Katherine Grimsley, MD

History: losing his ‘drive’

Mr. D, age 49, has been treated for major depressive disorder for approximately 1 year but reports only occasional minor symptom improvement. At presentation, he had been irritable and lethargic for about 2 weeks and had increased appetite, decreased concentration, and trouble falling asleep at night.

A once-gregarious family man, Mr. D had become apathetic and too tired to enjoy socializing. He denied suicidal thoughts or feelings of worthlessness and hopelessness but feared his fatigue was interfering with his job as a truck driver. He tired after driving only a few hours.

Mr. D had been diagnosed with sleep apnea when he was younger but had no other medical history. He said his erratic work schedule kept him from using his continuous positive airway pressure (CPAP) machine regularly. He was taking no medications and had not seen a primary care physician for more than 2 years because of lack of coverage. He denied past or current substance abuse.

The patient weighed 280 lbs at intake. His body mass index (BMI) was 37.5, indicating clinical obesity.

Because Mr. D lacked health insurance, we enrolled him 1 year ago in a free depression study at a psychiatric outpatient clinic. At intake, he said numerous life stresses—particularly the recent death of his brother in a motor vehicle accident—had left him feeling depressed.

We started Mr. D on citalopram, 20 mg/d, which was the study protocol. Two weeks later, he complained of dry mouth and sedation with minimal symptom improvement. We stopped citalopram and started sertraline, 25 mg/d.

Two weeks later, Mr. D again complained he had “no energy” and was “sleeping all day.” We titrated sertraline to 200 mg/d over 2 months, but his excessive tiredness, increased appetite, and decreased motivation persisted. Mr. D needed routine laboratory tests, so we referred him to a local clinic that charges on a sliding scale. He did not complete the tests, however, for fear of incurring medical expenses.

We tried to improve Mr. D’s mood symptoms by adding lithium—225 mg/d titrated to 675 mg/d over 7 weeks—but his depression and fatigue kept worsening. We tapered him off lithium and sertraline and switched to the monoamine oxidase inhibitor tranylcypromine, 30 mg/d, which was also part of the study protocol. We warned him not to eat pizza, fermented dry sausages, or other foods that could interact adversely with tranylcypromine. After 4 weeks, Mr. D stopped taking the agent, saying he could not follow the dietary restrictions while on the road.

We released Mr. D from the study because of nonresponse. Bupropion, started at 100 mg bid and titrated to 300 mg each morning and 150 mg nightly across 5 months, did not resolve his fatigue. He also started having agitation and “anger problems,” often getting into shouting matches over his CBradio with other truck drivers. We started quetiapine, 25 mg bid, hoping the low dose would calm his mood.

Until now, Mr. D has ignored our requests to undergo routine laboratory testing. We referred him to the local clinic four times over the past year but he has not complied, citing lack of health insurance and financial concerns.

The authors’ observations

Although Mr. D’s symptoms (constantly depressed mood, loss of interest in usual activities) clearly suggest treatment-resistant major depressive disorder, an underlying medical disorder cannot be ruled out, yet he refuses to get needed tests.

Medical comorbidities are more prevalent in patients with mental illness than in the general population.¹ As many as 43% of patients referred to some psychiatry clinics have medical disorders, and almost one-half the diagnoses were missed by the referring physician.²

Compared to patients without psychiatric diagnoses, those with mental illness have more difficulty gaining access to medical care and are less likely to receive and follow guidelines for preventive care. Mental illness symptoms often compromise one’s ability to seek health care or follow a doctor’s orders. For example, a psychotic person may be overly suspicious of doctors, whereas someone with anxiety may seek care inappropriately.^3,4 Also, some studies estimate that 1 in 5 persons with mental illness are uninsured.^1,5,6

Mr. D denies substance abuse, but primary care and behavioral health clinicians often miss substance use disorders.⁷ Accuracy of substance abuse self-reports varies widely; some studies report high accuracy, whereas almost 33% of patients in other studies do not disclose substance abuse.⁸

Testing: stimulating findings

At his next visit, Mr. D reports worsening thirst and increased urination and complains of increased appetite, easy bruising, excessive sleepiness, and apathy. He also reveals that for 2 months he has been taking 2 to 3 fat-burning stimulant capsules a day to stay awake while driving.

 

Alarmed by his elevated blood pressure (177/99 mm Hg) and worsening physical symptoms, Mr. D finally consents to baseline laboratory testing. Blood glucose is 306 mg/dL (normal 70 to 110 mg/dL), and glycosylated hemoglobin is 12% (normal

Mr. D, who now weighs 270 lbs, is diagnosed as having hypertension and type 2 diabetes mellitus. Clinic doctors start him on metformin, 500 mg bid titrated to 1,000 mg bid, and glyburide, 5 mg/d, to control his glucose, and lisinopril, 10 mg/d, to control his hypertension, reduce cardiovascular risk, and preserve renal function. Clinicians also order Mr. D to follow an 1,800-calorie, American Diabetes Association-approved diet. We stop quetiapine and bupropion.

Mr. D’s diabetes and hypertension diagnosis, combined with his habitus and history of easy bruising, suggest Cushing’s syndrome. Doctors rule out this disorder based on a 24-hour free cortisol reading of 59 mg/L and normal dexamethasone suppression. Lab findings suggest he is not taking stimulants away from work.

The authors’ observations

Ideally, Mr. D should have undergone laboratory testing after the initial intake visit, before psychotropics were started. Routine vital signs also should have been taken.

Symptoms of major depressive disorder and early type 2 diabetes are strikingly similar (Table 1). For example, early diabetes symptoms such as fatigue can mimic depression or other medical problems. In one study of 69 diabetic patients who were referred by their primary care doctors to a psychiatric clinic, 57 had not been diagnosed as having diabetes before referral.⁹

Aside from its medical complications, diabetes also doubles the risk of comorbid depression, which can alter diabetes’ course and outcome.¹⁰

Earlier laboratory testing could have uncovered Mr. D’s comorbid stimulant abuse, which also can mimic depression and complicate its treatment.¹¹ Signs of amphetamine withdrawal—such as dysphoric mood, fatigue, insomnia or hypersomnia, increased appetite, and psychomotor retardation—can be mistaken for depression (Table 1).

Patients with Cushing’s syndrome may present with nonspecific complaints of fatigue, decreased energy, apathy, depressed mood, and hypersomnia. A 24-hour free cortisol reading and dexamethasone suppression testing can differentiate Cushing’s syndrome from depression.

Costly, unnecessary care. Missing a medical cause of apparent psychiatric symptoms can lead to unnecessary treatment and needless expense. A complete metabolic profile and urine drug screen—approximately $60—could have saved the nearly $5,000 spent on treating Mr. D’s “resistant” depression ( Table 2).

Psychiatrists need to watch for potential medical problems and for cormorbidities associated with mental illness. Patients with frequent mental distress—defined as ≥ 14 mentally unhealthy days within 30 days—were found to be more likely to smoke, drink heavily, and be physically inactive and obese than were mentally healthy persons. Mentally distressed patients also were more likely to lack health care coverage and to engage in multiple adverse behaviors, increasing their risk for mental and physical illness.¹²

Ensuring proper medical care. Based on our experience with Mr. D, routine vital signs—including BMI, weight, blood pressure, and pulse rate—should be recorded at each visit. At intake, we recommend that psychiatrists:

• find out when the patient last saw a primary health provider other than in the emergency room, and whether the patient is receiving preventive medical care
  
• assess for unhealthy lifestyle habits (smoking, drug use, poor diet) or family history of serious medical illnesses.
  

Mr. D, for example, had not received preventative care for at least 2 to 3 years and had obesity, a family history of diabetes, a sedentary lifestyle, and an unhealthy diet.

Educate patients about the interplay between physical and mental illness to help them understand the importance of seeing a primary care doctor. Finally, be familiar with local indigent health clinics and their fee scales.

