients with AVNRT, the results of these tests will be normal. A Holter monitor can be used to document an arrhythmia if the episodes are relatively frequent or an event monitor can be used if the episodes are infrequent.⁵

EKG findings. When patients are actively experiencing SVT, EKG findings include a P wave obscured by the QRS complex, sometimes manifesting as a pseudo-R wave in the V1 lead and a pseudo-S wave in leads II, III, and AVF. The QRS complex is narrow and the R-R interval is regular.⁶

Types of treatment

Valsalva maneuvers. Treatment of AVNRT in pregnancy should first involve addressing any precipitating causes, including metabolic and endocrine abnormalities.³ As virtually all antiarrhythmic drugs cross the placenta and are traceable in breast milk,^2,3 patients should be counseled to try to stop episodes using Valsalva maneuvers before moving to pharmacologic treatment.

Antiarrhythmics. First-line pharmacologic treatment for the prevention of AVNRT in pregnancy is metoprolol or verapamil.^2,5 Neither drug has been associated with adverse outcomes in infants, although there is a large body of evidence suggesting that low levels of metoprolol are present in breast milk.⁷

Continue to: Acute episodes of SVT that are refractory to...

Acute episodes of SVT that are refractory to vagal maneuvers or occur despite medical management can be treated acutely in pregnancy with adenosine, which effectively stops episodes about 90% of the time.² (See the TABLE^8,9 for a list of antiarrhythmics that may be used to treat AVNRT.)

Catheter ablation is first-line treatment for AVNRT in nonpregnant patients.^1,5 The risks of undergoing ablation during pregnancy include fetal exposure to radiation and anesthetic drugs.^2,3 Therefore, this treatment should be used only when pharmacologic treatment is unsuccessful and risks to the mother and fetus due to the arrhythmia outweigh the risks of the procedure. Ablation can be offered postpartum as more definitive therapy.

Our patient was started on metoprolol tartrate 12.5 mg bid at 35 weeks’ gestation due to increasingly common and persistent palpitations. This helped control the episodes for 2 weeks, at which point they increased again in frequency. These were terminated using Valsalva maneuvers; increasing the metoprolol dosage was prohibitive due to patient intolerance.

Tachyarrhythmias such as atrioventricular nodal reentry tachycardia may worsen or manifest with physiologic changes that occur during pregnancy.

Following an uncomplicated delivery, and discontinuation of metoprolol, the patient reported a decrease in both the number of episodes and the duration of SVT. Ultimately, she opted for a catheter ablation to prevent SVT exacerbation during subsequent pregnancies.

THE TAKEAWAY

AVNRT (and other tachyarrhythmias) may worsen or manifest with physiologic changes that occur during pregnancy. After establishing the diagnosis, effort should be made to manage the condition conservatively with Valsalva maneuvers and medication. Catheter ablation should be offered postpartum as a more definitive treatment option.

CORRESPONDENCE
Joseph Lane Wilson, MD, ECU Brody School of Medicine, Department of Family Medicine Medical Director, 101 Heart Drive, Greenville, NC 27834; [email protected].

THE CASE

A 29-year-old G1P0 woman at 13 weeks’ gestation came in for a routine prenatal visit complaining of sudden-onset heart palpitations that were occurring about once a week. Each episode lasted between 15 and 60 minutes and was accompanied by chest tightness, with no identifiable cause. The patient could inconsistently terminate the episodes with Valsalva maneuvers. She reported having had 2 similar incidents of palpitations within the past year. Her family history was significant for sudden cardiac death of her father and paternal grandfather in their fifth decades of life.

A cardiovascular exam was normal; heart auscultation revealed a regular rate and rhythm without murmurs, rubs, or gallops, and the peripheral pulses were normal. A thyroid-stimulating hormone (TSH) level, basic metabolic panel (BMP), and complete blood count (CBC) were within normal limits. A transthoracic echocardiogram was negative for structural heart disease.

THE DIAGNOSIS

An initial Holter monitor study failed to capture an episode of her palpitations. The frequency of her palpitations increased as her pregnancy progressed, occurring almost daily by the second half of the third trimester, and a repeat Holter monitor study in the third trimester was significant for a 3-minute episode of supraventricular tachycardia (SVT) that correlated with patient-recorded symptoms (FIGURE).

Based on these results, we diagnosed the patient with an atrioventricular nodal reentry tachycardia (AVNRT). Although atrioventricular reciprocating tachycardia (AVRT) remained a remote possibility, it is far less common, and a 12-lead electrocardiogram (EKG) showed no evidence of pre-excitation.

DISCUSSION

AVNRT is the most common form of paroxysmal supraventricular tachycardia (PSVT). It occurs more frequently in women and typically manifests in the second to fourth decades of life.¹ AVNRT is a narrow complex tachycardia characterized by a heart rate of 120 to >200 beats/min.

Hemodynamic changes in pregnancy can trigger arrhythmias

During pregnancy, hemodynamic changes (including increased blood volume and cardiac output) are thought to stimulate stretch-activated ion channels within the walls of the heart.^2-4 Such changes may exacerbate previously existing cardiac arrhythmias or (less commonly) cause new-onset arrhythmias.^3,4 A family history positive for arrhythmias or sudden cardiac death increases the likelihood of developing tachyarrhythmia during pregnancy.³ Women with a known history of PSVT might experience symptom exacerbation despite being on prophylactic therapy.⁴

Detection and diagnosis

While AVNRT is relatively benign in pregnancy, other cardiac arrhythmias (eg, atrial fibrillation/flutter, ventricular tachycardia) carry a greater risk for fetal and maternal complications, underscoring the need to correctly identify the type of arrhythmia.^2,3

Continue to: Physical exam findings

Physical exam findings are often unremarkable unless the patient is actively experiencing SVT in the office, in which case prominent jugular pulsations may be seen due to simultaneous contraction of the atria and ventricles.

The initial evaluation of a pregnant patient presenting with tachycardia should include a BMP, TSH, 12-lead EKG, and transthoracic echocardiography.^3,5 In most patients with AVNRT, the results of these tests will be normal. A Holter monitor can be used to document an arrhythmia if the episodes are relatively frequent or an event monitor can be used if the episodes are infrequent.⁵

EKG findings. When patients are actively experiencing SVT, EKG findings include a P wave obscured by the QRS complex, sometimes manifesting as a pseudo-R wave in the V1 lead and a pseudo-S wave in leads II, III, and AVF. The QRS complex is narrow and the R-R interval is regular.⁶

Types of treatment

Valsalva maneuvers. Treatment of AVNRT in pregnancy should first involve addressing any precipitating causes, including metabolic and endocrine abnormalities.³ As virtually all antiarrhythmic drugs cross the placenta and are traceable in breast milk,^2,3 patients should be counseled to try to stop episodes using Valsalva maneuvers before moving to pharmacologic treatment.

Antiarrhythmics. First-line pharmacologic treatment for the prevention of AVNRT in pregnancy is metoprolol or verapamil.^2,5 Neither drug has been associated with adverse outcomes in infants, although there is a large body of evidence suggesting that low levels of metoprolol are present in breast milk.⁷

Continue to: Acute episodes of SVT that are refractory to...

Acute episodes of SVT that are refractory to vagal maneuvers or occur despite medical management can be treated acutely in pregnancy with adenosine, which effectively stops episodes about 90% of the time.² (See the TABLE^8,9 for a list of antiarrhythmics that may be used to treat AVNRT.)

Catheter ablation is first-line treatment for AVNRT in nonpregnant patients.^1,5 The risks of undergoing ablation during pregnancy include fetal exposure to radiation and anesthetic drugs.^2,3 Therefore, this treatment should be used only when pharmacologic treatment is unsuccessful and risks to the mother and fetus due to the arrhythmia outweigh the risks of the procedure. Ablation can be offered postpartum as more definitive therapy.

Our patient was started on metoprolol tartrate 12.5 mg bid at 35 weeks’ gestation due to increasingly common and persistent palpitations. This helped control the episodes for 2 weeks, at which point they increased again in frequency. These were terminated using Valsalva maneuvers; increasing the metoprolol dosage was prohibitive due to patient intolerance.

Tachyarrhythmias such as atrioventricular nodal reentry tachycardia may worsen or manifest with physiologic changes that occur during pregnancy.

Following an uncomplicated delivery, and discontinuation of metoprolol, the patient reported a decrease in both the number of episodes and the duration of SVT. Ultimately, she opted for a catheter ablation to prevent SVT exacerbation during subsequent pregnancies.

THE TAKEAWAY

AVNRT (and other tachyarrhythmias) may worsen or manifest with physiologic changes that occur during pregnancy. After establishing the diagnosis, effort should be made to manage the condition conservatively with Valsalva maneuvers and medication. Catheter ablation should be offered postpartum as a more definitive treatment option.

CORRESPONDENCE
Joseph Lane Wilson, MD, ECU Brody School of Medicine, Department of Family Medicine Medical Director, 101 Heart Drive, Greenville, NC 27834; [email protected].

A 52-year-old woman presented to the emergency department (ED) with a 4-month history of recurrent painful blisters on her fingertips and the tips of her toes (FIGURE 1), arthralgias, painful discoloration of her distal toes and fingers when exposed to cold, and painful nodules on her forearms. She was started on prednisone and was sent to our clinic for follow-up.

At her initial visit to our office, she was continued on prednisone and referred to Rheumatology and Interventional Cardiology, where a work-up for rheumatoid arthritis, systemic lupus erythematosus, and other vasculitides was negative. The patient had normal arterial pressures and a normal echocardiogram. An angiogram revealed segmental occlusions of the distal vessels in her arms and legs. The patient denied chest pain, syncope, dyspnea on exertion, or fever. She reported a >30 pack-year history of cigarette smoking.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Thromboangiitis obliterans (TAO), or Buerger’s disease, is a rare nonatherosclerotic disease that affects the medium and small arteries. The disease has a male predominance, primarily occurs in those younger than 45 years of age, and is most common in people from the Middle and Far East.¹ Its distinctive features include ulcerations of the distal extremities and symptoms of claudication and pain at rest. More than 40% of affected patients develop Raynaud’s phenomenon.¹ Superficial thrombophlebitis in the form of painful nodules has also been described.²

The etiology of TAO is likely due to disordered inflammation of endothelial cells, which has a strong association with smoking.³ The exact pathogenesis is unknown, but genetics and autoimmunity are suspected contributing factors.

The diagnosis is based on exclusion of other causes

The differential diagnosis includes diabetic angiopathy, embolic disease, atherosclerosis, hypercoagulability/thrombophilia, vasculitis or connective tissue diseases, and drug-associated (eg, cocaine) vasculitis.⁴

The diagnosis of TAO is based on the exclusion of other causes, although several diagnostic criteria have been proposed, including:

• age <45 years
• current or recent history of tobacco use
• distal extremity involvement (ulcers, claudication, or pain at rest)
• exclusion of diabetes, peripheral artery disease, thrombophilia, or embolic disease
• typical arteriographic findings on imaging, including distal small to medium vessel involvement, segmental occlusions, and “corkscrew-shaped” collaterals.^1,2,5,6

Continue to: Lab tests

Lab tests. There are no specific laboratory markers for TAO. The initial evaluation should include an erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complete metabolic panel (CMP), and urinalysis (UA). Tests to exclude other autoimmune diseases include rheumatoid factor, antinuclear antibody, anticentromere antibody and Scl-70 to exclude CREST syndrome and scleroderma, antiphospholipid antibodies to exclude disorders of hypercoagulability, and drug testing and history-taking to evaluate for drug-related (eg, cocaine) etiologies. Further studies should be performed based on clinical suspicion.

Imaging. Patients with suspected TAO should undergo an arteriogram of the affected extremities and large arteries. Other imaging modalities include computed tomographic angiography and magnetic resonance angiography. Biopsy is rarely indicated, unless there are atypical findings, such as large artery involvement or arterial nodules. Interestingly, a positive Allen test in a young smoker can be highly suggestive of TAO.¹ (For a demonstration of the Allen test, see https://www.youtube.com/watch?v=D1tJO0RW9UM.)

Our patient tested negative for rheumatoid arthritis, CREST, and scleroderma and had a normal UA and CMP. She did have a slightly elevated anticardiolipin antibody test, but a negative lupus anticoagulant test, the significance of which is uncertain. Her CRP and ESR were elevated.

Complete smoking cessation is essential for treatment

Several treatments have been proposed, including prostanoids and surgery (surgical revascularization or endovascular therapy).^1,4 In severe cases, amputation may be required to remove the affected extremity. However, the most important and most effective treatment for TAO is smoking cessation.¹ Of note, several case reports have found that replacing smoking with other nicotine-containing products (eg, chewing tobacco) may not prevent limb loss.^7-9

Our patient was tapered off prednisone and was continued on amlodipine 5 mg/d for vasospasm. She was started on varenicline 0.5 mg/d, which was increased to twice daily by Day 4 to aid with smoking cessation. Two months later, the patient’s pain and ulcerations had almost completely resolved (FIGURE 2). She experienced occasional relapses with smoking, during which her ulcerations and Raynaud’s would return. This case reinforces the age-old aphorism of “no tobacco, no Buerger’s disease.”⁴

CORRESPONDENCE
Seth Mathern, MD, 14300 Orchard Parkway, Westminster, CO 80023; [email protected].

A 52-year-old woman presented to the emergency department (ED) with a 4-month history of recurrent painful blisters on her fingertips and the tips of her toes (FIGURE 1), arthralgias, painful discoloration of her distal toes and fingers when exposed to cold, and painful nodules on her forearms. She was started on prednisone and was sent to our clinic for follow-up.

At her initial visit to our office, she was continued on prednisone and referred to Rheumatology and Interventional Cardiology, where a work-up for rheumatoid arthritis, systemic lupus erythematosus, and other vasculitides was negative. The patient had normal arterial pressures and a normal echocardiogram. An angiogram revealed segmental occlusions of the distal vessels in her arms and legs. The patient denied chest pain, syncope, dyspnea on exertion, or fever. She reported a >30 pack-year history of cigarette smoking.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Thromboangiitis obliterans (TAO), or Buerger’s disease, is a rare nonatherosclerotic disease that affects the medium and small arteries. The disease has a male predominance, primarily occurs in those younger than 45 years of age, and is most common in people from the Middle and Far East.¹ Its distinctive features include ulcerations of the distal extremities and symptoms of claudication and pain at rest. More than 40% of affected patients develop Raynaud’s phenomenon.¹ Superficial thrombophlebitis in the form of painful nodules has also been described.²

The etiology of TAO is likely due to disordered inflammation of endothelial cells, which has a strong association with smoking.³ The exact pathogenesis is unknown, but genetics and autoimmunity are suspected contributing factors.

