Current Psychiatry

Most of the research and diagnostic and treatment guidance regarding bipolar disorder focuses on depression (“Controversies in bipolar disorder: Trust evidence or experience?” Current Psychiatry). Why is there not more focus on the mania, which can be as debilitating and lethal as depression? What therapeutic guidance is there for bipolar patients in whom mania is the predominant state and who no longer want to live with minds that are bombarded day and night with inescapable, racing thoughts?

Jeannette Smith
Canadian Agency for Drugs and Technologies in Health
Ottawa, Ontario, Canada

Drs. Miller and Noel respond

We agree that manic episodes can be debilitating for the patient. Marital strife, job loss, legal problems, financial extravagance, sexual indiscretion, and embarrassment are some potential adverse consequences of untreated mania.

However, it is uncommon to see patients in whom mania is the predominant state. While classical elated mania rarely is seen in clinical practice, patients with bipolar depression often describe concurrent manic symptoms such as racing thoughts without fully meeting DSMIV-TR criteria for a mixed state. The therapeutic guidance we offer for such patients is to begin with a mood stabilizer (eg, divalproex) and an atypical antipsychotic (eg, aripiprazole), to assess thyroid status and supplement if necessary, and—as a last resort if these measures fail to achieve stability for the patient—to start an anti-depressant (eg, sertraline) at a low dose.

Unlike bipolar depression with or without manic features, mania is relatively easy to treat and responds to virtually every antipsychotic—both old and new—most mood stabilizers, benzodiazepines and, in olden days, barbiturates.

In their prospective natural history studies of bipolar I and II patients, Judd et al^1,2 found that depression—not mania or hypomania—is the predominant feature of bipolar disorder. Treatment of bipolar depression presents the greatest challenge to clinicians and is the subject of the controversy about use of antidepressants discussed in our article.

Gary E. Miller, MD
Clinical professor of psychiatry

Richard L. Noel, MD
Assistant clinical professor of psychiatry
University of Texas Health Science Center
Houston, TX

Most of the research and diagnostic and treatment guidance regarding bipolar disorder focuses on depression (“Controversies in bipolar disorder: Trust evidence or experience?” Current Psychiatry). Why is there not more focus on the mania, which can be as debilitating and lethal as depression? What therapeutic guidance is there for bipolar patients in whom mania is the predominant state and who no longer want to live with minds that are bombarded day and night with inescapable, racing thoughts?

Jeannette Smith
Canadian Agency for Drugs and Technologies in Health
Ottawa, Ontario, Canada

Drs. Miller and Noel respond

We agree that manic episodes can be debilitating for the patient. Marital strife, job loss, legal problems, financial extravagance, sexual indiscretion, and embarrassment are some potential adverse consequences of untreated mania.

However, it is uncommon to see patients in whom mania is the predominant state. While classical elated mania rarely is seen in clinical practice, patients with bipolar depression often describe concurrent manic symptoms such as racing thoughts without fully meeting DSMIV-TR criteria for a mixed state. The therapeutic guidance we offer for such patients is to begin with a mood stabilizer (eg, divalproex) and an atypical antipsychotic (eg, aripiprazole), to assess thyroid status and supplement if necessary, and—as a last resort if these measures fail to achieve stability for the patient—to start an anti-depressant (eg, sertraline) at a low dose.

Unlike bipolar depression with or without manic features, mania is relatively easy to treat and responds to virtually every antipsychotic—both old and new—most mood stabilizers, benzodiazepines and, in olden days, barbiturates.

In their prospective natural history studies of bipolar I and II patients, Judd et al^1,2 found that depression—not mania or hypomania—is the predominant feature of bipolar disorder. Treatment of bipolar depression presents the greatest challenge to clinicians and is the subject of the controversy about use of antidepressants discussed in our article.

Gary E. Miller, MD
Clinical professor of psychiatry

Richard L. Noel, MD
Assistant clinical professor of psychiatry
University of Texas Health Science Center
Houston, TX

Most of the research and diagnostic and treatment guidance regarding bipolar disorder focuses on depression (“Controversies in bipolar disorder: Trust evidence or experience?” Current Psychiatry). Why is there not more focus on the mania, which can be as debilitating and lethal as depression? What therapeutic guidance is there for bipolar patients in whom mania is the predominant state and who no longer want to live with minds that are bombarded day and night with inescapable, racing thoughts?

Jeannette Smith
Canadian Agency for Drugs and Technologies in Health
Ottawa, Ontario, Canada

Drs. Miller and Noel respond

We agree that manic episodes can be debilitating for the patient. Marital strife, job loss, legal problems, financial extravagance, sexual indiscretion, and embarrassment are some potential adverse consequences of untreated mania.

However, it is uncommon to see patients in whom mania is the predominant state. While classical elated mania rarely is seen in clinical practice, patients with bipolar depression often describe concurrent manic symptoms such as racing thoughts without fully meeting DSMIV-TR criteria for a mixed state. The therapeutic guidance we offer for such patients is to begin with a mood stabilizer (eg, divalproex) and an atypical antipsychotic (eg, aripiprazole), to assess thyroid status and supplement if necessary, and—as a last resort if these measures fail to achieve stability for the patient—to start an anti-depressant (eg, sertraline) at a low dose.

Unlike bipolar depression with or without manic features, mania is relatively easy to treat and responds to virtually every antipsychotic—both old and new—most mood stabilizers, benzodiazepines and, in olden days, barbiturates.

In their prospective natural history studies of bipolar I and II patients, Judd et al^1,2 found that depression—not mania or hypomania—is the predominant feature of bipolar disorder. Treatment of bipolar depression presents the greatest challenge to clinicians and is the subject of the controversy about use of antidepressants discussed in our article.

Gary E. Miller, MD
Clinical professor of psychiatry

Richard L. Noel, MD
Assistant clinical professor of psychiatry
University of Texas Health Science Center
Houston, TX

Although any attention to the intersubjective realm is welcome in a time dominated by a biological model, it was disappointing to read Drs. Muskin and Epstein’s “classic Freudian” approach to countertransference (“Clinical guide to countertransference” Current Psychiatry).

For at least 50 years, modern clinical theory has observed and incorporated the simple fact that the physician-patient interaction always involves 2 minds, with unconscious elements. Our ability to decipher the unconscious communication—often captured in what could be mistaken for distracted thoughts as well as intense emotional reactions—is what distinguishes clinicians from their patients.

Most clinicians—unlike consultation-liaison psychiatrists who have focused on this interpersonal domain—have come to accept the fact that the distinction between “the patient’s stuff” and “our stuff” is tricky to maintain. We always are working through our own internal world; it is always an interaction. Perhaps this article and audio was aimed at nonpsychiatric physicians and therefore was made more accessible and formulaic. Hopefully, in the future, a more sophisticated discussion can be offered.

Sara Hartley, MD
Clinical faculty
University of California School of Public Health
Berkeley, CA

Drs. Muskin and Epstein respond

We thank Drs. Hartley and McFadden and Ms. Sawicki for their comments regarding our article on countertransference. In the limited space, we could not cover all of the areas germane to the topic. Our approach permits consideration of what is transference and what is countertransference, particularly in the general hospital environment.

The directionality of the “stuff” Dr. Hartley mentions is important because some reactions to patients occur in the absence of any transference originating from the patient. This is unique to the nonpsychiatric environment but may play an important role in shaping the care of the patient. We are sorry that she is disappointed in our approach, as it is one that stands the test of time in its utility.

Philip R. Muskin, MD
Professor of clinical psychiatry

Lucy A. Epstein, MD
Postdoctoral clinical fellow in psychosomatic medicine
Columbia University
College of Physicians and Surgeons
New York, NY

Although any attention to the intersubjective realm is welcome in a time dominated by a biological model, it was disappointing to read Drs. Muskin and Epstein’s “classic Freudian” approach to countertransference (“Clinical guide to countertransference” Current Psychiatry).

For at least 50 years, modern clinical theory has observed and incorporated the simple fact that the physician-patient interaction always involves 2 minds, with unconscious elements. Our ability to decipher the unconscious communication—often captured in what could be mistaken for distracted thoughts as well as intense emotional reactions—is what distinguishes clinicians from their patients.

Most clinicians—unlike consultation-liaison psychiatrists who have focused on this interpersonal domain—have come to accept the fact that the distinction between “the patient’s stuff” and “our stuff” is tricky to maintain. We always are working through our own internal world; it is always an interaction. Perhaps this article and audio was aimed at nonpsychiatric physicians and therefore was made more accessible and formulaic. Hopefully, in the future, a more sophisticated discussion can be offered.

Sara Hartley, MD
Clinical faculty
University of California School of Public Health
Berkeley, CA

Drs. Muskin and Epstein respond

We thank Drs. Hartley and McFadden and Ms. Sawicki for their comments regarding our article on countertransference. In the limited space, we could not cover all of the areas germane to the topic. Our approach permits consideration of what is transference and what is countertransference, particularly in the general hospital environment.

The directionality of the “stuff” Dr. Hartley mentions is important because some reactions to patients occur in the absence of any transference originating from the patient. This is unique to the nonpsychiatric environment but may play an important role in shaping the care of the patient. We are sorry that she is disappointed in our approach, as it is one that stands the test of time in its utility.

Philip R. Muskin, MD
Professor of clinical psychiatry

Lucy A. Epstein, MD
Postdoctoral clinical fellow in psychosomatic medicine
Columbia University
College of Physicians and Surgeons
New York, NY

Although any attention to the intersubjective realm is welcome in a time dominated by a biological model, it was disappointing to read Drs. Muskin and Epstein’s “classic Freudian” approach to countertransference (“Clinical guide to countertransference” Current Psychiatry).

For at least 50 years, modern clinical theory has observed and incorporated the simple fact that the physician-patient interaction always involves 2 minds, with unconscious elements. Our ability to decipher the unconscious communication—often captured in what could be mistaken for distracted thoughts as well as intense emotional reactions—is what distinguishes clinicians from their patients.

Most clinicians—unlike consultation-liaison psychiatrists who have focused on this interpersonal domain—have come to accept the fact that the distinction between “the patient’s stuff” and “our stuff” is tricky to maintain. We always are working through our own internal world; it is always an interaction. Perhaps this article and audio was aimed at nonpsychiatric physicians and therefore was made more accessible and formulaic. Hopefully, in the future, a more sophisticated discussion can be offered.

Sara Hartley, MD
Clinical faculty
University of California School of Public Health
Berkeley, CA

Drs. Muskin and Epstein respond

We thank Drs. Hartley and McFadden and Ms. Sawicki for their comments regarding our article on countertransference. In the limited space, we could not cover all of the areas germane to the topic. Our approach permits consideration of what is transference and what is countertransference, particularly in the general hospital environment.

The directionality of the “stuff” Dr. Hartley mentions is important because some reactions to patients occur in the absence of any transference originating from the patient. This is unique to the nonpsychiatric environment but may play an important role in shaping the care of the patient. We are sorry that she is disappointed in our approach, as it is one that stands the test of time in its utility.

Philip R. Muskin, MD
Professor of clinical psychiatry

Lucy A. Epstein, MD
Postdoctoral clinical fellow in psychosomatic medicine
Columbia University
College of Physicians and Surgeons
New York, NY

Drs. Muskin and Epstein bring much needed attention to the clinical usefulness of countertransference and to the challenges psychiatrists face in helping medical colleagues and staff deal with their reactions to “difficult” patients (“Clinical guide to countertransference,” Current Psychiatry). Their article, however, fails to recognize categories of reactions to patients other than countertransference, nor does it offer any systematic approach for preparing medical professionals to deal thoughtfully with their reactions to difficult patients.

For instance, projective identification is given mention only as a potential problem in working with borderline personality disorder patients. Furthermore, no specific mention is given to the range of reactions that would be considered justifiable and would not require additional reflection and analysis.

At Jefferson Medical College in Philadelphia, PA, we have developed a didactic conference entitled “Difficult patients and our reactions to them,” taught to third-year medical students during their psychiatry clerkship. The conference distinguishes among types of reactions students may have to patients, including justified reactions, projective identification reactions,¹ and countertransference reactions. A key point emphasized to students is that not all of their reactions to patients are dictated by their subconscious.

Drs. Muskin and Epstein’s article provides an initial road map for acting as a consultant to other medical professionals’ problematic reactions. Our hope is to take the next step and expose future physicians in a range of specialties to a method of thinking through their reactions to difficult patients.

Robert F. McFadden, MD
Instructor
Department of Psychiatry and Human Behavior

Alexandra H. Sawicki
Medical student
Jefferson Medical College
Philadelphia, PA

Drs. Muskin and Epstein bring much needed attention to the clinical usefulness of countertransference and to the challenges psychiatrists face in helping medical colleagues and staff deal with their reactions to “difficult” patients (“Clinical guide to countertransference,” Current Psychiatry). Their article, however, fails to recognize categories of reactions to patients other than countertransference, nor does it offer any systematic approach for preparing medical professionals to deal thoughtfully with their reactions to difficult patients.

For instance, projective identification is given mention only as a potential problem in working with borderline personality disorder patients. Furthermore, no specific mention is given to the range of reactions that would be considered justifiable and would not require additional reflection and analysis.

At Jefferson Medical College in Philadelphia, PA, we have developed a didactic conference entitled “Difficult patients and our reactions to them,” taught to third-year medical students during their psychiatry clerkship. The conference distinguishes among types of reactions students may have to patients, including justified reactions, projective identification reactions,¹ and countertransference reactions. A key point emphasized to students is that not all of their reactions to patients are dictated by their subconscious.

Drs. Muskin and Epstein’s article provides an initial road map for acting as a consultant to other medical professionals’ problematic reactions. Our hope is to take the next step and expose future physicians in a range of specialties to a method of thinking through their reactions to difficult patients.

Robert F. McFadden, MD
Instructor
Department of Psychiatry and Human Behavior

Alexandra H. Sawicki
Medical student
Jefferson Medical College
Philadelphia, PA

Drs. Muskin and Epstein bring much needed attention to the clinical usefulness of countertransference and to the challenges psychiatrists face in helping medical colleagues and staff deal with their reactions to “difficult” patients (“Clinical guide to countertransference,” Current Psychiatry). Their article, however, fails to recognize categories of reactions to patients other than countertransference, nor does it offer any systematic approach for preparing medical professionals to deal thoughtfully with their reactions to difficult patients.

For instance, projective identification is given mention only as a potential problem in working with borderline personality disorder patients. Furthermore, no specific mention is given to the range of reactions that would be considered justifiable and would not require additional reflection and analysis.

At Jefferson Medical College in Philadelphia, PA, we have developed a didactic conference entitled “Difficult patients and our reactions to them,” taught to third-year medical students during their psychiatry clerkship. The conference distinguishes among types of reactions students may have to patients, including justified reactions, projective identification reactions,¹ and countertransference reactions. A key point emphasized to students is that not all of their reactions to patients are dictated by their subconscious.

Drs. Muskin and Epstein’s article provides an initial road map for acting as a consultant to other medical professionals’ problematic reactions. Our hope is to take the next step and expose future physicians in a range of specialties to a method of thinking through their reactions to difficult patients.

Robert F. McFadden, MD
Instructor
Department of Psychiatry and Human Behavior

Alexandra H. Sawicki
Medical student
Jefferson Medical College
Philadelphia, PA

Diagnostic criteria for schizophrenia emphasize positive and negative symptoms at the expense of other domains, such as cognition or affective states. For a comprehensive, cross-sectional diagnostic assessment, I suggest looking for 6 symptom clusters—motor symptoms, disorganization, delusions and hallucinations, negative symptoms, cognitive symptoms, and affective symptoms—when treating patients with psychotic disorders.

Depicting these 6 symptom clusters graphically—in your mind or on paper—allows you to appreciate your patient’s problems and target interventions appropriately. View the diagram of a sample schizophrenia patient’s symptom clusters. A graph drawn on a blackboard or a piece of paper also is a good tool to educate patients and their friends, families, and caregivers about key aspects of schizophrenia beyond psychosis.

1 Motor symptoms

Note symptoms associated with antipsychotics (ie, iatrogenic morbidity), such as the restlessness with akathisia, tremor and bradykinesia with pseudoparkinsonism, and irregular abnormal movements with tardive dyskinesia. Consider catatonia if you see paucity of movement or peculiar motor behaviors.

2 Disorganization

Note speech, thinking, appearance, and behaviors that suggest disorganization. Symptoms in this cluster often make patients look “psychiatric.”

3 Delusions and hallucinations

For some patients with schizophrenia, symptoms in this cluster prevent treatment engagement (such as impairing paranoia) or pose a risk to the patient or the community (such as command hallucinations). Delusions and hallucinations often remit or are functionally irrelevant in patients who are treated successfully.

4 Negative symptoms

This symptom cluster, often associated with functional impairment, includes the 2 observable symptoms of blunted affect and alogia.

5 Cognitive symptoms

Executive dysfunction and verbal memory impairment also are associated with functional impairment but may not be apparent during the clinical encounter. To screen for typical problems in this cluster, I include tests of verbal fluency and word list recall during the interview.

6 Affective symptoms

Depression, anxiety, demoralization, and suicidality can affect your patient’s quality of life. Also look on the opposite pole for maniform or “mania-like” presentations, such as lack of inhibition, excitability, and irritability.

Diagnostic criteria for schizophrenia emphasize positive and negative symptoms at the expense of other domains, such as cognition or affective states. For a comprehensive, cross-sectional diagnostic assessment, I suggest looking for 6 symptom clusters—motor symptoms, disorganization, delusions and hallucinations, negative symptoms, cognitive symptoms, and affective symptoms—when treating patients with psychotic disorders.