Table 1

Medical symptoms that mimic depression

Symptom	Amphetamine withdrawal	Cushing’s syndrome	Diabetes
Anxiety		×
Dysphoric mood	×
Fatigue	×	×	×
Hypersomnia	×
Increased appetite	×		×
Insomnia	×
Irritability		×	×
Muscle aches and cramps			×
Psychomotor retardation	×
Vivid, unpleasant dreams	×
Weakness		×
Weight gain or loss			×

Table 2

The cost of treating Mr. D’s ‘resistant depression’

Medication/dosage	Start date	Stop date	Approximate cost
Citalopram, 20 mg/d	10/3/03	10/24/03	$58.50
Sertraline, 25 to 200 mg/d	10/24/03	12/24/03	$283.00
Sertraline 150 mg/d, with lithium, 225 to 675 mg/d	12/24/03	2/6/04	$343.00
Tranylcypromine, 10 mg each morning, 20 mg at bedtime	2/27/04	4/20/04	$322.00
Bupropion (sustained release) up to 450 mg/d	5/7/04	8/30/04	$372.00
Bupropion (sustained release), 450 mg/d, plus quetiapine, 25 mg/d	8/30/04	11/8/04	$554.00
Total cost of psychotropics			$1,932.50
Total cost of office visits ($95 X 30 visits)			$2,850.00
TOTAL COST OF TREATMENT			$4,782.50
Source: Walgreens Co. retail prices in Wichita, KS

Follow-up: 30 lbs in 4 months

Mr. D has lost >30 lbs over 4 months, and his blood pressure and serum glucose are normal. BMI is now 32, in the lower range of clinical obesity. He feels more energetic and active, no longer reports excessive sedation and apathy, and has stopped taking stimulants. His depressive symptoms have remitted.

 

Related resources

• WrongDiagnosis.com. Information on differential diagnosis of medical and psychiatric problems. www.wrongdiagnosis.com.
  
• Mauksch LB, Tucker SM, Katon WJ, et al. Mental illness, functional impairment, and patient preferences for collaborative care in an uninsured, primary care population. J Fam Pract 2001;50:41-7.
  
• Glied S, Little SE. The uninsured and the benefits of medical progress. Health Aff (Millwood) 2003;22:210-9.
  

Drug brand names

• Bupropion • Wellbutrin
  
• Citalopram • Celexa
  
• Dexamethasone • Ciprodex, others
  
• Glucophage • Metformin
  
• Glyburide • DiaBeta, others
  
• Lisinopril • Prinivil, Zestril
  
• Lithium • Eskalith, others
  
• Quetiapine • Seroquel
  
• Sertraline • Zoloft
  
• Tranylcypromine •Parnate
  

Disclosure

Dr. Khan is a speaker for Wyeth Pharmaceuticals.

Dr. Grimsley reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

History: losing his ‘drive’

Mr. D, age 49, has been treated for major depressive disorder for approximately 1 year but reports only occasional minor symptom improvement. At presentation, he had been irritable and lethargic for about 2 weeks and had increased appetite, decreased concentration, and trouble falling asleep at night.

A once-gregarious family man, Mr. D had become apathetic and too tired to enjoy socializing. He denied suicidal thoughts or feelings of worthlessness and hopelessness but feared his fatigue was interfering with his job as a truck driver. He tired after driving only a few hours.

Mr. D had been diagnosed with sleep apnea when he was younger but had no other medical history. He said his erratic work schedule kept him from using his continuous positive airway pressure (CPAP) machine regularly. He was taking no medications and had not seen a primary care physician for more than 2 years because of lack of coverage. He denied past or current substance abuse.

The patient weighed 280 lbs at intake. His body mass index (BMI) was 37.5, indicating clinical obesity.

Because Mr. D lacked health insurance, we enrolled him 1 year ago in a free depression study at a psychiatric outpatient clinic. At intake, he said numerous life stresses—particularly the recent death of his brother in a motor vehicle accident—had left him feeling depressed.

We started Mr. D on citalopram, 20 mg/d, which was the study protocol. Two weeks later, he complained of dry mouth and sedation with minimal symptom improvement. We stopped citalopram and started sertraline, 25 mg/d.

Two weeks later, Mr. D again complained he had “no energy” and was “sleeping all day.” We titrated sertraline to 200 mg/d over 2 months, but his excessive tiredness, increased appetite, and decreased motivation persisted. Mr. D needed routine laboratory tests, so we referred him to a local clinic that charges on a sliding scale. He did not complete the tests, however, for fear of incurring medical expenses.

We tried to improve Mr. D’s mood symptoms by adding lithium—225 mg/d titrated to 675 mg/d over 7 weeks—but his depression and fatigue kept worsening. We tapered him off lithium and sertraline and switched to the monoamine oxidase inhibitor tranylcypromine, 30 mg/d, which was also part of the study protocol. We warned him not to eat pizza, fermented dry sausages, or other foods that could interact adversely with tranylcypromine. After 4 weeks, Mr. D stopped taking the agent, saying he could not follow the dietary restrictions while on the road.

We released Mr. D from the study because of nonresponse. Bupropion, started at 100 mg bid and titrated to 300 mg each morning and 150 mg nightly across 5 months, did not resolve his fatigue. He also started having agitation and “anger problems,” often getting into shouting matches over his CBradio with other truck drivers. We started quetiapine, 25 mg bid, hoping the low dose would calm his mood.

Until now, Mr. D has ignored our requests to undergo routine laboratory testing. We referred him to the local clinic four times over the past year but he has not complied, citing lack of health insurance and financial concerns.

The authors’ observations

Although Mr. D’s symptoms (constantly depressed mood, loss of interest in usual activities) clearly suggest treatment-resistant major depressive disorder, an underlying medical disorder cannot be ruled out, yet he refuses to get needed tests.

Medical comorbidities are more prevalent in patients with mental illness than in the general population.¹ As many as 43% of patients referred to some psychiatry clinics have medical disorders, and almost one-half the diagnoses were missed by the referring physician.²

Compared to patients without psychiatric diagnoses, those with mental illness have more difficulty gaining access to medical care and are less likely to receive and follow guidelines for preventive care. Mental illness symptoms often compromise one’s ability to seek health care or follow a doctor’s orders. For example, a psychotic person may be overly suspicious of doctors, whereas someone with anxiety may seek care inappropriately.^3,4 Also, some studies estimate that 1 in 5 persons with mental illness are uninsured.^1,5,6

Mr. D denies substance abuse, but primary care and behavioral health clinicians often miss substance use disorders.⁷ Accuracy of substance abuse self-reports varies widely; some studies report high accuracy, whereas almost 33% of patients in other studies do not disclose substance abuse.⁸

Testing: stimulating findings

At his next visit, Mr. D reports worsening thirst and increased urination and complains of increased appetite, easy bruising, excessive sleepiness, and apathy. He also reveals that for 2 months he has been taking 2 to 3 fat-burning stimulant capsules a day to stay awake while driving.

 

Alarmed by his elevated blood pressure (177/99 mm Hg) and worsening physical symptoms, Mr. D finally consents to baseline laboratory testing. Blood glucose is 306 mg/dL (normal 70 to 110 mg/dL), and glycosylated hemoglobin is 12% (normal

Mr. D, who now weighs 270 lbs, is diagnosed as having hypertension and type 2 diabetes mellitus. Clinic doctors start him on metformin, 500 mg bid titrated to 1,000 mg bid, and glyburide, 5 mg/d, to control his glucose, and lisinopril, 10 mg/d, to control his hypertension, reduce cardiovascular risk, and preserve renal function. Clinicians also order Mr. D to follow an 1,800-calorie, American Diabetes Association-approved diet. We stop quetiapine and bupropion.

Mr. D’s diabetes and hypertension diagnosis, combined with his habitus and history of easy bruising, suggest Cushing’s syndrome. Doctors rule out this disorder based on a 24-hour free cortisol reading of 59 mg/L and normal dexamethasone suppression. Lab findings suggest he is not taking stimulants away from work.

The authors’ observations

Ideally, Mr. D should have undergone laboratory testing after the initial intake visit, before psychotropics were started. Routine vital signs also should have been taken.

