Evidence-Based Reviews

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Many psychiatric and medical illnesses—as well as normal reactions to stressors—have symptoms that overlap with those of depressive disorders, including outwardly sad or dysphoric appearance, irritability, apathy or amotivation, fatigue, difficulty making decisions, social withdrawal, and sleep disturbances. This cluster of symptoms forms a readily observable behavioral phenotype that clinicians may label as depression before considering a broader differential diagnosis.

To better understand what other conditions belong in the differential diagnosis, we reviewed a sample of 100 consecutive medical/surgical inpatients referred to our consultation-liaison psychiatry practice for evaluation of “depression.” Ultimately, only 29 of these patients received a depression diagnosis. Many of the other diagnoses given in our sample required attention during inpatient medical or surgical care because they were potentially life-threatening if left unaddressed—such as delirium—or they interfered with managing the primary medical or surgical condition for which the patient was hospitalized.

Hurried or uncertain primary care clinicians frequently use “depression” as a catch-all term when requesting psychiatric consultation for patients who seem depressed. A wide range of conditions can mimic depression, and the art of psychosomatic psychiatry includes considering protean possibilities when assessing a patient. We identified 7 diagnoses that mimic major depression and developed our “8 D” differential to help clinicians properly diagnose “depressed” patients who have something other than a depressive disorder. Although our sample consisted of hospitalized patients, these mimics of depression may be found among patients referred from other clinical settings for evaluation of possible depression.

The perils of misdiagnosis

Depression is common among patients hospitalized with medical or surgical conditions. DSM-IV-TR diagnostic criteria for a major depressive episode (MDE) include the presence of low mood and/or anhedonia, plus ≥4 other depressive symptoms for ≥2 weeks.¹ Growing evidence suggests that the relationship between depression and morbidity and mortality in medical illness is bidirectional, and nonpsychiatrists are becoming increasingly aware of major depression’s serious impact on their patients’ physical health.^2-5

Although improving nonpsychiatrists’ recognition of depression in medically ill patients is laudable, it comes with a high false-positive rate. In a study of primary care outpatients, Berardi et al found that 45% of patients labeled “depressed” did not meet ICD-10 criteria for major depression, but >25% of those patients were prescribed an antidepressant.⁶ In a large retrospective study, Boland et al found that approximately 40% of patients referred to an inpatient psychiatric consultation service for depression did not meet criteria for a depressive illness, and primary medical services often confused organic syndromes such as delirium and dementia with depression.⁷ Similarly, Clarke et al found that 26% of medical and surgical inpatients referred to psychiatry with “depression” had another diagnosis—commonly delirium—that better accounted for their symptoms.⁸

What is the harm in overdiagnosing depression? Missing a serious or life-threatening diagnosis is a primary concern. For example, unrecognized delirium, which frequently was misdiagnosed as depression in the Berardi,⁶ Boland,⁷ and Clarke⁸ studies, is associated with myriad difficulties, including higher morbidity and mortality.⁹ Substance use disorders, which also commonly masquerade as depression, frequently are comorbid with medical illness. Delays in appropriate treatment of withdrawal syndromes—particularly of alcohol and sedative/hypnotic medications—are risk factors for increased mortality in these illnesses.¹⁰

Inappropriate, potentially harmful interventions are another concern. Many patients diagnosed with depression are prescribed antidepressants, but this is not always a benign intervention. Smith et al found that >10% of adult medical inpatients referred to a psychiatry consultation service who were started on an antidepressant had an adverse drug reaction severe enough to warrant discontinuing the medication.¹¹ Antidepressant side effects relevant to medically ill patients include hyponatremia, serotonin syndrome, and exacerbation of delirium.¹²

Polypharmacy in medically ill patients increases the risk for serious drug-drug interactions. For example, serotonergic antidepressants can increase the risk for serotonin syndrome when combined with the analgesic tramadol, which has serotonergic activity,¹³ or the antibiotic linezolid, which is a reversible monoamine oxidase inhibitor.¹⁴ Many antidepressants—including paroxetine, fluoxetine, bupropion, sertraline, and duloxetine—are moderate to strong inhibitors of cytochrome P450 2D6 and therefore affect metabolism of many medications, including several beta blockers and antiarrhythmics, as well as the anti-estrogen tamoxifen. In the case of tamoxifen, which is a prodrug converted to active form by 2D6, concomitant use of a 2D6 inhibitor can substantially reduce the medication’s in vivo efficacy and lead to higher morbidity and mortality in breast cancer patients.¹⁵ As with any treatment, a decision to prescribe antidepressants needs to carefully be weighed in light of individual risks and benefits. This analysis starts by ensuring that an antidepressant is indicated.