Depicting these 6 symptom clusters graphically—in your mind or on paper—allows you to appreciate your patient’s problems and target interventions appropriately. View the diagram of a sample schizophrenia patient’s symptom clusters. A graph drawn on a blackboard or a piece of paper also is a good tool to educate patients and their friends, families, and caregivers about key aspects of schizophrenia beyond psychosis.

1 Motor symptoms

Note symptoms associated with antipsychotics (ie, iatrogenic morbidity), such as the restlessness with akathisia, tremor and bradykinesia with pseudoparkinsonism, and irregular abnormal movements with tardive dyskinesia. Consider catatonia if you see paucity of movement or peculiar motor behaviors.

2 Disorganization

Note speech, thinking, appearance, and behaviors that suggest disorganization. Symptoms in this cluster often make patients look “psychiatric.”

3 Delusions and hallucinations

For some patients with schizophrenia, symptoms in this cluster prevent treatment engagement (such as impairing paranoia) or pose a risk to the patient or the community (such as command hallucinations). Delusions and hallucinations often remit or are functionally irrelevant in patients who are treated successfully.

4 Negative symptoms

This symptom cluster, often associated with functional impairment, includes the 2 observable symptoms of blunted affect and alogia.

5 Cognitive symptoms

Executive dysfunction and verbal memory impairment also are associated with functional impairment but may not be apparent during the clinical encounter. To screen for typical problems in this cluster, I include tests of verbal fluency and word list recall during the interview.

6 Affective symptoms

Depression, anxiety, demoralization, and suicidality can affect your patient’s quality of life. Also look on the opposite pole for maniform or “mania-like” presentations, such as lack of inhibition, excitability, and irritability.

Diagnostic criteria for schizophrenia emphasize positive and negative symptoms at the expense of other domains, such as cognition or affective states. For a comprehensive, cross-sectional diagnostic assessment, I suggest looking for 6 symptom clusters—motor symptoms, disorganization, delusions and hallucinations, negative symptoms, cognitive symptoms, and affective symptoms—when treating patients with psychotic disorders.

Depicting these 6 symptom clusters graphically—in your mind or on paper—allows you to appreciate your patient’s problems and target interventions appropriately. View the diagram of a sample schizophrenia patient’s symptom clusters. A graph drawn on a blackboard or a piece of paper also is a good tool to educate patients and their friends, families, and caregivers about key aspects of schizophrenia beyond psychosis.

1 Motor symptoms

Note symptoms associated with antipsychotics (ie, iatrogenic morbidity), such as the restlessness with akathisia, tremor and bradykinesia with pseudoparkinsonism, and irregular abnormal movements with tardive dyskinesia. Consider catatonia if you see paucity of movement or peculiar motor behaviors.

2 Disorganization

Note speech, thinking, appearance, and behaviors that suggest disorganization. Symptoms in this cluster often make patients look “psychiatric.”

3 Delusions and hallucinations

For some patients with schizophrenia, symptoms in this cluster prevent treatment engagement (such as impairing paranoia) or pose a risk to the patient or the community (such as command hallucinations). Delusions and hallucinations often remit or are functionally irrelevant in patients who are treated successfully.

4 Negative symptoms

This symptom cluster, often associated with functional impairment, includes the 2 observable symptoms of blunted affect and alogia.

5 Cognitive symptoms

Executive dysfunction and verbal memory impairment also are associated with functional impairment but may not be apparent during the clinical encounter. To screen for typical problems in this cluster, I include tests of verbal fluency and word list recall during the interview.

6 Affective symptoms

Depression, anxiety, demoralization, and suicidality can affect your patient’s quality of life. Also look on the opposite pole for maniform or “mania-like” presentations, such as lack of inhibition, excitability, and irritability.

Discussants: Sarah K. Rivelli, MD, and Andrew J. Muzyk, PharmD

Dr. Rivelli is associate program director, internal medicine-psychiatry residency, departments of internal medicine and psychiatry, and Dr. Muzyk is a clinical pharmacist, Duke University Medical Center, Durham, NC.

Principal Source: Richards JB, Papaioannou A, Adachi JD, et al, and the Canadian Multicentre Osteoporosis Study Research Group. Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch Intern Med. 2007;167(2):188-194.

An increased risk of developing osteoporosis may be a hazard of some psychiatric medications and disorders. Osteoporosis is common among postmenopausal women, and additional risk factors for women and men include certain psychiatric disorders (anorexia nervosa and alcohol abuse) and medications such as lithium and some anticonvulsants. In addition:

• Tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) are associated with decreased bone mineral density and increased risk of hip fractures.^1,2
• A population-based prospective cohort study found that community-dwelling adults age ≥50 who took SSRIs had double the risk of incident fragility fractures over 5 years,¹ although corticosteroid and anticonvulsant use was more common among those taking SSRIs compared with controls and may have contributed to the higher risk.
• Some studies have suggested that depression may be associated with bone loss.³

Osteoporosis is diagnosed by the presence of a low-impact fracture, a spontaneous fracture—also called fragility fracture—or by decreased bone mineral density testing measured by dual x-ray absorptiometry (DXA) of the lumbar spine and proximal femur.⁴ Bone mineral density measured by DXA that is ≥2.5 standard deviations below the young adult female reference mean—called a T-score ≤-2.5—is consistent with a osteoporosis diagnosis. Blood tests are not necessary for diagnosis but may detect abnormal calcium or phosphorus metabolism related to comorbid disorders.

The U.S. Preventive Services Task Force recommends osteoporosis screening for all women age ≥65 and women age <65 who have risk factors for fracture (Table 1).⁵ There is no consensus on when to screen men, although all adults with a fragility fracture should undergo bone mineral density testing.

Consider screening men and women age >65 if secondary causes of osteoporosis—such as hypogonadism, hyperparathyroidism, hyperthyroidism, Cushing’s syndrome, inflammatory bowel disease, inflammatory arthritis, and hematologic cancers—are present.⁴

Table 1

Osteoporosis risk factors*

Prevention. A diet rich in calcium and vitamin D is essential for healthy bone growth.⁴ Daily requirements increase with age and are highest among adults age >50 (Table 2).⁶ Because the typical U.S. diet has poor calcium content, most adults and children will need calcium supplementation to meet daily requirements. Additional healthy bone lifestyle measures include avoiding caffeine and limiting alcohol consumption to <2 drinks/day.

Physical activity reduces the risk of falls and fractures by increasing muscle strength, coordination, and mobility. Weight-bearing exercise delays osteoporosis onset by promoting strong bone development. When possible, avoid prescribing medications that increase the risk of falls, such as sedative-hypnotics, benzodiazepines, and anticholinergics, or cause bone loss, such as phenytoin, glucocorticoids, and phenobarbital.

Table 2

Daily calcium and vitamin D requirements for adults by age

Treatment. First-line pharmacologic treatment of osteoporosis includes calcium plus vitamin D and a bisphosphonate.⁶

Calcium plus vitamin D increases calcium absorption and has been shown to significantly reduce fracture risk. Calcium typically is prescribed in a carbonate or citrate formulation.

• Calcium carbonate must be taken with meals because it requires an acidic environment for absorption.
• Calcium citrate may cause fewer gastrointestinal side effects, such as constipation.

Because one-time calcium absorption is limited to <600 mg, multiple daily dosing is required. The National Osteoporosis Foundation recommends >800 IU of vitamin D daily to reduce fracture risk in patients age >50 and in those with osteoporosis.⁷

Bisphosphonates have been shown to reduce fracture risk and increase bone mineral density, primarily in the spine and hip and sometimes within 6 months. Once-weekly alendronate and once-monthly risedronate and oral ibandronate are FDA-approved for prevention and treatment of osteoporosis in postmenopausal women. Quarterly ibandronate and once-yearly zoledronic acid injections are approved for osteoporosis treatment. Alendronate and risedronate also are approved to treat osteoporosis caused by glucocorticoid therapy and in men.

Although bisphosphonates do not cause adverse psychiatric effects or interactions with psychotropic medications, bisphosphonates must be taken at least 30 minutes before any other medications. Adverse effects from oral bisphosphonates often are gastrointestinal—such as nausea, heartburn, pain, irritation, and ulceration—and patients should take these medications with only a glass of water and remain upright for at least 30 minutes after ingestion.

Other therapeutic options include teriparatide—a synthetic form of parathyroid hormone injected daily—calcitonin, and raloxifene. Estrogen therapy increases bone density in postmenopausal women but is not recommended for routine use because of increased risk of stroke, thromboembolism, heart disease, and breast cancer.

Related resources

• World Health Organization Fracture Risk Assessment tool. www.shef.ac.uk/FRAX.
• National Osteoporosis Foundation. www.nof.org.

Drug brand names

• Alendronate • Fosamax
• Calcitonin • Miacalcin
• Ibandronate • Boniva
• Lithium • various
• Phenobarbital • various
• Phenytoin • Dilantin
• Prednisone • Deltasone, Meticorten
• Raloxifene • Evista
• Risedronate • Actonel
• Teriparatide • Forteo
• Valproic acid • Depakene
• Zoledronic acid • Reclast

Disclosure

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

Discussants: Sarah K. Rivelli, MD, and Andrew J. Muzyk, PharmD

Dr. Rivelli is associate program director, internal medicine-psychiatry residency, departments of internal medicine and psychiatry, and Dr. Muzyk is a clinical pharmacist, Duke University Medical Center, Durham, NC.

Principal Source: Richards JB, Papaioannou A, Adachi JD, et al, and the Canadian Multicentre Osteoporosis Study Research Group. Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch Intern Med. 2007;167(2):188-194.

An increased risk of developing osteoporosis may be a hazard of some psychiatric medications and disorders. Osteoporosis is common among postmenopausal women, and additional risk factors for women and men include certain psychiatric disorders (anorexia nervosa and alcohol abuse) and medications such as lithium and some anticonvulsants. In addition:

• Tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) are associated with decreased bone mineral density and increased risk of hip fractures.^1,2
• A population-based prospective cohort study found that community-dwelling adults age ≥50 who took SSRIs had double the risk of incident fragility fractures over 5 years,¹ although corticosteroid and anticonvulsant use was more common among those taking SSRIs compared with controls and may have contributed to the higher risk.
• Some studies have suggested that depression may be associated with bone loss.³

Osteoporosis is diagnosed by the presence of a low-impact fracture, a spontaneous fracture—also called fragility fracture—or by decreased bone mineral density testing measured by dual x-ray absorptiometry (DXA) of the lumbar spine and proximal femur.⁴ Bone mineral density measured by DXA that is ≥2.5 standard deviations below the young adult female reference mean—called a T-score ≤-2.5—is consistent with a osteoporosis diagnosis. Blood tests are not necessary for diagnosis but may detect abnormal calcium or phosphorus metabolism related to comorbid disorders.

The U.S. Preventive Services Task Force recommends osteoporosis screening for all women age ≥65 and women age <65 who have risk factors for fracture (Table 1).⁵ There is no consensus on when to screen men, although all adults with a fragility fracture should undergo bone mineral density testing.

Consider screening men and women age >65 if secondary causes of osteoporosis—such as hypogonadism, hyperparathyroidism, hyperthyroidism, Cushing’s syndrome, inflammatory bowel disease, inflammatory arthritis, and hematologic cancers—are present.⁴

Table 1

Osteoporosis risk factors*

Prevention. A diet rich in calcium and vitamin D is essential for healthy bone growth.⁴ Daily requirements increase with age and are highest among adults age >50 (Table 2).⁶ Because the typical U.S. diet has poor calcium content, most adults and children will need calcium supplementation to meet daily requirements. Additional healthy bone lifestyle measures include avoiding caffeine and limiting alcohol consumption to <2 drinks/day.

Physical activity reduces the risk of falls and fractures by increasing muscle strength, coordination, and mobility. Weight-bearing exercise delays osteoporosis onset by promoting strong bone development. When possible, avoid prescribing medications that increase the risk of falls, such as sedative-hypnotics, benzodiazepines, and anticholinergics, or cause bone loss, such as phenytoin, glucocorticoids, and phenobarbital.

Table 2

Daily calcium and vitamin D requirements for adults by age

Treatment. First-line pharmacologic treatment of osteoporosis includes calcium plus vitamin D and a bisphosphonate.⁶

Calcium plus vitamin D increases calcium absorption and has been shown to significantly reduce fracture risk. Calcium typically is prescribed in a carbonate or citrate formulation.

• Calcium carbonate must be taken with meals because it requires an acidic environment for absorption.
• Calcium citrate may cause fewer gastrointestinal side effects, such as constipation.

Because one-time calcium absorption is limited to <600 mg, multiple daily dosing is required. The National Osteoporosis Foundation recommends >800 IU of vitamin D daily to reduce fracture risk in patients age >50 and in those with osteoporosis.⁷

Bisphosphonates have been shown to reduce fracture risk and increase bone mineral density, primarily in the spine and hip and sometimes within 6 months. Once-weekly alendronate and once-monthly risedronate and oral ibandronate are FDA-approved for prevention and treatment of osteoporosis in postmenopausal women. Quarterly ibandronate and once-yearly zoledronic acid injections are approved for osteoporosis treatment. Alendronate and risedronate also are approved to treat osteoporosis caused by glucocorticoid therapy and in men.

Although bisphosphonates do not cause adverse psychiatric effects or interactions with psychotropic medications, bisphosphonates must be taken at least 30 minutes before any other medications. Adverse effects from oral bisphosphonates often are gastrointestinal—such as nausea, heartburn, pain, irritation, and ulceration—and patients should take these medications with only a glass of water and remain upright for at least 30 minutes after ingestion.

Other therapeutic options include teriparatide—a synthetic form of parathyroid hormone injected daily—calcitonin, and raloxifene. Estrogen therapy increases bone density in postmenopausal women but is not recommended for routine use because of increased risk of stroke, thromboembolism, heart disease, and breast cancer.

Related resources

• World Health Organization Fracture Risk Assessment tool. www.shef.ac.uk/FRAX.
• National Osteoporosis Foundation. www.nof.org.

Drug brand names

• Alendronate • Fosamax
• Calcitonin • Miacalcin
• Ibandronate • Boniva
• Lithium • various
• Phenobarbital • various
• Phenytoin • Dilantin
• Prednisone • Deltasone, Meticorten
• Raloxifene • Evista
• Risedronate • Actonel
• Teriparatide • Forteo
• Valproic acid • Depakene
• Zoledronic acid • Reclast

Disclosure

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

Discussants: Sarah K. Rivelli, MD, and Andrew J. Muzyk, PharmD

Dr. Rivelli is associate program director, internal medicine-psychiatry residency, departments of internal medicine and psychiatry, and Dr. Muzyk is a clinical pharmacist, Duke University Medical Center, Durham, NC.

Principal Source: Richards JB, Papaioannou A, Adachi JD, et al, and the Canadian Multicentre Osteoporosis Study Research Group. Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch Intern Med. 2007;167(2):188-194.

An increased risk of developing osteoporosis may be a hazard of some psychiatric medications and disorders. Osteoporosis is common among postmenopausal women, and additional risk factors for women and men include certain psychiatric disorders (anorexia nervosa and alcohol abuse) and medications such as lithium and some anticonvulsants. In addition:

• Tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) are associated with decreased bone mineral density and increased risk of hip fractures.^1,2
• A population-based prospective cohort study found that community-dwelling adults age ≥50 who took SSRIs had double the risk of incident fragility fractures over 5 years,¹ although corticosteroid and anticonvulsant use was more common among those taking SSRIs compared with controls and may have contributed to the higher risk.
• Some studies have suggested that depression may be associated with bone loss.³

Osteoporosis is diagnosed by the presence of a low-impact fracture, a spontaneous fracture—also called fragility fracture—or by decreased bone mineral density testing measured by dual x-ray absorptiometry (DXA) of the lumbar spine and proximal femur.⁴ Bone mineral density measured by DXA that is ≥2.5 standard deviations below the young adult female reference mean—called a T-score ≤-2.5—is consistent with a osteoporosis diagnosis. Blood tests are not necessary for diagnosis but may detect abnormal calcium or phosphorus metabolism related to comorbid disorders.

The U.S. Preventive Services Task Force recommends osteoporosis screening for all women age ≥65 and women age <65 who have risk factors for fracture (Table 1).⁵ There is no consensus on when to screen men, although all adults with a fragility fracture should undergo bone mineral density testing.

Consider screening men and women age >65 if secondary causes of osteoporosis—such as hypogonadism, hyperparathyroidism, hyperthyroidism, Cushing’s syndrome, inflammatory bowel disease, inflammatory arthritis, and hematologic cancers—are present.⁴

Table 1

Osteoporosis risk factors*

Prevention. A diet rich in calcium and vitamin D is essential for healthy bone growth.⁴ Daily requirements increase with age and are highest among adults age >50 (Table 2).⁶ Because the typical U.S. diet has poor calcium content, most adults and children will need calcium supplementation to meet daily requirements. Additional healthy bone lifestyle measures include avoiding caffeine and limiting alcohol consumption to <2 drinks/day.

Physical activity reduces the risk of falls and fractures by increasing muscle strength, coordination, and mobility. Weight-bearing exercise delays osteoporosis onset by promoting strong bone development. When possible, avoid prescribing medications that increase the risk of falls, such as sedative-hypnotics, benzodiazepines, and anticholinergics, or cause bone loss, such as phenytoin, glucocorticoids, and phenobarbital.