Symptoms of major depressive disorder and early type 2 diabetes are strikingly similar (Table 1). For example, early diabetes symptoms such as fatigue can mimic depression or other medical problems. In one study of 69 diabetic patients who were referred by their primary care doctors to a psychiatric clinic, 57 had not been diagnosed as having diabetes before referral.⁹

Aside from its medical complications, diabetes also doubles the risk of comorbid depression, which can alter diabetes’ course and outcome.¹⁰

Earlier laboratory testing could have uncovered Mr. D’s comorbid stimulant abuse, which also can mimic depression and complicate its treatment.¹¹ Signs of amphetamine withdrawal—such as dysphoric mood, fatigue, insomnia or hypersomnia, increased appetite, and psychomotor retardation—can be mistaken for depression (Table 1).

Patients with Cushing’s syndrome may present with nonspecific complaints of fatigue, decreased energy, apathy, depressed mood, and hypersomnia. A 24-hour free cortisol reading and dexamethasone suppression testing can differentiate Cushing’s syndrome from depression.

Costly, unnecessary care. Missing a medical cause of apparent psychiatric symptoms can lead to unnecessary treatment and needless expense. A complete metabolic profile and urine drug screen—approximately $60—could have saved the nearly $5,000 spent on treating Mr. D’s “resistant” depression ( Table 2).

Psychiatrists need to watch for potential medical problems and for cormorbidities associated with mental illness. Patients with frequent mental distress—defined as ≥ 14 mentally unhealthy days within 30 days—were found to be more likely to smoke, drink heavily, and be physically inactive and obese than were mentally healthy persons. Mentally distressed patients also were more likely to lack health care coverage and to engage in multiple adverse behaviors, increasing their risk for mental and physical illness.¹²

Ensuring proper medical care. Based on our experience with Mr. D, routine vital signs—including BMI, weight, blood pressure, and pulse rate—should be recorded at each visit. At intake, we recommend that psychiatrists:

• find out when the patient last saw a primary health provider other than in the emergency room, and whether the patient is receiving preventive medical care
  
• assess for unhealthy lifestyle habits (smoking, drug use, poor diet) or family history of serious medical illnesses.
  

Mr. D, for example, had not received preventative care for at least 2 to 3 years and had obesity, a family history of diabetes, a sedentary lifestyle, and an unhealthy diet.

Educate patients about the interplay between physical and mental illness to help them understand the importance of seeing a primary care doctor. Finally, be familiar with local indigent health clinics and their fee scales.

Table 1

Medical symptoms that mimic depression

Symptom	Amphetamine withdrawal	Cushing’s syndrome	Diabetes
Anxiety		×
Dysphoric mood	×
Fatigue	×	×	×
Hypersomnia	×
Increased appetite	×		×
Insomnia	×
Irritability		×	×
Muscle aches and cramps			×
Psychomotor retardation	×
Vivid, unpleasant dreams	×
Weakness		×
Weight gain or loss			×

Table 2

The cost of treating Mr. D’s ‘resistant depression’

Medication/dosage	Start date	Stop date	Approximate cost
Citalopram, 20 mg/d	10/3/03	10/24/03	$58.50
Sertraline, 25 to 200 mg/d	10/24/03	12/24/03	$283.00
Sertraline 150 mg/d, with lithium, 225 to 675 mg/d	12/24/03	2/6/04	$343.00
Tranylcypromine, 10 mg each morning, 20 mg at bedtime	2/27/04	4/20/04	$322.00
Bupropion (sustained release) up to 450 mg/d	5/7/04	8/30/04	$372.00
Bupropion (sustained release), 450 mg/d, plus quetiapine, 25 mg/d	8/30/04	11/8/04	$554.00
Total cost of psychotropics			$1,932.50
Total cost of office visits ($95 X 30 visits)			$2,850.00
TOTAL COST OF TREATMENT			$4,782.50
Source: Walgreens Co. retail prices in Wichita, KS

Follow-up: 30 lbs in 4 months

Mr. D has lost >30 lbs over 4 months, and his blood pressure and serum glucose are normal. BMI is now 32, in the lower range of clinical obesity. He feels more energetic and active, no longer reports excessive sedation and apathy, and has stopped taking stimulants. His depressive symptoms have remitted.

 

Related resources

• WrongDiagnosis.com. Information on differential diagnosis of medical and psychiatric problems. www.wrongdiagnosis.com.
  
• Mauksch LB, Tucker SM, Katon WJ, et al. Mental illness, functional impairment, and patient preferences for collaborative care in an uninsured, primary care population. J Fam Pract 2001;50:41-7.
  
• Glied S, Little SE. The uninsured and the benefits of medical progress. Health Aff (Millwood) 2003;22:210-9.
  

Drug brand names

• Bupropion • Wellbutrin
  
• Citalopram • Celexa
  
• Dexamethasone • Ciprodex, others
  
• Glucophage • Metformin
  
• Glyburide • DiaBeta, others
  
• Lisinopril • Prinivil, Zestril
  
• Lithium • Eskalith, others
  
• Quetiapine • Seroquel
  
• Sertraline • Zoloft
  
• Tranylcypromine •Parnate
  

Disclosure

Dr. Khan is a speaker for Wyeth Pharmaceuticals.

Dr. Grimsley reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

History: losing his ‘drive’

Mr. D, age 49, has been treated for major depressive disorder for approximately 1 year but reports only occasional minor symptom improvement. At presentation, he had been irritable and lethargic for about 2 weeks and had increased appetite, decreased concentration, and trouble falling asleep at night.

A once-gregarious family man, Mr. D had become apathetic and too tired to enjoy socializing. He denied suicidal thoughts or feelings of worthlessness and hopelessness but feared his fatigue was interfering with his job as a truck driver. He tired after driving only a few hours.

Mr. D had been diagnosed with sleep apnea when he was younger but had no other medical history. He said his erratic work schedule kept him from using his continuous positive airway pressure (CPAP) machine regularly. He was taking no medications and had not seen a primary care physician for more than 2 years because of lack of coverage. He denied past or current substance abuse.

The patient weighed 280 lbs at intake. His body mass index (BMI) was 37.5, indicating clinical obesity.

Because Mr. D lacked health insurance, we enrolled him 1 year ago in a free depression study at a psychiatric outpatient clinic. At intake, he said numerous life stresses—particularly the recent death of his brother in a motor vehicle accident—had left him feeling depressed.

We started Mr. D on citalopram, 20 mg/d, which was the study protocol. Two weeks later, he complained of dry mouth and sedation with minimal symptom improvement. We stopped citalopram and started sertraline, 25 mg/d.

Two weeks later, Mr. D again complained he had “no energy” and was “sleeping all day.” We titrated sertraline to 200 mg/d over 2 months, but his excessive tiredness, increased appetite, and decreased motivation persisted. Mr. D needed routine laboratory tests, so we referred him to a local clinic that charges on a sliding scale. He did not complete the tests, however, for fear of incurring medical expenses.

We tried to improve Mr. D’s mood symptoms by adding lithium—225 mg/d titrated to 675 mg/d over 7 weeks—but his depression and fatigue kept worsening. We tapered him off lithium and sertraline and switched to the monoamine oxidase inhibitor tranylcypromine, 30 mg/d, which was also part of the study protocol. We warned him not to eat pizza, fermented dry sausages, or other foods that could interact adversely with tranylcypromine. After 4 weeks, Mr. D stopped taking the agent, saying he could not follow the dietary restrictions while on the road.

We released Mr. D from the study because of nonresponse. Bupropion, started at 100 mg bid and titrated to 300 mg each morning and 150 mg nightly across 5 months, did not resolve his fatigue. He also started having agitation and “anger problems,” often getting into shouting matches over his CBradio with other truck drivers. We started quetiapine, 25 mg bid, hoping the low dose would calm his mood.

Until now, Mr. D has ignored our requests to undergo routine laboratory testing. We referred him to the local clinic four times over the past year but he has not complied, citing lack of health insurance and financial concerns.