The diagnosis is based on exclusion of other causes

The differential diagnosis includes diabetic angiopathy, embolic disease, atherosclerosis, hypercoagulability/thrombophilia, vasculitis or connective tissue diseases, and drug-associated (eg, cocaine) vasculitis.⁴

The diagnosis of TAO is based on the exclusion of other causes, although several diagnostic criteria have been proposed, including:

• age <45 years
• current or recent history of tobacco use
• distal extremity involvement (ulcers, claudication, or pain at rest)
• exclusion of diabetes, peripheral artery disease, thrombophilia, or embolic disease
• typical arteriographic findings on imaging, including distal small to medium vessel involvement, segmental occlusions, and “corkscrew-shaped” collaterals.^1,2,5,6

Continue to: Lab tests

Lab tests. There are no specific laboratory markers for TAO. The initial evaluation should include an erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complete metabolic panel (CMP), and urinalysis (UA). Tests to exclude other autoimmune diseases include rheumatoid factor, antinuclear antibody, anticentromere antibody and Scl-70 to exclude CREST syndrome and scleroderma, antiphospholipid antibodies to exclude disorders of hypercoagulability, and drug testing and history-taking to evaluate for drug-related (eg, cocaine) etiologies. Further studies should be performed based on clinical suspicion.

Imaging. Patients with suspected TAO should undergo an arteriogram of the affected extremities and large arteries. Other imaging modalities include computed tomographic angiography and magnetic resonance angiography. Biopsy is rarely indicated, unless there are atypical findings, such as large artery involvement or arterial nodules. Interestingly, a positive Allen test in a young smoker can be highly suggestive of TAO.¹ (For a demonstration of the Allen test, see https://www.youtube.com/watch?v=D1tJO0RW9UM.)

Our patient tested negative for rheumatoid arthritis, CREST, and scleroderma and had a normal UA and CMP. She did have a slightly elevated anticardiolipin antibody test, but a negative lupus anticoagulant test, the significance of which is uncertain. Her CRP and ESR were elevated.

Complete smoking cessation is essential for treatment

Several treatments have been proposed, including prostanoids and surgery (surgical revascularization or endovascular therapy).^1,4 In severe cases, amputation may be required to remove the affected extremity. However, the most important and most effective treatment for TAO is smoking cessation.¹ Of note, several case reports have found that replacing smoking with other nicotine-containing products (eg, chewing tobacco) may not prevent limb loss.^7-9

Our patient was tapered off prednisone and was continued on amlodipine 5 mg/d for vasospasm. She was started on varenicline 0.5 mg/d, which was increased to twice daily by Day 4 to aid with smoking cessation. Two months later, the patient’s pain and ulcerations had almost completely resolved (FIGURE 2). She experienced occasional relapses with smoking, during which her ulcerations and Raynaud’s would return. This case reinforces the age-old aphorism of “no tobacco, no Buerger’s disease.”⁴

CORRESPONDENCE
Seth Mathern, MD, 14300 Orchard Parkway, Westminster, CO 80023; [email protected].

A 52-year-old woman presented to the emergency department (ED) with a 4-month history of recurrent painful blisters on her fingertips and the tips of her toes (FIGURE 1), arthralgias, painful discoloration of her distal toes and fingers when exposed to cold, and painful nodules on her forearms. She was started on prednisone and was sent to our clinic for follow-up.

At her initial visit to our office, she was continued on prednisone and referred to Rheumatology and Interventional Cardiology, where a work-up for rheumatoid arthritis, systemic lupus erythematosus, and other vasculitides was negative. The patient had normal arterial pressures and a normal echocardiogram. An angiogram revealed segmental occlusions of the distal vessels in her arms and legs. The patient denied chest pain, syncope, dyspnea on exertion, or fever. She reported a >30 pack-year history of cigarette smoking.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Thromboangiitis obliterans (TAO), or Buerger’s disease, is a rare nonatherosclerotic disease that affects the medium and small arteries. The disease has a male predominance, primarily occurs in those younger than 45 years of age, and is most common in people from the Middle and Far East.¹ Its distinctive features include ulcerations of the distal extremities and symptoms of claudication and pain at rest. More than 40% of affected patients develop Raynaud’s phenomenon.¹ Superficial thrombophlebitis in the form of painful nodules has also been described.²

The etiology of TAO is likely due to disordered inflammation of endothelial cells, which has a strong association with smoking.³ The exact pathogenesis is unknown, but genetics and autoimmunity are suspected contributing factors.

The diagnosis is based on exclusion of other causes

The differential diagnosis includes diabetic angiopathy, embolic disease, atherosclerosis, hypercoagulability/thrombophilia, vasculitis or connective tissue diseases, and drug-associated (eg, cocaine) vasculitis.⁴

The diagnosis of TAO is based on the exclusion of other causes, although several diagnostic criteria have been proposed, including:

• age <45 years
• current or recent history of tobacco use
• distal extremity involvement (ulcers, claudication, or pain at rest)
• exclusion of diabetes, peripheral artery disease, thrombophilia, or embolic disease
• typical arteriographic findings on imaging, including distal small to medium vessel involvement, segmental occlusions, and “corkscrew-shaped” collaterals.^1,2,5,6

Continue to: Lab tests

Lab tests. There are no specific laboratory markers for TAO. The initial evaluation should include an erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complete metabolic panel (CMP), and urinalysis (UA). Tests to exclude other autoimmune diseases include rheumatoid factor, antinuclear antibody, anticentromere antibody and Scl-70 to exclude CREST syndrome and scleroderma, antiphospholipid antibodies to exclude disorders of hypercoagulability, and drug testing and history-taking to evaluate for drug-related (eg, cocaine) etiologies. Further studies should be performed based on clinical suspicion.

Imaging. Patients with suspected TAO should undergo an arteriogram of the affected extremities and large arteries. Other imaging modalities include computed tomographic angiography and magnetic resonance angiography. Biopsy is rarely indicated, unless there are atypical findings, such as large artery involvement or arterial nodules. Interestingly, a positive Allen test in a young smoker can be highly suggestive of TAO.¹ (For a demonstration of the Allen test, see https://www.youtube.com/watch?v=D1tJO0RW9UM.)

Our patient tested negative for rheumatoid arthritis, CREST, and scleroderma and had a normal UA and CMP. She did have a slightly elevated anticardiolipin antibody test, but a negative lupus anticoagulant test, the significance of which is uncertain. Her CRP and ESR were elevated.

Complete smoking cessation is essential for treatment

Several treatments have been proposed, including prostanoids and surgery (surgical revascularization or endovascular therapy).^1,4 In severe cases, amputation may be required to remove the affected extremity. However, the most important and most effective treatment for TAO is smoking cessation.¹ Of note, several case reports have found that replacing smoking with other nicotine-containing products (eg, chewing tobacco) may not prevent limb loss.^7-9

Our patient was tapered off prednisone and was continued on amlodipine 5 mg/d for vasospasm. She was started on varenicline 0.5 mg/d, which was increased to twice daily by Day 4 to aid with smoking cessation. Two months later, the patient’s pain and ulcerations had almost completely resolved (FIGURE 2). She experienced occasional relapses with smoking, during which her ulcerations and Raynaud’s would return. This case reinforces the age-old aphorism of “no tobacco, no Buerger’s disease.”⁴

CORRESPONDENCE
Seth Mathern, MD, 14300 Orchard Parkway, Westminster, CO 80023; [email protected].

ILLUSTRATIVE CASE

Your practice manager comes to you to discuss ways that you can reduce expenses. He asks whether the practice could reduce the amount of money spent on gloves for procedures. How do you reply?

A decision involving a small difference, spread over a larger number of events, can have a sizable effect. An example is whether to use sterile vs nonsterile gloves for minor procedures. The cost difference between a box of sterile gloves and a box of nonsterile gloves is relatively small, and certainly worth the difference if the more expensive sterile gloves reduce the number of surgical site infections (SSIs).

However, if there is no difference in the number of SSIs, there may be no value to the extra cost, which, given the number of such procedures, becomes a large unnecessary expense. The choice to use sterile gloves often stems from habit, product availability, or the perceived benefit of fewer SSIs.² While some evidence exists comparing glove choice, there is wide variability in physicians’ choice of gloves.^3-5 This large systematic review compared rates of SSIs using sterile vs nonsterile gloves.

STUDY SUMMARY

RCTs/observational studies find sterile no better than nonsterile gloves

This systematic review and meta-analysis of 13 randomized controlled trials (RCTs) and observational (prospective or retrospective) studies compared infection rates using sterile vs nonsterile gloves in 11,071 unique patients undergoing cutaneous surgery, including Mohs microsurgery or outpatient dental procedures. The methods used in the review followed the Cochrane collaboration guidelines.⁶ The inclusion criteria were that the studies had to be either RCTs or observational studies. Patients included in each study underwent outpatient cutaneous or mucosal surgical procedures, including laceration repair, standard excisions, Mohs micrographic surgery, or tooth extractions. In addition to glove type, documentation of postoperative SSI was necessary for inclusion.

Methodology. The authors of the analysis reviewed a total of 512 publications for inclusion; of these, 14 met the inclusion criteria. One study was later removed due to incomplete data, leaving a total of 13 trials for the analysis. Of the 11,071 patients included in the final analysis, 1360 patients were randomly assigned to treatment with sterile gloves, while 1381 patients were assigned to treatment with nonsterile gloves as the intervention in a clinical trial. The remaining patients participated in either prospective or retrospective observational trials; 4680 patients were treated with sterile gloves, and 3650 patients were treated with nonsterile gloves. Heterogeneity was low for the included studies. Of note, the researchers performed a subgroup analysis on 9 total studies (4 RCTs and 5 observational studies) involving cutaneous surgeries only. These represented procedures most likely performed in the primary care setting.

The primary outcome of this review was postoperative wound infection. The results did not show any difference in SSIs between sterile vs nonsterile gloves in all trials (2% vs 2.1%; relative risk [RR]=1.06; 95% confidence interval [CI], 0.81-1.39). There was also no difference in infection rates in the subgroup analysis of 9 trials limited to cutaneous surgery (2.2% vs 2.2%, respectively; RR=1.02; 95% CI, 0.78-1.34) or when the analysis was limited to only RCTs.

[polldaddy:10063798]

Continue to: WHAT'S NEW

WHAT’S NEW

Highest-quality evidence shows no difference in SSIs

This systematic review found no difference in SSI rates when using sterile vs nonsterile gloves. Given that the analysis represents the highest-quality level of evidence (a systematic review of RCTs) and that sterile gloves are several times more expensive per pair than nonsterile gloves, the findings should impact future practice.

CAVEATS

A risk of bias and limited applicability

Not every trial in this meta-analysis was an RCT, and the inclusion of observational studies increases the risk of bias. However, the results of the observational studies were similar to those of the RCTs, somewhat alleviating this potential threat to validity.

The results did not show any difference in surgical site infections between sterile and nonsterile gloves.

It is worth noting that more extensive surgeries and more complicated repairs were not included in the trials, meaning that the findings are limited to oral surgery, Mohs micrographic surgery, standard incisions, and laceration repairs.

CHALLENGES TO IMPLEMENTATION

Inertia, medicolegal concerns, and personal preference

Clinical inertia may lead to slow adoption of these recommendations. Physicians may worry about potential medicolegal ramifications from this change.¹ Lastly, some physicians may prefer the fit and feel of sterile gloves for their procedures.

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.

ILLUSTRATIVE CASE

Your practice manager comes to you to discuss ways that you can reduce expenses. He asks whether the practice could reduce the amount of money spent on gloves for procedures. How do you reply?

A decision involving a small difference, spread over a larger number of events, can have a sizable effect. An example is whether to use sterile vs nonsterile gloves for minor procedures. The cost difference between a box of sterile gloves and a box of nonsterile gloves is relatively small, and certainly worth the difference if the more expensive sterile gloves reduce the number of surgical site infections (SSIs).

However, if there is no difference in the number of SSIs, there may be no value to the extra cost, which, given the number of such procedures, becomes a large unnecessary expense. The choice to use sterile gloves often stems from habit, product availability, or the perceived benefit of fewer SSIs.² While some evidence exists comparing glove choice, there is wide variability in physicians’ choice of gloves.^3-5 This large systematic review compared rates of SSIs using sterile vs nonsterile gloves.

STUDY SUMMARY

RCTs/observational studies find sterile no better than nonsterile gloves

This systematic review and meta-analysis of 13 randomized controlled trials (RCTs) and observational (prospective or retrospective) studies compared infection rates using sterile vs nonsterile gloves in 11,071 unique patients undergoing cutaneous surgery, including Mohs microsurgery or outpatient dental procedures. The methods used in the review followed the Cochrane collaboration guidelines.⁶ The inclusion criteria were that the studies had to be either RCTs or observational studies. Patients included in each study underwent outpatient cutaneous or mucosal surgical procedures, including laceration repair, standard excisions, Mohs micrographic surgery, or tooth extractions. In addition to glove type, documentation of postoperative SSI was necessary for inclusion.

Methodology. The authors of the analysis reviewed a total of 512 publications for inclusion; of these, 14 met the inclusion criteria. One study was later removed due to incomplete data, leaving a total of 13 trials for the analysis. Of the 11,071 patients included in the final analysis, 1360 patients were randomly assigned to treatment with sterile gloves, while 1381 patients were assigned to treatment with nonsterile gloves as the intervention in a clinical trial. The remaining patients participated in either prospective or retrospective observational trials; 4680 patients were treated with sterile gloves, and 3650 patients were treated with nonsterile gloves. Heterogeneity was low for the included studies. Of note, the researchers performed a subgroup analysis on 9 total studies (4 RCTs and 5 observational studies) involving cutaneous surgeries only. These represented procedures most likely performed in the primary care setting.

The primary outcome of this review was postoperative wound infection. The results did not show any difference in SSIs between sterile vs nonsterile gloves in all trials (2% vs 2.1%; relative risk [RR]=1.06; 95% confidence interval [CI], 0.81-1.39). There was also no difference in infection rates in the subgroup analysis of 9 trials limited to cutaneous surgery (2.2% vs 2.2%, respectively; RR=1.02; 95% CI, 0.78-1.34) or when the analysis was limited to only RCTs.