Another concern is failing to recognize immediate human suffering for what it is. Hospitals and doctors’ offices are places of pain and loss as patients encounter morbidity and mortality in themselves and their loved ones. Rushing to pathologize the psychological or social manifestations of this pain can be invalidating to patients and may impair the doctor-patient relationship.

The 8 Ds

To determine what these “depression lookalike” syndromes could be, we identified 100 consecutive consultations to our adult inpatient psychiatry consultation-liaison team with a question of “depression.” We reviewed each patient’s chart, and recorded the diagnosis the psychiatrist gave to explain the patient’s depressed appearance. Data were recorded without patient identifiers, and the Mayo Clinic institutional review board (IRB) determined this study was exempt from IRB review.

Our sample included 45 men and 55 women with an average age of 48 (range: 18 to 91). On evaluation, 3 patients were given no psychiatric diagnosis, 29 were categorized as depressed, and 68 fell into one of 7 other “D” categories we describe below.

Depressed. These patients met criteria for a MDE in the context of major depressive disorder (MDD) or bipolar disorder, dysthymic disorder, mood disorder due to a general medical condition, substance-induced mood disorder, or depressive disorder not otherwise specified.

Demoralized. Patients who had difficulty adjusting to or coping with illness, and received a DSM-IV-TR diagnosis of adjustment disorder with the illness as the inciting stressor were placed in this category. Consistent with adjustment disorder criteria, these patients did not have depressive symptoms of sufficient intensity or duration to meet criteria for MDD or another primary mood disorder.

Difficult. For these patients, the primary issue was a breakdown in the therapeutic alliance with their treatment team. They received DSM-IV-TR diagnoses of personality disorder, noncompliance with treatment, or adult antisocial behavior.

Drugged. Patients in this category appeared depressed as a result of illicit substance use or misuse of alcohol or pharmaceuticals. DSM-IV-TR diagnoses included substance intoxication or withdrawal and substance abuse or dependence.

Delirious. This group consisted of patients with acute disruption in attention and level of consciousness that met DSM-IV-TR criteria for delirium. Patients whose delirious appearance was the result of illicit substance use or pharmaceutical misuse were categorized as “Drugged” rather than “Delirious.”

Disaffiliated. Patients in this category had dysphoria not commensurate with a full-blown mood disorder but attributable to grief from losing a major relationship to death, separation, or divorce. These patients received a DSM-IV-TR diagnosis of bereavement or a partner relational problem.

Delusional. These patients demonstrated amotivation and affective blunting as a result of a primary psychotic disorder such as schizophrenia. In preparation for emergent surgery, these patients had been prevented from taking anything orally, including antipsychotics, and their antipsychotics had not been restarted, which precipitated a gradual return of psychotic symptoms in the days after surgery.

Dulled. Two patients in our sample had irreversible cognitive deficits that explained their withdrawal and blunted affect; 1 had dementia and the other had mental retardation.

Managing the other Ds

In our sample, the most commonly misdiagnosed patients were those having difficulty adjusting to illness (Demoralized) or to other life events (Disaffiliated) (Table 1). In these cases, misdiagnosis has substantial treatment implications because these patients are better served by acute, illness-specific interventions that bolster coping skills, rather than pharmacotherapy or psychotherapy that targets entrenched depressive symptoms. For these patients, psychiatrists may “prescribe” interventions such as visits with a chaplain or other spiritual advisor, telephone calls or visits from family, friends, and other social supports, participation in physical or occupational therapy to improve adaptive functioning, or connecting with other patients in similar situations. Often, the key with these patients is to identify ways they have managed previous stressors and creatively use those resources to adapt to their new situation.