The authors’ observations

Although Mr. D’s symptoms (constantly depressed mood, loss of interest in usual activities) clearly suggest treatment-resistant major depressive disorder, an underlying medical disorder cannot be ruled out, yet he refuses to get needed tests.

Medical comorbidities are more prevalent in patients with mental illness than in the general population.¹ As many as 43% of patients referred to some psychiatry clinics have medical disorders, and almost one-half the diagnoses were missed by the referring physician.²

Compared to patients without psychiatric diagnoses, those with mental illness have more difficulty gaining access to medical care and are less likely to receive and follow guidelines for preventive care. Mental illness symptoms often compromise one’s ability to seek health care or follow a doctor’s orders. For example, a psychotic person may be overly suspicious of doctors, whereas someone with anxiety may seek care inappropriately.^3,4 Also, some studies estimate that 1 in 5 persons with mental illness are uninsured.^1,5,6

Mr. D denies substance abuse, but primary care and behavioral health clinicians often miss substance use disorders.⁷ Accuracy of substance abuse self-reports varies widely; some studies report high accuracy, whereas almost 33% of patients in other studies do not disclose substance abuse.⁸

Testing: stimulating findings

At his next visit, Mr. D reports worsening thirst and increased urination and complains of increased appetite, easy bruising, excessive sleepiness, and apathy. He also reveals that for 2 months he has been taking 2 to 3 fat-burning stimulant capsules a day to stay awake while driving.

 

Alarmed by his elevated blood pressure (177/99 mm Hg) and worsening physical symptoms, Mr. D finally consents to baseline laboratory testing. Blood glucose is 306 mg/dL (normal 70 to 110 mg/dL), and glycosylated hemoglobin is 12% (normal

Mr. D, who now weighs 270 lbs, is diagnosed as having hypertension and type 2 diabetes mellitus. Clinic doctors start him on metformin, 500 mg bid titrated to 1,000 mg bid, and glyburide, 5 mg/d, to control his glucose, and lisinopril, 10 mg/d, to control his hypertension, reduce cardiovascular risk, and preserve renal function. Clinicians also order Mr. D to follow an 1,800-calorie, American Diabetes Association-approved diet. We stop quetiapine and bupropion.

Mr. D’s diabetes and hypertension diagnosis, combined with his habitus and history of easy bruising, suggest Cushing’s syndrome. Doctors rule out this disorder based on a 24-hour free cortisol reading of 59 mg/L and normal dexamethasone suppression. Lab findings suggest he is not taking stimulants away from work.

The authors’ observations

Ideally, Mr. D should have undergone laboratory testing after the initial intake visit, before psychotropics were started. Routine vital signs also should have been taken.

Symptoms of major depressive disorder and early type 2 diabetes are strikingly similar (Table 1). For example, early diabetes symptoms such as fatigue can mimic depression or other medical problems. In one study of 69 diabetic patients who were referred by their primary care doctors to a psychiatric clinic, 57 had not been diagnosed as having diabetes before referral.⁹

Aside from its medical complications, diabetes also doubles the risk of comorbid depression, which can alter diabetes’ course and outcome.¹⁰

Earlier laboratory testing could have uncovered Mr. D’s comorbid stimulant abuse, which also can mimic depression and complicate its treatment.¹¹ Signs of amphetamine withdrawal—such as dysphoric mood, fatigue, insomnia or hypersomnia, increased appetite, and psychomotor retardation—can be mistaken for depression (Table 1).

Patients with Cushing’s syndrome may present with nonspecific complaints of fatigue, decreased energy, apathy, depressed mood, and hypersomnia. A 24-hour free cortisol reading and dexamethasone suppression testing can differentiate Cushing’s syndrome from depression.

Costly, unnecessary care. Missing a medical cause of apparent psychiatric symptoms can lead to unnecessary treatment and needless expense. A complete metabolic profile and urine drug screen—approximately $60—could have saved the nearly $5,000 spent on treating Mr. D’s “resistant” depression ( Table 2).

Psychiatrists need to watch for potential medical problems and for cormorbidities associated with mental illness. Patients with frequent mental distress—defined as ≥ 14 mentally unhealthy days within 30 days—were found to be more likely to smoke, drink heavily, and be physically inactive and obese than were mentally healthy persons. Mentally distressed patients also were more likely to lack health care coverage and to engage in multiple adverse behaviors, increasing their risk for mental and physical illness.¹²

Ensuring proper medical care. Based on our experience with Mr. D, routine vital signs—including BMI, weight, blood pressure, and pulse rate—should be recorded at each visit. At intake, we recommend that psychiatrists:

• find out when the patient last saw a primary health provider other than in the emergency room, and whether the patient is receiving preventive medical care
  
• assess for unhealthy lifestyle habits (smoking, drug use, poor diet) or family history of serious medical illnesses.
  

Mr. D, for example, had not received preventative care for at least 2 to 3 years and had obesity, a family history of diabetes, a sedentary lifestyle, and an unhealthy diet.

Educate patients about the interplay between physical and mental illness to help them understand the importance of seeing a primary care doctor. Finally, be familiar with local indigent health clinics and their fee scales.

Table 1

Medical symptoms that mimic depression

Symptom	Amphetamine withdrawal	Cushing’s syndrome	Diabetes
Anxiety		×
Dysphoric mood	×
Fatigue	×	×	×
Hypersomnia	×
Increased appetite	×		×
Insomnia	×
Irritability		×	×
Muscle aches and cramps			×
Psychomotor retardation	×
Vivid, unpleasant dreams	×
Weakness		×
Weight gain or loss			×

Table 2

The cost of treating Mr. D’s ‘resistant depression’

Medication/dosage	Start date	Stop date	Approximate cost
Citalopram, 20 mg/d	10/3/03	10/24/03	$58.50
Sertraline, 25 to 200 mg/d	10/24/03	12/24/03	$283.00
Sertraline 150 mg/d, with lithium, 225 to 675 mg/d	12/24/03	2/6/04	$343.00
Tranylcypromine, 10 mg each morning, 20 mg at bedtime	2/27/04	4/20/04	$322.00
Bupropion (sustained release) up to 450 mg/d	5/7/04	8/30/04	$372.00
Bupropion (sustained release), 450 mg/d, plus quetiapine, 25 mg/d	8/30/04	11/8/04	$554.00
Total cost of psychotropics			$1,932.50
Total cost of office visits ($95 X 30 visits)			$2,850.00
TOTAL COST OF TREATMENT			$4,782.50
Source: Walgreens Co. retail prices in Wichita, KS

Follow-up: 30 lbs in 4 months

Mr. D has lost >30 lbs over 4 months, and his blood pressure and serum glucose are normal. BMI is now 32, in the lower range of clinical obesity. He feels more energetic and active, no longer reports excessive sedation and apathy, and has stopped taking stimulants. His depressive symptoms have remitted.

 

Related resources

• WrongDiagnosis.com. Information on differential diagnosis of medical and psychiatric problems. www.wrongdiagnosis.com.
  
• Mauksch LB, Tucker SM, Katon WJ, et al. Mental illness, functional impairment, and patient preferences for collaborative care in an uninsured, primary care population. J Fam Pract 2001;50:41-7.
  
• Glied S, Little SE. The uninsured and the benefits of medical progress. Health Aff (Millwood) 2003;22:210-9.
  

Drug brand names

• Bupropion • Wellbutrin
  
• Citalopram • Celexa
  
• Dexamethasone • Ciprodex, others
  
• Glucophage • Metformin
  
• Glyburide • DiaBeta, others
  
• Lisinopril • Prinivil, Zestril
  
• Lithium • Eskalith, others
  
• Quetiapine • Seroquel
  
• Sertraline • Zoloft
  
• Tranylcypromine •Parnate
  

Disclosure

Dr. Khan is a speaker for Wyeth Pharmaceuticals.

Dr. Grimsley reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

HISTORY: LIFE AT HOME

For nearly 10 years Mr. P, age 50, has had episodes of shortness of breath, increasing perspiration, and faintness that occur 2 to 3 times a month, usually when he’s out of the house. Fearing his legs will give out in public, he never goes out except to shop with his wife.