[polldaddy:10063798]

Continue to: WHAT'S NEW

WHAT’S NEW

Highest-quality evidence shows no difference in SSIs

This systematic review found no difference in SSI rates when using sterile vs nonsterile gloves. Given that the analysis represents the highest-quality level of evidence (a systematic review of RCTs) and that sterile gloves are several times more expensive per pair than nonsterile gloves, the findings should impact future practice.

CAVEATS

A risk of bias and limited applicability

Not every trial in this meta-analysis was an RCT, and the inclusion of observational studies increases the risk of bias. However, the results of the observational studies were similar to those of the RCTs, somewhat alleviating this potential threat to validity.

The results did not show any difference in surgical site infections between sterile and nonsterile gloves.

It is worth noting that more extensive surgeries and more complicated repairs were not included in the trials, meaning that the findings are limited to oral surgery, Mohs micrographic surgery, standard incisions, and laceration repairs.

CHALLENGES TO IMPLEMENTATION

Inertia, medicolegal concerns, and personal preference

Clinical inertia may lead to slow adoption of these recommendations. Physicians may worry about potential medicolegal ramifications from this change.¹ Lastly, some physicians may prefer the fit and feel of sterile gloves for their procedures.

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.

ILLUSTRATIVE CASE

Your practice manager comes to you to discuss ways that you can reduce expenses. He asks whether the practice could reduce the amount of money spent on gloves for procedures. How do you reply?

A decision involving a small difference, spread over a larger number of events, can have a sizable effect. An example is whether to use sterile vs nonsterile gloves for minor procedures. The cost difference between a box of sterile gloves and a box of nonsterile gloves is relatively small, and certainly worth the difference if the more expensive sterile gloves reduce the number of surgical site infections (SSIs).

However, if there is no difference in the number of SSIs, there may be no value to the extra cost, which, given the number of such procedures, becomes a large unnecessary expense. The choice to use sterile gloves often stems from habit, product availability, or the perceived benefit of fewer SSIs.² While some evidence exists comparing glove choice, there is wide variability in physicians’ choice of gloves.^3-5 This large systematic review compared rates of SSIs using sterile vs nonsterile gloves.

STUDY SUMMARY

RCTs/observational studies find sterile no better than nonsterile gloves

This systematic review and meta-analysis of 13 randomized controlled trials (RCTs) and observational (prospective or retrospective) studies compared infection rates using sterile vs nonsterile gloves in 11,071 unique patients undergoing cutaneous surgery, including Mohs microsurgery or outpatient dental procedures. The methods used in the review followed the Cochrane collaboration guidelines.⁶ The inclusion criteria were that the studies had to be either RCTs or observational studies. Patients included in each study underwent outpatient cutaneous or mucosal surgical procedures, including laceration repair, standard excisions, Mohs micrographic surgery, or tooth extractions. In addition to glove type, documentation of postoperative SSI was necessary for inclusion.

Methodology. The authors of the analysis reviewed a total of 512 publications for inclusion; of these, 14 met the inclusion criteria. One study was later removed due to incomplete data, leaving a total of 13 trials for the analysis. Of the 11,071 patients included in the final analysis, 1360 patients were randomly assigned to treatment with sterile gloves, while 1381 patients were assigned to treatment with nonsterile gloves as the intervention in a clinical trial. The remaining patients participated in either prospective or retrospective observational trials; 4680 patients were treated with sterile gloves, and 3650 patients were treated with nonsterile gloves. Heterogeneity was low for the included studies. Of note, the researchers performed a subgroup analysis on 9 total studies (4 RCTs and 5 observational studies) involving cutaneous surgeries only. These represented procedures most likely performed in the primary care setting.

The primary outcome of this review was postoperative wound infection. The results did not show any difference in SSIs between sterile vs nonsterile gloves in all trials (2% vs 2.1%; relative risk [RR]=1.06; 95% confidence interval [CI], 0.81-1.39). There was also no difference in infection rates in the subgroup analysis of 9 trials limited to cutaneous surgery (2.2% vs 2.2%, respectively; RR=1.02; 95% CI, 0.78-1.34) or when the analysis was limited to only RCTs.

[polldaddy:10063798]

Continue to: WHAT'S NEW

WHAT’S NEW

Highest-quality evidence shows no difference in SSIs

This systematic review found no difference in SSI rates when using sterile vs nonsterile gloves. Given that the analysis represents the highest-quality level of evidence (a systematic review of RCTs) and that sterile gloves are several times more expensive per pair than nonsterile gloves, the findings should impact future practice.

CAVEATS

A risk of bias and limited applicability

Not every trial in this meta-analysis was an RCT, and the inclusion of observational studies increases the risk of bias. However, the results of the observational studies were similar to those of the RCTs, somewhat alleviating this potential threat to validity.

The results did not show any difference in surgical site infections between sterile and nonsterile gloves.

It is worth noting that more extensive surgeries and more complicated repairs were not included in the trials, meaning that the findings are limited to oral surgery, Mohs micrographic surgery, standard incisions, and laceration repairs.

CHALLENGES TO IMPLEMENTATION

Inertia, medicolegal concerns, and personal preference

Clinical inertia may lead to slow adoption of these recommendations. Physicians may worry about potential medicolegal ramifications from this change.¹ Lastly, some physicians may prefer the fit and feel of sterile gloves for their procedures.

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.

THE CASE

A 22-year-old man presented to our family medicine clinic with hip pain of 2 weeks’ duration. The patient played hockey around the time of onset, but denied any specific injury. The pain, which affected the anterolateral aspect of the patient’s right hip, first started when he stood up after eating a meal. He rated the pain as an 8/10 on average and said that it was worse with movement. The patient had not shown improvement with conservative therapy (rest, ice, and ibuprofen). His medical and surgical history were noted as noncontributory. He was not taking any medications other than over-the-counter pain medication, did not drink alcohol or use tobacco, and he exercised regularly. A review of systems was negative except for right hip pain.

The physical exam revealed pain on active flexion and abduction of the hip. Passive range of motion (ROM) was negative for pain. The right hip was grossly normal with no pain on palpation or crepitus. There was no associated muscle tenderness. The patient was advised to continue to rest and ice the hip, as well as to take ibuprofen for pain relief. He was referred to Physical Therapy.

He returned to our clinic 4 weeks later with no improvement in his symptoms despite several sessions of physical therapy. We ordered radiographic images and magnetic resonance imaging (MRI) of the right hip.

THE DIAGNOSIS

Plain films (FIGURE 1A) showed bilateral avascular necrosis (AVN) of the femoral heads, which was worse on the right side than the left. An MRI (FIGURE 1B) further supported this diagnosis, revealing changes in the femoral neck consistent with a stress reaction and no significant collapse of the femoral head.

DISCUSSION

AVN of the hip has an incidence ranging from 10,000 to 20,000 new cases annually.^1,2 It has many possible causes, including trauma, systemic lupus erythematosus, glucocorticoid use, and chronic excessive alcohol use. Although the underlying pathophysiology varies, experts hypothesize that most cases are caused by a disruption of the blood supply, which leads to hyperemia and cortical destruction and collapse.^1,2

Certain medications can cause AVN

A more thorough history-taking at this patient’s initial visit would have prompted imaging at that time and ensured that the standard of care was met. Upon further investigation at his follow-up appointment, it was discovered that he had been diagnosed with acute pre-B cell lymphoblastic leukemia (ALL) 2 years earlier and had undergone chemotherapy with cytarabine, vincristine, L-asparaginase, daunorubicin, methotrexate, and glucocorticoids. This discovery, along with the lack of symptom improvement, prompted the ordering of his imaging studies. Long-term glucocorticoid therapy is the second leading cause of AVN, following traumatic events.³ High daily dosages (>40 mg/d) and high cumulative dosages of glucocorticoids are associated with a significantly increased risk for AVN.^4,5

The other chemotherapy agents with which our patient had been treated (cytarabine, vincristine, L-asparaginase, daunorubicin, and methotrexate) have no reported links to AVN. When mentioned in the literature, however, they are usually coupled with the use of dexamethasone or prednisone.

Continue to: One case report described a patient with...

One case report described a patient with acute promyelocytic leukemia who was treated with all-transretinoic acid, daunomycin, cytarabine, and a short course of dexamethasone, and was diagnosed with AVN 2 years after the cessation of chemotherapy.⁶ This demonstrates that steroid use does not need to be recent to have a contributory effect.

Did leukemic burden play a role?

We also considered whether the patient’s leukemic burden contributed to his osteonecrosis. Leukemia and its therapy regimens have been reported to cause cerebrovascular complications,⁷ so it would be logical to postulate that they might also pose a risk to the vasculature of the femoral head. One case report describes hip pain and AVN as the initial manifestation of chronic myeloid leukemia (CML).⁸ But CML is more often associated with a severely increased white blood cell (WBC) count than is ALL, and our patient’s WBC count was in the expected range for a patient in the maintenance phase of chemotherapy, making leukemic burden a less likely culprit.

Know your patient’s history

Our patient had received an initial dose of approximately 120 mg/d prednisone alone during the first 28 days of his induction therapy for ALL. In addition, he received dexamethasone maintenance therapy, which can accumulate to >140 mg/m² over the course of therapy.⁹ This information was ultimately integral to his diagnosis and treatment.

Our patient was referred to Orthopedics. He underwent therapy with alendronate and did not require surgical intervention.

THE TAKEAWAY

This case illustrates the importance of obtaining a thorough medical history, including previous drug exposures, as a means to raise or lower one’s index of suspicion appropriately.

CORRESPONDENCE
Patrick Basile, 7124 Bristol Boulevard, Edina, MN 55435; [email protected].

THE CASE

A 22-year-old man presented to our family medicine clinic with hip pain of 2 weeks’ duration. The patient played hockey around the time of onset, but denied any specific injury. The pain, which affected the anterolateral aspect of the patient’s right hip, first started when he stood up after eating a meal. He rated the pain as an 8/10 on average and said that it was worse with movement. The patient had not shown improvement with conservative therapy (rest, ice, and ibuprofen). His medical and surgical history were noted as noncontributory. He was not taking any medications other than over-the-counter pain medication, did not drink alcohol or use tobacco, and he exercised regularly. A review of systems was negative except for right hip pain.

The physical exam revealed pain on active flexion and abduction of the hip. Passive range of motion (ROM) was negative for pain. The right hip was grossly normal with no pain on palpation or crepitus. There was no associated muscle tenderness. The patient was advised to continue to rest and ice the hip, as well as to take ibuprofen for pain relief. He was referred to Physical Therapy.

He returned to our clinic 4 weeks later with no improvement in his symptoms despite several sessions of physical therapy. We ordered radiographic images and magnetic resonance imaging (MRI) of the right hip.

THE DIAGNOSIS

Plain films (FIGURE 1A) showed bilateral avascular necrosis (AVN) of the femoral heads, which was worse on the right side than the left. An MRI (FIGURE 1B) further supported this diagnosis, revealing changes in the femoral neck consistent with a stress reaction and no significant collapse of the femoral head.

DISCUSSION

AVN of the hip has an incidence ranging from 10,000 to 20,000 new cases annually.^1,2 It has many possible causes, including trauma, systemic lupus erythematosus, glucocorticoid use, and chronic excessive alcohol use. Although the underlying pathophysiology varies, experts hypothesize that most cases are caused by a disruption of the blood supply, which leads to hyperemia and cortical destruction and collapse.^1,2

Certain medications can cause AVN

A more thorough history-taking at this patient’s initial visit would have prompted imaging at that time and ensured that the standard of care was met. Upon further investigation at his follow-up appointment, it was discovered that he had been diagnosed with acute pre-B cell lymphoblastic leukemia (ALL) 2 years earlier and had undergone chemotherapy with cytarabine, vincristine, L-asparaginase, daunorubicin, methotrexate, and glucocorticoids. This discovery, along with the lack of symptom improvement, prompted the ordering of his imaging studies. Long-term glucocorticoid therapy is the second leading cause of AVN, following traumatic events.³ High daily dosages (>40 mg/d) and high cumulative dosages of glucocorticoids are associated with a significantly increased risk for AVN.^4,5

The other chemotherapy agents with which our patient had been treated (cytarabine, vincristine, L-asparaginase, daunorubicin, and methotrexate) have no reported links to AVN. When mentioned in the literature, however, they are usually coupled with the use of dexamethasone or prednisone.

Continue to: One case report described a patient with...

One case report described a patient with acute promyelocytic leukemia who was treated with all-transretinoic acid, daunomycin, cytarabine, and a short course of dexamethasone, and was diagnosed with AVN 2 years after the cessation of chemotherapy.⁶ This demonstrates that steroid use does not need to be recent to have a contributory effect.

Did leukemic burden play a role?

We also considered whether the patient’s leukemic burden contributed to his osteonecrosis. Leukemia and its therapy regimens have been reported to cause cerebrovascular complications,⁷ so it would be logical to postulate that they might also pose a risk to the vasculature of the femoral head. One case report describes hip pain and AVN as the initial manifestation of chronic myeloid leukemia (CML).⁸ But CML is more often associated with a severely increased white blood cell (WBC) count than is ALL, and our patient’s WBC count was in the expected range for a patient in the maintenance phase of chemotherapy, making leukemic burden a less likely culprit.

Know your patient’s history

Our patient had received an initial dose of approximately 120 mg/d prednisone alone during the first 28 days of his induction therapy for ALL. In addition, he received dexamethasone maintenance therapy, which can accumulate to >140 mg/m² over the course of therapy.⁹ This information was ultimately integral to his diagnosis and treatment.

Our patient was referred to Orthopedics. He underwent therapy with alendronate and did not require surgical intervention.

THE TAKEAWAY

This case illustrates the importance of obtaining a thorough medical history, including previous drug exposures, as a means to raise or lower one’s index of suspicion appropriately.

CORRESPONDENCE
Patrick Basile, 7124 Bristol Boulevard, Edina, MN 55435; [email protected].