Table 2

Daily calcium and vitamin D requirements for adults by age

Treatment. First-line pharmacologic treatment of osteoporosis includes calcium plus vitamin D and a bisphosphonate.⁶

Calcium plus vitamin D increases calcium absorption and has been shown to significantly reduce fracture risk. Calcium typically is prescribed in a carbonate or citrate formulation.

• Calcium carbonate must be taken with meals because it requires an acidic environment for absorption.
• Calcium citrate may cause fewer gastrointestinal side effects, such as constipation.

Because one-time calcium absorption is limited to <600 mg, multiple daily dosing is required. The National Osteoporosis Foundation recommends >800 IU of vitamin D daily to reduce fracture risk in patients age >50 and in those with osteoporosis.⁷

Bisphosphonates have been shown to reduce fracture risk and increase bone mineral density, primarily in the spine and hip and sometimes within 6 months. Once-weekly alendronate and once-monthly risedronate and oral ibandronate are FDA-approved for prevention and treatment of osteoporosis in postmenopausal women. Quarterly ibandronate and once-yearly zoledronic acid injections are approved for osteoporosis treatment. Alendronate and risedronate also are approved to treat osteoporosis caused by glucocorticoid therapy and in men.

Although bisphosphonates do not cause adverse psychiatric effects or interactions with psychotropic medications, bisphosphonates must be taken at least 30 minutes before any other medications. Adverse effects from oral bisphosphonates often are gastrointestinal—such as nausea, heartburn, pain, irritation, and ulceration—and patients should take these medications with only a glass of water and remain upright for at least 30 minutes after ingestion.

Other therapeutic options include teriparatide—a synthetic form of parathyroid hormone injected daily—calcitonin, and raloxifene. Estrogen therapy increases bone density in postmenopausal women but is not recommended for routine use because of increased risk of stroke, thromboembolism, heart disease, and breast cancer.

Related resources

• World Health Organization Fracture Risk Assessment tool. www.shef.ac.uk/FRAX.
• National Osteoporosis Foundation. www.nof.org.

Drug brand names

• Alendronate • Fosamax
• Calcitonin • Miacalcin
• Ibandronate • Boniva
• Lithium • various
• Phenobarbital • various
• Phenytoin • Dilantin
• Prednisone • Deltasone, Meticorten
• Raloxifene • Evista
• Risedronate • Actonel
• Teriparatide • Forteo
• Valproic acid • Depakene
• Zoledronic acid • Reclast

Disclosure

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

During this economic recession, it feels as if the entire country is suffering from an “adjustment disorder with anxiety and dysphoria.” I don’t want to depress you further, but doesn’t it seem that psychiatry is having its own recession, reflected in our profession’s collective psyche?

Despite breathtaking discoveries in neuroscience, clinical advances are stalling because of a “perfect storm” of setbacks for our profession. For example:

• Second-generation “atypical” antipsychotics seem to be falling from grace after several effectiveness studies denigrated them for metabolic side effects and claimed they are not more efficacious than the older generation agents. Disillusionment followed.
• Hopes for a new generation of glutamatergic antipsychotics were dashed when clinical trials failed to show that a novel metabotropic glutamate partial agonist was superior to placebo.
• A palpable “funk” prevails as clinicians yearn for better antidepressants, with a more rapid onset of action, antisuicidal efficacy, and minimal side effects. The wait continues.
• The media and idealistic crusaders criticize off-label prescribing, without knowing that 85% of psychiatric diagnoses in DSM-IV-TR have no approved medications. Because symptoms of many psychiatric disorders overlap, we try to relieve patients’ suffering by prescribing medications that are FDA-approved for other indications. When it comes to off-label prescribing, it seems we’re damned if we do and damned if we don’t.
• Relentless demonization of pharmaceutical companies has made them the whipping boy for corporate America. No wonder they are downsizing and investing less in drug research and development; the return on their investments has become unpredictable. No one else develops new psychiatric drugs, so our patients will suffer if the pharmaceutical slump worsens.
• Academic researchers have been publicly “tarred and feathered” for collaborating with and advising pharmaceutical companies (such as in conducting FDA clinical trials) because they—like researchers in other fields—receive consulting income from those companies. This perception that any link with the “evil” pharmaceutical companies is a major sin has cast a pall over vital academic-industry collaborative research to develop new drug treatments for severe and disabling psychiatric disorders.
• Even the American Psychiatric Association (APA) is under enormous stress. In response to political pressure, APA is divesting itself of $1.5 million in CME grants from pharmaceutical sponsors.¹ The popular industry-sponsored symposia were cut back at APA’s 2009 meeting and are being eliminated in 2010. Because of this abrupt loss of revenue, APA has deeply cut its organizational structure and function, adding to the “recession atmosphere” in psychiatry.
• DSM-V committee members also are being scrutinized for ties to the pharmaceutical industry. I have faith in my colleagues’ objectivity and believe they will base their decisions on scientific evidence alone. Because perception is everything, however, some highly qualified psychiatric nosologists could not participate because they had received honoraria from pharmaceutical companies—a routine activity for a research expert. Attacks on the credibility of leading psychiatrists are demoralizing to these individuals who have made important contributions and puzzling to the many psychiatrists who look up to them.
• Psychiatrists also have been accused of “overdiagnosing” attention-deficit/hyperactivity disorder and bipolar disorder in children. Yet it may be that advances in recognizing these disorders in children have led to better and earlier identification. Psychiatrists who are diagnosing and treating those seriously ill children feel unappreciated and unfairly accused by persons who know little about mental illnesses.

A ‘TARP’ for psychiatry?

In this economic recession, the U.S. government created the Troubled Asset Relief Program (TARP) for stressed financial institutions. Does psychiatry need its own “TARP” (Targeted Assistance to Revive Psychiatry)?

I think we can help ourselves by educating the media, politicians, and community leaders about psychiatry’s tremendous contributions to the mental health and well-being of children, adults, and the elderly. We can and should refurbish our image and support each other until psychiatry’s recession is over. Just as we always reassure our patients, let’s remind ourselves that “this too shall pass.”

During this economic recession, it feels as if the entire country is suffering from an “adjustment disorder with anxiety and dysphoria.” I don’t want to depress you further, but doesn’t it seem that psychiatry is having its own recession, reflected in our profession’s collective psyche?

Despite breathtaking discoveries in neuroscience, clinical advances are stalling because of a “perfect storm” of setbacks for our profession. For example:

• Second-generation “atypical” antipsychotics seem to be falling from grace after several effectiveness studies denigrated them for metabolic side effects and claimed they are not more efficacious than the older generation agents. Disillusionment followed.
• Hopes for a new generation of glutamatergic antipsychotics were dashed when clinical trials failed to show that a novel metabotropic glutamate partial agonist was superior to placebo.
• A palpable “funk” prevails as clinicians yearn for better antidepressants, with a more rapid onset of action, antisuicidal efficacy, and minimal side effects. The wait continues.
• The media and idealistic crusaders criticize off-label prescribing, without knowing that 85% of psychiatric diagnoses in DSM-IV-TR have no approved medications. Because symptoms of many psychiatric disorders overlap, we try to relieve patients’ suffering by prescribing medications that are FDA-approved for other indications. When it comes to off-label prescribing, it seems we’re damned if we do and damned if we don’t.
• Relentless demonization of pharmaceutical companies has made them the whipping boy for corporate America. No wonder they are downsizing and investing less in drug research and development; the return on their investments has become unpredictable. No one else develops new psychiatric drugs, so our patients will suffer if the pharmaceutical slump worsens.
• Academic researchers have been publicly “tarred and feathered” for collaborating with and advising pharmaceutical companies (such as in conducting FDA clinical trials) because they—like researchers in other fields—receive consulting income from those companies. This perception that any link with the “evil” pharmaceutical companies is a major sin has cast a pall over vital academic-industry collaborative research to develop new drug treatments for severe and disabling psychiatric disorders.
• Even the American Psychiatric Association (APA) is under enormous stress. In response to political pressure, APA is divesting itself of $1.5 million in CME grants from pharmaceutical sponsors.¹ The popular industry-sponsored symposia were cut back at APA’s 2009 meeting and are being eliminated in 2010. Because of this abrupt loss of revenue, APA has deeply cut its organizational structure and function, adding to the “recession atmosphere” in psychiatry.
• DSM-V committee members also are being scrutinized for ties to the pharmaceutical industry. I have faith in my colleagues’ objectivity and believe they will base their decisions on scientific evidence alone. Because perception is everything, however, some highly qualified psychiatric nosologists could not participate because they had received honoraria from pharmaceutical companies—a routine activity for a research expert. Attacks on the credibility of leading psychiatrists are demoralizing to these individuals who have made important contributions and puzzling to the many psychiatrists who look up to them.
• Psychiatrists also have been accused of “overdiagnosing” attention-deficit/hyperactivity disorder and bipolar disorder in children. Yet it may be that advances in recognizing these disorders in children have led to better and earlier identification. Psychiatrists who are diagnosing and treating those seriously ill children feel unappreciated and unfairly accused by persons who know little about mental illnesses.

A ‘TARP’ for psychiatry?

In this economic recession, the U.S. government created the Troubled Asset Relief Program (TARP) for stressed financial institutions. Does psychiatry need its own “TARP” (Targeted Assistance to Revive Psychiatry)?

I think we can help ourselves by educating the media, politicians, and community leaders about psychiatry’s tremendous contributions to the mental health and well-being of children, adults, and the elderly. We can and should refurbish our image and support each other until psychiatry’s recession is over. Just as we always reassure our patients, let’s remind ourselves that “this too shall pass.”

During this economic recession, it feels as if the entire country is suffering from an “adjustment disorder with anxiety and dysphoria.” I don’t want to depress you further, but doesn’t it seem that psychiatry is having its own recession, reflected in our profession’s collective psyche?

Despite breathtaking discoveries in neuroscience, clinical advances are stalling because of a “perfect storm” of setbacks for our profession. For example:

• Second-generation “atypical” antipsychotics seem to be falling from grace after several effectiveness studies denigrated them for metabolic side effects and claimed they are not more efficacious than the older generation agents. Disillusionment followed.
• Hopes for a new generation of glutamatergic antipsychotics were dashed when clinical trials failed to show that a novel metabotropic glutamate partial agonist was superior to placebo.
• A palpable “funk” prevails as clinicians yearn for better antidepressants, with a more rapid onset of action, antisuicidal efficacy, and minimal side effects. The wait continues.
• The media and idealistic crusaders criticize off-label prescribing, without knowing that 85% of psychiatric diagnoses in DSM-IV-TR have no approved medications. Because symptoms of many psychiatric disorders overlap, we try to relieve patients’ suffering by prescribing medications that are FDA-approved for other indications. When it comes to off-label prescribing, it seems we’re damned if we do and damned if we don’t.
• Relentless demonization of pharmaceutical companies has made them the whipping boy for corporate America. No wonder they are downsizing and investing less in drug research and development; the return on their investments has become unpredictable. No one else develops new psychiatric drugs, so our patients will suffer if the pharmaceutical slump worsens.
• Academic researchers have been publicly “tarred and feathered” for collaborating with and advising pharmaceutical companies (such as in conducting FDA clinical trials) because they—like researchers in other fields—receive consulting income from those companies. This perception that any link with the “evil” pharmaceutical companies is a major sin has cast a pall over vital academic-industry collaborative research to develop new drug treatments for severe and disabling psychiatric disorders.
• Even the American Psychiatric Association (APA) is under enormous stress. In response to political pressure, APA is divesting itself of $1.5 million in CME grants from pharmaceutical sponsors.¹ The popular industry-sponsored symposia were cut back at APA’s 2009 meeting and are being eliminated in 2010. Because of this abrupt loss of revenue, APA has deeply cut its organizational structure and function, adding to the “recession atmosphere” in psychiatry.
• DSM-V committee members also are being scrutinized for ties to the pharmaceutical industry. I have faith in my colleagues’ objectivity and believe they will base their decisions on scientific evidence alone. Because perception is everything, however, some highly qualified psychiatric nosologists could not participate because they had received honoraria from pharmaceutical companies—a routine activity for a research expert. Attacks on the credibility of leading psychiatrists are demoralizing to these individuals who have made important contributions and puzzling to the many psychiatrists who look up to them.
• Psychiatrists also have been accused of “overdiagnosing” attention-deficit/hyperactivity disorder and bipolar disorder in children. Yet it may be that advances in recognizing these disorders in children have led to better and earlier identification. Psychiatrists who are diagnosing and treating those seriously ill children feel unappreciated and unfairly accused by persons who know little about mental illnesses.

A ‘TARP’ for psychiatry?

In this economic recession, the U.S. government created the Troubled Asset Relief Program (TARP) for stressed financial institutions. Does psychiatry need its own “TARP” (Targeted Assistance to Revive Psychiatry)?

I think we can help ourselves by educating the media, politicians, and community leaders about psychiatry’s tremendous contributions to the mental health and well-being of children, adults, and the elderly. We can and should refurbish our image and support each other until psychiatry’s recession is over. Just as we always reassure our patients, let’s remind ourselves that “this too shall pass.”

CASE: Disabling anxiety

Mr. B, age 35, has a history of schizophrenia, chronic paranoid type and has been hospitalized more than 12 times since its onset 10 years ago. He received clozapine during his most recent hospitalization approximately 5 years ago and experienced full symptom response without the motor side effects he developed in response to other medications. He visits a psychiatrist monthly for medications and supportive psychotherapy, and he receives intensive case management and housing from a community mental health center.

When Mr. B is assigned to my (CK) care, his psychotic symptoms are in remission, but he complains of anxiety that leaves him almost homebound. He has intense fear of bridges, upper-floor windows, express buses, subways, riding in speeding vehicles, and having a seizure.

If Mr. B faces any of these triggers, he experiences harmful thoughts—such as jumping out a window or off a bridge—even though he does not endorse suicidality. These thoughts are intrusive, ego-dystonic, and ruminative. He avoids these triggers at all costs, which compromises his housing and employment opportunities. He experienced a single panic attack in the subway 1 year earlier. Mr. B firmly believes that any intense anxiety he experiences will trigger a psychotic episode. When faced with sudden urges, he believes his illness would interfere with his ability to control his impulses.

He reports that these symptoms started when he began clozapine and have worsened. Mr. B says he experiences a feeling of “uneasiness” approximately 2 hours after taking clozapine that is exacerbated if he faces a trigger. He describes the uneasiness as “the feeling of being about to have a seizure” during which he would “lose control” of his body.

When I begin treating Mr. B, he is receiving clozapine, 125 mg bid. In an effort to combat Mr. B’s anxiety, a previous psychiatrist had titrated clonazepam up to 5 mg/d as needed. Mr. B is compliant with his medications and appointments but refuses to change his psychotropic or psychotherapy regimen.

The authors’ observations

Approximately 50% of patients with schizophrenia have at least 1 anxiety disorder, and close to 30% meet criteria for >1 anxiety disorder.¹ Social anxiety disorder (SAD), generalized anxiety disorder, panic disorder, posttraumatic stress disorder, and obsessive-compulsive disorder (OCD) have been found comorbid with schizophrenia, with rates as high as 30% for each.¹

Possible causes of unusually high rates of anxiety disorders in schizophrenia include trauma history, delusional conviction and inflexibility of abstract thought,² and passive coping mechanisms.

Schizophrenic illnesses may be linked to anxiety antecedents such as panic or social phobia that:

• develop into more profound psychopathology
  
• or bring about anxiety symptoms, given the severity of the subjective psychotic experience.
  

Comorbid OCD, panic disorder, and SAD frequently persist after remission of psychotic symptoms. Comorbid anxiety disorders may play a role in the psychotic symptoms themselves (such as panic and social anxiety related to paranoia, OCD, and bizarre behavior) and negatively impact quality of life.⁴

• increased hallucinations
  
• poor psychosocial function
  
• hopelessness.⁵
  

Table 1

Treatment options for comorbid schizophrenia and anxiety

HISTORY: Propensity for violence

Mr. B was born in a large city and raised by his single mother. He denies childhood physical or sexual abuse. Mr. B reports engaging in violent activity since he was an adolescent, but this activity is undocumented because he has never been arrested. Mr. B still belongs to a gang he joined after being assaulted at age 16.

Mr. B was diagnosed with schizophrenia at age 20 following an overt psychotic episode and suicide attempt by hanging. During his psychotic episodes, he thinks groups of people are plotting to kill him. He hears people talking about him or voices telling him about others’ plots against him. Mr. B probably has experienced these symptoms since early childhood, as evidenced by reports of attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder, and tics.

Numerous medication trials failed. Antipsychotics were ineffective or poorly tolerated because of motor side effects or intense sedation. Mr. B did not tolerate selective serotonin reuptake inhibitors (SSRIs) because of akathisia or sexual side effects. Mr. B had a history of poor medication compliance until he began clozapine treatment.

Mr. B used cannabis daily until 10 years ago. He smokes cigarettes and reports occasional alcohol use. He has no history of chronic substance or alcohol use, withdrawal symptoms, or complications from intoxication.

Mr. B is unemployed and receives Supplemental Security Income. He has never married or had children.

Medical comorbidities include a white blood cell count and absolute neutrophil count that have been chronically in the lower limit range, and dyslipidemia and diabetes, for which Mr. B receives statins and oral hypoglycemics. He has no history of seizures or brain trauma. His family history includes substance dependence on his mother’s side and schizophrenia in 2 paternal cousins.

The authors’ observations

Mr. B’s anxiety disorder has not been clearly elucidated. He does not seem to meet criteria for:

• panic disorder (only 1 panic attack)
  
• OCD (no compulsions to diminish anxiety)
  
• specific phobia (phobias were too broad and lacked fear of an object itself).
  