Once a welder for an aircraft company, he has been unable to work for 6 years. He worries incessantly about his medical expenses, and smokes 1 pack of cigarettes per day to help control the anxiety.

Baseline laboratory tests reveal a low-density lipoprotein cholesterol level of 199 mg/dL, exceeding the optimal range by 100 mg/dL. Total cholesterol is 288 mg/dL and triglycerides are 244 mg/dL. Thyroid stimulating hormone, liver function, renal function, serum electrolytes, and serum glucose are normal. Mr. P meets DSM-IV-TR criteria for panic disorder with agoraphobia and is started on citalopram, 20 mg/d.

At follow-up 2 weeks later, Mr. P complains that the citalopram is causing ‘aches and pains’ in his back and legs, so we switch to controlled-release paroxetine, 12.5 mg/d, which we found in clinical practice to be more tolerable than immediate-release paroxetine. After 2 weeks, he says he cannot tolerate the paroxetine because of ‘body aches.’

At Mr. P’s insistence, we switch to alprazolam, 0.5 mg tid, although his desire to start taking alprazolam makes us suspect that he might be trying to obtain this benzodiazepine for illicit use.

Neuropsychological tests—including a diagnostic interview, Minnesota Multiphasic Personality Inventory, and Millon Clinical Multiaxial Inventory—are ordered after Mr. P’s third visit. He seems guarded when answering questions about himself during these interviews. He acknowledges having severe physical symptoms but appears unwilling to accept a psychiatric diagnosis for them.

The authors’ observations

Panic disorder is usually chronic and can cause considerable morbidity. DSM-IV-TR criteria for panic disorder include recurrent or unexpected panic attacks and persistent fear of additional attacks and their implications and consequences.¹ Panic disorder can also lead to social problems including unemployment, financial dependence, and substance abuse or dependence.²

Mr. P’s anxiety, shortness of breath, faintness, and profuse sweating during episodes match DSM-IV-TR criteria for panic attacks (Table 1). His ruminative and obsessive attitude toward his physical problems does not suggest somatoform disorder because he also thinks obsessively about other issues, such as his medical expenses.

We will watch for signs of prescription drug abuse, including premature requests for refills, use of multiple pharmacies, or complaints of lost prescription or medication.³

FURTHER HISTORY: FAINT MEMORY

Mr. P first sought medical help in 1996 after fainting at home while standing up. A few weeks later he experienced sudden dizziness, faintness, and perspiration while shopping with his wife. During that episode, he said, he barely made it out of the store before passing out in his truck. His wife described him as ‘pale and gray’ and rushed him to the emergency room. The ER physician suspected that Mr. P suffered a ‘convulsive episode’ and ordered testing. Results of awake and sleep EEG and head MRI were normal. Laboratory work revealed a positive antinuclear antibody (ANA) and rheumatoid factor (RF), suggesting pulmonary vasculitis.

Table 1

DSM-IV-TR criteria for panic attack

A discrete period of intense fear or discomfort, in which four (or more) of the following symptoms developed abruptly and reached a peak within 10 minutes: palpitations sweating trembling or shaking shortness of breath or smothering feeling of choking chest pain or discomfort nausea or abdominal distress feeling dizzy, unsteady, lightheaded, or faint derealization or depersonalization fear of losing control or going crazy fear of dying paresthesias chills or hot flushes

Source: Adapted and reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders (4th ed, text revision). Copyright 2000. American Psychiatric Association.

Mr. P, who was still working at the aircraft company, continued to seek medical opinions. He was diagnosed alternately as having chronic fatigue syndrome, fibromyalgia, and sleep apnea. He said a pulmonologist told him he had lung fibrosis but that the disorder would resolve without treatment. At one point, he was prescribed a continuous positive airway pressure device (CPAP) to manage what was thought to be sleep apnea.

Two years and 17 doctors later, Mr. P’s physical symptoms persisted. He stopped working and began collecting disability insurance benefits. Frustrated over the lack of a definitive diagnosis, he then went 6 years without seeing a doctor.

TREATMENT: INTENSE ‘PANIC’

Mr. P has been coming to our clinic for 8 months. He takes 0.5 mg of alprazolam twice daily—less frequently than prescribed—and has never prematurely requested a refill, so prescription abuse is ruled out. He joins a fibromyalgia support group but laments that his symptoms differ from those of other group members. During follow-up visits, he continues to focus on his somatic symptoms.

 

During a routine visit, Mr. P tells us that he recently suffered an intense ‘panic’ episode—consisting of shortness of breath, dizziness, diaphoresis, chest pain, palpitations, and near syncope—less than 15 minutes after he started clearing brush in his backyard. We notice marked clubbing on Mr. P’s fingers, a physical sign seen in congenital heart disease, infective endocarditis, pulmonary fibrosis, and numerous other diseases.⁴

The clubbing prompts us to ask about his occupational history in detail, as work-related exposure to chemicals or fumes may result in pulmonary fibrosis. We then learn that for approximately 20 years before joining the aircraft company, Mr. P welded without wearing protective equipment—all that time inhaling noxious fumes while working.

We refer Mr. P to an internist, who finds clubbing of the fingers, decreased breath sounds, and increased pulmonic second heart sound (P2) on auscultation. The internist then orders:

• ECG, which reveals right axis deviation, incomplete right bundle branch block, and right ventricular hypertrophy (RVH)
  
• Pulmonary function tests, which show decreased diffusing capacity. Subsequent heart catheterization reveals RVH and concentric left ventricular hypertrophy.
  

Mr. P is told to quit smoking and to use his CPAP nightly to minimize progression of his right ventricular dysfunction. He had been using his CPAP sporadically because he found it uncomfortable.

The authors’ observations

Panic attacks often mimic symptoms of cardiac or pulmonary disease. By the same token, symptoms of an underlying cardiac or pulmonary disease can be mistaken for panic disorder, particularly in patients whose past episodes appear to meet DSM-IV-TR panic attack criteria (Table 2).⁵

Table 2

Panic attack symptoms that may suggest a cardiopulmonary disease

Panic attack symptom	Possible cardiopulmonary disorder
Palpitations, chest discomfort, feeling faint	Cardiac arrhythmia
Breathlessness, fatigue, weakness	Heart failure
Weakness, nausea, diaphoresis, feelings of hot/cold associated with diaphoresis, paresthesias, lightheadedness, fear of dying	Cardiac or neurologic syncope
Intense, escalating chest pain/discomfort; may be accompanied by nausea, diaphoresis, dizziness, feelings of hot/cold associated with diaphoresis	Acute myocardial infarction
Shortness of breath, fatigue, weakness, feeling of choking	Pulmonary congestion*
* Because the lung parenchyma and visceral pleura lack pain fibers, pulmonary abnormalities related to these structures can be advanced before symptoms are noticed.
Source: reference 5

Patients with panic disorder seek medical help more frequently than do patients with other anxiety disorders.⁶ About one-third of patients with panic disorder seek psychiatric treatment, and almost as many seek medical help,⁶ possibly because of the complicated array of symptoms simultaneously involving cardiac and pulmonary systems.

To avoid unnecessary referrals, psychiatrists need to quickly and accurately discern:

• when a medical problem is causing the patient’s symptoms
  
• how far to carry the medical evaluation, particularly for patients with palpitations, chest pain, or shortness of breath.
  

No reliable screening tool exists for differentiating panic from cardiopulmonary symptoms. A screening inventory developed by Barsky et al⁷ for patients complaining of palpitations focuses on somatization and hypochondriacal attitudes, which are common among psychiatric patients. This tool, however, does not take into account presence of cardiac risk factors.

Also, a psychiatric patient whose mental disorder or comorbid axis II pathology compromises speech or cognitive function may have trouble communicating potentially serious medical problems to other clinicians. Mr. P’s guarded demeanor and obsession toward his physical problems may have kept him from accurately describing his symptoms in a clinical setting. Alternately, he might have misinterpreted his pulmonologist’s explanation of pulmonary fibrosis, thus believing the disorder was not serious.