THE CASE

A 22-year-old man presented to our family medicine clinic with hip pain of 2 weeks’ duration. The patient played hockey around the time of onset, but denied any specific injury. The pain, which affected the anterolateral aspect of the patient’s right hip, first started when he stood up after eating a meal. He rated the pain as an 8/10 on average and said that it was worse with movement. The patient had not shown improvement with conservative therapy (rest, ice, and ibuprofen). His medical and surgical history were noted as noncontributory. He was not taking any medications other than over-the-counter pain medication, did not drink alcohol or use tobacco, and he exercised regularly. A review of systems was negative except for right hip pain.

The physical exam revealed pain on active flexion and abduction of the hip. Passive range of motion (ROM) was negative for pain. The right hip was grossly normal with no pain on palpation or crepitus. There was no associated muscle tenderness. The patient was advised to continue to rest and ice the hip, as well as to take ibuprofen for pain relief. He was referred to Physical Therapy.

He returned to our clinic 4 weeks later with no improvement in his symptoms despite several sessions of physical therapy. We ordered radiographic images and magnetic resonance imaging (MRI) of the right hip.

THE DIAGNOSIS

Plain films (FIGURE 1A) showed bilateral avascular necrosis (AVN) of the femoral heads, which was worse on the right side than the left. An MRI (FIGURE 1B) further supported this diagnosis, revealing changes in the femoral neck consistent with a stress reaction and no significant collapse of the femoral head.

DISCUSSION

AVN of the hip has an incidence ranging from 10,000 to 20,000 new cases annually.^1,2 It has many possible causes, including trauma, systemic lupus erythematosus, glucocorticoid use, and chronic excessive alcohol use. Although the underlying pathophysiology varies, experts hypothesize that most cases are caused by a disruption of the blood supply, which leads to hyperemia and cortical destruction and collapse.^1,2

Certain medications can cause AVN

A more thorough history-taking at this patient’s initial visit would have prompted imaging at that time and ensured that the standard of care was met. Upon further investigation at his follow-up appointment, it was discovered that he had been diagnosed with acute pre-B cell lymphoblastic leukemia (ALL) 2 years earlier and had undergone chemotherapy with cytarabine, vincristine, L-asparaginase, daunorubicin, methotrexate, and glucocorticoids. This discovery, along with the lack of symptom improvement, prompted the ordering of his imaging studies. Long-term glucocorticoid therapy is the second leading cause of AVN, following traumatic events.³ High daily dosages (>40 mg/d) and high cumulative dosages of glucocorticoids are associated with a significantly increased risk for AVN.^4,5

The other chemotherapy agents with which our patient had been treated (cytarabine, vincristine, L-asparaginase, daunorubicin, and methotrexate) have no reported links to AVN. When mentioned in the literature, however, they are usually coupled with the use of dexamethasone or prednisone.

Continue to: One case report described a patient with...

One case report described a patient with acute promyelocytic leukemia who was treated with all-transretinoic acid, daunomycin, cytarabine, and a short course of dexamethasone, and was diagnosed with AVN 2 years after the cessation of chemotherapy.⁶ This demonstrates that steroid use does not need to be recent to have a contributory effect.

Did leukemic burden play a role?

We also considered whether the patient’s leukemic burden contributed to his osteonecrosis. Leukemia and its therapy regimens have been reported to cause cerebrovascular complications,⁷ so it would be logical to postulate that they might also pose a risk to the vasculature of the femoral head. One case report describes hip pain and AVN as the initial manifestation of chronic myeloid leukemia (CML).⁸ But CML is more often associated with a severely increased white blood cell (WBC) count than is ALL, and our patient’s WBC count was in the expected range for a patient in the maintenance phase of chemotherapy, making leukemic burden a less likely culprit.

Know your patient’s history

Our patient had received an initial dose of approximately 120 mg/d prednisone alone during the first 28 days of his induction therapy for ALL. In addition, he received dexamethasone maintenance therapy, which can accumulate to >140 mg/m² over the course of therapy.⁹ This information was ultimately integral to his diagnosis and treatment.

Our patient was referred to Orthopedics. He underwent therapy with alendronate and did not require surgical intervention.

THE TAKEAWAY

This case illustrates the importance of obtaining a thorough medical history, including previous drug exposures, as a means to raise or lower one’s index of suspicion appropriately.

CORRESPONDENCE
Patrick Basile, 7124 Bristol Boulevard, Edina, MN 55435; [email protected].

THE CASE

A 35-year-old police officer visited his family physician (FP) with complaints of low energy, trouble sleeping, a lack of enjoyment in life, and feelings of hopelessness that have persisted for several months. He was worried about the impact they were having on his marriage and work. He had not experienced suicidal thoughts. His Patient Health Questionnaire (PHQ9) score was 18 (moderately severe depression). He had been seen intermittently for similar complaints and had tried several medications (fluoxetine, bupropion, and citalopram) without much effect. He was taking no medications now other than an over-the-counter multivitamin. He had one brother with anxiety and depression. He said his marriage counselor expressed concerns that he might have bipolar disorder or borderline personality disorder.

How would you proceed with this patient?

The prevalence of a spectrum of bipolarity in the community has been shown to be 6.4%.¹ Depressive episodes predominate in bipolar disorder (BPD),² with patients spending less time in manic or hypomanic states.³ Not surprisingly, then, depressive episodes are the most common presentation of BPD.

The depressive symptoms of BPD and unipolar depression, or major depressive disorder (MDD), are similar, making it difficult to distinguish between the disorders.³ As a result, BPD is often misdiagnosed as MDD.^4,5 Zimmerman et al point out that “bipolar disorder is prone to being overlooked because its diagnosis is more often based on retrospective report rather than presenting symptoms of mania or hypomania assessment.”⁶

Accurately recognizing BPD is essential in selecting effective treatment. It’s estimated that approximately one-third of patients given antidepressants for major depression show no treatment response,⁷ possibly due in part to undiagnosed BPD being more prevalent than previously thought.^4,8 Failure to distinguish between depressive episodes of BPD and MDD before prescribing medication introduces the risk of ineffective or suboptimal treatment. Inappropriate treatment can worsen or destabilize the course of bipolar illness by, for instance, inducing rapid cycling or, less commonly, manic symptoms.

Screen for BPD when depressive symptoms are present

Identifying BPD in a patient with current or past depressive symptoms requires screening for manic, hypomanic, and mixed episodes (TABLE 1⁹). Two brief, complementary screening tools — the Mood Disorder Questionnaire (MDQ) and the 9-item PHQ9—are helpful in this assessment. Both questionnaires (TABLE 2^8,10-14) can be conveniently completed by the patient in the waiting room or with staff assistance before the physician encounter.

The MDQ screen is for past/lifetime or current manic/hypomanic symptoms (https://www.integration.samhsa.gov/images/res/MDQ.pdf). A positive screen requires answering “Yes” to at least 7 of the 13 items on question 1, answering “yes” on question 2, and answering “moderate problems” or “serious problems” on question 3. One study done in the primary care setting found that the MDQ most accurately identified BPD when using a cutoff of 5 “Yes” answers to question 1.¹⁴ (During the clinical interview, discussed in a bit, confirming the positive MDQ items with DSM-5 criteria requires only current presentation or history of 3 symptoms of euphoric manic episode and 4 symptoms of irritable mania for bipolar I and II [may be less for bipolar spectrum].) Although the MDQ was originally developed to be clinician administered, later evidence and clinical experience found that it can also be self-administered.^6,15

Continue to: The PHQ9 screens for...

The PHQ9 screens for current depressive symptoms/episodes (https://www.uspreventiveservicestaskforce.org/Home/GetFileByID/218).

The value of combining the MDQ and PHQ9. The PHQ9 screens for and assesses the severity of depressive episodes along with clinician assessment, but it cannot distinguish between depressive episodes of MDD or BPD. A brief instrument, such as MDQ, screens for current or past manic or hypomanic symptoms, which, when combined with the clinical interview and patient history, enables detection of BPD if present and avoids erroneously assigning depressive symptoms to MDD.

One cross-sectional study found that the combined MDQ and PHQ9 questionnaires have a higher sensitivity in detecting mood disorder than does routine assessment by general practitioners (0.8 [95% confidence interval (CI), 0.71-0.81] vs 0.2 [95% CI, 0.12- 0.25]) and without loss of specificity (0.9 [95% CI, 0.86-0.96] vs 0.9 [95% CI, 0.88-0.97]).¹⁵ In this same study, using a structured clinical interview for DSM-III-R Axis I Disorders (SCID-I) as the gold standard, researchers also found the screening tools to be more accurate (Cohen’s Kappa 0.7 [SE=0.05; 95% CI, 0.5-0.7]) than the general practitioner assessment (Cohen’s Kappa 0.2 [SE=0.07 (95% CI, 0.12-0.27]).¹⁵

Delve deeper with a patient interview

Use targeted questions and laboratory tests to rule out other possible causes of depressed mood, such as substance abuse or medical conditions (eg, hypothyroidism). Keep in mind that even when MDD or BPD is present, other medical disorders or substance abuse could be coexistent. Also ask about a personal or family psychiatric history and assess for suicidality. If family members are available, they may be able to help in identifying the patient’s age when symptoms first appeared or in adding information about the affective episode or behavior that the patient may not recollect.

Depressive episodes predominate in bipolar disorder and symptoms can be indistinguishable from those of unipolar depression.

Beyond a history of manic, hypomanic, or mixed episodes, other symptoms and features may assist in distinguishing between bipolar and unipolar depression or in helping the clinician identify depressed patients who may be at higher risk for, or have, BPD. One meta-analysis of 3 multicenter clinical trials assessed sociodemographic factors and clinical features of BPD compared with unipolar depression. The average age of onset of mood symptoms in individuals with BPD was significantly younger (21.2 years) than that of patients with MDD (29.7 years).¹⁶ Another study found that patients with either bipolar I or bipolar II similarly experienced their first mood disorder episode 10 years earlier than those with MDD.¹⁷

Continue to: BPD is often associated with...

Final thoughts

Increased awareness and screening for BPD in primary care—where most individuals with depressive symptoms are first encountered—should lead to more accurate diagnoses and decrease the years-long gaps between symptom onset and detection of BPD,^4,5 thereby improving treatment and patient outcomes. Still, some cases of BPD may be difficult to recognize—particularly patients who present predominantly with depression with past irritability and other hypomanic symptoms (but not euphoria).

A positive MDQ screen should also prompt, if possible, a more detailed clinical interview by a mental health care professional, particularly if there is uncertainty about the diagnosis. Complex cases of BPD may require the expertise of a psychiatrist.

THE CASE

The patient’s FP referred him to a psychiatrist colleague, whose inquiry also revealed low mood, anhedonia, hopelessness, difficulty sleeping, low energy, poor appetite, guilt, poor concentration, and psychomotor retardation. The patient had experienced multiple depressive episodes over the past 20 years. Significant interpersonal conflicts frequently triggered his depressive episodes, which were accompanied by mood irritability, racing thoughts, distractibility, increased libido, excessive spending, increased energy, and engagement in risky behaviors.

The MDQ and PHQ9 questionnaires, used together, are more sensitive in detecting mood disorder than is routine assessment by general practitioners alone.

The patient’s score on the MDQ administered by the psychiatrist was positive, with 7 points on question 1. He also had posttraumatic symptoms related to his police work, which were not the main reason for the visit. He had been divorced 3 times. In prior manic episodes, he had not displayed euphoria, grandiosity, psychotic symptoms, or anxiety, but rather irritability with other manic symptoms.

Continue to: Based on his MDQ results...

CORRESPONDENCE
Nagy A. Youssef, MD, Medical College of Georgia at Augusta University, 997 St. Sebastian Way, Augusta, GA 30912; [email protected].

SUPPORT AND ACKNOWLEDGMENT
Dr. Youssef’s work on this paper was supported by the Office of Academic Affairs, Medical College of Georgia at Augusta University. We thank Mark Yassa, BS, for his assistance in editing.

THE CASE

A 35-year-old police officer visited his family physician (FP) with complaints of low energy, trouble sleeping, a lack of enjoyment in life, and feelings of hopelessness that have persisted for several months. He was worried about the impact they were having on his marriage and work. He had not experienced suicidal thoughts. His Patient Health Questionnaire (PHQ9) score was 18 (moderately severe depression). He had been seen intermittently for similar complaints and had tried several medications (fluoxetine, bupropion, and citalopram) without much effect. He was taking no medications now other than an over-the-counter multivitamin. He had one brother with anxiety and depression. He said his marriage counselor expressed concerns that he might have bipolar disorder or borderline personality disorder.

How would you proceed with this patient?

The prevalence of a spectrum of bipolarity in the community has been shown to be 6.4%.¹ Depressive episodes predominate in bipolar disorder (BPD),² with patients spending less time in manic or hypomanic states.³ Not surprisingly, then, depressive episodes are the most common presentation of BPD.

The depressive symptoms of BPD and unipolar depression, or major depressive disorder (MDD), are similar, making it difficult to distinguish between the disorders.³ As a result, BPD is often misdiagnosed as MDD.^4,5 Zimmerman et al point out that “bipolar disorder is prone to being overlooked because its diagnosis is more often based on retrospective report rather than presenting symptoms of mania or hypomania assessment.”⁶

Accurately recognizing BPD is essential in selecting effective treatment. It’s estimated that approximately one-third of patients given antidepressants for major depression show no treatment response,⁷ possibly due in part to undiagnosed BPD being more prevalent than previously thought.^4,8 Failure to distinguish between depressive episodes of BPD and MDD before prescribing medication introduces the risk of ineffective or suboptimal treatment. Inappropriate treatment can worsen or destabilize the course of bipolar illness by, for instance, inducing rapid cycling or, less commonly, manic symptoms.

Screen for BPD when depressive symptoms are present

Identifying BPD in a patient with current or past depressive symptoms requires screening for manic, hypomanic, and mixed episodes (TABLE 1⁹). Two brief, complementary screening tools — the Mood Disorder Questionnaire (MDQ) and the 9-item PHQ9—are helpful in this assessment. Both questionnaires (TABLE 2^8,10-14) can be conveniently completed by the patient in the waiting room or with staff assistance before the physician encounter.

The MDQ screen is for past/lifetime or current manic/hypomanic symptoms (https://www.integration.samhsa.gov/images/res/MDQ.pdf). A positive screen requires answering “Yes” to at least 7 of the 13 items on question 1, answering “yes” on question 2, and answering “moderate problems” or “serious problems” on question 3. One study done in the primary care setting found that the MDQ most accurately identified BPD when using a cutoff of 5 “Yes” answers to question 1.¹⁴ (During the clinical interview, discussed in a bit, confirming the positive MDQ items with DSM-5 criteria requires only current presentation or history of 3 symptoms of euphoric manic episode and 4 symptoms of irritable mania for bipolar I and II [may be less for bipolar spectrum].) Although the MDQ was originally developed to be clinician administered, later evidence and clinical experience found that it can also be self-administered.^6,15

Continue to: The PHQ9 screens for...