A second large group in our sample consisted of patients actively or passively fighting with their treatment team—the Difficult (Table 2). The treatment team or the patient’s caregivers and loved ones often are more distressed by the “difficult” patient’s symptoms than the patient, who may instead focus on his or her disappointment with caregivers who are unable to meet the patient’s unreasonable expectations. These challenges typically can be addressed by clarifying the salient issues for both the patient and team and establishing a liaison between patient and team to improve communication among all parties. Multidisciplinary care conferences can be an excellent way to ensure that the care team provides the patient with consistent communication and care.

A third group had potentially life-threatening conditions such as substance abuse/withdrawal or delirium as the cause of their “depressive” symptoms—the Drugged and the Delirious (Table 3). Recognizing an organic etiology of mood or behavioral symptoms is important because managing the underlying problem is the primary treatment strategy, not psychopharmacologic or psychotherapeutic intervention. Early identification and appropriate management of these patients could prevent further deterioration, improve medical outcomes, and shorten length of hospital stay.

A final group of patients was those whose chronic psychiatric and cognitive issues may go unrecognized or unappreciated until they interfere with the patient’s medical care—the Delusional and the Dulled (Table 2). In these cases, the correct diagnosis often hinges on obtaining a thorough history through collateral sources. The consulting psychiatrist can be crucial in co-managing these patients by establishing a liaison with outpatient providers, suggesting in-hospital management strategies such as alternate routes of administration of antipsychotics for patients with psychotic disorders, and connecting patients with outpatient supports after hospitalization. Continuity between inpatient and outpatient management is necessary to ensure a successful medical and psychiatric outcome.

Our 8 Ds are limited to the subset of patients referred by their medical teams with a question of depression. These referrals may have been motivated by a variety of patient, family, and team factors above and beyond the categories discussed in this article, and therefore may not accurately represent all patients who present with depressive symptoms in an inpatient setting. However, we hope that providing a mnemonic that suggests an extensive differential for a depressed phenotype may improve identification and management of these issues.

Table 1

Psychological crises that may look like depression

Table 2

Differentiating patients with social challenges from those with depression

Table 3

Substance abuse and delirium can mimic depression

Related Resources

• Stern TA, Fricchione GL, Cassem NH, et al, eds. Massachusetts General Hospital handbook of general hospital psychiatry, 6th ed. Philadelphia, PA: Saunders Elsevier; 2010.
• Levenson JL, ed. The American Psychiatric Publishing textbook of psychosomatic medicine. 2nd ed. Arlington, VA: American Psychiatric Publishing, Inc.; 2011.
• Academy of Psychosomatic Medicine. www.apm.org.
• Caplan JP, Stern TA. Mnemonics in a mnutshell: 32 aids to psychiatric diagnosis. Current Psychiatry. 2008;7(10):27-33.

Drug Brand Names

• Bupropion • Wellbutrin, Zyban
• Duloxetine • Cymbalta
• Fluoxetine • Prozac
• Linezolid • Zyvox
• Paroxetine • Paxil
• Sertraline • Zoloft
• Tamoxifen • Nolvadex
• Tramadol • Ultracet

Disclosures

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

Dr. Rackley receives research/grant support from the Maternal and Child Health Bureau, Health Resources and Services Administration, U.S. Department of Health and Human Services, for a Collaborative Office Rounds program with primary care pediatricians.

Discuss this article at www.facebook.com/CurrentPsychiatry

Many psychiatric and medical illnesses—as well as normal reactions to stressors—have symptoms that overlap with those of depressive disorders, including outwardly sad or dysphoric appearance, irritability, apathy or amotivation, fatigue, difficulty making decisions, social withdrawal, and sleep disturbances. This cluster of symptoms forms a readily observable behavioral phenotype that clinicians may label as depression before considering a broader differential diagnosis.

To better understand what other conditions belong in the differential diagnosis, we reviewed a sample of 100 consecutive medical/surgical inpatients referred to our consultation-liaison psychiatry practice for evaluation of “depression.” Ultimately, only 29 of these patients received a depression diagnosis. Many of the other diagnoses given in our sample required attention during inpatient medical or surgical care because they were potentially life-threatening if left unaddressed—such as delirium—or they interfered with managing the primary medical or surgical condition for which the patient was hospitalized.