Finally, patients with panic disorder are more aware of their heartbeats and physiologic responses than are persons without panic disorder,⁸ thus further complicating diagnosis.

UNCOVERING A MEDICAL CAUSE

Suspect an underlying heart or lung problem when panic symptoms affect breathing or resemble a heart attack.

Check for predisposing risk factors for cardiac disease. Ask the patient detailed questions about past and current medical problems, including:

• smoking
  
• hyperlipidemia
  
• diabetes
  
• heart problems
  
• pulmonary disease
  
• family history of any medical problems
  
• work-related exposure to any metal that may increase risk of cardiopulmonary disease.
  

Refer the patient for medical evaluation if any of the above risk factors are discovered.

Review medical treatment history. Mentally ill persons are more likely than those without a mental illness to receive inadequate general medical and preventative care.⁹ Patient, provider, and health care system issues—such as lack of insurance or the patient’s inability to recognize or describe symptoms—may impede medical care delivery to the mentally ill.⁹

Review overall history. A deeper look into Mr. P’s work and diagnostic history uncovered numerous possible causes of right heart failure, including:

• pulmonary fibrosis secondary to inhalational injury
  
• possible pulmonary vasculitis as indicated by his positive ANA and RF.
  

As time progressed, either of these underlying lung pathologies amid sleep apnea and smoking could have increased Mr. P’s cardiopulmonary risk.

 

FOLLOW-UP: A PANIC-FREE FUTURE

Over the next 4 weeks, Mr. P has stopped taking alprazolam and begins to understand that his episodes were secondary to cardiopulmonary dysfunction. No longer afraid of developing a panic attack, he is going out more often.

Mr. P recently told us that he started a part-time job, decreased his smoking to a half pack/day, and has a plan to quit smoking completely. He adds that he is using his CPAP machine regularly and has remained free of panic-like episodes. He limits physical exertion to avoid cardiopulmonary symptoms.

Related resources

• Raj A, Sheehan DV. Medical evaluation of panic attacks. J Clin Psychiatry 1987;48:309-13.
  
• Jones DR, Macias C, Barreira PJ, et al. Prevalence, severity, and co-occurrence of chronic physical health problems of persons with serious mental illness. Psychiatr Serv 2004;55:1250-7.
  

Drug brand names

• Alprazolam • Xanax
  
• Citalopram • Celexa
  
• Paroxetine • Paxil
  

Disclosure

Dr. Khan is a speaker for Wyeth Pharmaceuticals.

Dr. Grimsley reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

HISTORY: LIFE AT HOME

For nearly 10 years Mr. P, age 50, has had episodes of shortness of breath, increasing perspiration, and faintness that occur 2 to 3 times a month, usually when he’s out of the house. Fearing his legs will give out in public, he never goes out except to shop with his wife.

Once a welder for an aircraft company, he has been unable to work for 6 years. He worries incessantly about his medical expenses, and smokes 1 pack of cigarettes per day to help control the anxiety.

Baseline laboratory tests reveal a low-density lipoprotein cholesterol level of 199 mg/dL, exceeding the optimal range by 100 mg/dL. Total cholesterol is 288 mg/dL and triglycerides are 244 mg/dL. Thyroid stimulating hormone, liver function, renal function, serum electrolytes, and serum glucose are normal. Mr. P meets DSM-IV-TR criteria for panic disorder with agoraphobia and is started on citalopram, 20 mg/d.

At follow-up 2 weeks later, Mr. P complains that the citalopram is causing ‘aches and pains’ in his back and legs, so we switch to controlled-release paroxetine, 12.5 mg/d, which we found in clinical practice to be more tolerable than immediate-release paroxetine. After 2 weeks, he says he cannot tolerate the paroxetine because of ‘body aches.’

At Mr. P’s insistence, we switch to alprazolam, 0.5 mg tid, although his desire to start taking alprazolam makes us suspect that he might be trying to obtain this benzodiazepine for illicit use.

Neuropsychological tests—including a diagnostic interview, Minnesota Multiphasic Personality Inventory, and Millon Clinical Multiaxial Inventory—are ordered after Mr. P’s third visit. He seems guarded when answering questions about himself during these interviews. He acknowledges having severe physical symptoms but appears unwilling to accept a psychiatric diagnosis for them.

The authors’ observations

Panic disorder is usually chronic and can cause considerable morbidity. DSM-IV-TR criteria for panic disorder include recurrent or unexpected panic attacks and persistent fear of additional attacks and their implications and consequences.¹ Panic disorder can also lead to social problems including unemployment, financial dependence, and substance abuse or dependence.²

Mr. P’s anxiety, shortness of breath, faintness, and profuse sweating during episodes match DSM-IV-TR criteria for panic attacks (Table 1). His ruminative and obsessive attitude toward his physical problems does not suggest somatoform disorder because he also thinks obsessively about other issues, such as his medical expenses.

We will watch for signs of prescription drug abuse, including premature requests for refills, use of multiple pharmacies, or complaints of lost prescription or medication.³

FURTHER HISTORY: FAINT MEMORY

Mr. P first sought medical help in 1996 after fainting at home while standing up. A few weeks later he experienced sudden dizziness, faintness, and perspiration while shopping with his wife. During that episode, he said, he barely made it out of the store before passing out in his truck. His wife described him as ‘pale and gray’ and rushed him to the emergency room. The ER physician suspected that Mr. P suffered a ‘convulsive episode’ and ordered testing. Results of awake and sleep EEG and head MRI were normal. Laboratory work revealed a positive antinuclear antibody (ANA) and rheumatoid factor (RF), suggesting pulmonary vasculitis.

Table 1

DSM-IV-TR criteria for panic attack

A discrete period of intense fear or discomfort, in which four (or more) of the following symptoms developed abruptly and reached a peak within 10 minutes: palpitations sweating trembling or shaking shortness of breath or smothering feeling of choking chest pain or discomfort nausea or abdominal distress feeling dizzy, unsteady, lightheaded, or faint derealization or depersonalization fear of losing control or going crazy fear of dying paresthesias chills or hot flushes

Source: Adapted and reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders (4th ed, text revision). Copyright 2000. American Psychiatric Association.

Mr. P, who was still working at the aircraft company, continued to seek medical opinions. He was diagnosed alternately as having chronic fatigue syndrome, fibromyalgia, and sleep apnea. He said a pulmonologist told him he had lung fibrosis but that the disorder would resolve without treatment. At one point, he was prescribed a continuous positive airway pressure device (CPAP) to manage what was thought to be sleep apnea.

Two years and 17 doctors later, Mr. P’s physical symptoms persisted. He stopped working and began collecting disability insurance benefits. Frustrated over the lack of a definitive diagnosis, he then went 6 years without seeing a doctor.

TREATMENT: INTENSE ‘PANIC’

Mr. P has been coming to our clinic for 8 months. He takes 0.5 mg of alprazolam twice daily—less frequently than prescribed—and has never prematurely requested a refill, so prescription abuse is ruled out. He joins a fibromyalgia support group but laments that his symptoms differ from those of other group members. During follow-up visits, he continues to focus on his somatic symptoms.

 

During a routine visit, Mr. P tells us that he recently suffered an intense ‘panic’ episode—consisting of shortness of breath, dizziness, diaphoresis, chest pain, palpitations, and near syncope—less than 15 minutes after he started clearing brush in his backyard. We notice marked clubbing on Mr. P’s fingers, a physical sign seen in congenital heart disease, infective endocarditis, pulmonary fibrosis, and numerous other diseases.⁴

The clubbing prompts us to ask about his occupational history in detail, as work-related exposure to chemicals or fumes may result in pulmonary fibrosis. We then learn that for approximately 20 years before joining the aircraft company, Mr. P welded without wearing protective equipment—all that time inhaling noxious fumes while working.