The PHQ9 screens for current depressive symptoms/episodes (https://www.uspreventiveservicestaskforce.org/Home/GetFileByID/218).

The value of combining the MDQ and PHQ9. The PHQ9 screens for and assesses the severity of depressive episodes along with clinician assessment, but it cannot distinguish between depressive episodes of MDD or BPD. A brief instrument, such as MDQ, screens for current or past manic or hypomanic symptoms, which, when combined with the clinical interview and patient history, enables detection of BPD if present and avoids erroneously assigning depressive symptoms to MDD.

One cross-sectional study found that the combined MDQ and PHQ9 questionnaires have a higher sensitivity in detecting mood disorder than does routine assessment by general practitioners (0.8 [95% confidence interval (CI), 0.71-0.81] vs 0.2 [95% CI, 0.12- 0.25]) and without loss of specificity (0.9 [95% CI, 0.86-0.96] vs 0.9 [95% CI, 0.88-0.97]).¹⁵ In this same study, using a structured clinical interview for DSM-III-R Axis I Disorders (SCID-I) as the gold standard, researchers also found the screening tools to be more accurate (Cohen’s Kappa 0.7 [SE=0.05; 95% CI, 0.5-0.7]) than the general practitioner assessment (Cohen’s Kappa 0.2 [SE=0.07 (95% CI, 0.12-0.27]).¹⁵

Delve deeper with a patient interview

Use targeted questions and laboratory tests to rule out other possible causes of depressed mood, such as substance abuse or medical conditions (eg, hypothyroidism). Keep in mind that even when MDD or BPD is present, other medical disorders or substance abuse could be coexistent. Also ask about a personal or family psychiatric history and assess for suicidality. If family members are available, they may be able to help in identifying the patient’s age when symptoms first appeared or in adding information about the affective episode or behavior that the patient may not recollect.

Depressive episodes predominate in bipolar disorder and symptoms can be indistinguishable from those of unipolar depression.

Beyond a history of manic, hypomanic, or mixed episodes, other symptoms and features may assist in distinguishing between bipolar and unipolar depression or in helping the clinician identify depressed patients who may be at higher risk for, or have, BPD. One meta-analysis of 3 multicenter clinical trials assessed sociodemographic factors and clinical features of BPD compared with unipolar depression. The average age of onset of mood symptoms in individuals with BPD was significantly younger (21.2 years) than that of patients with MDD (29.7 years).¹⁶ Another study found that patients with either bipolar I or bipolar II similarly experienced their first mood disorder episode 10 years earlier than those with MDD.¹⁷

Continue to: BPD is often associated with...

Final thoughts

Increased awareness and screening for BPD in primary care—where most individuals with depressive symptoms are first encountered—should lead to more accurate diagnoses and decrease the years-long gaps between symptom onset and detection of BPD,^4,5 thereby improving treatment and patient outcomes. Still, some cases of BPD may be difficult to recognize—particularly patients who present predominantly with depression with past irritability and other hypomanic symptoms (but not euphoria).

A positive MDQ screen should also prompt, if possible, a more detailed clinical interview by a mental health care professional, particularly if there is uncertainty about the diagnosis. Complex cases of BPD may require the expertise of a psychiatrist.

THE CASE

The patient’s FP referred him to a psychiatrist colleague, whose inquiry also revealed low mood, anhedonia, hopelessness, difficulty sleeping, low energy, poor appetite, guilt, poor concentration, and psychomotor retardation. The patient had experienced multiple depressive episodes over the past 20 years. Significant interpersonal conflicts frequently triggered his depressive episodes, which were accompanied by mood irritability, racing thoughts, distractibility, increased libido, excessive spending, increased energy, and engagement in risky behaviors.

The MDQ and PHQ9 questionnaires, used together, are more sensitive in detecting mood disorder than is routine assessment by general practitioners alone.

The patient’s score on the MDQ administered by the psychiatrist was positive, with 7 points on question 1. He also had posttraumatic symptoms related to his police work, which were not the main reason for the visit. He had been divorced 3 times. In prior manic episodes, he had not displayed euphoria, grandiosity, psychotic symptoms, or anxiety, but rather irritability with other manic symptoms.

Continue to: Based on his MDQ results...

CORRESPONDENCE
Nagy A. Youssef, MD, Medical College of Georgia at Augusta University, 997 St. Sebastian Way, Augusta, GA 30912; [email protected].

SUPPORT AND ACKNOWLEDGMENT
Dr. Youssef’s work on this paper was supported by the Office of Academic Affairs, Medical College of Georgia at Augusta University. We thank Mark Yassa, BS, for his assistance in editing.

THE CASE

A 35-year-old police officer visited his family physician (FP) with complaints of low energy, trouble sleeping, a lack of enjoyment in life, and feelings of hopelessness that have persisted for several months. He was worried about the impact they were having on his marriage and work. He had not experienced suicidal thoughts. His Patient Health Questionnaire (PHQ9) score was 18 (moderately severe depression). He had been seen intermittently for similar complaints and had tried several medications (fluoxetine, bupropion, and citalopram) without much effect. He was taking no medications now other than an over-the-counter multivitamin. He had one brother with anxiety and depression. He said his marriage counselor expressed concerns that he might have bipolar disorder or borderline personality disorder.

How would you proceed with this patient?

The prevalence of a spectrum of bipolarity in the community has been shown to be 6.4%.¹ Depressive episodes predominate in bipolar disorder (BPD),² with patients spending less time in manic or hypomanic states.³ Not surprisingly, then, depressive episodes are the most common presentation of BPD.

The depressive symptoms of BPD and unipolar depression, or major depressive disorder (MDD), are similar, making it difficult to distinguish between the disorders.³ As a result, BPD is often misdiagnosed as MDD.^4,5 Zimmerman et al point out that “bipolar disorder is prone to being overlooked because its diagnosis is more often based on retrospective report rather than presenting symptoms of mania or hypomania assessment.”⁶

Accurately recognizing BPD is essential in selecting effective treatment. It’s estimated that approximately one-third of patients given antidepressants for major depression show no treatment response,⁷ possibly due in part to undiagnosed BPD being more prevalent than previously thought.^4,8 Failure to distinguish between depressive episodes of BPD and MDD before prescribing medication introduces the risk of ineffective or suboptimal treatment. Inappropriate treatment can worsen or destabilize the course of bipolar illness by, for instance, inducing rapid cycling or, less commonly, manic symptoms.

Screen for BPD when depressive symptoms are present

Identifying BPD in a patient with current or past depressive symptoms requires screening for manic, hypomanic, and mixed episodes (TABLE 1⁹). Two brief, complementary screening tools — the Mood Disorder Questionnaire (MDQ) and the 9-item PHQ9—are helpful in this assessment. Both questionnaires (TABLE 2^8,10-14) can be conveniently completed by the patient in the waiting room or with staff assistance before the physician encounter.

The MDQ screen is for past/lifetime or current manic/hypomanic symptoms (https://www.integration.samhsa.gov/images/res/MDQ.pdf). A positive screen requires answering “Yes” to at least 7 of the 13 items on question 1, answering “yes” on question 2, and answering “moderate problems” or “serious problems” on question 3. One study done in the primary care setting found that the MDQ most accurately identified BPD when using a cutoff of 5 “Yes” answers to question 1.¹⁴ (During the clinical interview, discussed in a bit, confirming the positive MDQ items with DSM-5 criteria requires only current presentation or history of 3 symptoms of euphoric manic episode and 4 symptoms of irritable mania for bipolar I and II [may be less for bipolar spectrum].) Although the MDQ was originally developed to be clinician administered, later evidence and clinical experience found that it can also be self-administered.^6,15

Continue to: The PHQ9 screens for...

The PHQ9 screens for current depressive symptoms/episodes (https://www.uspreventiveservicestaskforce.org/Home/GetFileByID/218).

The value of combining the MDQ and PHQ9. The PHQ9 screens for and assesses the severity of depressive episodes along with clinician assessment, but it cannot distinguish between depressive episodes of MDD or BPD. A brief instrument, such as MDQ, screens for current or past manic or hypomanic symptoms, which, when combined with the clinical interview and patient history, enables detection of BPD if present and avoids erroneously assigning depressive symptoms to MDD.

One cross-sectional study found that the combined MDQ and PHQ9 questionnaires have a higher sensitivity in detecting mood disorder than does routine assessment by general practitioners (0.8 [95% confidence interval (CI), 0.71-0.81] vs 0.2 [95% CI, 0.12- 0.25]) and without loss of specificity (0.9 [95% CI, 0.86-0.96] vs 0.9 [95% CI, 0.88-0.97]).¹⁵ In this same study, using a structured clinical interview for DSM-III-R Axis I Disorders (SCID-I) as the gold standard, researchers also found the screening tools to be more accurate (Cohen’s Kappa 0.7 [SE=0.05; 95% CI, 0.5-0.7]) than the general practitioner assessment (Cohen’s Kappa 0.2 [SE=0.07 (95% CI, 0.12-0.27]).¹⁵

Delve deeper with a patient interview

Use targeted questions and laboratory tests to rule out other possible causes of depressed mood, such as substance abuse or medical conditions (eg, hypothyroidism). Keep in mind that even when MDD or BPD is present, other medical disorders or substance abuse could be coexistent. Also ask about a personal or family psychiatric history and assess for suicidality. If family members are available, they may be able to help in identifying the patient’s age when symptoms first appeared or in adding information about the affective episode or behavior that the patient may not recollect.

Depressive episodes predominate in bipolar disorder and symptoms can be indistinguishable from those of unipolar depression.

Beyond a history of manic, hypomanic, or mixed episodes, other symptoms and features may assist in distinguishing between bipolar and unipolar depression or in helping the clinician identify depressed patients who may be at higher risk for, or have, BPD. One meta-analysis of 3 multicenter clinical trials assessed sociodemographic factors and clinical features of BPD compared with unipolar depression. The average age of onset of mood symptoms in individuals with BPD was significantly younger (21.2 years) than that of patients with MDD (29.7 years).¹⁶ Another study found that patients with either bipolar I or bipolar II similarly experienced their first mood disorder episode 10 years earlier than those with MDD.¹⁷

Continue to: BPD is often associated with...

Final thoughts

Increased awareness and screening for BPD in primary care—where most individuals with depressive symptoms are first encountered—should lead to more accurate diagnoses and decrease the years-long gaps between symptom onset and detection of BPD,^4,5 thereby improving treatment and patient outcomes. Still, some cases of BPD may be difficult to recognize—particularly patients who present predominantly with depression with past irritability and other hypomanic symptoms (but not euphoria).

A positive MDQ screen should also prompt, if possible, a more detailed clinical interview by a mental health care professional, particularly if there is uncertainty about the diagnosis. Complex cases of BPD may require the expertise of a psychiatrist.

THE CASE

The patient’s FP referred him to a psychiatrist colleague, whose inquiry also revealed low mood, anhedonia, hopelessness, difficulty sleeping, low energy, poor appetite, guilt, poor concentration, and psychomotor retardation. The patient had experienced multiple depressive episodes over the past 20 years. Significant interpersonal conflicts frequently triggered his depressive episodes, which were accompanied by mood irritability, racing thoughts, distractibility, increased libido, excessive spending, increased energy, and engagement in risky behaviors.

The MDQ and PHQ9 questionnaires, used together, are more sensitive in detecting mood disorder than is routine assessment by general practitioners alone.

The patient’s score on the MDQ administered by the psychiatrist was positive, with 7 points on question 1. He also had posttraumatic symptoms related to his police work, which were not the main reason for the visit. He had been divorced 3 times. In prior manic episodes, he had not displayed euphoria, grandiosity, psychotic symptoms, or anxiety, but rather irritability with other manic symptoms.

Continue to: Based on his MDQ results...

CORRESPONDENCE
Nagy A. Youssef, MD, Medical College of Georgia at Augusta University, 997 St. Sebastian Way, Augusta, GA 30912; [email protected].

SUPPORT AND ACKNOWLEDGMENT
Dr. Youssef’s work on this paper was supported by the Office of Academic Affairs, Medical College of Georgia at Augusta University. We thank Mark Yassa, BS, for his assistance in editing.

ABSTRACT

Purpose In 2013-14, 2 clinics in the Watertown Regional Medical Center (WRMC; in southern Wisconsin) launched a new delivery model, “TEAM (Together Each person Achieves More) Primary Care,” as part of a quality improvement project to enhance the delivery experience for the patient, physician, and medical assistant (MA). New work flows, roles, and responsibilities were designed to reduce cycle time, increase patient time with physicians and staff, and reduce patient wait times.

Methods The new model increased the ratio of MAs to physicians from a baseline MA:MD ratio of 1:1 to 3:2, and trained MAs to assume expanded roles during exam-room entry and discharge, including assisting with documentation during the patient visit. A process engineer timed patient visits. The process engineer and a human resources associate conducted surveys to assess the level of satisfaction for patients, physicians, and MAs.

Results Cycle time decreased by a mean of 6 minutes, from 44 to 38 minutes per patient; time with staff increased a mean of 2 minutes, from 24 to 26 minutes per patient; and waiting time decreased from 9 to 2 minutes per patient. Qualitative interviews with patients, physicians, and MAs identified a high level of satisfaction with the new model.

Conclusion The higher staffing ratios and expanded roles for MAs in the new model improved workflow, increased the face time between patients and their physician and MA, and decreased patient wait times. The TEAM model also appeared to improve patient, physician, and MA satisfaction. We faced many challenges while implementing the new model, which could be further evaluated during wide adoption.