The phenomenology of his symptoms appears to be linked to his psychodynamic development, but previous therapists had not explored this. In addition, his relationships with his therapists, illness, and medications are complex. Mr. B is poorly engaged, lacks motivation toward recovery goals, and does not trust me. However, he holds high expectations of the potential damage or benefits of medication.

Table 2

Anxiety: How to differentiate disorders and symptoms

Mr. B was taking clonazepam when our work began, and discontinuing it would have increased his risk for seizures and the possibility of him seeking illicit benzodiazepines. Furthermore, discontinuing clonazepam might have thwarted an emerging therapeutic relationship that would become key to enhancing his motivation and exploring the antisocial and narcissistic traits that were limiting his recovery.

I carefully and slowly change Mr. B’s medications. First I increase his clozapine to 300 mg/d in 150 mg divided doses in an attempt to cover the possibility of residual paranoia, and for anxiolytic sedation without introducing a new medication. However, Mr. B’s anxiety symptoms worsen, so I resume the baseline dosage (125 mg bid). I choose not to switch to another antipsychotic because the risk for psychotic decompensation outweighs the potential benefits. I lower clonazepam to 2 mg/d in split doses. I teach Mr. B anxiety management techniques, including distraction, exposure, and anxiety tolerance training.

Because Mr. B refuses to start an SSRI for his anxiety symptoms, I prescribe bupropion and monitor him closely for dopamine agonism as evidenced by a re-emergence of psychosis. Once again, his anxiety symptoms worsen.

I stop bupropion and switch Mr. B to gabapentin, titrated to 400 mg tid. I chose this medication because of its sedation properties and relatively safe side effect profile. Mr. B was willing to try gabapentin—which was first approved to treat epilepsy—because he was afraid of having a seizure and also because it is not associated with sexual side effects. Furthermore, its GABA-mimetic actions made it a plausible alternative to replicate the benefits he was getting from clonazepam.

TREATMENT: An effective drug

Mr. B tolerates gabapentin well and his anxiety symptoms are much more sporadic, shorter, and more easily controlled by conscious exercise. The content of his thoughts is less disastrous and less ego-dystonic. He feels less dysphoria associated with clozapine and does not need as much clonazepam. He overcomes his avoidance of all fear-provoking triggers except walking across bridges.

Mr. B continues his regimen of clozapine, clonazepam, and gabapentin. He moves to independent housing and applies for employment.

Related resource

• Garrett M, Lerman M. CBT for psychosis for long-term inpatients with a forensic history. Psychiatr Serv. 2007;58(5):712-713.
  

• Aripiprazole • Abilify
  
• Bupropion • Wellbutrin
  
• Clonazepam • Klonopin
  
• Clozapine • Clozaril
  
• Gabapentin • Neurontin
  
• Olanzapine • Zyprexa
  
• Ziprasidone • Geodon
  

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

CASE: Disabling anxiety

Mr. B, age 35, has a history of schizophrenia, chronic paranoid type and has been hospitalized more than 12 times since its onset 10 years ago. He received clozapine during his most recent hospitalization approximately 5 years ago and experienced full symptom response without the motor side effects he developed in response to other medications. He visits a psychiatrist monthly for medications and supportive psychotherapy, and he receives intensive case management and housing from a community mental health center.

When Mr. B is assigned to my (CK) care, his psychotic symptoms are in remission, but he complains of anxiety that leaves him almost homebound. He has intense fear of bridges, upper-floor windows, express buses, subways, riding in speeding vehicles, and having a seizure.

If Mr. B faces any of these triggers, he experiences harmful thoughts—such as jumping out a window or off a bridge—even though he does not endorse suicidality. These thoughts are intrusive, ego-dystonic, and ruminative. He avoids these triggers at all costs, which compromises his housing and employment opportunities. He experienced a single panic attack in the subway 1 year earlier. Mr. B firmly believes that any intense anxiety he experiences will trigger a psychotic episode. When faced with sudden urges, he believes his illness would interfere with his ability to control his impulses.

He reports that these symptoms started when he began clozapine and have worsened. Mr. B says he experiences a feeling of “uneasiness” approximately 2 hours after taking clozapine that is exacerbated if he faces a trigger. He describes the uneasiness as “the feeling of being about to have a seizure” during which he would “lose control” of his body.

When I begin treating Mr. B, he is receiving clozapine, 125 mg bid. In an effort to combat Mr. B’s anxiety, a previous psychiatrist had titrated clonazepam up to 5 mg/d as needed. Mr. B is compliant with his medications and appointments but refuses to change his psychotropic or psychotherapy regimen.

The authors’ observations

Approximately 50% of patients with schizophrenia have at least 1 anxiety disorder, and close to 30% meet criteria for >1 anxiety disorder.¹ Social anxiety disorder (SAD), generalized anxiety disorder, panic disorder, posttraumatic stress disorder, and obsessive-compulsive disorder (OCD) have been found comorbid with schizophrenia, with rates as high as 30% for each.¹

Possible causes of unusually high rates of anxiety disorders in schizophrenia include trauma history, delusional conviction and inflexibility of abstract thought,² and passive coping mechanisms.

Schizophrenic illnesses may be linked to anxiety antecedents such as panic or social phobia that:

• develop into more profound psychopathology
  
• or bring about anxiety symptoms, given the severity of the subjective psychotic experience.
  

Comorbid OCD, panic disorder, and SAD frequently persist after remission of psychotic symptoms. Comorbid anxiety disorders may play a role in the psychotic symptoms themselves (such as panic and social anxiety related to paranoia, OCD, and bizarre behavior) and negatively impact quality of life.⁴

• increased hallucinations
  
• poor psychosocial function
  
• hopelessness.⁵
  

Table 1

Treatment options for comorbid schizophrenia and anxiety

HISTORY: Propensity for violence

Mr. B was born in a large city and raised by his single mother. He denies childhood physical or sexual abuse. Mr. B reports engaging in violent activity since he was an adolescent, but this activity is undocumented because he has never been arrested. Mr. B still belongs to a gang he joined after being assaulted at age 16.

Mr. B was diagnosed with schizophrenia at age 20 following an overt psychotic episode and suicide attempt by hanging. During his psychotic episodes, he thinks groups of people are plotting to kill him. He hears people talking about him or voices telling him about others’ plots against him. Mr. B probably has experienced these symptoms since early childhood, as evidenced by reports of attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder, and tics.

Numerous medication trials failed. Antipsychotics were ineffective or poorly tolerated because of motor side effects or intense sedation. Mr. B did not tolerate selective serotonin reuptake inhibitors (SSRIs) because of akathisia or sexual side effects. Mr. B had a history of poor medication compliance until he began clozapine treatment.

Mr. B used cannabis daily until 10 years ago. He smokes cigarettes and reports occasional alcohol use. He has no history of chronic substance or alcohol use, withdrawal symptoms, or complications from intoxication.

Mr. B is unemployed and receives Supplemental Security Income. He has never married or had children.

Medical comorbidities include a white blood cell count and absolute neutrophil count that have been chronically in the lower limit range, and dyslipidemia and diabetes, for which Mr. B receives statins and oral hypoglycemics. He has no history of seizures or brain trauma. His family history includes substance dependence on his mother’s side and schizophrenia in 2 paternal cousins.

The authors’ observations

Mr. B’s anxiety disorder has not been clearly elucidated. He does not seem to meet criteria for:

• panic disorder (only 1 panic attack)
  
• OCD (no compulsions to diminish anxiety)
  
• specific phobia (phobias were too broad and lacked fear of an object itself).
  

The phenomenology of his symptoms appears to be linked to his psychodynamic development, but previous therapists had not explored this. In addition, his relationships with his therapists, illness, and medications are complex. Mr. B is poorly engaged, lacks motivation toward recovery goals, and does not trust me. However, he holds high expectations of the potential damage or benefits of medication.

Table 2

Anxiety: How to differentiate disorders and symptoms

Mr. B was taking clonazepam when our work began, and discontinuing it would have increased his risk for seizures and the possibility of him seeking illicit benzodiazepines. Furthermore, discontinuing clonazepam might have thwarted an emerging therapeutic relationship that would become key to enhancing his motivation and exploring the antisocial and narcissistic traits that were limiting his recovery.

I carefully and slowly change Mr. B’s medications. First I increase his clozapine to 300 mg/d in 150 mg divided doses in an attempt to cover the possibility of residual paranoia, and for anxiolytic sedation without introducing a new medication. However, Mr. B’s anxiety symptoms worsen, so I resume the baseline dosage (125 mg bid). I choose not to switch to another antipsychotic because the risk for psychotic decompensation outweighs the potential benefits. I lower clonazepam to 2 mg/d in split doses. I teach Mr. B anxiety management techniques, including distraction, exposure, and anxiety tolerance training.

Because Mr. B refuses to start an SSRI for his anxiety symptoms, I prescribe bupropion and monitor him closely for dopamine agonism as evidenced by a re-emergence of psychosis. Once again, his anxiety symptoms worsen.

I stop bupropion and switch Mr. B to gabapentin, titrated to 400 mg tid. I chose this medication because of its sedation properties and relatively safe side effect profile. Mr. B was willing to try gabapentin—which was first approved to treat epilepsy—because he was afraid of having a seizure and also because it is not associated with sexual side effects. Furthermore, its GABA-mimetic actions made it a plausible alternative to replicate the benefits he was getting from clonazepam.

TREATMENT: An effective drug

Mr. B tolerates gabapentin well and his anxiety symptoms are much more sporadic, shorter, and more easily controlled by conscious exercise. The content of his thoughts is less disastrous and less ego-dystonic. He feels less dysphoria associated with clozapine and does not need as much clonazepam. He overcomes his avoidance of all fear-provoking triggers except walking across bridges.

Mr. B continues his regimen of clozapine, clonazepam, and gabapentin. He moves to independent housing and applies for employment.

Related resource

• Garrett M, Lerman M. CBT for psychosis for long-term inpatients with a forensic history. Psychiatr Serv. 2007;58(5):712-713.
  

• Aripiprazole • Abilify
  
• Bupropion • Wellbutrin
  
• Clonazepam • Klonopin
  
• Clozapine • Clozaril
  
• Gabapentin • Neurontin
  
• Olanzapine • Zyprexa
  
• Ziprasidone • Geodon
  

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

CASE: Disabling anxiety

Mr. B, age 35, has a history of schizophrenia, chronic paranoid type and has been hospitalized more than 12 times since its onset 10 years ago. He received clozapine during his most recent hospitalization approximately 5 years ago and experienced full symptom response without the motor side effects he developed in response to other medications. He visits a psychiatrist monthly for medications and supportive psychotherapy, and he receives intensive case management and housing from a community mental health center.

When Mr. B is assigned to my (CK) care, his psychotic symptoms are in remission, but he complains of anxiety that leaves him almost homebound. He has intense fear of bridges, upper-floor windows, express buses, subways, riding in speeding vehicles, and having a seizure.

If Mr. B faces any of these triggers, he experiences harmful thoughts—such as jumping out a window or off a bridge—even though he does not endorse suicidality. These thoughts are intrusive, ego-dystonic, and ruminative. He avoids these triggers at all costs, which compromises his housing and employment opportunities. He experienced a single panic attack in the subway 1 year earlier. Mr. B firmly believes that any intense anxiety he experiences will trigger a psychotic episode. When faced with sudden urges, he believes his illness would interfere with his ability to control his impulses.

He reports that these symptoms started when he began clozapine and have worsened. Mr. B says he experiences a feeling of “uneasiness” approximately 2 hours after taking clozapine that is exacerbated if he faces a trigger. He describes the uneasiness as “the feeling of being about to have a seizure” during which he would “lose control” of his body.

When I begin treating Mr. B, he is receiving clozapine, 125 mg bid. In an effort to combat Mr. B’s anxiety, a previous psychiatrist had titrated clonazepam up to 5 mg/d as needed. Mr. B is compliant with his medications and appointments but refuses to change his psychotropic or psychotherapy regimen.

The authors’ observations

Approximately 50% of patients with schizophrenia have at least 1 anxiety disorder, and close to 30% meet criteria for >1 anxiety disorder.¹ Social anxiety disorder (SAD), generalized anxiety disorder, panic disorder, posttraumatic stress disorder, and obsessive-compulsive disorder (OCD) have been found comorbid with schizophrenia, with rates as high as 30% for each.¹

Possible causes of unusually high rates of anxiety disorders in schizophrenia include trauma history, delusional conviction and inflexibility of abstract thought,² and passive coping mechanisms.

Schizophrenic illnesses may be linked to anxiety antecedents such as panic or social phobia that:

• develop into more profound psychopathology
  
• or bring about anxiety symptoms, given the severity of the subjective psychotic experience.
  

Comorbid OCD, panic disorder, and SAD frequently persist after remission of psychotic symptoms. Comorbid anxiety disorders may play a role in the psychotic symptoms themselves (such as panic and social anxiety related to paranoia, OCD, and bizarre behavior) and negatively impact quality of life.⁴

• increased hallucinations
  
• poor psychosocial function
  
• hopelessness.⁵
  

Table 1

Treatment options for comorbid schizophrenia and anxiety

HISTORY: Propensity for violence

Mr. B was born in a large city and raised by his single mother. He denies childhood physical or sexual abuse. Mr. B reports engaging in violent activity since he was an adolescent, but this activity is undocumented because he has never been arrested. Mr. B still belongs to a gang he joined after being assaulted at age 16.

Mr. B was diagnosed with schizophrenia at age 20 following an overt psychotic episode and suicide attempt by hanging. During his psychotic episodes, he thinks groups of people are plotting to kill him. He hears people talking about him or voices telling him about others’ plots against him. Mr. B probably has experienced these symptoms since early childhood, as evidenced by reports of attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder, and tics.

Numerous medication trials failed. Antipsychotics were ineffective or poorly tolerated because of motor side effects or intense sedation. Mr. B did not tolerate selective serotonin reuptake inhibitors (SSRIs) because of akathisia or sexual side effects. Mr. B had a history of poor medication compliance until he began clozapine treatment.

Mr. B used cannabis daily until 10 years ago. He smokes cigarettes and reports occasional alcohol use. He has no history of chronic substance or alcohol use, withdrawal symptoms, or complications from intoxication.

Mr. B is unemployed and receives Supplemental Security Income. He has never married or had children.

Medical comorbidities include a white blood cell count and absolute neutrophil count that have been chronically in the lower limit range, and dyslipidemia and diabetes, for which Mr. B receives statins and oral hypoglycemics. He has no history of seizures or brain trauma. His family history includes substance dependence on his mother’s side and schizophrenia in 2 paternal cousins.

The authors’ observations

Mr. B’s anxiety disorder has not been clearly elucidated. He does not seem to meet criteria for:

• panic disorder (only 1 panic attack)
  
• OCD (no compulsions to diminish anxiety)
  
• specific phobia (phobias were too broad and lacked fear of an object itself).
  

The phenomenology of his symptoms appears to be linked to his psychodynamic development, but previous therapists had not explored this. In addition, his relationships with his therapists, illness, and medications are complex. Mr. B is poorly engaged, lacks motivation toward recovery goals, and does not trust me. However, he holds high expectations of the potential damage or benefits of medication.

Table 2

Anxiety: How to differentiate disorders and symptoms

Mr. B was taking clonazepam when our work began, and discontinuing it would have increased his risk for seizures and the possibility of him seeking illicit benzodiazepines. Furthermore, discontinuing clonazepam might have thwarted an emerging therapeutic relationship that would become key to enhancing his motivation and exploring the antisocial and narcissistic traits that were limiting his recovery.

I carefully and slowly change Mr. B’s medications. First I increase his clozapine to 300 mg/d in 150 mg divided doses in an attempt to cover the possibility of residual paranoia, and for anxiolytic sedation without introducing a new medication. However, Mr. B’s anxiety symptoms worsen, so I resume the baseline dosage (125 mg bid). I choose not to switch to another antipsychotic because the risk for psychotic decompensation outweighs the potential benefits. I lower clonazepam to 2 mg/d in split doses. I teach Mr. B anxiety management techniques, including distraction, exposure, and anxiety tolerance training.

Because Mr. B refuses to start an SSRI for his anxiety symptoms, I prescribe bupropion and monitor him closely for dopamine agonism as evidenced by a re-emergence of psychosis. Once again, his anxiety symptoms worsen.

I stop bupropion and switch Mr. B to gabapentin, titrated to 400 mg tid. I chose this medication because of its sedation properties and relatively safe side effect profile. Mr. B was willing to try gabapentin—which was first approved to treat epilepsy—because he was afraid of having a seizure and also because it is not associated with sexual side effects. Furthermore, its GABA-mimetic actions made it a plausible alternative to replicate the benefits he was getting from clonazepam.

TREATMENT: An effective drug

Mr. B tolerates gabapentin well and his anxiety symptoms are much more sporadic, shorter, and more easily controlled by conscious exercise. The content of his thoughts is less disastrous and less ego-dystonic. He feels less dysphoria associated with clozapine and does not need as much clonazepam. He overcomes his avoidance of all fear-provoking triggers except walking across bridges.

Mr. B continues his regimen of clozapine, clonazepam, and gabapentin. He moves to independent housing and applies for employment.

Related resource

• Garrett M, Lerman M. CBT for psychosis for long-term inpatients with a forensic history. Psychiatr Serv. 2007;58(5):712-713.
  