We refer Mr. P to an internist, who finds clubbing of the fingers, decreased breath sounds, and increased pulmonic second heart sound (P2) on auscultation. The internist then orders:

• ECG, which reveals right axis deviation, incomplete right bundle branch block, and right ventricular hypertrophy (RVH)
  
• Pulmonary function tests, which show decreased diffusing capacity. Subsequent heart catheterization reveals RVH and concentric left ventricular hypertrophy.
  

Mr. P is told to quit smoking and to use his CPAP nightly to minimize progression of his right ventricular dysfunction. He had been using his CPAP sporadically because he found it uncomfortable.

The authors’ observations

Panic attacks often mimic symptoms of cardiac or pulmonary disease. By the same token, symptoms of an underlying cardiac or pulmonary disease can be mistaken for panic disorder, particularly in patients whose past episodes appear to meet DSM-IV-TR panic attack criteria (Table 2).⁵

Table 2

Panic attack symptoms that may suggest a cardiopulmonary disease

Panic attack symptom	Possible cardiopulmonary disorder
Palpitations, chest discomfort, feeling faint	Cardiac arrhythmia
Breathlessness, fatigue, weakness	Heart failure
Weakness, nausea, diaphoresis, feelings of hot/cold associated with diaphoresis, paresthesias, lightheadedness, fear of dying	Cardiac or neurologic syncope
Intense, escalating chest pain/discomfort; may be accompanied by nausea, diaphoresis, dizziness, feelings of hot/cold associated with diaphoresis	Acute myocardial infarction
Shortness of breath, fatigue, weakness, feeling of choking	Pulmonary congestion*
* Because the lung parenchyma and visceral pleura lack pain fibers, pulmonary abnormalities related to these structures can be advanced before symptoms are noticed.
Source: reference 5

Patients with panic disorder seek medical help more frequently than do patients with other anxiety disorders.⁶ About one-third of patients with panic disorder seek psychiatric treatment, and almost as many seek medical help,⁶ possibly because of the complicated array of symptoms simultaneously involving cardiac and pulmonary systems.

To avoid unnecessary referrals, psychiatrists need to quickly and accurately discern:

• when a medical problem is causing the patient’s symptoms
  
• how far to carry the medical evaluation, particularly for patients with palpitations, chest pain, or shortness of breath.
  

No reliable screening tool exists for differentiating panic from cardiopulmonary symptoms. A screening inventory developed by Barsky et al⁷ for patients complaining of palpitations focuses on somatization and hypochondriacal attitudes, which are common among psychiatric patients. This tool, however, does not take into account presence of cardiac risk factors.

Also, a psychiatric patient whose mental disorder or comorbid axis II pathology compromises speech or cognitive function may have trouble communicating potentially serious medical problems to other clinicians. Mr. P’s guarded demeanor and obsession toward his physical problems may have kept him from accurately describing his symptoms in a clinical setting. Alternately, he might have misinterpreted his pulmonologist’s explanation of pulmonary fibrosis, thus believing the disorder was not serious.

Finally, patients with panic disorder are more aware of their heartbeats and physiologic responses than are persons without panic disorder,⁸ thus further complicating diagnosis.

UNCOVERING A MEDICAL CAUSE

Suspect an underlying heart or lung problem when panic symptoms affect breathing or resemble a heart attack.

Check for predisposing risk factors for cardiac disease. Ask the patient detailed questions about past and current medical problems, including:

• smoking
  
• hyperlipidemia
  
• diabetes
  
• heart problems
  
• pulmonary disease
  
• family history of any medical problems
  
• work-related exposure to any metal that may increase risk of cardiopulmonary disease.
  

Refer the patient for medical evaluation if any of the above risk factors are discovered.

Review medical treatment history. Mentally ill persons are more likely than those without a mental illness to receive inadequate general medical and preventative care.⁹ Patient, provider, and health care system issues—such as lack of insurance or the patient’s inability to recognize or describe symptoms—may impede medical care delivery to the mentally ill.⁹

Review overall history. A deeper look into Mr. P’s work and diagnostic history uncovered numerous possible causes of right heart failure, including:

• pulmonary fibrosis secondary to inhalational injury
  
• possible pulmonary vasculitis as indicated by his positive ANA and RF.
  

As time progressed, either of these underlying lung pathologies amid sleep apnea and smoking could have increased Mr. P’s cardiopulmonary risk.

 

FOLLOW-UP: A PANIC-FREE FUTURE

Over the next 4 weeks, Mr. P has stopped taking alprazolam and begins to understand that his episodes were secondary to cardiopulmonary dysfunction. No longer afraid of developing a panic attack, he is going out more often.

Mr. P recently told us that he started a part-time job, decreased his smoking to a half pack/day, and has a plan to quit smoking completely. He adds that he is using his CPAP machine regularly and has remained free of panic-like episodes. He limits physical exertion to avoid cardiopulmonary symptoms.

Related resources

• Raj A, Sheehan DV. Medical evaluation of panic attacks. J Clin Psychiatry 1987;48:309-13.
  
• Jones DR, Macias C, Barreira PJ, et al. Prevalence, severity, and co-occurrence of chronic physical health problems of persons with serious mental illness. Psychiatr Serv 2004;55:1250-7.
  

Drug brand names

• Alprazolam • Xanax
  
• Citalopram • Celexa
  
• Paroxetine • Paxil
  

Disclosure

Dr. Khan is a speaker for Wyeth Pharmaceuticals.

Dr. Grimsley reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

HISTORY: LIFE AT HOME

For nearly 10 years Mr. P, age 50, has had episodes of shortness of breath, increasing perspiration, and faintness that occur 2 to 3 times a month, usually when he’s out of the house. Fearing his legs will give out in public, he never goes out except to shop with his wife.

Once a welder for an aircraft company, he has been unable to work for 6 years. He worries incessantly about his medical expenses, and smokes 1 pack of cigarettes per day to help control the anxiety.

Baseline laboratory tests reveal a low-density lipoprotein cholesterol level of 199 mg/dL, exceeding the optimal range by 100 mg/dL. Total cholesterol is 288 mg/dL and triglycerides are 244 mg/dL. Thyroid stimulating hormone, liver function, renal function, serum electrolytes, and serum glucose are normal. Mr. P meets DSM-IV-TR criteria for panic disorder with agoraphobia and is started on citalopram, 20 mg/d.

At follow-up 2 weeks later, Mr. P complains that the citalopram is causing ‘aches and pains’ in his back and legs, so we switch to controlled-release paroxetine, 12.5 mg/d, which we found in clinical practice to be more tolerable than immediate-release paroxetine. After 2 weeks, he says he cannot tolerate the paroxetine because of ‘body aches.’

At Mr. P’s insistence, we switch to alprazolam, 0.5 mg tid, although his desire to start taking alprazolam makes us suspect that he might be trying to obtain this benzodiazepine for illicit use.

Neuropsychological tests—including a diagnostic interview, Minnesota Multiphasic Personality Inventory, and Millon Clinical Multiaxial Inventory—are ordered after Mr. P’s third visit. He seems guarded when answering questions about himself during these interviews. He acknowledges having severe physical symptoms but appears unwilling to accept a psychiatric diagnosis for them.

The authors’ observations

Panic disorder is usually chronic and can cause considerable morbidity. DSM-IV-TR criteria for panic disorder include recurrent or unexpected panic attacks and persistent fear of additional attacks and their implications and consequences.¹ Panic disorder can also lead to social problems including unemployment, financial dependence, and substance abuse or dependence.²

Mr. P’s anxiety, shortness of breath, faintness, and profuse sweating during episodes match DSM-IV-TR criteria for panic attacks (Table 1). His ruminative and obsessive attitude toward his physical problems does not suggest somatoform disorder because he also thinks obsessively about other issues, such as his medical expenses.

We will watch for signs of prescription drug abuse, including premature requests for refills, use of multiple pharmacies, or complaints of lost prescription or medication.³

FURTHER HISTORY: FAINT MEMORY

Mr. P first sought medical help in 1996 after fainting at home while standing up. A few weeks later he experienced sudden dizziness, faintness, and perspiration while shopping with his wife. During that episode, he said, he barely made it out of the store before passing out in his truck. His wife described him as ‘pale and gray’ and rushed him to the emergency room. The ER physician suspected that Mr. P suffered a ‘convulsive episode’ and ordered testing. Results of awake and sleep EEG and head MRI were normal. Laboratory work revealed a positive antinuclear antibody (ANA) and rheumatoid factor (RF), suggesting pulmonary vasculitis.