In recent years, we observed that our physicians, nurses, and medical assistants (MAs) appeared to be spending more time on administrative and clerical tasks—including tasks in the exam room with the patient—and less time engaged in direct patient care.^1,2 We recognized these factors contribute to burnout and threaten staff retention and anticipated that a new model would improve physician time spent in direct patient care, decrease the demands of administrative tasks, and increase patient, physician, and MA satisfaction.^3-6 Burnout, known to affect more than half of US physicians, has a negative impact on quality of care and patient safety and satisfaction.^7-11 Improving workflow has been shown to reduce burnout.¹²

Watertown Regional Medical Center (WRMC) is a small, financially stable integrated delivery system in rural southern Wisconsin, composed of a 90-bed hospital, 10 primary care clinics (7 owned and 3 affiliated), and 24 employed physicians in 9 specialties. Two clinics within WRMC launched a new delivery model, “TEAM (Together Each person Achieves More) Primary Care,” to improve the delivery experience for the entire team, defined as the patient, physician, and MA. New workflows, roles, and responsibilities were designed to reduce cycle time (the total amount of time patients spent in the clinic from check-in to check-out), increase the total time a patient spent with staff (physician and MA or in point-of-care testing and radiology), and reduce the total time a patient spent waiting.¹³

We describe here WRMC’s experience in developing and implementing workflow improvements as a means of reducing burnout and improving satisfaction.

Continue to: METHODS

METHODS

We selected 2 WRMC sites for TEAM re-engineering based on their experience with quality-improvement projects and perceived likelihood of success with a new transformation initiative. In early 2013, WRMC charged one physician (JM), 2 MAs, the clinic scheduler, and the clinic administrator with designing the details of the model including evaluation metrics. WRMC provided a .5 FTE process engineer (MS) to assist with the design and implementation of the model at no extra expense to the clinics. The model was implemented in late 2013 and into 2014 after regular TEAM planning meetings and observational visits to non-WRMC sites identified as examples of best practices in improving outpatient primary care patient satisfaction: Bellin Health (Green Bay, Wis); ThedaCare (Appleton, Wis); the University of Utah (Salt Lake City); and the University of Wisconsin Health Yahara Clinic (Madison, Wis).

TEAM model

The TEAM model—so named to create top-of-mind awareness of its benefits—increased the MA:MD ratio, maintained consistent team composition so that physician/MA teams learned to work together and become more efficient, and added new MA responsibilities. We trained MAs to assist with documentation in the exam room to ensure that physician time was spent in face-to-face direct patient care.^14-20 In these ways, we sought not only to increase patient satisfaction but also to enhance our own “joy in practice,” defined primarily by a high level of work-life satisfaction, a low level of burnout, and a feeling that the medical practice is fulfilling.²¹

In our traditional model, an MA retrieved the patient from the waiting room, conducted initial assessment in the exam room, and then left the patient to wait for the physician to enter. Once the physician entered and conducted the exam, the patient would be left alone again to wait for the MA to return. In our revised model (TABLE 1), we assigned one MA to each patient from arrival to discharge. After greeting the patient in the waiting room, the MA conducted an initial patient interview in the exam room, then remained in the room with the physician to document the visit. After the physician exited the exam room, the MA completed follow-up orders and provided the patient with a visit summary.

To facilitate consistency throughout the day, we designed a workflow similar to those created in lean models originally designed to increase efficiency in the manufacturing industry (TABLE 2). Visual and electronic cues triggered each step of the process and coordinated the movement of MAs and MDs. Cues included the conventional flag system outside each exam room, an electronic messaging system within the electronic health record (EHR) to indicate when a patient was ready to be seen, and a whiteboard in an area visible to all team members on which we wrote lab and radiology requests.

The TEAM model reduced wait time and increased staff interaction time with patients.

We experimented with the MA:MD ratio to identify the most effective and efficient team composition. On alternating weeks, we assigned one MA to one MD, 2 MAs to one MD, or 3 MAs to 2 MDs. Additionally, with the 2:1 MA:MD ratio, we varied the visit length in 2 tests; one spanning 30 minutes and the other 20 minutes. The MDs and MAs were seated at side-by-side workstations to make communication easier. We developed protocols and checklists that allowed MAs to enter health maintenance orders and conduct point-of-care testing before the physician entered the room. Such details included immunization management, strep screens, urine analyses, diabetic foot exams, extremity x-ray films, and mammogram and colonoscopy referrals.

Continue to: To prepare MAs...

To prepare MAs, we obtained special permission for team documentation from our Chief Information Officer and developed associated policies and procedures. A physician assistant (PA) trained each MA, introducing the structure and content of subjective, objective, assessment, and plan (SOAP) notes. Training was continuous, as PAs provided feedback when MAs began team documentation. The MAs documented visits using templates, free form, and quick text. We measured visit cycle-time, face time with staff, and patient waiting times. A process engineer with a stopwatch observed and timed the flow (but did not enter the exam room). We also conducted patient interviews immediately post-visit and administered anonymous questionnaires to clinic staff at different phases of the model. Physicians and MAs met weekly to evaluate the design.

We used qualitative interviews of patients, physicians, and MAs to identify the level of satisfaction with the new model. During the first week of implementation, a nurse and our process engineer conducted brief in-person surveys with approximately 20 post-visit patients. Patients, chosen by convenience, were asked if the visit addressed their concerns, whether they left with a thorough understanding of next steps, and if their wait time was acceptable. Twice during the implementation phase, a human resources associate distributed 9-item anonymous questionnaires to staff members during scheduled department meetings.

RESULTS

Times per activity with different MA:MD ratios and visit lengths are shown in TABLE 3. After 6 months, cycle time decreased by a mean of 6 minutes, from 44 to 38 minutes per patient; time with staff increased by a mean of 2 minutes, from 24 to 26 minutes per patient; and wait time decreased by a mean of 7 minutes, from 9 to 2 minutes per patient. We concluded the MA:MD ratio of 3:2 was most efficient because the 2:1 model left MAs with excess non-patient time.

Our delivery model received consistently positive comments from patients. Many expressed gratitude for the extra set of ears and eyes guiding them through the process. One recalled the “old days” when a nurse joined the doctor in the exam room. Another appreciated that both the MA and physician could answer follow-up questions over the phone.

Employee satisfaction

Surveys to assess satisfaction were distributed to all employees whether they were involved in the new model or not. Sixteen employees responded to the pre-implementation questionnaire and 18 responded to the post-implementation one distributed 7 months later. The questionnaires showed an increase in employee satisfaction scores from 3.70 to 3.89 on a 5-point Likert scale, with 5 ranking highest. “I am learning from [Dr. Milford] and understanding things more fully,” wrote one respondent. Another said, “Dr. Milford and his clinical support staff are less stressed.” Individual observations such as, “I can leave sooner with less work left to do,” and “All documentation is done before [the] patient leaves,” reflect the reduction in time that patient records remained open or incomplete. Some physicians reported a reduction in at-home or after-hours work, from about 2 to 4 hours per day to approximately one hour per day.

Continue to: Additional outcomes

The TEAM model allowed us to more easily integrate new initiatives into our practice and meet quality metrics by placing needed components within our workflow and checklist. For example, achieving Stage II Meaningful Use measures required that we print and furnish patients with a visit summary and a reminder to access our portal; something we easily incorporated into the MAs’ expanded responsibilities. We also met specific predetermined quality metrics that were part of a payment-withhold program. During the study period, we achieved scores at the 90th percentile and earned back our total withhold.

Finally, more of our patients completed advanced care planning discussions than the other 7 sites in our Honoring Choices Wisconsin cohort. This was achieved not only by integrating the process into our checklist, but because the MAs observed the MD-led patient conversations which they then emulated, presenting the advanced care planning information to patients before or after MD time with the patient.

Errors and defects in care

With ongoing provider guidance and reinforcement, MAs became integral members of the primary care team. They were empowered through protocols to manage and order health maintenance testing and provide needed immunizations. They also began to identify potentially overlooked aspects of care. For example, MAs prompted physicians to retake vital signs, adjust medications, order labs, discuss previous lab results, and pursue specialty referrals or follow-up care.

Billing

Although we tracked billing, the TEAM model was not designed to influence revenue. We noted no significant change in level of evaluation and management billed regardless of staffing ratio. While our panel size increased as we implemented the new process, this change could have been due to normal variation. We do see opportunity to affect future billing by having coders train MAs, which could enhance documentation and increase revenue.

DISCUSSION

The TEAM Primary Care model reduced the time our patients sat unattended, increased our opportunities to meaningfully interact with them, and seemed to reduce our administrative load. By identifying and implementing ways to work as a more cohesive, interconnected unit, we began to address our work as a team rather than as individuals. After implementing the model, we noted several instances where the MAs caught potential errors in care, although we did not consistently track or measure changes in the rate of these occurrences.

Continue to: Achieving these results also came with...

Achieving these results also came with challenges. Investing in and maintaining a new model opened our eyes to unforeseen inconsistencies in our staff profile and to the cost and administrative support needed for implementation. Moreover, our entire team (patients, MAs, and physicians) had to undergo a major cultural shift to adopt a new model.

Personnel variation

We discovered that implementing and sustaining organization change is highly dependent on constancy in human resources. When one team member was on vacation, sick, or leaving the practice, the process tended to fall apart. Hiring replacements and training employees well enough to fill in at a moment’s notice proved difficult. Bringing new employees into this process was also labor intensive. Despite team members being very engaged in change, these staffing inconsistencies caused significant stress and necessitated pauses in the implementation of the new model (reflected in the timeline of our measures). Larger organizational buy-in and support would allow us to hire and train a larger pool of MAs in anticipation of these fluctuations.

Cost

Our small, rural family practice took advantage of WRMC’s Primary Care Transformation project and the half-time process engineer and additional MA they provided. We question whether this model could be implemented without such support. While a process engineer might not prove necessary, expertise in process improvement is vital to help design and measure workflow and to identify opportunities for improvement.

Cultural change

Adopting a new model required asking every member of the team (patient, MA, and physician) to accommodate change and tolerate disruption. We anticipated patients might resist having an additional person in the room. All patients were informed of our new model at the beginning of the visit and told they could opt out. While we did not document patient resistance, JM recalled only 2 patients who expressed a desire not to have the MA present because of personal and sensitive issues. It’s possible some patients did not feel comfortable opting out. But many patients expressed gratitude for having an extra set of ears and eyes to guide them through the visit.

With the TEAM model, we noted several instances where the MAs caught potential errors in care.

It was more challenging to support MAs as they stepped out of their comfort zone to assist with documentation. It took time for MAs to grow accustomed to the protocols and checklists essential to our workflow. Without protocols, any point-of-care testing that could have been completed at the beginning of the appointment had to be done at the end. This disrupted our workflow and increased patient wait times.

Continue to: We correctly predicted MAs would have...

We correctly predicted MAs would have difficulty documenting the assessment, plan, and medical decision making. We discovered that MAs more easily categorized and articulated information when we reframed the assessment and plan in first-person and placed it under “Patient instructions.” For this to occur, physicians had to learn to accurately articulate their thought process and instructions to the patient.

When training was provided, as previously described, MAs grasped the subjective section quickly. Surprisingly, they had most difficulty understanding terminology within the objective section. In the future, we would avert this problem by working closely with the human resource department. We believe there should be a newly defined position and additional training for MAs in these roles, since duties such as patient-coaching and documentation assistance may warrant separate certification.

Limitations

Our findings should be interpreted in light of several limitations. Implementing the new model was carried out in a single organization. The patients who were selected and agreed to be interviewed may have differed from the patient population as a whole. We did not measure some important outcomes, such as cost effectiveness and patient morbidity. We did not analyze the data to determine whether the apparent improvements in wait time and cycle time were statistically significant. In addition, measurement of any adverse effects was beyond the scope of this study.

Looking forward

The traditional model of physicians working individually with minimal support staff is no longer viable. To echo our co-author (CAS)’s recent statements on physician dissatisfaction, “The days of hero medicine, with the doctor doing it all, belong in the past.”²¹ The new model appeared to alleviate some administrative burdens and increase physician time with patients. Pressures to achieve quality measures and growing administrative tasks have altered the role and responsibilities of each member of the team.

It's possible some patients might have felt uneasy with the TEAM approach, but many expressed gratitude for an extra set of ears and eyes to guide them through the visit.

Any sustainable system must address the larger crisis of physician dissatisfaction.^7,22 We cannot focus on a single perspective—patient, physician, or MA—at the expense of the system as a whole. If the health care system is to resolve the epidemic of burnout and physician dissatisfaction, new approaches to patient care must be imagined and realized. Although we faced many challenges in implementing and evaluating the TEAM model, attempts to overcome these challenges appear justified because of our overall favorable impression of it. Innovations like the TEAM Primary Care model may help us improve the well-being of not just our patients but also our health professionals and the health care industry as a whole.

CORRESPONDENCE
James Milford, MD, Three Oaks Health, S.C., 480 Village Walk Lane, Suite F, Johnson Creek, WI 53038; [email protected].

SUPPORT
Although the Watertown Regional Medical Center has provided general funding for its Primary Care Transformation project, no dollars were specifically earmarked for the TEAM Primary Care process. Support for editorial services in preparing this article was provided by Dr. James Milford.

PRIOR PRESENTATIONS
Co-author Michael R. Strasser, MPA, presented this project at the 2015 i-PrACTISE conference in Madison, Wis, April 12-14, 2015. http://www.fammed.wisc.edu/i-practise/. The proceedings were not published or recorded.

ACKNOWLEDGMENT
We thank Annalynn Skipper and Masarah Van Eyck for their valuable edits.

ABSTRACT

Purpose In 2013-14, 2 clinics in the Watertown Regional Medical Center (WRMC; in southern Wisconsin) launched a new delivery model, “TEAM (Together Each person Achieves More) Primary Care,” as part of a quality improvement project to enhance the delivery experience for the patient, physician, and medical assistant (MA). New work flows, roles, and responsibilities were designed to reduce cycle time, increase patient time with physicians and staff, and reduce patient wait times.

Methods The new model increased the ratio of MAs to physicians from a baseline MA:MD ratio of 1:1 to 3:2, and trained MAs to assume expanded roles during exam-room entry and discharge, including assisting with documentation during the patient visit. A process engineer timed patient visits. The process engineer and a human resources associate conducted surveys to assess the level of satisfaction for patients, physicians, and MAs.

Results Cycle time decreased by a mean of 6 minutes, from 44 to 38 minutes per patient; time with staff increased a mean of 2 minutes, from 24 to 26 minutes per patient; and waiting time decreased from 9 to 2 minutes per patient. Qualitative interviews with patients, physicians, and MAs identified a high level of satisfaction with the new model.

Conclusion The higher staffing ratios and expanded roles for MAs in the new model improved workflow, increased the face time between patients and their physician and MA, and decreased patient wait times. The TEAM model also appeared to improve patient, physician, and MA satisfaction. We faced many challenges while implementing the new model, which could be further evaluated during wide adoption.