Hurried or uncertain primary care clinicians frequently use “depression” as a catch-all term when requesting psychiatric consultation for patients who seem depressed. A wide range of conditions can mimic depression, and the art of psychosomatic psychiatry includes considering protean possibilities when assessing a patient. We identified 7 diagnoses that mimic major depression and developed our “8 D” differential to help clinicians properly diagnose “depressed” patients who have something other than a depressive disorder. Although our sample consisted of hospitalized patients, these mimics of depression may be found among patients referred from other clinical settings for evaluation of possible depression.

The perils of misdiagnosis

Depression is common among patients hospitalized with medical or surgical conditions. DSM-IV-TR diagnostic criteria for a major depressive episode (MDE) include the presence of low mood and/or anhedonia, plus ≥4 other depressive symptoms for ≥2 weeks.¹ Growing evidence suggests that the relationship between depression and morbidity and mortality in medical illness is bidirectional, and nonpsychiatrists are becoming increasingly aware of major depression’s serious impact on their patients’ physical health.^2-5

Although improving nonpsychiatrists’ recognition of depression in medically ill patients is laudable, it comes with a high false-positive rate. In a study of primary care outpatients, Berardi et al found that 45% of patients labeled “depressed” did not meet ICD-10 criteria for major depression, but >25% of those patients were prescribed an antidepressant.⁶ In a large retrospective study, Boland et al found that approximately 40% of patients referred to an inpatient psychiatric consultation service for depression did not meet criteria for a depressive illness, and primary medical services often confused organic syndromes such as delirium and dementia with depression.⁷ Similarly, Clarke et al found that 26% of medical and surgical inpatients referred to psychiatry with “depression” had another diagnosis—commonly delirium—that better accounted for their symptoms.⁸

What is the harm in overdiagnosing depression? Missing a serious or life-threatening diagnosis is a primary concern. For example, unrecognized delirium, which frequently was misdiagnosed as depression in the Berardi,⁶ Boland,⁷ and Clarke⁸ studies, is associated with myriad difficulties, including higher morbidity and mortality.⁹ Substance use disorders, which also commonly masquerade as depression, frequently are comorbid with medical illness. Delays in appropriate treatment of withdrawal syndromes—particularly of alcohol and sedative/hypnotic medications—are risk factors for increased mortality in these illnesses.¹⁰

Inappropriate, potentially harmful interventions are another concern. Many patients diagnosed with depression are prescribed antidepressants, but this is not always a benign intervention. Smith et al found that >10% of adult medical inpatients referred to a psychiatry consultation service who were started on an antidepressant had an adverse drug reaction severe enough to warrant discontinuing the medication.¹¹ Antidepressant side effects relevant to medically ill patients include hyponatremia, serotonin syndrome, and exacerbation of delirium.¹²

Polypharmacy in medically ill patients increases the risk for serious drug-drug interactions. For example, serotonergic antidepressants can increase the risk for serotonin syndrome when combined with the analgesic tramadol, which has serotonergic activity,¹³ or the antibiotic linezolid, which is a reversible monoamine oxidase inhibitor.¹⁴ Many antidepressants—including paroxetine, fluoxetine, bupropion, sertraline, and duloxetine—are moderate to strong inhibitors of cytochrome P450 2D6 and therefore affect metabolism of many medications, including several beta blockers and antiarrhythmics, as well as the anti-estrogen tamoxifen. In the case of tamoxifen, which is a prodrug converted to active form by 2D6, concomitant use of a 2D6 inhibitor can substantially reduce the medication’s in vivo efficacy and lead to higher morbidity and mortality in breast cancer patients.¹⁵ As with any treatment, a decision to prescribe antidepressants needs to carefully be weighed in light of individual risks and benefits. This analysis starts by ensuring that an antidepressant is indicated.

Another concern is failing to recognize immediate human suffering for what it is. Hospitals and doctors’ offices are places of pain and loss as patients encounter morbidity and mortality in themselves and their loved ones. Rushing to pathologize the psychological or social manifestations of this pain can be invalidating to patients and may impair the doctor-patient relationship.