• Aripiprazole • Abilify
  
• Bupropion • Wellbutrin
  
• Clonazepam • Klonopin
  
• Clozapine • Clozaril
  
• Gabapentin • Neurontin
  
• Olanzapine • Zyprexa
  
• Ziprasidone • Geodon
  

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

Comment on this article

Ms. F, a 53-year-old high school English teacher, is referred to you by her family physician after she was suspended from work for suspected intoxication. She was divorced 2 years ago from her husband of 20 years, and she says her drinking has escalated to 2 bottles of wine every night. She wants to reduce her alcohol use but experiences shakiness, nausea, and diaphoresis when she tries to cut back.

Ms. F began drinking at age 16 “to feel more comfortable in social situations” and has experienced binge drinking with intermittent blackouts. She denies illicit drug use and legal consequences from drinking. Her father died from cirrhosis at age 58. Her mother suffers from depression but is in remission with medication.

Ms. F is hesitant to date or establish intimate relationships. She has stopped attending church, a book club, and her 15-year-old daughter’s booster club activities.

For years, little was known about alcohol use and alcohol-related problems in women such as Ms. F.¹ Alcohol dependence studies rarely included women, so findings and treatment outcomes observed in men were assumed to apply to both genders.

Awareness of gender differences in addiction has grown (Box 1).^2-5 Biological and psychosocial differences between alcohol-dependent women and men now are understood to influence etiology, epidemiology, psychiatric and medical comorbidity, course of illness, and treatment outcomes. This article discusses recent insights into planning treatment to address specific needs of alcohol-dependent women.

Box 1

Accelerated consequences

As a group, women may consume less alcohol than men but progress more rapidly to alcohol-related illnesses and negative consequences. Specifically, alcohol-dependent women develop liver disease, hypertension, and gastrointestinal hemorrhage more rapidly than alcohol-dependent men.³ Cognitive deficits and brain atrophy also develop sooner in alcohol-dependent women than men.⁶ Causes of this accelerated progression—”telescoping”—include gender-specific biological differences:

• Women have lower levels of gastric alcohol dehydrogenase—the enzyme that initiates alcohol metabolism—and therefore experience a higher blood alcohol concentration than men drinking the same amount of alcohol.
  
• Women have less total body water and less capacity to dilute alcohol than men.
  

‘At-risk’ drinking. Gender-related physiologic differences have led to different thresholds for defining “at-risk drinking” and binge drinking for men and women (Table 1).⁷ Alcohol use also has negative effects on women’s reproductive system and menstrual cycle. Women with alcohol dependence have higher rates of sexual dysfunction, irregular menstrual cycles, early menopause, and amenorrhea as compared with nonalcohol-dependent women.⁸

Table 1

Different thresholds: Number of drinks* that increases risk for alcohol-related problems

Motives for drinking

Research suggests different motives for alcohol use in girls and women vs boys and men. Women appear more likely to use alcohol to “self-medicate” negative affect or emotional pain (Box 2).^9-12 Men are more likely to use alcohol to enhance pleasurable emotional states, “feel high” or because of social pressures to conform.⁵

Box 2

• Young women with alcohol use problems may benefit from learning strategies to regulate negative emotions and alleviate depression or anxiety symptoms that may be contributing to their drinking.
  
• Young men with alcohol use problems may benefit from learning to manage peer pressure and from finding alternate sources of pleasure enhancement.⁵
  

CASE CONTINUED: Depressed and anxious

Ms. F admits to depressed mood, crying episodes, isolation from others, anhedonia, feelings of guilt, low motivation, difficulty concentrating at work, restless sleep, and weight loss. These symptoms recurred soon after she and her husband separated 4 years ago. She denies suicidal thoughts or suicide attempts.

She suffered similar episodes in the past, including when she was breastfeeding and abstinent from alcohol after the birth of her daughter. Her obstetrician treated her depression with fluoxetine. Problems with anxiety began in high school, especially associated with parties and dating. In college, she often would drink beer before class presentations.

You diagnose alcohol dependence, major depressive disorder, and social phobia. You also ask Ms. F about a history of trauma. She reports that her father was “real harsh” when he was drinking and often hit her and her sister. She also relates being struck by her ex-husband during arguments. Screening with the Clinician-Administered PTSD Scale is negative for posttraumatic stress disorder (PTSD), however.

Comorbid psychiatric disorders

Gender differences in reasons for alcohol use may be related to women’s higher rate of medical and psychiatric comorbidity (Table 2).^6,8,15,16 Vital signs, physical examination, and lab work are helpful for diagnosis and monitoring of medical comorbidities and complications. The gamma-glutamyl transferase (GGT) test for liver disease and carbohydrate deficient transferrin (CDT) test for chronic heavy alcohol consumption are less sensitive and specific in women than in men.¹⁷ Even so, monitoring GGT and CDT results over time may serve as a valuable marker of continued drinking by women.

Mood and anxiety disorders are significantly more common in women than in men among individuals with alcohol use disorders.^15,16 This pattern is not unique to alcohol-dependent persons, however. In the general population:

• women are more likely than men to meet diagnostic criteria for anxiety, depression, bulimia nervosa, and borderline personality disorder
  
• men are more likely than women to meet diagnostic criteria for antisocial personality disorder.¹⁸
  

Comorbid disorders in women with alcohol dependence

Suicide risk. A recent study by Connor et al²⁰ examined suicidal ideation, planning, and attempts in 3,729 alcohol dependent subjects (35% female) and found an association between female gender and both planned (odds ratio [OR] = 3.4) and unplanned suicide attempts (OR = 3.8). Further research is needed to clarify the relationship between female gender, alcohol dependence, and suicide risk, behaviors, and attempts.

Anxiety disorders are the most common psychiatric disorders in women,²¹ and social anxiety and social phobia may play a predisposing role in alcohol dependence.²² Individuals with social anxiety may self-medicate with alcohol as a social lubricant. Some research suggests that anxiety disorders are more severe in alcohol-dependent women than in men with similarly severe alcohol dependence.²²

Therefore, when assessing and treating alcohol-dependent women, screen for trauma history as well as mood and anxiety disorders. To optimize outcomes, treat these disorders simultaneously with the alcohol use disorder.²⁴

Treatment planning

Underuse of treatment programs. Women with alcohol dependence are more likely to seek treatment in primary care or mental health settings, rather than in alcohol treatment settings.^25,26 Women’s underuse of alcohol treatment programs is likely related to:

• greater stigma associated with alcohol use for women as compared with men
  
• socioeconomic factors, including pregnancy, child care, and concerns about child custody issues.²⁵
  

Gender-specific treatment? Women-only treatment programs have been studied because of observed differences in men’s and women’s interaction styles and the hypothesis that men’s traditional societal dominance could negatively affect women in mixed-gender groups.²⁵ Better treatment outcomes have been hypothesized if treatment is tailored to address women’s unique issues: risk factors for alcohol dependence, course of disease progression, medical problems associated with alcohol dependence, and reasons for relapse.

Gender-specific treatment may provide an environment where women—particularly those with a history of trauma from a male perpetrator—feel safe discussing issues related to their alcohol problems. For practical purposes, these programs also may be more likely to address women’s needs for on-site child care, prenatal care, and mental health programming.

A recent study compared a manual-based 12-session women’s recovery group with mixed-gender, manualized group drug counseling (GDC). The women’s recovery group focused on gender-specific topics such as relationships, the caregiver role, trauma, comorbid psychiatric conditions (including eating, mood, and anxiety disorders), and the effects of drug and alcohol use on women’s health. The women’s recovery group was:

• as effective as mixed-gender GDC in reducing substance use during the 12-week treatment
  
• significantly more effective during the 6-month post-treatment phase.²⁸
  

CASE CONTINUED: Developing a treatment plan

Ms. F identifies 3 triggers for her alcohol use: a stressful day at school, arguments with her ex-husband, and feeling lonely. Because these are high-risk situations for relapse, you incorporate strategies to deal with them into her treatment plan. Other factors to consider:

• whether she requires detoxification
  
• an FDA-approved medication for alcohol dependence (acamprosate, oral or injectable naltrexone, or disulfiram)
  
• cognitive-behavioral therapy and medication for major depression and social phobia
  
• referral to psychosocial support groups (such as Alcoholics Anonymous).
  

Three factors determine the need for detoxification: the course of previous alcohol withdrawals (alcoholic hallucinosis, seizures, or delirium tremens), elevated vital signs or other evidence of autonomic hyperactivity such as diaphoresis or tremors, and the patient’s general medical condition. During early recovery, monitor patients closely to assess mood and anxiety symptoms. Blood alcohol tests or GGT and CDT are useful to monitor self-reported abstinence.

Related resources

• National Clearing House for Alcohol and Drug Information. Publications and materials on women and substance abuse. Substance Abuse and Mental Health Services Administration. http://ncadistore.samhsa.gov/catalogresults.aspx?h=drugs&topic=11.
  
• National Institute on Drug Abuse (www.nida.nih.gov). Articles that address women’s health and gender differences. www.drugabuse.gov/NIDA_Notes/NN0013.html.
  

• Acamprosate • Campral
  
• Disulfiram • Antabuse
  
• Fluoxetine • Prozac
  
• Naltrexone • Vivitrol, ReVia
  

Drs. Payne, Back, Wright, and Hartwell report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Brady receives research support from Abbott Laboratories, GlaxoSmithKline, Forest Pharmaceuticals, and Wyeth. She is a consultant and speaker for Pfizer Inc., Eli Lilly and Company, Abbott Laboratories, GlaxoSmithKline, and Forest Pharmaceuticals.

Comment on this article

Ms. F, a 53-year-old high school English teacher, is referred to you by her family physician after she was suspended from work for suspected intoxication. She was divorced 2 years ago from her husband of 20 years, and she says her drinking has escalated to 2 bottles of wine every night. She wants to reduce her alcohol use but experiences shakiness, nausea, and diaphoresis when she tries to cut back.

Ms. F began drinking at age 16 “to feel more comfortable in social situations” and has experienced binge drinking with intermittent blackouts. She denies illicit drug use and legal consequences from drinking. Her father died from cirrhosis at age 58. Her mother suffers from depression but is in remission with medication.

Ms. F is hesitant to date or establish intimate relationships. She has stopped attending church, a book club, and her 15-year-old daughter’s booster club activities.

For years, little was known about alcohol use and alcohol-related problems in women such as Ms. F.¹ Alcohol dependence studies rarely included women, so findings and treatment outcomes observed in men were assumed to apply to both genders.

Awareness of gender differences in addiction has grown (Box 1).^2-5 Biological and psychosocial differences between alcohol-dependent women and men now are understood to influence etiology, epidemiology, psychiatric and medical comorbidity, course of illness, and treatment outcomes. This article discusses recent insights into planning treatment to address specific needs of alcohol-dependent women.

Box 1

Accelerated consequences

As a group, women may consume less alcohol than men but progress more rapidly to alcohol-related illnesses and negative consequences. Specifically, alcohol-dependent women develop liver disease, hypertension, and gastrointestinal hemorrhage more rapidly than alcohol-dependent men.³ Cognitive deficits and brain atrophy also develop sooner in alcohol-dependent women than men.⁶ Causes of this accelerated progression—”telescoping”—include gender-specific biological differences:

• Women have lower levels of gastric alcohol dehydrogenase—the enzyme that initiates alcohol metabolism—and therefore experience a higher blood alcohol concentration than men drinking the same amount of alcohol.
  
• Women have less total body water and less capacity to dilute alcohol than men.
  

‘At-risk’ drinking. Gender-related physiologic differences have led to different thresholds for defining “at-risk drinking” and binge drinking for men and women (Table 1).⁷ Alcohol use also has negative effects on women’s reproductive system and menstrual cycle. Women with alcohol dependence have higher rates of sexual dysfunction, irregular menstrual cycles, early menopause, and amenorrhea as compared with nonalcohol-dependent women.⁸

Table 1

Different thresholds: Number of drinks* that increases risk for alcohol-related problems

Motives for drinking

Research suggests different motives for alcohol use in girls and women vs boys and men. Women appear more likely to use alcohol to “self-medicate” negative affect or emotional pain (Box 2).^9-12 Men are more likely to use alcohol to enhance pleasurable emotional states, “feel high” or because of social pressures to conform.⁵

Box 2

• Young women with alcohol use problems may benefit from learning strategies to regulate negative emotions and alleviate depression or anxiety symptoms that may be contributing to their drinking.
  
• Young men with alcohol use problems may benefit from learning to manage peer pressure and from finding alternate sources of pleasure enhancement.⁵
  

CASE CONTINUED: Depressed and anxious

Ms. F admits to depressed mood, crying episodes, isolation from others, anhedonia, feelings of guilt, low motivation, difficulty concentrating at work, restless sleep, and weight loss. These symptoms recurred soon after she and her husband separated 4 years ago. She denies suicidal thoughts or suicide attempts.

She suffered similar episodes in the past, including when she was breastfeeding and abstinent from alcohol after the birth of her daughter. Her obstetrician treated her depression with fluoxetine. Problems with anxiety began in high school, especially associated with parties and dating. In college, she often would drink beer before class presentations.

You diagnose alcohol dependence, major depressive disorder, and social phobia. You also ask Ms. F about a history of trauma. She reports that her father was “real harsh” when he was drinking and often hit her and her sister. She also relates being struck by her ex-husband during arguments. Screening with the Clinician-Administered PTSD Scale is negative for posttraumatic stress disorder (PTSD), however.

Comorbid psychiatric disorders

Gender differences in reasons for alcohol use may be related to women’s higher rate of medical and psychiatric comorbidity (Table 2).^6,8,15,16 Vital signs, physical examination, and lab work are helpful for diagnosis and monitoring of medical comorbidities and complications. The gamma-glutamyl transferase (GGT) test for liver disease and carbohydrate deficient transferrin (CDT) test for chronic heavy alcohol consumption are less sensitive and specific in women than in men.¹⁷ Even so, monitoring GGT and CDT results over time may serve as a valuable marker of continued drinking by women.

Mood and anxiety disorders are significantly more common in women than in men among individuals with alcohol use disorders.^15,16 This pattern is not unique to alcohol-dependent persons, however. In the general population:

• women are more likely than men to meet diagnostic criteria for anxiety, depression, bulimia nervosa, and borderline personality disorder
  
• men are more likely than women to meet diagnostic criteria for antisocial personality disorder.¹⁸
  

Comorbid disorders in women with alcohol dependence

Suicide risk. A recent study by Connor et al²⁰ examined suicidal ideation, planning, and attempts in 3,729 alcohol dependent subjects (35% female) and found an association between female gender and both planned (odds ratio [OR] = 3.4) and unplanned suicide attempts (OR = 3.8). Further research is needed to clarify the relationship between female gender, alcohol dependence, and suicide risk, behaviors, and attempts.

Anxiety disorders are the most common psychiatric disorders in women,²¹ and social anxiety and social phobia may play a predisposing role in alcohol dependence.²² Individuals with social anxiety may self-medicate with alcohol as a social lubricant. Some research suggests that anxiety disorders are more severe in alcohol-dependent women than in men with similarly severe alcohol dependence.²²

Therefore, when assessing and treating alcohol-dependent women, screen for trauma history as well as mood and anxiety disorders. To optimize outcomes, treat these disorders simultaneously with the alcohol use disorder.²⁴

Treatment planning

Underuse of treatment programs. Women with alcohol dependence are more likely to seek treatment in primary care or mental health settings, rather than in alcohol treatment settings.^25,26 Women’s underuse of alcohol treatment programs is likely related to:

• greater stigma associated with alcohol use for women as compared with men
  
• socioeconomic factors, including pregnancy, child care, and concerns about child custody issues.²⁵
  

Gender-specific treatment? Women-only treatment programs have been studied because of observed differences in men’s and women’s interaction styles and the hypothesis that men’s traditional societal dominance could negatively affect women in mixed-gender groups.²⁵ Better treatment outcomes have been hypothesized if treatment is tailored to address women’s unique issues: risk factors for alcohol dependence, course of disease progression, medical problems associated with alcohol dependence, and reasons for relapse.

Gender-specific treatment may provide an environment where women—particularly those with a history of trauma from a male perpetrator—feel safe discussing issues related to their alcohol problems. For practical purposes, these programs also may be more likely to address women’s needs for on-site child care, prenatal care, and mental health programming.

A recent study compared a manual-based 12-session women’s recovery group with mixed-gender, manualized group drug counseling (GDC). The women’s recovery group focused on gender-specific topics such as relationships, the caregiver role, trauma, comorbid psychiatric conditions (including eating, mood, and anxiety disorders), and the effects of drug and alcohol use on women’s health. The women’s recovery group was:

• as effective as mixed-gender GDC in reducing substance use during the 12-week treatment
  
• significantly more effective during the 6-month post-treatment phase.²⁸
  

CASE CONTINUED: Developing a treatment plan

Ms. F identifies 3 triggers for her alcohol use: a stressful day at school, arguments with her ex-husband, and feeling lonely. Because these are high-risk situations for relapse, you incorporate strategies to deal with them into her treatment plan. Other factors to consider:

• whether she requires detoxification
  
• an FDA-approved medication for alcohol dependence (acamprosate, oral or injectable naltrexone, or disulfiram)
  
• cognitive-behavioral therapy and medication for major depression and social phobia
  
• referral to psychosocial support groups (such as Alcoholics Anonymous).
  

Three factors determine the need for detoxification: the course of previous alcohol withdrawals (alcoholic hallucinosis, seizures, or delirium tremens), elevated vital signs or other evidence of autonomic hyperactivity such as diaphoresis or tremors, and the patient’s general medical condition. During early recovery, monitor patients closely to assess mood and anxiety symptoms. Blood alcohol tests or GGT and CDT are useful to monitor self-reported abstinence.