In recent years, we observed that our physicians, nurses, and medical assistants (MAs) appeared to be spending more time on administrative and clerical tasks—including tasks in the exam room with the patient—and less time engaged in direct patient care.^1,2 We recognized these factors contribute to burnout and threaten staff retention and anticipated that a new model would improve physician time spent in direct patient care, decrease the demands of administrative tasks, and increase patient, physician, and MA satisfaction.^3-6 Burnout, known to affect more than half of US physicians, has a negative impact on quality of care and patient safety and satisfaction.^7-11 Improving workflow has been shown to reduce burnout.¹²

Watertown Regional Medical Center (WRMC) is a small, financially stable integrated delivery system in rural southern Wisconsin, composed of a 90-bed hospital, 10 primary care clinics (7 owned and 3 affiliated), and 24 employed physicians in 9 specialties. Two clinics within WRMC launched a new delivery model, “TEAM (Together Each person Achieves More) Primary Care,” to improve the delivery experience for the entire team, defined as the patient, physician, and MA. New workflows, roles, and responsibilities were designed to reduce cycle time (the total amount of time patients spent in the clinic from check-in to check-out), increase the total time a patient spent with staff (physician and MA or in point-of-care testing and radiology), and reduce the total time a patient spent waiting.¹³

We describe here WRMC’s experience in developing and implementing workflow improvements as a means of reducing burnout and improving satisfaction.

Continue to: METHODS

METHODS

We selected 2 WRMC sites for TEAM re-engineering based on their experience with quality-improvement projects and perceived likelihood of success with a new transformation initiative. In early 2013, WRMC charged one physician (JM), 2 MAs, the clinic scheduler, and the clinic administrator with designing the details of the model including evaluation metrics. WRMC provided a .5 FTE process engineer (MS) to assist with the design and implementation of the model at no extra expense to the clinics. The model was implemented in late 2013 and into 2014 after regular TEAM planning meetings and observational visits to non-WRMC sites identified as examples of best practices in improving outpatient primary care patient satisfaction: Bellin Health (Green Bay, Wis); ThedaCare (Appleton, Wis); the University of Utah (Salt Lake City); and the University of Wisconsin Health Yahara Clinic (Madison, Wis).

TEAM model

The TEAM model—so named to create top-of-mind awareness of its benefits—increased the MA:MD ratio, maintained consistent team composition so that physician/MA teams learned to work together and become more efficient, and added new MA responsibilities. We trained MAs to assist with documentation in the exam room to ensure that physician time was spent in face-to-face direct patient care.^14-20 In these ways, we sought not only to increase patient satisfaction but also to enhance our own “joy in practice,” defined primarily by a high level of work-life satisfaction, a low level of burnout, and a feeling that the medical practice is fulfilling.²¹

In our traditional model, an MA retrieved the patient from the waiting room, conducted initial assessment in the exam room, and then left the patient to wait for the physician to enter. Once the physician entered and conducted the exam, the patient would be left alone again to wait for the MA to return. In our revised model (TABLE 1), we assigned one MA to each patient from arrival to discharge. After greeting the patient in the waiting room, the MA conducted an initial patient interview in the exam room, then remained in the room with the physician to document the visit. After the physician exited the exam room, the MA completed follow-up orders and provided the patient with a visit summary.

To facilitate consistency throughout the day, we designed a workflow similar to those created in lean models originally designed to increase efficiency in the manufacturing industry (TABLE 2). Visual and electronic cues triggered each step of the process and coordinated the movement of MAs and MDs. Cues included the conventional flag system outside each exam room, an electronic messaging system within the electronic health record (EHR) to indicate when a patient was ready to be seen, and a whiteboard in an area visible to all team members on which we wrote lab and radiology requests.

The TEAM model reduced wait time and increased staff interaction time with patients.

We experimented with the MA:MD ratio to identify the most effective and efficient team composition. On alternating weeks, we assigned one MA to one MD, 2 MAs to one MD, or 3 MAs to 2 MDs. Additionally, with the 2:1 MA:MD ratio, we varied the visit length in 2 tests; one spanning 30 minutes and the other 20 minutes. The MDs and MAs were seated at side-by-side workstations to make communication easier. We developed protocols and checklists that allowed MAs to enter health maintenance orders and conduct point-of-care testing before the physician entered the room. Such details included immunization management, strep screens, urine analyses, diabetic foot exams, extremity x-ray films, and mammogram and colonoscopy referrals.

Continue to: To prepare MAs...

To prepare MAs, we obtained special permission for team documentation from our Chief Information Officer and developed associated policies and procedures. A physician assistant (PA) trained each MA, introducing the structure and content of subjective, objective, assessment, and plan (SOAP) notes. Training was continuous, as PAs provided feedback when MAs began team documentation. The MAs documented visits using templates, free form, and quick text. We measured visit cycle-time, face time with staff, and patient waiting times. A process engineer with a stopwatch observed and timed the flow (but did not enter the exam room). We also conducted patient interviews immediately post-visit and administered anonymous questionnaires to clinic staff at different phases of the model. Physicians and MAs met weekly to evaluate the design.

We used qualitative interviews of patients, physicians, and MAs to identify the level of satisfaction with the new model. During the first week of implementation, a nurse and our process engineer conducted brief in-person surveys with approximately 20 post-visit patients. Patients, chosen by convenience, were asked if the visit addressed their concerns, whether they left with a thorough understanding of next steps, and if their wait time was acceptable. Twice during the implementation phase, a human resources associate distributed 9-item anonymous questionnaires to staff members during scheduled department meetings.

RESULTS

Times per activity with different MA:MD ratios and visit lengths are shown in TABLE 3. After 6 months, cycle time decreased by a mean of 6 minutes, from 44 to 38 minutes per patient; time with staff increased by a mean of 2 minutes, from 24 to 26 minutes per patient; and wait time decreased by a mean of 7 minutes, from 9 to 2 minutes per patient. We concluded the MA:MD ratio of 3:2 was most efficient because the 2:1 model left MAs with excess non-patient time.

Our delivery model received consistently positive comments from patients. Many expressed gratitude for the extra set of ears and eyes guiding them through the process. One recalled the “old days” when a nurse joined the doctor in the exam room. Another appreciated that both the MA and physician could answer follow-up questions over the phone.

Employee satisfaction

Surveys to assess satisfaction were distributed to all employees whether they were involved in the new model or not. Sixteen employees responded to the pre-implementation questionnaire and 18 responded to the post-implementation one distributed 7 months later. The questionnaires showed an increase in employee satisfaction scores from 3.70 to 3.89 on a 5-point Likert scale, with 5 ranking highest. “I am learning from [Dr. Milford] and understanding things more fully,” wrote one respondent. Another said, “Dr. Milford and his clinical support staff are less stressed.” Individual observations such as, “I can leave sooner with less work left to do,” and “All documentation is done before [the] patient leaves,” reflect the reduction in time that patient records remained open or incomplete. Some physicians reported a reduction in at-home or after-hours work, from about 2 to 4 hours per day to approximately one hour per day.

Continue to: Additional outcomes

The TEAM model allowed us to more easily integrate new initiatives into our practice and meet quality metrics by placing needed components within our workflow and checklist. For example, achieving Stage II Meaningful Use measures required that we print and furnish patients with a visit summary and a reminder to access our portal; something we easily incorporated into the MAs’ expanded responsibilities. We also met specific predetermined quality metrics that were part of a payment-withhold program. During the study period, we achieved scores at the 90th percentile and earned back our total withhold.

Finally, more of our patients completed advanced care planning discussions than the other 7 sites in our Honoring Choices Wisconsin cohort. This was achieved not only by integrating the process into our checklist, but because the MAs observed the MD-led patient conversations which they then emulated, presenting the advanced care planning information to patients before or after MD time with the patient.

Errors and defects in care

With ongoing provider guidance and reinforcement, MAs became integral members of the primary care team. They were empowered through protocols to manage and order health maintenance testing and provide needed immunizations. They also began to identify potentially overlooked aspects of care. For example, MAs prompted physicians to retake vital signs, adjust medications, order labs, discuss previous lab results, and pursue specialty referrals or follow-up care.

Billing

Although we tracked billing, the TEAM model was not designed to influence revenue. We noted no significant change in level of evaluation and management billed regardless of staffing ratio. While our panel size increased as we implemented the new process, this change could have been due to normal variation. We do see opportunity to affect future billing by having coders train MAs, which could enhance documentation and increase revenue.

DISCUSSION

The TEAM Primary Care model reduced the time our patients sat unattended, increased our opportunities to meaningfully interact with them, and seemed to reduce our administrative load. By identifying and implementing ways to work as a more cohesive, interconnected unit, we began to address our work as a team rather than as individuals. After implementing the model, we noted several instances where the MAs caught potential errors in care, although we did not consistently track or measure changes in the rate of these occurrences.

Continue to: Achieving these results also came with...

Achieving these results also came with challenges. Investing in and maintaining a new model opened our eyes to unforeseen inconsistencies in our staff profile and to the cost and administrative support needed for implementation. Moreover, our entire team (patients, MAs, and physicians) had to undergo a major cultural shift to adopt a new model.

Personnel variation

We discovered that implementing and sustaining organization change is highly dependent on constancy in human resources. When one team member was on vacation, sick, or leaving the practice, the process tended to fall apart. Hiring replacements and training employees well enough to fill in at a moment’s notice proved difficult. Bringing new employees into this process was also labor intensive. Despite team members being very engaged in change, these staffing inconsistencies caused significant stress and necessitated pauses in the implementation of the new model (reflected in the timeline of our measures). Larger organizational buy-in and support would allow us to hire and train a larger pool of MAs in anticipation of these fluctuations.

Cost

Our small, rural family practice took advantage of WRMC’s Primary Care Transformation project and the half-time process engineer and additional MA they provided. We question whether this model could be implemented without such support. While a process engineer might not prove necessary, expertise in process improvement is vital to help design and measure workflow and to identify opportunities for improvement.

Cultural change

Adopting a new model required asking every member of the team (patient, MA, and physician) to accommodate change and tolerate disruption. We anticipated patients might resist having an additional person in the room. All patients were informed of our new model at the beginning of the visit and told they could opt out. While we did not document patient resistance, JM recalled only 2 patients who expressed a desire not to have the MA present because of personal and sensitive issues. It’s possible some patients did not feel comfortable opting out. But many patients expressed gratitude for having an extra set of ears and eyes to guide them through the visit.

With the TEAM model, we noted several instances where the MAs caught potential errors in care.

It was more challenging to support MAs as they stepped out of their comfort zone to assist with documentation. It took time for MAs to grow accustomed to the protocols and checklists essential to our workflow. Without protocols, any point-of-care testing that could have been completed at the beginning of the appointment had to be done at the end. This disrupted our workflow and increased patient wait times.

Continue to: We correctly predicted MAs would have...

We correctly predicted MAs would have difficulty documenting the assessment, plan, and medical decision making. We discovered that MAs more easily categorized and articulated information when we reframed the assessment and plan in first-person and placed it under “Patient instructions.” For this to occur, physicians had to learn to accurately articulate their thought process and instructions to the patient.

When training was provided, as previously described, MAs grasped the subjective section quickly. Surprisingly, they had most difficulty understanding terminology within the objective section. In the future, we would avert this problem by working closely with the human resource department. We believe there should be a newly defined position and additional training for MAs in these roles, since duties such as patient-coaching and documentation assistance may warrant separate certification.

Limitations

Our findings should be interpreted in light of several limitations. Implementing the new model was carried out in a single organization. The patients who were selected and agreed to be interviewed may have differed from the patient population as a whole. We did not measure some important outcomes, such as cost effectiveness and patient morbidity. We did not analyze the data to determine whether the apparent improvements in wait time and cycle time were statistically significant. In addition, measurement of any adverse effects was beyond the scope of this study.

Looking forward

The traditional model of physicians working individually with minimal support staff is no longer viable. To echo our co-author (CAS)’s recent statements on physician dissatisfaction, “The days of hero medicine, with the doctor doing it all, belong in the past.”²¹ The new model appeared to alleviate some administrative burdens and increase physician time with patients. Pressures to achieve quality measures and growing administrative tasks have altered the role and responsibilities of each member of the team.

It's possible some patients might have felt uneasy with the TEAM approach, but many expressed gratitude for an extra set of ears and eyes to guide them through the visit.

Any sustainable system must address the larger crisis of physician dissatisfaction.^7,22 We cannot focus on a single perspective—patient, physician, or MA—at the expense of the system as a whole. If the health care system is to resolve the epidemic of burnout and physician dissatisfaction, new approaches to patient care must be imagined and realized. Although we faced many challenges in implementing and evaluating the TEAM model, attempts to overcome these challenges appear justified because of our overall favorable impression of it. Innovations like the TEAM Primary Care model may help us improve the well-being of not just our patients but also our health professionals and the health care industry as a whole.

CORRESPONDENCE
James Milford, MD, Three Oaks Health, S.C., 480 Village Walk Lane, Suite F, Johnson Creek, WI 53038; [email protected].

SUPPORT
Although the Watertown Regional Medical Center has provided general funding for its Primary Care Transformation project, no dollars were specifically earmarked for the TEAM Primary Care process. Support for editorial services in preparing this article was provided by Dr. James Milford.

PRIOR PRESENTATIONS
Co-author Michael R. Strasser, MPA, presented this project at the 2015 i-PrACTISE conference in Madison, Wis, April 12-14, 2015. http://www.fammed.wisc.edu/i-practise/. The proceedings were not published or recorded.

ACKNOWLEDGMENT
We thank Annalynn Skipper and Masarah Van Eyck for their valuable edits.

ABSTRACT

Purpose In 2013-14, 2 clinics in the Watertown Regional Medical Center (WRMC; in southern Wisconsin) launched a new delivery model, “TEAM (Together Each person Achieves More) Primary Care,” as part of a quality improvement project to enhance the delivery experience for the patient, physician, and medical assistant (MA). New work flows, roles, and responsibilities were designed to reduce cycle time, increase patient time with physicians and staff, and reduce patient wait times.

Methods The new model increased the ratio of MAs to physicians from a baseline MA:MD ratio of 1:1 to 3:2, and trained MAs to assume expanded roles during exam-room entry and discharge, including assisting with documentation during the patient visit. A process engineer timed patient visits. The process engineer and a human resources associate conducted surveys to assess the level of satisfaction for patients, physicians, and MAs.