The 8 Ds

To determine what these “depression lookalike” syndromes could be, we identified 100 consecutive consultations to our adult inpatient psychiatry consultation-liaison team with a question of “depression.” We reviewed each patient’s chart, and recorded the diagnosis the psychiatrist gave to explain the patient’s depressed appearance. Data were recorded without patient identifiers, and the Mayo Clinic institutional review board (IRB) determined this study was exempt from IRB review.

Our sample included 45 men and 55 women with an average age of 48 (range: 18 to 91). On evaluation, 3 patients were given no psychiatric diagnosis, 29 were categorized as depressed, and 68 fell into one of 7 other “D” categories we describe below.

Depressed. These patients met criteria for a MDE in the context of major depressive disorder (MDD) or bipolar disorder, dysthymic disorder, mood disorder due to a general medical condition, substance-induced mood disorder, or depressive disorder not otherwise specified.

Demoralized. Patients who had difficulty adjusting to or coping with illness, and received a DSM-IV-TR diagnosis of adjustment disorder with the illness as the inciting stressor were placed in this category. Consistent with adjustment disorder criteria, these patients did not have depressive symptoms of sufficient intensity or duration to meet criteria for MDD or another primary mood disorder.

Difficult. For these patients, the primary issue was a breakdown in the therapeutic alliance with their treatment team. They received DSM-IV-TR diagnoses of personality disorder, noncompliance with treatment, or adult antisocial behavior.

Drugged. Patients in this category appeared depressed as a result of illicit substance use or misuse of alcohol or pharmaceuticals. DSM-IV-TR diagnoses included substance intoxication or withdrawal and substance abuse or dependence.

Delirious. This group consisted of patients with acute disruption in attention and level of consciousness that met DSM-IV-TR criteria for delirium. Patients whose delirious appearance was the result of illicit substance use or pharmaceutical misuse were categorized as “Drugged” rather than “Delirious.”

Disaffiliated. Patients in this category had dysphoria not commensurate with a full-blown mood disorder but attributable to grief from losing a major relationship to death, separation, or divorce. These patients received a DSM-IV-TR diagnosis of bereavement or a partner relational problem.

Delusional. These patients demonstrated amotivation and affective blunting as a result of a primary psychotic disorder such as schizophrenia. In preparation for emergent surgery, these patients had been prevented from taking anything orally, including antipsychotics, and their antipsychotics had not been restarted, which precipitated a gradual return of psychotic symptoms in the days after surgery.

Dulled. Two patients in our sample had irreversible cognitive deficits that explained their withdrawal and blunted affect; 1 had dementia and the other had mental retardation.

Managing the other Ds

In our sample, the most commonly misdiagnosed patients were those having difficulty adjusting to illness (Demoralized) or to other life events (Disaffiliated) (Table 1). In these cases, misdiagnosis has substantial treatment implications because these patients are better served by acute, illness-specific interventions that bolster coping skills, rather than pharmacotherapy or psychotherapy that targets entrenched depressive symptoms. For these patients, psychiatrists may “prescribe” interventions such as visits with a chaplain or other spiritual advisor, telephone calls or visits from family, friends, and other social supports, participation in physical or occupational therapy to improve adaptive functioning, or connecting with other patients in similar situations. Often, the key with these patients is to identify ways they have managed previous stressors and creatively use those resources to adapt to their new situation.

A second large group in our sample consisted of patients actively or passively fighting with their treatment team—the Difficult (Table 2). The treatment team or the patient’s caregivers and loved ones often are more distressed by the “difficult” patient’s symptoms than the patient, who may instead focus on his or her disappointment with caregivers who are unable to meet the patient’s unreasonable expectations. These challenges typically can be addressed by clarifying the salient issues for both the patient and team and establishing a liaison between patient and team to improve communication among all parties. Multidisciplinary care conferences can be an excellent way to ensure that the care team provides the patient with consistent communication and care.

A third group had potentially life-threatening conditions such as substance abuse/withdrawal or delirium as the cause of their “depressive” symptoms—the Drugged and the Delirious (Table 3). Recognizing an organic etiology of mood or behavioral symptoms is important because managing the underlying problem is the primary treatment strategy, not psychopharmacologic or psychotherapeutic intervention. Early identification and appropriate management of these patients could prevent further deterioration, improve medical outcomes, and shorten length of hospital stay.