Related resources

• National Clearing House for Alcohol and Drug Information. Publications and materials on women and substance abuse. Substance Abuse and Mental Health Services Administration. http://ncadistore.samhsa.gov/catalogresults.aspx?h=drugs&topic=11.
  
• National Institute on Drug Abuse (www.nida.nih.gov). Articles that address women’s health and gender differences. www.drugabuse.gov/NIDA_Notes/NN0013.html.
  

• Acamprosate • Campral
  
• Disulfiram • Antabuse
  
• Fluoxetine • Prozac
  
• Naltrexone • Vivitrol, ReVia
  

Drs. Payne, Back, Wright, and Hartwell report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Brady receives research support from Abbott Laboratories, GlaxoSmithKline, Forest Pharmaceuticals, and Wyeth. She is a consultant and speaker for Pfizer Inc., Eli Lilly and Company, Abbott Laboratories, GlaxoSmithKline, and Forest Pharmaceuticals.

Comment on this article

Ms. F, a 53-year-old high school English teacher, is referred to you by her family physician after she was suspended from work for suspected intoxication. She was divorced 2 years ago from her husband of 20 years, and she says her drinking has escalated to 2 bottles of wine every night. She wants to reduce her alcohol use but experiences shakiness, nausea, and diaphoresis when she tries to cut back.

Ms. F began drinking at age 16 “to feel more comfortable in social situations” and has experienced binge drinking with intermittent blackouts. She denies illicit drug use and legal consequences from drinking. Her father died from cirrhosis at age 58. Her mother suffers from depression but is in remission with medication.

Ms. F is hesitant to date or establish intimate relationships. She has stopped attending church, a book club, and her 15-year-old daughter’s booster club activities.

For years, little was known about alcohol use and alcohol-related problems in women such as Ms. F.¹ Alcohol dependence studies rarely included women, so findings and treatment outcomes observed in men were assumed to apply to both genders.

Awareness of gender differences in addiction has grown (Box 1).^2-5 Biological and psychosocial differences between alcohol-dependent women and men now are understood to influence etiology, epidemiology, psychiatric and medical comorbidity, course of illness, and treatment outcomes. This article discusses recent insights into planning treatment to address specific needs of alcohol-dependent women.

Box 1

Accelerated consequences

As a group, women may consume less alcohol than men but progress more rapidly to alcohol-related illnesses and negative consequences. Specifically, alcohol-dependent women develop liver disease, hypertension, and gastrointestinal hemorrhage more rapidly than alcohol-dependent men.³ Cognitive deficits and brain atrophy also develop sooner in alcohol-dependent women than men.⁶ Causes of this accelerated progression—”telescoping”—include gender-specific biological differences:

• Women have lower levels of gastric alcohol dehydrogenase—the enzyme that initiates alcohol metabolism—and therefore experience a higher blood alcohol concentration than men drinking the same amount of alcohol.
  
• Women have less total body water and less capacity to dilute alcohol than men.
  

‘At-risk’ drinking. Gender-related physiologic differences have led to different thresholds for defining “at-risk drinking” and binge drinking for men and women (Table 1).⁷ Alcohol use also has negative effects on women’s reproductive system and menstrual cycle. Women with alcohol dependence have higher rates of sexual dysfunction, irregular menstrual cycles, early menopause, and amenorrhea as compared with nonalcohol-dependent women.⁸

Table 1

Different thresholds: Number of drinks* that increases risk for alcohol-related problems

Motives for drinking

Research suggests different motives for alcohol use in girls and women vs boys and men. Women appear more likely to use alcohol to “self-medicate” negative affect or emotional pain (Box 2).^9-12 Men are more likely to use alcohol to enhance pleasurable emotional states, “feel high” or because of social pressures to conform.⁵

Box 2

• Young women with alcohol use problems may benefit from learning strategies to regulate negative emotions and alleviate depression or anxiety symptoms that may be contributing to their drinking.
  
• Young men with alcohol use problems may benefit from learning to manage peer pressure and from finding alternate sources of pleasure enhancement.⁵
  

CASE CONTINUED: Depressed and anxious

Ms. F admits to depressed mood, crying episodes, isolation from others, anhedonia, feelings of guilt, low motivation, difficulty concentrating at work, restless sleep, and weight loss. These symptoms recurred soon after she and her husband separated 4 years ago. She denies suicidal thoughts or suicide attempts.

She suffered similar episodes in the past, including when she was breastfeeding and abstinent from alcohol after the birth of her daughter. Her obstetrician treated her depression with fluoxetine. Problems with anxiety began in high school, especially associated with parties and dating. In college, she often would drink beer before class presentations.

You diagnose alcohol dependence, major depressive disorder, and social phobia. You also ask Ms. F about a history of trauma. She reports that her father was “real harsh” when he was drinking and often hit her and her sister. She also relates being struck by her ex-husband during arguments. Screening with the Clinician-Administered PTSD Scale is negative for posttraumatic stress disorder (PTSD), however.

Comorbid psychiatric disorders

Gender differences in reasons for alcohol use may be related to women’s higher rate of medical and psychiatric comorbidity (Table 2).^6,8,15,16 Vital signs, physical examination, and lab work are helpful for diagnosis and monitoring of medical comorbidities and complications. The gamma-glutamyl transferase (GGT) test for liver disease and carbohydrate deficient transferrin (CDT) test for chronic heavy alcohol consumption are less sensitive and specific in women than in men.¹⁷ Even so, monitoring GGT and CDT results over time may serve as a valuable marker of continued drinking by women.

Mood and anxiety disorders are significantly more common in women than in men among individuals with alcohol use disorders.^15,16 This pattern is not unique to alcohol-dependent persons, however. In the general population:

• women are more likely than men to meet diagnostic criteria for anxiety, depression, bulimia nervosa, and borderline personality disorder
  
• men are more likely than women to meet diagnostic criteria for antisocial personality disorder.¹⁸
  

Comorbid disorders in women with alcohol dependence

Suicide risk. A recent study by Connor et al²⁰ examined suicidal ideation, planning, and attempts in 3,729 alcohol dependent subjects (35% female) and found an association between female gender and both planned (odds ratio [OR] = 3.4) and unplanned suicide attempts (OR = 3.8). Further research is needed to clarify the relationship between female gender, alcohol dependence, and suicide risk, behaviors, and attempts.

Anxiety disorders are the most common psychiatric disorders in women,²¹ and social anxiety and social phobia may play a predisposing role in alcohol dependence.²² Individuals with social anxiety may self-medicate with alcohol as a social lubricant. Some research suggests that anxiety disorders are more severe in alcohol-dependent women than in men with similarly severe alcohol dependence.²²

Therefore, when assessing and treating alcohol-dependent women, screen for trauma history as well as mood and anxiety disorders. To optimize outcomes, treat these disorders simultaneously with the alcohol use disorder.²⁴

Treatment planning

Underuse of treatment programs. Women with alcohol dependence are more likely to seek treatment in primary care or mental health settings, rather than in alcohol treatment settings.^25,26 Women’s underuse of alcohol treatment programs is likely related to:

• greater stigma associated with alcohol use for women as compared with men
  
• socioeconomic factors, including pregnancy, child care, and concerns about child custody issues.²⁵
  

Gender-specific treatment? Women-only treatment programs have been studied because of observed differences in men’s and women’s interaction styles and the hypothesis that men’s traditional societal dominance could negatively affect women in mixed-gender groups.²⁵ Better treatment outcomes have been hypothesized if treatment is tailored to address women’s unique issues: risk factors for alcohol dependence, course of disease progression, medical problems associated with alcohol dependence, and reasons for relapse.

Gender-specific treatment may provide an environment where women—particularly those with a history of trauma from a male perpetrator—feel safe discussing issues related to their alcohol problems. For practical purposes, these programs also may be more likely to address women’s needs for on-site child care, prenatal care, and mental health programming.

A recent study compared a manual-based 12-session women’s recovery group with mixed-gender, manualized group drug counseling (GDC). The women’s recovery group focused on gender-specific topics such as relationships, the caregiver role, trauma, comorbid psychiatric conditions (including eating, mood, and anxiety disorders), and the effects of drug and alcohol use on women’s health. The women’s recovery group was:

• as effective as mixed-gender GDC in reducing substance use during the 12-week treatment
  
• significantly more effective during the 6-month post-treatment phase.²⁸
  

CASE CONTINUED: Developing a treatment plan

Ms. F identifies 3 triggers for her alcohol use: a stressful day at school, arguments with her ex-husband, and feeling lonely. Because these are high-risk situations for relapse, you incorporate strategies to deal with them into her treatment plan. Other factors to consider:

• whether she requires detoxification
  
• an FDA-approved medication for alcohol dependence (acamprosate, oral or injectable naltrexone, or disulfiram)
  
• cognitive-behavioral therapy and medication for major depression and social phobia
  
• referral to psychosocial support groups (such as Alcoholics Anonymous).
  

Three factors determine the need for detoxification: the course of previous alcohol withdrawals (alcoholic hallucinosis, seizures, or delirium tremens), elevated vital signs or other evidence of autonomic hyperactivity such as diaphoresis or tremors, and the patient’s general medical condition. During early recovery, monitor patients closely to assess mood and anxiety symptoms. Blood alcohol tests or GGT and CDT are useful to monitor self-reported abstinence.

Related resources

• National Clearing House for Alcohol and Drug Information. Publications and materials on women and substance abuse. Substance Abuse and Mental Health Services Administration. http://ncadistore.samhsa.gov/catalogresults.aspx?h=drugs&topic=11.
  
• National Institute on Drug Abuse (www.nida.nih.gov). Articles that address women’s health and gender differences. www.drugabuse.gov/NIDA_Notes/NN0013.html.
  

• Acamprosate • Campral
  
• Disulfiram • Antabuse
  
• Fluoxetine • Prozac
  
• Naltrexone • Vivitrol, ReVia
  

Drs. Payne, Back, Wright, and Hartwell report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Brady receives research support from Abbott Laboratories, GlaxoSmithKline, Forest Pharmaceuticals, and Wyeth. She is a consultant and speaker for Pfizer Inc., Eli Lilly and Company, Abbott Laboratories, GlaxoSmithKline, and Forest Pharmaceuticals.

Comment on this article

Mrs. S, age 44, is on leave from her job as a bank cashier because depressive symptoms interfered with her performance. At a university-based psychiatric clinic she reports feeling depressed, reduced interest in daily activities, problems with sleep onset and maintenance, inconsistent appetite, low energy, hopelessness, and decreased memory and concentration.

The resident psychiatrist diagnoses major depressive disorder (MDD) and starts Mrs. S on sertraline, 50 mg/d. The dosage is gradually titrated to 200 mg/d, and after 8 weeks she reports substantial improvement.

Mrs. S returns to her job but experiences residual low energy, lethargy, and inconsistent sleep. Her work schedule and caring for her 2 children at home prevent her from continuing weekly cognitive-behavioral therapy (CBT), but she soon notices that she feels more energetic. She reports that because of high gasoline prices she has been walking several miles daily to commute by train to work. The resident psychiatrist sees this as an opportunity to reinforce the benefits of exercise for depression.

Antidepressants alone do not adequately treat many patients with depression. In the STAR*D Project—which compared long-term outcomes of various depression treatments—only 28% to 33% of outpatients achieved remission with selective serotonin reuptake inhibitor (SSRI) monotherapy. Rates were somewhat higher with bupropion or serotonin norepinephrine reuptake inhibitor (SNRI) monotherapy, but greater benefit was obtained from augmenting SSRIs.¹

Combining antidepressants with psychotherapy² and lifestyle changes—particularly exercise—makes sense intuitively and is supported by well-designed studies:

• The 60% of adults in the National Comorbidity Survey who said they exercised regularly reported lower rates of depression and anxiety, compared with less active adults.³
• A meta-analysis of 11 randomized, controlled trials supports the use of exercise as an effective intervention for clinical depression.⁴

Box 1

This article examines the evidence supporting exercise for treating and preventing clinical depression. We begin by addressing clinicians’ concerns about motivating depressed patients to exercise.

Overcoming barriers

Physician issues. Busy physicians often omit discussions about exercise during brief office visits. Only 34% of 9,299 patients in a population-based survey⁵ reported that their doctors counseled them about exercise during their most recent visits. Counseling patients does not have to be time-intensive, however. A study of the Physician-based Assessment and Counseling for Exercise (PACE) project showed that 70% of physicians could provide exercise counseling in 3 to 5 minutes, and most patients reported following their physicians’ advice.⁶

Highly depressed individuals are at risk to quit when they encounter barriers to exercise and to respond to difficulties with frustration and self-disappointment. Thus, depressed patients may need support and encouragement to initiate and maintain regular exercise routines.⁷ Set small, realistic goals for them, and discuss how to solve problems and remove barriers to increase their likelihood to exercise.

Interventions are most likely to be effective when you counsel patients about exercise as prescription and discuss exercise at each visit.⁸ Previously sedentary patients have shown short-term moderate increases in physical activity in response to physician counseling. In a study of 212 adults (mean age 39, 84% female), the PACE project significantly increased minutes of weekly walking.⁹ More than one-half (52%) of patients increased their physical activity, compared with 12% of controls whose physicians did not provide the PACE intervention.

Patient issues. Lack of time and no appropriate space to exercise are common complaints, particularly among residents of regions with long, cold winters. Some patients perceive regular exercise as monotonous or boring, and others may lack the necessary initiative because of poor physical health, fear, negative experiences, or lack of knowledge about exercising. These barriers can be pronounced in older depressed persons. In a cross-sectional study of 645 residents of Jyväskylä, Finland, those age >75 with depressive symptoms were more than twice as likely to be physically inactive as nondepressed residents.¹⁰

An intensive exercise program is not the optimal starting point for many patients. Even walking or light jogging can be an effective exercise for depressed individuals with physical limitations. For these patients, a consultation with their primary physician may be necessary if a more intensive program has to be recommended.

Exercise as monotherapy

A dose-response relationship? Various mechanisms have been suggested for the benefits of exercise in depression (Box 1). Exercise alone—without medication—may be an effective treatment for mild and in some cases moderate MDD, and aerobic exercise may reduce depressive symptoms in a dose-response relationship.¹¹

A study of exercise in a supervised laboratory setting demonstrated this relationship in 80 adults age 20 to 45 with mild-to-moderate depressive symptoms. Subjects were randomly assigned to an exercise control group (3 days/week of flexibility exercise) or 1 of 4 aerobic exercise groups that varied in total energy expenditure (a “low dose” of 7.0 kcal/kg/week or a “public health dose” of 17.5 kcal/kg/week). The 17-item Hamilton Rating Scale for Depression (HRSD) was the primary outcome measure.

After 12 weeks, HRSD scores declined from baseline by 47% in subjects engaged in the public health dose of aerobic exercise—a significant reduction. Depressive symptoms declined by 30% in the low-dose exercisers, but this was comparable to the 29% reduction in the control group.

Comment. The effective exercise dose in this study is similar to the public health recommendation of 30 minutes of moderate-to-vigorous activity on all or most days per week (see Related Resources). Antidepressant effects have been associated with more modest physical activity, however, which may be easier to initiate and maintain for individuals with depression. The study did not find significant differences in outcomes based on the subjects’ age, gender, or exercise frequency. Nevertheless, the exercise dose may be important to produce an antidepressant effect.

An inverse relationship? Compared with occasional exercise, habitual physical activity usually is associated with greater cardiorespiratory fitness. Whether habitual activity also results in fewer depressive symptoms and greater emotional well-being remains to be seen.

A large, cross-sectional, National Institutes of Health-funded study of 5,451 men and 1,277 women¹² suggests an inverse relationship between physical activity and depressive symptoms. Subjects underwent a treadmill exercise test to evaluate physical fitness. A 20-point self-report scale assessed depressive symptoms, and the General Well-Being Schedule¹³ was used to assess emotional well-being. Depressive symptoms were more severe in “inactive” and “insufficiently active” subjects compared with “sufficiently active” and “highly active” subjects.

On the other hand, although regular exercise may be associated with reduced depressive symptoms in the population at large, no cause-effect relationship was found in a population-based, longitudinal study of 5,952 twins.¹⁴

A prospective, randomized, controlled trial¹⁵ suggests that exercise could be an important treatment tool in patients diagnosed with MDD. The 202 adult subjects (153 women, 49 men) were randomly assigned to 1 of 4 treatments:

• supervised exercise in a group setting
• home-based exercise
• antidepressant medication (sertraline, 50 to 200 mg/d)
• placebo pills.

Patients underwent the structured clinical interview for depression and completed the HRSD. After 16 weeks, 41% of participants achieved remission, defined as no longer meeting MDD criteria and a HRSD score <8. Compared with placebo controls, patients receiving active treatments tended to have higher remission rates:

• 45% with supervised exercise
• 40% with home-based exercise
• 47% with medication
• 31% with placebo.

Comment. The placebo response rate was relatively high in this study, and antidepressant dosages might not have been optimal. These factors could explain why remission rates with supervised exercise and antidepressant medication were comparable. The study might have been more reliable if it had included a medication plus exercise arm. Patients treated in an office setting might not fare as well as these study subjects whose exercise was supervised.

Postpartum depression occurs in an estimated 13% of new mothers.¹⁶ In a controlled trial, 80 women with depression at 4 weeks postpartum were assigned to either:

• an exercise support program (1 hour supervised exercise and 2 sessions at home each week for 3 months)
• standard care.