Results Cycle time decreased by a mean of 6 minutes, from 44 to 38 minutes per patient; time with staff increased a mean of 2 minutes, from 24 to 26 minutes per patient; and waiting time decreased from 9 to 2 minutes per patient. Qualitative interviews with patients, physicians, and MAs identified a high level of satisfaction with the new model.

Conclusion The higher staffing ratios and expanded roles for MAs in the new model improved workflow, increased the face time between patients and their physician and MA, and decreased patient wait times. The TEAM model also appeared to improve patient, physician, and MA satisfaction. We faced many challenges while implementing the new model, which could be further evaluated during wide adoption.

In recent years, we observed that our physicians, nurses, and medical assistants (MAs) appeared to be spending more time on administrative and clerical tasks—including tasks in the exam room with the patient—and less time engaged in direct patient care.^1,2 We recognized these factors contribute to burnout and threaten staff retention and anticipated that a new model would improve physician time spent in direct patient care, decrease the demands of administrative tasks, and increase patient, physician, and MA satisfaction.^3-6 Burnout, known to affect more than half of US physicians, has a negative impact on quality of care and patient safety and satisfaction.^7-11 Improving workflow has been shown to reduce burnout.¹²

Watertown Regional Medical Center (WRMC) is a small, financially stable integrated delivery system in rural southern Wisconsin, composed of a 90-bed hospital, 10 primary care clinics (7 owned and 3 affiliated), and 24 employed physicians in 9 specialties. Two clinics within WRMC launched a new delivery model, “TEAM (Together Each person Achieves More) Primary Care,” to improve the delivery experience for the entire team, defined as the patient, physician, and MA. New workflows, roles, and responsibilities were designed to reduce cycle time (the total amount of time patients spent in the clinic from check-in to check-out), increase the total time a patient spent with staff (physician and MA or in point-of-care testing and radiology), and reduce the total time a patient spent waiting.¹³

We describe here WRMC’s experience in developing and implementing workflow improvements as a means of reducing burnout and improving satisfaction.

Continue to: METHODS

METHODS

We selected 2 WRMC sites for TEAM re-engineering based on their experience with quality-improvement projects and perceived likelihood of success with a new transformation initiative. In early 2013, WRMC charged one physician (JM), 2 MAs, the clinic scheduler, and the clinic administrator with designing the details of the model including evaluation metrics. WRMC provided a .5 FTE process engineer (MS) to assist with the design and implementation of the model at no extra expense to the clinics. The model was implemented in late 2013 and into 2014 after regular TEAM planning meetings and observational visits to non-WRMC sites identified as examples of best practices in improving outpatient primary care patient satisfaction: Bellin Health (Green Bay, Wis); ThedaCare (Appleton, Wis); the University of Utah (Salt Lake City); and the University of Wisconsin Health Yahara Clinic (Madison, Wis).

TEAM model

The TEAM model—so named to create top-of-mind awareness of its benefits—increased the MA:MD ratio, maintained consistent team composition so that physician/MA teams learned to work together and become more efficient, and added new MA responsibilities. We trained MAs to assist with documentation in the exam room to ensure that physician time was spent in face-to-face direct patient care.^14-20 In these ways, we sought not only to increase patient satisfaction but also to enhance our own “joy in practice,” defined primarily by a high level of work-life satisfaction, a low level of burnout, and a feeling that the medical practice is fulfilling.²¹

In our traditional model, an MA retrieved the patient from the waiting room, conducted initial assessment in the exam room, and then left the patient to wait for the physician to enter. Once the physician entered and conducted the exam, the patient would be left alone again to wait for the MA to return. In our revised model (TABLE 1), we assigned one MA to each patient from arrival to discharge. After greeting the patient in the waiting room, the MA conducted an initial patient interview in the exam room, then remained in the room with the physician to document the visit. After the physician exited the exam room, the MA completed follow-up orders and provided the patient with a visit summary.

To facilitate consistency throughout the day, we designed a workflow similar to those created in lean models originally designed to increase efficiency in the manufacturing industry (TABLE 2). Visual and electronic cues triggered each step of the process and coordinated the movement of MAs and MDs. Cues included the conventional flag system outside each exam room, an electronic messaging system within the electronic health record (EHR) to indicate when a patient was ready to be seen, and a whiteboard in an area visible to all team members on which we wrote lab and radiology requests.

The TEAM model reduced wait time and increased staff interaction time with patients.

We experimented with the MA:MD ratio to identify the most effective and efficient team composition. On alternating weeks, we assigned one MA to one MD, 2 MAs to one MD, or 3 MAs to 2 MDs. Additionally, with the 2:1 MA:MD ratio, we varied the visit length in 2 tests; one spanning 30 minutes and the other 20 minutes. The MDs and MAs were seated at side-by-side workstations to make communication easier. We developed protocols and checklists that allowed MAs to enter health maintenance orders and conduct point-of-care testing before the physician entered the room. Such details included immunization management, strep screens, urine analyses, diabetic foot exams, extremity x-ray films, and mammogram and colonoscopy referrals.

Continue to: To prepare MAs...

To prepare MAs, we obtained special permission for team documentation from our Chief Information Officer and developed associated policies and procedures. A physician assistant (PA) trained each MA, introducing the structure and content of subjective, objective, assessment, and plan (SOAP) notes. Training was continuous, as PAs provided feedback when MAs began team documentation. The MAs documented visits using templates, free form, and quick text. We measured visit cycle-time, face time with staff, and patient waiting times. A process engineer with a stopwatch observed and timed the flow (but did not enter the exam room). We also conducted patient interviews immediately post-visit and administered anonymous questionnaires to clinic staff at different phases of the model. Physicians and MAs met weekly to evaluate the design.

We used qualitative interviews of patients, physicians, and MAs to identify the level of satisfaction with the new model. During the first week of implementation, a nurse and our process engineer conducted brief in-person surveys with approximately 20 post-visit patients. Patients, chosen by convenience, were asked if the visit addressed their concerns, whether they left with a thorough understanding of next steps, and if their wait time was acceptable. Twice during the implementation phase, a human resources associate distributed 9-item anonymous questionnaires to staff members during scheduled department meetings.

RESULTS

Times per activity with different MA:MD ratios and visit lengths are shown in TABLE 3. After 6 months, cycle time decreased by a mean of 6 minutes, from 44 to 38 minutes per patient; time with staff increased by a mean of 2 minutes, from 24 to 26 minutes per patient; and wait time decreased by a mean of 7 minutes, from 9 to 2 minutes per patient. We concluded the MA:MD ratio of 3:2 was most efficient because the 2:1 model left MAs with excess non-patient time.

Our delivery model received consistently positive comments from patients. Many expressed gratitude for the extra set of ears and eyes guiding them through the process. One recalled the “old days” when a nurse joined the doctor in the exam room. Another appreciated that both the MA and physician could answer follow-up questions over the phone.

Employee satisfaction

Surveys to assess satisfaction were distributed to all employees whether they were involved in the new model or not. Sixteen employees responded to the pre-implementation questionnaire and 18 responded to the post-implementation one distributed 7 months later. The questionnaires showed an increase in employee satisfaction scores from 3.70 to 3.89 on a 5-point Likert scale, with 5 ranking highest. “I am learning from [Dr. Milford] and understanding things more fully,” wrote one respondent. Another said, “Dr. Milford and his clinical support staff are less stressed.” Individual observations such as, “I can leave sooner with less work left to do,” and “All documentation is done before [the] patient leaves,” reflect the reduction in time that patient records remained open or incomplete. Some physicians reported a reduction in at-home or after-hours work, from about 2 to 4 hours per day to approximately one hour per day.

Continue to: Additional outcomes

The TEAM model allowed us to more easily integrate new initiatives into our practice and meet quality metrics by placing needed components within our workflow and checklist. For example, achieving Stage II Meaningful Use measures required that we print and furnish patients with a visit summary and a reminder to access our portal; something we easily incorporated into the MAs’ expanded responsibilities. We also met specific predetermined quality metrics that were part of a payment-withhold program. During the study period, we achieved scores at the 90th percentile and earned back our total withhold.

Finally, more of our patients completed advanced care planning discussions than the other 7 sites in our Honoring Choices Wisconsin cohort. This was achieved not only by integrating the process into our checklist, but because the MAs observed the MD-led patient conversations which they then emulated, presenting the advanced care planning information to patients before or after MD time with the patient.

Errors and defects in care

With ongoing provider guidance and reinforcement, MAs became integral members of the primary care team. They were empowered through protocols to manage and order health maintenance testing and provide needed immunizations. They also began to identify potentially overlooked aspects of care. For example, MAs prompted physicians to retake vital signs, adjust medications, order labs, discuss previous lab results, and pursue specialty referrals or follow-up care.

Billing

Although we tracked billing, the TEAM model was not designed to influence revenue. We noted no significant change in level of evaluation and management billed regardless of staffing ratio. While our panel size increased as we implemented the new process, this change could have been due to normal variation. We do see opportunity to affect future billing by having coders train MAs, which could enhance documentation and increase revenue.

DISCUSSION

The TEAM Primary Care model reduced the time our patients sat unattended, increased our opportunities to meaningfully interact with them, and seemed to reduce our administrative load. By identifying and implementing ways to work as a more cohesive, interconnected unit, we began to address our work as a team rather than as individuals. After implementing the model, we noted several instances where the MAs caught potential errors in care, although we did not consistently track or measure changes in the rate of these occurrences.

Continue to: Achieving these results also came with...

Achieving these results also came with challenges. Investing in and maintaining a new model opened our eyes to unforeseen inconsistencies in our staff profile and to the cost and administrative support needed for implementation. Moreover, our entire team (patients, MAs, and physicians) had to undergo a major cultural shift to adopt a new model.

Personnel variation

We discovered that implementing and sustaining organization change is highly dependent on constancy in human resources. When one team member was on vacation, sick, or leaving the practice, the process tended to fall apart. Hiring replacements and training employees well enough to fill in at a moment’s notice proved difficult. Bringing new employees into this process was also labor intensive. Despite team members being very engaged in change, these staffing inconsistencies caused significant stress and necessitated pauses in the implementation of the new model (reflected in the timeline of our measures). Larger organizational buy-in and support would allow us to hire and train a larger pool of MAs in anticipation of these fluctuations.

Cost

Our small, rural family practice took advantage of WRMC’s Primary Care Transformation project and the half-time process engineer and additional MA they provided. We question whether this model could be implemented without such support. While a process engineer might not prove necessary, expertise in process improvement is vital to help design and measure workflow and to identify opportunities for improvement.

Cultural change

Adopting a new model required asking every member of the team (patient, MA, and physician) to accommodate change and tolerate disruption. We anticipated patients might resist having an additional person in the room. All patients were informed of our new model at the beginning of the visit and told they could opt out. While we did not document patient resistance, JM recalled only 2 patients who expressed a desire not to have the MA present because of personal and sensitive issues. It’s possible some patients did not feel comfortable opting out. But many patients expressed gratitude for having an extra set of ears and eyes to guide them through the visit.

With the TEAM model, we noted several instances where the MAs caught potential errors in care.

It was more challenging to support MAs as they stepped out of their comfort zone to assist with documentation. It took time for MAs to grow accustomed to the protocols and checklists essential to our workflow. Without protocols, any point-of-care testing that could have been completed at the beginning of the appointment had to be done at the end. This disrupted our workflow and increased patient wait times.

Continue to: We correctly predicted MAs would have...

We correctly predicted MAs would have difficulty documenting the assessment, plan, and medical decision making. We discovered that MAs more easily categorized and articulated information when we reframed the assessment and plan in first-person and placed it under “Patient instructions.” For this to occur, physicians had to learn to accurately articulate their thought process and instructions to the patient.

When training was provided, as previously described, MAs grasped the subjective section quickly. Surprisingly, they had most difficulty understanding terminology within the objective section. In the future, we would avert this problem by working closely with the human resource department. We believe there should be a newly defined position and additional training for MAs in these roles, since duties such as patient-coaching and documentation assistance may warrant separate certification.

Limitations

Our findings should be interpreted in light of several limitations. Implementing the new model was carried out in a single organization. The patients who were selected and agreed to be interviewed may have differed from the patient population as a whole. We did not measure some important outcomes, such as cost effectiveness and patient morbidity. We did not analyze the data to determine whether the apparent improvements in wait time and cycle time were statistically significant. In addition, measurement of any adverse effects was beyond the scope of this study.

Looking forward

The traditional model of physicians working individually with minimal support staff is no longer viable. To echo our co-author (CAS)’s recent statements on physician dissatisfaction, “The days of hero medicine, with the doctor doing it all, belong in the past.”²¹ The new model appeared to alleviate some administrative burdens and increase physician time with patients. Pressures to achieve quality measures and growing administrative tasks have altered the role and responsibilities of each member of the team.

It's possible some patients might have felt uneasy with the TEAM approach, but many expressed gratitude for an extra set of ears and eyes to guide them through the visit.

Any sustainable system must address the larger crisis of physician dissatisfaction.^7,22 We cannot focus on a single perspective—patient, physician, or MA—at the expense of the system as a whole. If the health care system is to resolve the epidemic of burnout and physician dissatisfaction, new approaches to patient care must be imagined and realized. Although we faced many challenges in implementing and evaluating the TEAM model, attempts to overcome these challenges appear justified because of our overall favorable impression of it. Innovations like the TEAM Primary Care model may help us improve the well-being of not just our patients but also our health professionals and the health care industry as a whole.

CORRESPONDENCE
James Milford, MD, Three Oaks Health, S.C., 480 Village Walk Lane, Suite F, Johnson Creek, WI 53038; [email protected].

SUPPORT
Although the Watertown Regional Medical Center has provided general funding for its Primary Care Transformation project, no dollars were specifically earmarked for the TEAM Primary Care process. Support for editorial services in preparing this article was provided by Dr. James Milford.

PRIOR PRESENTATIONS
Co-author Michael R. Strasser, MPA, presented this project at the 2015 i-PrACTISE conference in Madison, Wis, April 12-14, 2015. http://www.fammed.wisc.edu/i-practise/. The proceedings were not published or recorded.

ACKNOWLEDGMENT
We thank Annalynn Skipper and Masarah Van Eyck for their valuable edits.