A final group of patients was those whose chronic psychiatric and cognitive issues may go unrecognized or unappreciated until they interfere with the patient’s medical care—the Delusional and the Dulled (Table 2). In these cases, the correct diagnosis often hinges on obtaining a thorough history through collateral sources. The consulting psychiatrist can be crucial in co-managing these patients by establishing a liaison with outpatient providers, suggesting in-hospital management strategies such as alternate routes of administration of antipsychotics for patients with psychotic disorders, and connecting patients with outpatient supports after hospitalization. Continuity between inpatient and outpatient management is necessary to ensure a successful medical and psychiatric outcome.

Our 8 Ds are limited to the subset of patients referred by their medical teams with a question of depression. These referrals may have been motivated by a variety of patient, family, and team factors above and beyond the categories discussed in this article, and therefore may not accurately represent all patients who present with depressive symptoms in an inpatient setting. However, we hope that providing a mnemonic that suggests an extensive differential for a depressed phenotype may improve identification and management of these issues.

Table 1

Psychological crises that may look like depression

Table 2

Differentiating patients with social challenges from those with depression

Table 3

Substance abuse and delirium can mimic depression

Related Resources

• Stern TA, Fricchione GL, Cassem NH, et al, eds. Massachusetts General Hospital handbook of general hospital psychiatry, 6th ed. Philadelphia, PA: Saunders Elsevier; 2010.
• Levenson JL, ed. The American Psychiatric Publishing textbook of psychosomatic medicine. 2nd ed. Arlington, VA: American Psychiatric Publishing, Inc.; 2011.
• Academy of Psychosomatic Medicine. www.apm.org.
• Caplan JP, Stern TA. Mnemonics in a mnutshell: 32 aids to psychiatric diagnosis. Current Psychiatry. 2008;7(10):27-33.

Drug Brand Names

• Bupropion • Wellbutrin, Zyban
• Duloxetine • Cymbalta
• Fluoxetine • Prozac
• Linezolid • Zyvox
• Paroxetine • Paxil
• Sertraline • Zoloft
• Tamoxifen • Nolvadex
• Tramadol • Ultracet

Disclosures

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

Dr. Rackley receives research/grant support from the Maternal and Child Health Bureau, Health Resources and Services Administration, U.S. Department of Health and Human Services, for a Collaborative Office Rounds program with primary care pediatricians.

Discuss this article at www.facebook.com/CurrentPsychiatry

Many psychiatric and medical illnesses—as well as normal reactions to stressors—have symptoms that overlap with those of depressive disorders, including outwardly sad or dysphoric appearance, irritability, apathy or amotivation, fatigue, difficulty making decisions, social withdrawal, and sleep disturbances. This cluster of symptoms forms a readily observable behavioral phenotype that clinicians may label as depression before considering a broader differential diagnosis.

To better understand what other conditions belong in the differential diagnosis, we reviewed a sample of 100 consecutive medical/surgical inpatients referred to our consultation-liaison psychiatry practice for evaluation of “depression.” Ultimately, only 29 of these patients received a depression diagnosis. Many of the other diagnoses given in our sample required attention during inpatient medical or surgical care because they were potentially life-threatening if left unaddressed—such as delirium—or they interfered with managing the primary medical or surgical condition for which the patient was hospitalized.

Hurried or uncertain primary care clinicians frequently use “depression” as a catch-all term when requesting psychiatric consultation for patients who seem depressed. A wide range of conditions can mimic depression, and the art of psychosomatic psychiatry includes considering protean possibilities when assessing a patient. We identified 7 diagnoses that mimic major depression and developed our “8 D” differential to help clinicians properly diagnose “depressed” patients who have something other than a depressive disorder. Although our sample consisted of hospitalized patients, these mimics of depression may be found among patients referred from other clinical settings for evaluation of possible depression.