Box 2

No subjects received medication. Women in the exercise support program were less likely to have high scores on the Edinburgh Postnatal Depression Scale, compared with controls. Women who exercised also reported a greater sense of well-being. Differences between the 2 groups were not statistically significant at 4 weeks post partum but achieved significance at 5 months.¹⁷

Depressive symptoms may exacerbate fatigue in postpartum women.¹⁸ A study of 88 women with postpartum depression showed the benefits of a home-based exercise program on physical and mental fatigue.¹⁹ This finding may be important because fatigue often is associated with treatment-resistant depression and may increase the likelihood of relapse in women with postpartum depression.²⁰

Late-life depression. Exercise can benefit the depressed elderly as well. In a 10-week randomized, controlled trial²¹ of volunteers age ≥60 with major or minor depression or dysthymia, progressive resistance training (PRT) significantly reduced depression, as measured by the Beck Depression Inventory (BDI) and HRSD. PRT also improved quality of life, vitality, social functioning, and emotional well-being when compared with a control group (Box 2).

A dose-response relationship of exercise for treating late-life depression was shown in a blinded, controlled trial²² of 60 community-dwelling, depressed subjects age >60. These patients were randomly assigned to high-intensity PRT, low-intensity PRT, or standard care by a general practitioner (GP). A ≥50% reduction in HRSD score was achieved by:

• 61% of the high-intensity PRT group
• 29% of the low-intensity PRT group
• 21% of the GP care group.

Sleep quality improved in all participants, with the greatest relative change in the high-intensity PRT group.

Exercise vs psychotherapy. The benefits of exercise may be comparable or superior to those of cognitive or group psychotherapy.^23,24 This may be good news for patients such as Mrs. S who lack time or financial resources for regular psychotherapy.

Adjunctive exercise

In depressed patients, exercise may increase the perceived quality of life when combined with medication. This was demonstrated in a randomized, 32-week naturalistic study of 30 women, age 40 to 60, with treatment-resistant MDD.²⁵ The 10 women who received various antidepressants plus physical exercise showed significantly greater long-term improvement in depression symptoms, as measured by the HRSD and Global Assessment of Functioning (GAF) scores, compared with 20 women who received pharmacotherapy alone.²⁶ Study limitations included the absence of a placebo arm, small sample size, and inclusion of subjects with comorbid anxiety disorders.

Group aerobic exercise programs can be an effective and feasible treatment for depression, particularly for older adults. In a controlled trial,²⁷ 156 men and women age >50 with MDD were randomly assigned to 3 groups: a program of aerobic exercise; sertraline, ≤200 mg/d; or exercise plus sertraline. HRSD and BDI scores before and after treatment were the primary outcome measures. Secondary measures included aerobic capacity, life satisfaction, self-esteem, anxiety, and dysfunctional cognitions. After 16 weeks of treatment, similar percentages of patients in each group no longer met DSM-IV-TR criteria for MDD:

• 60.4% of patients in the exercise-only group
• 68.8% of patients in the medication-only group
• 65.5% of patients receiving exercise plus medication.

Depression severity appeared to predict the rate of response to the different treatments. Patients who received medication alone seemed to have the most rapid response to treatment. Patients with less severe depression appeared to respond more quickly to exercise plus medication than those with more severe depression.

Long-term benefits

Because depression is a chronic, relapsing illness, any treatment will be widely accepted only if its benefits are long-term. A study of aerobic exercise in 156 adults age ≥50 with MDD²⁸ found that benefits were sustained for >6 months.

Participants were randomly assigned to 4 months of aerobic exercise; sertraline, ≤200 mg/d; or a combination of exercise and sertraline. Aerobic exercise consisted of 30 minutes of brisk walking and jogging on a treadmill, with training ranges equivalent to 70% to 85% of individuals’ maximum heart rate. Appropriate warm-up and cool-down sessions of 5 to 10 minutes were included.

Depressive symptoms improved significantly from baseline in all 3 groups—as assessed by clinical interview, HRSD, and BDI—and after 4 months a comparable number in each group no longer met diagnostic criteria for MDD. When subjects were reassessed 6 months later, the exercisers had significantly lower relapse rates than those receiving medication (P=.01). Those who continued to exercise also were less likely to meet MDD criteria at the end of the 10-month study.

Box 3

Even when unsupervised, exercise can have long-term benefits—as was shown in a randomized, blinded, controlled study of 32 elderly subjects.²⁹ An active treatment group underwent 10 weeks of supervised weight lifting, followed by 10 weeks of unsupervised exercise. Controls received no active treatment. Depression scores as measured by BDI were significantly lower at 20 weeks and 26 months in exercisers compared with controls. An antidepressant effect was seen in 73% of exercisers vs 36% of controls at 20 weeks of treatment.

Comment. These studies show that exercise can maintain an anti depressant effect for 10 to 26 months, but additional randomized controlled studies are needed.

Preventing depression? Inactive nondepressed individuals may be at greater risk to develop depression compared with active individuals, according to a 29-year longitudinal study of Californians age 17 to 94. This association was somewhat diminished when findings were adjusted for the Alameda County residents’ physical health, socioeconomic status, social supports, life events, and other health habits.³⁰ The authors recommended that exercise programs be offered in community mental health programs.

Box 4

Simple steps to build physical activity into daily life

CASE CONTINUED: Removing barriers to exercise

The resident psychiatrist treating Mrs. S encourages her to join an aerobic exercise class at the nearby fitness facility. Because cost is a potential barrier, he helps her negotiate a discount for the first 6 months of membership. Her husband agrees in a joint counseling session to help more with the care of their children so that she can attend the classes.

With continued sertraline, 200 mg/d, and aerobic exercise, Mrs. S’s residual depressive symptoms gradually improve. She still has days when she is unable to attend the exercise classes, but she benefits from the program and is functioning better at work and home.

Getting started

We recommend that psychiatrists inquire about physical activity at every visit to gauge patients’ perception and motivation to exercise. Find ways to overcome patients’ fears and negative experiences with exercise. Provide information to help increase physical activity among patients with depressive symptoms¹⁰ (see Related Resources).

Encourage patients to take steps each day to increase their physical activity (Box 3). Depending on the severity of the individual’s depression and inactivity, a realistic starting point may be to take the stairs instead of an elevator, play with children and pets, or take short brisk walks in the yard or neighborhood (Box 4). Consider stationary bikes or swimming as alternatives for physically handicapped individuals and patients who have undergone knee replacements.

Related resources

• 2008 physical activity guidelines for Americans. U.S. Department of Health and Human Services; 2008:vi-viii. www.health.gov/paguidelines.
• American College of Sports Medicine/American Health Association physical activity guidelines and keys to exercise success. www.acsm.org.
• American Heart Association. www.americanheart.org.
• U.S. Department of Health and Human Services. Quick Guide for Healthy Living. Get Active. www.healthfinder.gov/prevention/ViewTopic.aspx?topicID=22.

Drug brand names

• Bupropion • Wellbutrin
• Sertraline • Zoloft

Disclosure

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

Comment on this article

Mrs. S, age 44, is on leave from her job as a bank cashier because depressive symptoms interfered with her performance. At a university-based psychiatric clinic she reports feeling depressed, reduced interest in daily activities, problems with sleep onset and maintenance, inconsistent appetite, low energy, hopelessness, and decreased memory and concentration.

The resident psychiatrist diagnoses major depressive disorder (MDD) and starts Mrs. S on sertraline, 50 mg/d. The dosage is gradually titrated to 200 mg/d, and after 8 weeks she reports substantial improvement.

Mrs. S returns to her job but experiences residual low energy, lethargy, and inconsistent sleep. Her work schedule and caring for her 2 children at home prevent her from continuing weekly cognitive-behavioral therapy (CBT), but she soon notices that she feels more energetic. She reports that because of high gasoline prices she has been walking several miles daily to commute by train to work. The resident psychiatrist sees this as an opportunity to reinforce the benefits of exercise for depression.

Antidepressants alone do not adequately treat many patients with depression. In the STAR*D Project—which compared long-term outcomes of various depression treatments—only 28% to 33% of outpatients achieved remission with selective serotonin reuptake inhibitor (SSRI) monotherapy. Rates were somewhat higher with bupropion or serotonin norepinephrine reuptake inhibitor (SNRI) monotherapy, but greater benefit was obtained from augmenting SSRIs.¹

Combining antidepressants with psychotherapy² and lifestyle changes—particularly exercise—makes sense intuitively and is supported by well-designed studies:

• The 60% of adults in the National Comorbidity Survey who said they exercised regularly reported lower rates of depression and anxiety, compared with less active adults.³
• A meta-analysis of 11 randomized, controlled trials supports the use of exercise as an effective intervention for clinical depression.⁴

Box 1

This article examines the evidence supporting exercise for treating and preventing clinical depression. We begin by addressing clinicians’ concerns about motivating depressed patients to exercise.

Overcoming barriers

Physician issues. Busy physicians often omit discussions about exercise during brief office visits. Only 34% of 9,299 patients in a population-based survey⁵ reported that their doctors counseled them about exercise during their most recent visits. Counseling patients does not have to be time-intensive, however. A study of the Physician-based Assessment and Counseling for Exercise (PACE) project showed that 70% of physicians could provide exercise counseling in 3 to 5 minutes, and most patients reported following their physicians’ advice.⁶

Highly depressed individuals are at risk to quit when they encounter barriers to exercise and to respond to difficulties with frustration and self-disappointment. Thus, depressed patients may need support and encouragement to initiate and maintain regular exercise routines.⁷ Set small, realistic goals for them, and discuss how to solve problems and remove barriers to increase their likelihood to exercise.

Interventions are most likely to be effective when you counsel patients about exercise as prescription and discuss exercise at each visit.⁸ Previously sedentary patients have shown short-term moderate increases in physical activity in response to physician counseling. In a study of 212 adults (mean age 39, 84% female), the PACE project significantly increased minutes of weekly walking.⁹ More than one-half (52%) of patients increased their physical activity, compared with 12% of controls whose physicians did not provide the PACE intervention.

Patient issues. Lack of time and no appropriate space to exercise are common complaints, particularly among residents of regions with long, cold winters. Some patients perceive regular exercise as monotonous or boring, and others may lack the necessary initiative because of poor physical health, fear, negative experiences, or lack of knowledge about exercising. These barriers can be pronounced in older depressed persons. In a cross-sectional study of 645 residents of Jyväskylä, Finland, those age >75 with depressive symptoms were more than twice as likely to be physically inactive as nondepressed residents.¹⁰

An intensive exercise program is not the optimal starting point for many patients. Even walking or light jogging can be an effective exercise for depressed individuals with physical limitations. For these patients, a consultation with their primary physician may be necessary if a more intensive program has to be recommended.

Exercise as monotherapy

A dose-response relationship? Various mechanisms have been suggested for the benefits of exercise in depression (Box 1). Exercise alone—without medication—may be an effective treatment for mild and in some cases moderate MDD, and aerobic exercise may reduce depressive symptoms in a dose-response relationship.¹¹

A study of exercise in a supervised laboratory setting demonstrated this relationship in 80 adults age 20 to 45 with mild-to-moderate depressive symptoms. Subjects were randomly assigned to an exercise control group (3 days/week of flexibility exercise) or 1 of 4 aerobic exercise groups that varied in total energy expenditure (a “low dose” of 7.0 kcal/kg/week or a “public health dose” of 17.5 kcal/kg/week). The 17-item Hamilton Rating Scale for Depression (HRSD) was the primary outcome measure.

After 12 weeks, HRSD scores declined from baseline by 47% in subjects engaged in the public health dose of aerobic exercise—a significant reduction. Depressive symptoms declined by 30% in the low-dose exercisers, but this was comparable to the 29% reduction in the control group.

Comment. The effective exercise dose in this study is similar to the public health recommendation of 30 minutes of moderate-to-vigorous activity on all or most days per week (see Related Resources). Antidepressant effects have been associated with more modest physical activity, however, which may be easier to initiate and maintain for individuals with depression. The study did not find significant differences in outcomes based on the subjects’ age, gender, or exercise frequency. Nevertheless, the exercise dose may be important to produce an antidepressant effect.

An inverse relationship? Compared with occasional exercise, habitual physical activity usually is associated with greater cardiorespiratory fitness. Whether habitual activity also results in fewer depressive symptoms and greater emotional well-being remains to be seen.

A large, cross-sectional, National Institutes of Health-funded study of 5,451 men and 1,277 women¹² suggests an inverse relationship between physical activity and depressive symptoms. Subjects underwent a treadmill exercise test to evaluate physical fitness. A 20-point self-report scale assessed depressive symptoms, and the General Well-Being Schedule¹³ was used to assess emotional well-being. Depressive symptoms were more severe in “inactive” and “insufficiently active” subjects compared with “sufficiently active” and “highly active” subjects.

On the other hand, although regular exercise may be associated with reduced depressive symptoms in the population at large, no cause-effect relationship was found in a population-based, longitudinal study of 5,952 twins.¹⁴

A prospective, randomized, controlled trial¹⁵ suggests that exercise could be an important treatment tool in patients diagnosed with MDD. The 202 adult subjects (153 women, 49 men) were randomly assigned to 1 of 4 treatments:

• supervised exercise in a group setting
• home-based exercise
• antidepressant medication (sertraline, 50 to 200 mg/d)
• placebo pills.

Patients underwent the structured clinical interview for depression and completed the HRSD. After 16 weeks, 41% of participants achieved remission, defined as no longer meeting MDD criteria and a HRSD score <8. Compared with placebo controls, patients receiving active treatments tended to have higher remission rates:

• 45% with supervised exercise
• 40% with home-based exercise
• 47% with medication
• 31% with placebo.

Comment. The placebo response rate was relatively high in this study, and antidepressant dosages might not have been optimal. These factors could explain why remission rates with supervised exercise and antidepressant medication were comparable. The study might have been more reliable if it had included a medication plus exercise arm. Patients treated in an office setting might not fare as well as these study subjects whose exercise was supervised.

Postpartum depression occurs in an estimated 13% of new mothers.¹⁶ In a controlled trial, 80 women with depression at 4 weeks postpartum were assigned to either:

• an exercise support program (1 hour supervised exercise and 2 sessions at home each week for 3 months)
• standard care.

Box 2

No subjects received medication. Women in the exercise support program were less likely to have high scores on the Edinburgh Postnatal Depression Scale, compared with controls. Women who exercised also reported a greater sense of well-being. Differences between the 2 groups were not statistically significant at 4 weeks post partum but achieved significance at 5 months.¹⁷

Depressive symptoms may exacerbate fatigue in postpartum women.¹⁸ A study of 88 women with postpartum depression showed the benefits of a home-based exercise program on physical and mental fatigue.¹⁹ This finding may be important because fatigue often is associated with treatment-resistant depression and may increase the likelihood of relapse in women with postpartum depression.²⁰

Late-life depression. Exercise can benefit the depressed elderly as well. In a 10-week randomized, controlled trial²¹ of volunteers age ≥60 with major or minor depression or dysthymia, progressive resistance training (PRT) significantly reduced depression, as measured by the Beck Depression Inventory (BDI) and HRSD. PRT also improved quality of life, vitality, social functioning, and emotional well-being when compared with a control group (Box 2).

A dose-response relationship of exercise for treating late-life depression was shown in a blinded, controlled trial²² of 60 community-dwelling, depressed subjects age >60. These patients were randomly assigned to high-intensity PRT, low-intensity PRT, or standard care by a general practitioner (GP). A ≥50% reduction in HRSD score was achieved by:

• 61% of the high-intensity PRT group
• 29% of the low-intensity PRT group
• 21% of the GP care group.

Sleep quality improved in all participants, with the greatest relative change in the high-intensity PRT group.

Exercise vs psychotherapy. The benefits of exercise may be comparable or superior to those of cognitive or group psychotherapy.^23,24 This may be good news for patients such as Mrs. S who lack time or financial resources for regular psychotherapy.

Adjunctive exercise

In depressed patients, exercise may increase the perceived quality of life when combined with medication. This was demonstrated in a randomized, 32-week naturalistic study of 30 women, age 40 to 60, with treatment-resistant MDD.²⁵ The 10 women who received various antidepressants plus physical exercise showed significantly greater long-term improvement in depression symptoms, as measured by the HRSD and Global Assessment of Functioning (GAF) scores, compared with 20 women who received pharmacotherapy alone.²⁶ Study limitations included the absence of a placebo arm, small sample size, and inclusion of subjects with comorbid anxiety disorders.

Group aerobic exercise programs can be an effective and feasible treatment for depression, particularly for older adults. In a controlled trial,²⁷ 156 men and women age >50 with MDD were randomly assigned to 3 groups: a program of aerobic exercise; sertraline, ≤200 mg/d; or exercise plus sertraline. HRSD and BDI scores before and after treatment were the primary outcome measures. Secondary measures included aerobic capacity, life satisfaction, self-esteem, anxiety, and dysfunctional cognitions. After 16 weeks of treatment, similar percentages of patients in each group no longer met DSM-IV-TR criteria for MDD:

• 60.4% of patients in the exercise-only group
• 68.8% of patients in the medication-only group
• 65.5% of patients receiving exercise plus medication.

Depression severity appeared to predict the rate of response to the different treatments. Patients who received medication alone seemed to have the most rapid response to treatment. Patients with less severe depression appeared to respond more quickly to exercise plus medication than those with more severe depression.

Long-term benefits

Because depression is a chronic, relapsing illness, any treatment will be widely accepted only if its benefits are long-term. A study of aerobic exercise in 156 adults age ≥50 with MDD²⁸ found that benefits were sustained for >6 months.