Table 1

DSM-IV-TR criteria for panic attack

A discrete period of intense fear or discomfort, in which four (or more) of the following symptoms developed abruptly and reached a peak within 10 minutes: palpitations sweating trembling or shaking shortness of breath or smothering feeling of choking chest pain or discomfort nausea or abdominal distress feeling dizzy, unsteady, lightheaded, or faint derealization or depersonalization fear of losing control or going crazy fear of dying paresthesias chills or hot flushes

Source: Adapted and reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders (4th ed, text revision). Copyright 2000. American Psychiatric Association.

Mr. P, who was still working at the aircraft company, continued to seek medical opinions. He was diagnosed alternately as having chronic fatigue syndrome, fibromyalgia, and sleep apnea. He said a pulmonologist told him he had lung fibrosis but that the disorder would resolve without treatment. At one point, he was prescribed a continuous positive airway pressure device (CPAP) to manage what was thought to be sleep apnea.

Two years and 17 doctors later, Mr. P’s physical symptoms persisted. He stopped working and began collecting disability insurance benefits. Frustrated over the lack of a definitive diagnosis, he then went 6 years without seeing a doctor.

TREATMENT: INTENSE ‘PANIC’

Mr. P has been coming to our clinic for 8 months. He takes 0.5 mg of alprazolam twice daily—less frequently than prescribed—and has never prematurely requested a refill, so prescription abuse is ruled out. He joins a fibromyalgia support group but laments that his symptoms differ from those of other group members. During follow-up visits, he continues to focus on his somatic symptoms.

 

During a routine visit, Mr. P tells us that he recently suffered an intense ‘panic’ episode—consisting of shortness of breath, dizziness, diaphoresis, chest pain, palpitations, and near syncope—less than 15 minutes after he started clearing brush in his backyard. We notice marked clubbing on Mr. P’s fingers, a physical sign seen in congenital heart disease, infective endocarditis, pulmonary fibrosis, and numerous other diseases.⁴

The clubbing prompts us to ask about his occupational history in detail, as work-related exposure to chemicals or fumes may result in pulmonary fibrosis. We then learn that for approximately 20 years before joining the aircraft company, Mr. P welded without wearing protective equipment—all that time inhaling noxious fumes while working.

We refer Mr. P to an internist, who finds clubbing of the fingers, decreased breath sounds, and increased pulmonic second heart sound (P2) on auscultation. The internist then orders:

• ECG, which reveals right axis deviation, incomplete right bundle branch block, and right ventricular hypertrophy (RVH)
  
• Pulmonary function tests, which show decreased diffusing capacity. Subsequent heart catheterization reveals RVH and concentric left ventricular hypertrophy.
  

Mr. P is told to quit smoking and to use his CPAP nightly to minimize progression of his right ventricular dysfunction. He had been using his CPAP sporadically because he found it uncomfortable.

The authors’ observations

Panic attacks often mimic symptoms of cardiac or pulmonary disease. By the same token, symptoms of an underlying cardiac or pulmonary disease can be mistaken for panic disorder, particularly in patients whose past episodes appear to meet DSM-IV-TR panic attack criteria (Table 2).⁵

Table 2

Panic attack symptoms that may suggest a cardiopulmonary disease

Panic attack symptom	Possible cardiopulmonary disorder
Palpitations, chest discomfort, feeling faint	Cardiac arrhythmia
Breathlessness, fatigue, weakness	Heart failure
Weakness, nausea, diaphoresis, feelings of hot/cold associated with diaphoresis, paresthesias, lightheadedness, fear of dying	Cardiac or neurologic syncope
Intense, escalating chest pain/discomfort; may be accompanied by nausea, diaphoresis, dizziness, feelings of hot/cold associated with diaphoresis	Acute myocardial infarction
Shortness of breath, fatigue, weakness, feeling of choking	Pulmonary congestion*
* Because the lung parenchyma and visceral pleura lack pain fibers, pulmonary abnormalities related to these structures can be advanced before symptoms are noticed.
Source: reference 5

Patients with panic disorder seek medical help more frequently than do patients with other anxiety disorders.⁶ About one-third of patients with panic disorder seek psychiatric treatment, and almost as many seek medical help,⁶ possibly because of the complicated array of symptoms simultaneously involving cardiac and pulmonary systems.

To avoid unnecessary referrals, psychiatrists need to quickly and accurately discern:

• when a medical problem is causing the patient’s symptoms
  
• how far to carry the medical evaluation, particularly for patients with palpitations, chest pain, or shortness of breath.
  

No reliable screening tool exists for differentiating panic from cardiopulmonary symptoms. A screening inventory developed by Barsky et al⁷ for patients complaining of palpitations focuses on somatization and hypochondriacal attitudes, which are common among psychiatric patients. This tool, however, does not take into account presence of cardiac risk factors.

Also, a psychiatric patient whose mental disorder or comorbid axis II pathology compromises speech or cognitive function may have trouble communicating potentially serious medical problems to other clinicians. Mr. P’s guarded demeanor and obsession toward his physical problems may have kept him from accurately describing his symptoms in a clinical setting. Alternately, he might have misinterpreted his pulmonologist’s explanation of pulmonary fibrosis, thus believing the disorder was not serious.

Finally, patients with panic disorder are more aware of their heartbeats and physiologic responses than are persons without panic disorder,⁸ thus further complicating diagnosis.

UNCOVERING A MEDICAL CAUSE

Suspect an underlying heart or lung problem when panic symptoms affect breathing or resemble a heart attack.

Check for predisposing risk factors for cardiac disease. Ask the patient detailed questions about past and current medical problems, including:

• smoking
  
• hyperlipidemia
  
• diabetes
  
• heart problems
  
• pulmonary disease
  
• family history of any medical problems
  
• work-related exposure to any metal that may increase risk of cardiopulmonary disease.
  

Refer the patient for medical evaluation if any of the above risk factors are discovered.

Review medical treatment history. Mentally ill persons are more likely than those without a mental illness to receive inadequate general medical and preventative care.⁹ Patient, provider, and health care system issues—such as lack of insurance or the patient’s inability to recognize or describe symptoms—may impede medical care delivery to the mentally ill.⁹

Review overall history. A deeper look into Mr. P’s work and diagnostic history uncovered numerous possible causes of right heart failure, including:

• pulmonary fibrosis secondary to inhalational injury
  
• possible pulmonary vasculitis as indicated by his positive ANA and RF.
  

As time progressed, either of these underlying lung pathologies amid sleep apnea and smoking could have increased Mr. P’s cardiopulmonary risk.

 

FOLLOW-UP: A PANIC-FREE FUTURE

Over the next 4 weeks, Mr. P has stopped taking alprazolam and begins to understand that his episodes were secondary to cardiopulmonary dysfunction. No longer afraid of developing a panic attack, he is going out more often.

Mr. P recently told us that he started a part-time job, decreased his smoking to a half pack/day, and has a plan to quit smoking completely. He adds that he is using his CPAP machine regularly and has remained free of panic-like episodes. He limits physical exertion to avoid cardiopulmonary symptoms.

Related resources

• Raj A, Sheehan DV. Medical evaluation of panic attacks. J Clin Psychiatry 1987;48:309-13.
  
• Jones DR, Macias C, Barreira PJ, et al. Prevalence, severity, and co-occurrence of chronic physical health problems of persons with serious mental illness. Psychiatr Serv 2004;55:1250-7.
  

Drug brand names

• Alprazolam • Xanax
  
• Citalopram • Celexa
  
• Paroxetine • Paxil
  

Disclosure

Dr. Khan is a speaker for Wyeth Pharmaceuticals.

Dr. Grimsley reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.