The perils of misdiagnosis

Depression is common among patients hospitalized with medical or surgical conditions. DSM-IV-TR diagnostic criteria for a major depressive episode (MDE) include the presence of low mood and/or anhedonia, plus ≥4 other depressive symptoms for ≥2 weeks.¹ Growing evidence suggests that the relationship between depression and morbidity and mortality in medical illness is bidirectional, and nonpsychiatrists are becoming increasingly aware of major depression’s serious impact on their patients’ physical health.^2-5

Although improving nonpsychiatrists’ recognition of depression in medically ill patients is laudable, it comes with a high false-positive rate. In a study of primary care outpatients, Berardi et al found that 45% of patients labeled “depressed” did not meet ICD-10 criteria for major depression, but >25% of those patients were prescribed an antidepressant.⁶ In a large retrospective study, Boland et al found that approximately 40% of patients referred to an inpatient psychiatric consultation service for depression did not meet criteria for a depressive illness, and primary medical services often confused organic syndromes such as delirium and dementia with depression.⁷ Similarly, Clarke et al found that 26% of medical and surgical inpatients referred to psychiatry with “depression” had another diagnosis—commonly delirium—that better accounted for their symptoms.⁸

What is the harm in overdiagnosing depression? Missing a serious or life-threatening diagnosis is a primary concern. For example, unrecognized delirium, which frequently was misdiagnosed as depression in the Berardi,⁶ Boland,⁷ and Clarke⁸ studies, is associated with myriad difficulties, including higher morbidity and mortality.⁹ Substance use disorders, which also commonly masquerade as depression, frequently are comorbid with medical illness. Delays in appropriate treatment of withdrawal syndromes—particularly of alcohol and sedative/hypnotic medications—are risk factors for increased mortality in these illnesses.¹⁰

Inappropriate, potentially harmful interventions are another concern. Many patients diagnosed with depression are prescribed antidepressants, but this is not always a benign intervention. Smith et al found that >10% of adult medical inpatients referred to a psychiatry consultation service who were started on an antidepressant had an adverse drug reaction severe enough to warrant discontinuing the medication.¹¹ Antidepressant side effects relevant to medically ill patients include hyponatremia, serotonin syndrome, and exacerbation of delirium.¹²

Polypharmacy in medically ill patients increases the risk for serious drug-drug interactions. For example, serotonergic antidepressants can increase the risk for serotonin syndrome when combined with the analgesic tramadol, which has serotonergic activity,¹³ or the antibiotic linezolid, which is a reversible monoamine oxidase inhibitor.¹⁴ Many antidepressants—including paroxetine, fluoxetine, bupropion, sertraline, and duloxetine—are moderate to strong inhibitors of cytochrome P450 2D6 and therefore affect metabolism of many medications, including several beta blockers and antiarrhythmics, as well as the anti-estrogen tamoxifen. In the case of tamoxifen, which is a prodrug converted to active form by 2D6, concomitant use of a 2D6 inhibitor can substantially reduce the medication’s in vivo efficacy and lead to higher morbidity and mortality in breast cancer patients.¹⁵ As with any treatment, a decision to prescribe antidepressants needs to carefully be weighed in light of individual risks and benefits. This analysis starts by ensuring that an antidepressant is indicated.

Another concern is failing to recognize immediate human suffering for what it is. Hospitals and doctors’ offices are places of pain and loss as patients encounter morbidity and mortality in themselves and their loved ones. Rushing to pathologize the psychological or social manifestations of this pain can be invalidating to patients and may impair the doctor-patient relationship.

The 8 Ds

To determine what these “depression lookalike” syndromes could be, we identified 100 consecutive consultations to our adult inpatient psychiatry consultation-liaison team with a question of “depression.” We reviewed each patient’s chart, and recorded the diagnosis the psychiatrist gave to explain the patient’s depressed appearance. Data were recorded without patient identifiers, and the Mayo Clinic institutional review board (IRB) determined this study was exempt from IRB review.

Our sample included 45 men and 55 women with an average age of 48 (range: 18 to 91). On evaluation, 3 patients were given no psychiatric diagnosis, 29 were categorized as depressed, and 68 fell into one of 7 other “D” categories we describe below.

Depressed. These patients met criteria for a MDE in the context of major depressive disorder (MDD) or bipolar disorder, dysthymic disorder, mood disorder due to a general medical condition, substance-induced mood disorder, or depressive disorder not otherwise specified.