Participants were randomly assigned to 4 months of aerobic exercise; sertraline, ≤200 mg/d; or a combination of exercise and sertraline. Aerobic exercise consisted of 30 minutes of brisk walking and jogging on a treadmill, with training ranges equivalent to 70% to 85% of individuals’ maximum heart rate. Appropriate warm-up and cool-down sessions of 5 to 10 minutes were included.

Depressive symptoms improved significantly from baseline in all 3 groups—as assessed by clinical interview, HRSD, and BDI—and after 4 months a comparable number in each group no longer met diagnostic criteria for MDD. When subjects were reassessed 6 months later, the exercisers had significantly lower relapse rates than those receiving medication (P=.01). Those who continued to exercise also were less likely to meet MDD criteria at the end of the 10-month study.

Box 3

Even when unsupervised, exercise can have long-term benefits—as was shown in a randomized, blinded, controlled study of 32 elderly subjects.²⁹ An active treatment group underwent 10 weeks of supervised weight lifting, followed by 10 weeks of unsupervised exercise. Controls received no active treatment. Depression scores as measured by BDI were significantly lower at 20 weeks and 26 months in exercisers compared with controls. An antidepressant effect was seen in 73% of exercisers vs 36% of controls at 20 weeks of treatment.

Comment. These studies show that exercise can maintain an anti depressant effect for 10 to 26 months, but additional randomized controlled studies are needed.

Preventing depression? Inactive nondepressed individuals may be at greater risk to develop depression compared with active individuals, according to a 29-year longitudinal study of Californians age 17 to 94. This association was somewhat diminished when findings were adjusted for the Alameda County residents’ physical health, socioeconomic status, social supports, life events, and other health habits.³⁰ The authors recommended that exercise programs be offered in community mental health programs.

Box 4

Simple steps to build physical activity into daily life

CASE CONTINUED: Removing barriers to exercise

The resident psychiatrist treating Mrs. S encourages her to join an aerobic exercise class at the nearby fitness facility. Because cost is a potential barrier, he helps her negotiate a discount for the first 6 months of membership. Her husband agrees in a joint counseling session to help more with the care of their children so that she can attend the classes.

With continued sertraline, 200 mg/d, and aerobic exercise, Mrs. S’s residual depressive symptoms gradually improve. She still has days when she is unable to attend the exercise classes, but she benefits from the program and is functioning better at work and home.

Getting started

We recommend that psychiatrists inquire about physical activity at every visit to gauge patients’ perception and motivation to exercise. Find ways to overcome patients’ fears and negative experiences with exercise. Provide information to help increase physical activity among patients with depressive symptoms¹⁰ (see Related Resources).

Encourage patients to take steps each day to increase their physical activity (Box 3). Depending on the severity of the individual’s depression and inactivity, a realistic starting point may be to take the stairs instead of an elevator, play with children and pets, or take short brisk walks in the yard or neighborhood (Box 4). Consider stationary bikes or swimming as alternatives for physically handicapped individuals and patients who have undergone knee replacements.

Related resources

• 2008 physical activity guidelines for Americans. U.S. Department of Health and Human Services; 2008:vi-viii. www.health.gov/paguidelines.
• American College of Sports Medicine/American Health Association physical activity guidelines and keys to exercise success. www.acsm.org.
• American Heart Association. www.americanheart.org.
• U.S. Department of Health and Human Services. Quick Guide for Healthy Living. Get Active. www.healthfinder.gov/prevention/ViewTopic.aspx?topicID=22.

Drug brand names

• Bupropion • Wellbutrin
• Sertraline • Zoloft

Disclosure

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

Comment on this article

Mrs. S, age 44, is on leave from her job as a bank cashier because depressive symptoms interfered with her performance. At a university-based psychiatric clinic she reports feeling depressed, reduced interest in daily activities, problems with sleep onset and maintenance, inconsistent appetite, low energy, hopelessness, and decreased memory and concentration.

The resident psychiatrist diagnoses major depressive disorder (MDD) and starts Mrs. S on sertraline, 50 mg/d. The dosage is gradually titrated to 200 mg/d, and after 8 weeks she reports substantial improvement.

Mrs. S returns to her job but experiences residual low energy, lethargy, and inconsistent sleep. Her work schedule and caring for her 2 children at home prevent her from continuing weekly cognitive-behavioral therapy (CBT), but she soon notices that she feels more energetic. She reports that because of high gasoline prices she has been walking several miles daily to commute by train to work. The resident psychiatrist sees this as an opportunity to reinforce the benefits of exercise for depression.

Antidepressants alone do not adequately treat many patients with depression. In the STAR*D Project—which compared long-term outcomes of various depression treatments—only 28% to 33% of outpatients achieved remission with selective serotonin reuptake inhibitor (SSRI) monotherapy. Rates were somewhat higher with bupropion or serotonin norepinephrine reuptake inhibitor (SNRI) monotherapy, but greater benefit was obtained from augmenting SSRIs.¹

Combining antidepressants with psychotherapy² and lifestyle changes—particularly exercise—makes sense intuitively and is supported by well-designed studies:

• The 60% of adults in the National Comorbidity Survey who said they exercised regularly reported lower rates of depression and anxiety, compared with less active adults.³
• A meta-analysis of 11 randomized, controlled trials supports the use of exercise as an effective intervention for clinical depression.⁴

Box 1

This article examines the evidence supporting exercise for treating and preventing clinical depression. We begin by addressing clinicians’ concerns about motivating depressed patients to exercise.

Overcoming barriers

Physician issues. Busy physicians often omit discussions about exercise during brief office visits. Only 34% of 9,299 patients in a population-based survey⁵ reported that their doctors counseled them about exercise during their most recent visits. Counseling patients does not have to be time-intensive, however. A study of the Physician-based Assessment and Counseling for Exercise (PACE) project showed that 70% of physicians could provide exercise counseling in 3 to 5 minutes, and most patients reported following their physicians’ advice.⁶

Highly depressed individuals are at risk to quit when they encounter barriers to exercise and to respond to difficulties with frustration and self-disappointment. Thus, depressed patients may need support and encouragement to initiate and maintain regular exercise routines.⁷ Set small, realistic goals for them, and discuss how to solve problems and remove barriers to increase their likelihood to exercise.

Interventions are most likely to be effective when you counsel patients about exercise as prescription and discuss exercise at each visit.⁸ Previously sedentary patients have shown short-term moderate increases in physical activity in response to physician counseling. In a study of 212 adults (mean age 39, 84% female), the PACE project significantly increased minutes of weekly walking.⁹ More than one-half (52%) of patients increased their physical activity, compared with 12% of controls whose physicians did not provide the PACE intervention.

Patient issues. Lack of time and no appropriate space to exercise are common complaints, particularly among residents of regions with long, cold winters. Some patients perceive regular exercise as monotonous or boring, and others may lack the necessary initiative because of poor physical health, fear, negative experiences, or lack of knowledge about exercising. These barriers can be pronounced in older depressed persons. In a cross-sectional study of 645 residents of Jyväskylä, Finland, those age >75 with depressive symptoms were more than twice as likely to be physically inactive as nondepressed residents.¹⁰

An intensive exercise program is not the optimal starting point for many patients. Even walking or light jogging can be an effective exercise for depressed individuals with physical limitations. For these patients, a consultation with their primary physician may be necessary if a more intensive program has to be recommended.

Exercise as monotherapy

A dose-response relationship? Various mechanisms have been suggested for the benefits of exercise in depression (Box 1). Exercise alone—without medication—may be an effective treatment for mild and in some cases moderate MDD, and aerobic exercise may reduce depressive symptoms in a dose-response relationship.¹¹

A study of exercise in a supervised laboratory setting demonstrated this relationship in 80 adults age 20 to 45 with mild-to-moderate depressive symptoms. Subjects were randomly assigned to an exercise control group (3 days/week of flexibility exercise) or 1 of 4 aerobic exercise groups that varied in total energy expenditure (a “low dose” of 7.0 kcal/kg/week or a “public health dose” of 17.5 kcal/kg/week). The 17-item Hamilton Rating Scale for Depression (HRSD) was the primary outcome measure.

After 12 weeks, HRSD scores declined from baseline by 47% in subjects engaged in the public health dose of aerobic exercise—a significant reduction. Depressive symptoms declined by 30% in the low-dose exercisers, but this was comparable to the 29% reduction in the control group.

Comment. The effective exercise dose in this study is similar to the public health recommendation of 30 minutes of moderate-to-vigorous activity on all or most days per week (see Related Resources). Antidepressant effects have been associated with more modest physical activity, however, which may be easier to initiate and maintain for individuals with depression. The study did not find significant differences in outcomes based on the subjects’ age, gender, or exercise frequency. Nevertheless, the exercise dose may be important to produce an antidepressant effect.

An inverse relationship? Compared with occasional exercise, habitual physical activity usually is associated with greater cardiorespiratory fitness. Whether habitual activity also results in fewer depressive symptoms and greater emotional well-being remains to be seen.

A large, cross-sectional, National Institutes of Health-funded study of 5,451 men and 1,277 women¹² suggests an inverse relationship between physical activity and depressive symptoms. Subjects underwent a treadmill exercise test to evaluate physical fitness. A 20-point self-report scale assessed depressive symptoms, and the General Well-Being Schedule¹³ was used to assess emotional well-being. Depressive symptoms were more severe in “inactive” and “insufficiently active” subjects compared with “sufficiently active” and “highly active” subjects.

On the other hand, although regular exercise may be associated with reduced depressive symptoms in the population at large, no cause-effect relationship was found in a population-based, longitudinal study of 5,952 twins.¹⁴

A prospective, randomized, controlled trial¹⁵ suggests that exercise could be an important treatment tool in patients diagnosed with MDD. The 202 adult subjects (153 women, 49 men) were randomly assigned to 1 of 4 treatments:

• supervised exercise in a group setting
• home-based exercise
• antidepressant medication (sertraline, 50 to 200 mg/d)
• placebo pills.

Patients underwent the structured clinical interview for depression and completed the HRSD. After 16 weeks, 41% of participants achieved remission, defined as no longer meeting MDD criteria and a HRSD score <8. Compared with placebo controls, patients receiving active treatments tended to have higher remission rates:

• 45% with supervised exercise
• 40% with home-based exercise
• 47% with medication
• 31% with placebo.

Comment. The placebo response rate was relatively high in this study, and antidepressant dosages might not have been optimal. These factors could explain why remission rates with supervised exercise and antidepressant medication were comparable. The study might have been more reliable if it had included a medication plus exercise arm. Patients treated in an office setting might not fare as well as these study subjects whose exercise was supervised.

Postpartum depression occurs in an estimated 13% of new mothers.¹⁶ In a controlled trial, 80 women with depression at 4 weeks postpartum were assigned to either:

• an exercise support program (1 hour supervised exercise and 2 sessions at home each week for 3 months)
• standard care.

Box 2

No subjects received medication. Women in the exercise support program were less likely to have high scores on the Edinburgh Postnatal Depression Scale, compared with controls. Women who exercised also reported a greater sense of well-being. Differences between the 2 groups were not statistically significant at 4 weeks post partum but achieved significance at 5 months.¹⁷

Depressive symptoms may exacerbate fatigue in postpartum women.¹⁸ A study of 88 women with postpartum depression showed the benefits of a home-based exercise program on physical and mental fatigue.¹⁹ This finding may be important because fatigue often is associated with treatment-resistant depression and may increase the likelihood of relapse in women with postpartum depression.²⁰

Late-life depression. Exercise can benefit the depressed elderly as well. In a 10-week randomized, controlled trial²¹ of volunteers age ≥60 with major or minor depression or dysthymia, progressive resistance training (PRT) significantly reduced depression, as measured by the Beck Depression Inventory (BDI) and HRSD. PRT also improved quality of life, vitality, social functioning, and emotional well-being when compared with a control group (Box 2).

A dose-response relationship of exercise for treating late-life depression was shown in a blinded, controlled trial²² of 60 community-dwelling, depressed subjects age >60. These patients were randomly assigned to high-intensity PRT, low-intensity PRT, or standard care by a general practitioner (GP). A ≥50% reduction in HRSD score was achieved by:

• 61% of the high-intensity PRT group
• 29% of the low-intensity PRT group
• 21% of the GP care group.

Sleep quality improved in all participants, with the greatest relative change in the high-intensity PRT group.

Exercise vs psychotherapy. The benefits of exercise may be comparable or superior to those of cognitive or group psychotherapy.^23,24 This may be good news for patients such as Mrs. S who lack time or financial resources for regular psychotherapy.

Adjunctive exercise

In depressed patients, exercise may increase the perceived quality of life when combined with medication. This was demonstrated in a randomized, 32-week naturalistic study of 30 women, age 40 to 60, with treatment-resistant MDD.²⁵ The 10 women who received various antidepressants plus physical exercise showed significantly greater long-term improvement in depression symptoms, as measured by the HRSD and Global Assessment of Functioning (GAF) scores, compared with 20 women who received pharmacotherapy alone.²⁶ Study limitations included the absence of a placebo arm, small sample size, and inclusion of subjects with comorbid anxiety disorders.

Group aerobic exercise programs can be an effective and feasible treatment for depression, particularly for older adults. In a controlled trial,²⁷ 156 men and women age >50 with MDD were randomly assigned to 3 groups: a program of aerobic exercise; sertraline, ≤200 mg/d; or exercise plus sertraline. HRSD and BDI scores before and after treatment were the primary outcome measures. Secondary measures included aerobic capacity, life satisfaction, self-esteem, anxiety, and dysfunctional cognitions. After 16 weeks of treatment, similar percentages of patients in each group no longer met DSM-IV-TR criteria for MDD:

• 60.4% of patients in the exercise-only group
• 68.8% of patients in the medication-only group
• 65.5% of patients receiving exercise plus medication.

Depression severity appeared to predict the rate of response to the different treatments. Patients who received medication alone seemed to have the most rapid response to treatment. Patients with less severe depression appeared to respond more quickly to exercise plus medication than those with more severe depression.

Long-term benefits

Because depression is a chronic, relapsing illness, any treatment will be widely accepted only if its benefits are long-term. A study of aerobic exercise in 156 adults age ≥50 with MDD²⁸ found that benefits were sustained for >6 months.

Participants were randomly assigned to 4 months of aerobic exercise; sertraline, ≤200 mg/d; or a combination of exercise and sertraline. Aerobic exercise consisted of 30 minutes of brisk walking and jogging on a treadmill, with training ranges equivalent to 70% to 85% of individuals’ maximum heart rate. Appropriate warm-up and cool-down sessions of 5 to 10 minutes were included.

Depressive symptoms improved significantly from baseline in all 3 groups—as assessed by clinical interview, HRSD, and BDI—and after 4 months a comparable number in each group no longer met diagnostic criteria for MDD. When subjects were reassessed 6 months later, the exercisers had significantly lower relapse rates than those receiving medication (P=.01). Those who continued to exercise also were less likely to meet MDD criteria at the end of the 10-month study.

Box 3

Even when unsupervised, exercise can have long-term benefits—as was shown in a randomized, blinded, controlled study of 32 elderly subjects.²⁹ An active treatment group underwent 10 weeks of supervised weight lifting, followed by 10 weeks of unsupervised exercise. Controls received no active treatment. Depression scores as measured by BDI were significantly lower at 20 weeks and 26 months in exercisers compared with controls. An antidepressant effect was seen in 73% of exercisers vs 36% of controls at 20 weeks of treatment.

Comment. These studies show that exercise can maintain an anti depressant effect for 10 to 26 months, but additional randomized controlled studies are needed.

Preventing depression? Inactive nondepressed individuals may be at greater risk to develop depression compared with active individuals, according to a 29-year longitudinal study of Californians age 17 to 94. This association was somewhat diminished when findings were adjusted for the Alameda County residents’ physical health, socioeconomic status, social supports, life events, and other health habits.³⁰ The authors recommended that exercise programs be offered in community mental health programs.

Box 4

Simple steps to build physical activity into daily life

CASE CONTINUED: Removing barriers to exercise

The resident psychiatrist treating Mrs. S encourages her to join an aerobic exercise class at the nearby fitness facility. Because cost is a potential barrier, he helps her negotiate a discount for the first 6 months of membership. Her husband agrees in a joint counseling session to help more with the care of their children so that she can attend the classes.

With continued sertraline, 200 mg/d, and aerobic exercise, Mrs. S’s residual depressive symptoms gradually improve. She still has days when she is unable to attend the exercise classes, but she benefits from the program and is functioning better at work and home.

Getting started

We recommend that psychiatrists inquire about physical activity at every visit to gauge patients’ perception and motivation to exercise. Find ways to overcome patients’ fears and negative experiences with exercise. Provide information to help increase physical activity among patients with depressive symptoms¹⁰ (see Related Resources).

Encourage patients to take steps each day to increase their physical activity (Box 3). Depending on the severity of the individual’s depression and inactivity, a realistic starting point may be to take the stairs instead of an elevator, play with children and pets, or take short brisk walks in the yard or neighborhood (Box 4). Consider stationary bikes or swimming as alternatives for physically handicapped individuals and patients who have undergone knee replacements.

Related resources

• 2008 physical activity guidelines for Americans. U.S. Department of Health and Human Services; 2008:vi-viii. www.health.gov/paguidelines.
• American College of Sports Medicine/American Health Association physical activity guidelines and keys to exercise success. www.acsm.org.
• American Heart Association. www.americanheart.org.
• U.S. Department of Health and Human Services. Quick Guide for Healthy Living. Get Active. www.healthfinder.gov/prevention/ViewTopic.aspx?topicID=22.

Drug brand names

• Bupropion • Wellbutrin
• Sertraline • Zoloft

Disclosure

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