Demoralized. Patients who had difficulty adjusting to or coping with illness, and received a DSM-IV-TR diagnosis of adjustment disorder with the illness as the inciting stressor were placed in this category. Consistent with adjustment disorder criteria, these patients did not have depressive symptoms of sufficient intensity or duration to meet criteria for MDD or another primary mood disorder.

Difficult. For these patients, the primary issue was a breakdown in the therapeutic alliance with their treatment team. They received DSM-IV-TR diagnoses of personality disorder, noncompliance with treatment, or adult antisocial behavior.

Drugged. Patients in this category appeared depressed as a result of illicit substance use or misuse of alcohol or pharmaceuticals. DSM-IV-TR diagnoses included substance intoxication or withdrawal and substance abuse or dependence.

Delirious. This group consisted of patients with acute disruption in attention and level of consciousness that met DSM-IV-TR criteria for delirium. Patients whose delirious appearance was the result of illicit substance use or pharmaceutical misuse were categorized as “Drugged” rather than “Delirious.”

Disaffiliated. Patients in this category had dysphoria not commensurate with a full-blown mood disorder but attributable to grief from losing a major relationship to death, separation, or divorce. These patients received a DSM-IV-TR diagnosis of bereavement or a partner relational problem.

Delusional. These patients demonstrated amotivation and affective blunting as a result of a primary psychotic disorder such as schizophrenia. In preparation for emergent surgery, these patients had been prevented from taking anything orally, including antipsychotics, and their antipsychotics had not been restarted, which precipitated a gradual return of psychotic symptoms in the days after surgery.

Dulled. Two patients in our sample had irreversible cognitive deficits that explained their withdrawal and blunted affect; 1 had dementia and the other had mental retardation.

Managing the other Ds

In our sample, the most commonly misdiagnosed patients were those having difficulty adjusting to illness (Demoralized) or to other life events (Disaffiliated) (Table 1). In these cases, misdiagnosis has substantial treatment implications because these patients are better served by acute, illness-specific interventions that bolster coping skills, rather than pharmacotherapy or psychotherapy that targets entrenched depressive symptoms. For these patients, psychiatrists may “prescribe” interventions such as visits with a chaplain or other spiritual advisor, telephone calls or visits from family, friends, and other social supports, participation in physical or occupational therapy to improve adaptive functioning, or connecting with other patients in similar situations. Often, the key with these patients is to identify ways they have managed previous stressors and creatively use those resources to adapt to their new situation.

A second large group in our sample consisted of patients actively or passively fighting with their treatment team—the Difficult (Table 2). The treatment team or the patient’s caregivers and loved ones often are more distressed by the “difficult” patient’s symptoms than the patient, who may instead focus on his or her disappointment with caregivers who are unable to meet the patient’s unreasonable expectations. These challenges typically can be addressed by clarifying the salient issues for both the patient and team and establishing a liaison between patient and team to improve communication among all parties. Multidisciplinary care conferences can be an excellent way to ensure that the care team provides the patient with consistent communication and care.

A third group had potentially life-threatening conditions such as substance abuse/withdrawal or delirium as the cause of their “depressive” symptoms—the Drugged and the Delirious (Table 3). Recognizing an organic etiology of mood or behavioral symptoms is important because managing the underlying problem is the primary treatment strategy, not psychopharmacologic or psychotherapeutic intervention. Early identification and appropriate management of these patients could prevent further deterioration, improve medical outcomes, and shorten length of hospital stay.

A final group of patients was those whose chronic psychiatric and cognitive issues may go unrecognized or unappreciated until they interfere with the patient’s medical care—the Delusional and the Dulled (Table 2). In these cases, the correct diagnosis often hinges on obtaining a thorough history through collateral sources. The consulting psychiatrist can be crucial in co-managing these patients by establishing a liaison with outpatient providers, suggesting in-hospital management strategies such as alternate routes of administration of antipsychotics for patients with psychotic disorders, and connecting patients with outpatient supports after hospitalization. Continuity between inpatient and outpatient management is necessary to ensure a successful medical and psychiatric outcome.

Our 8 Ds are limited to the subset of patients referred by their medical teams with a question of depression. These referrals may have been motivated by a variety of patient, family, and team factors above and beyond the categories discussed in this article, and therefore may not accurately represent all patients who present with depressive symptoms in an inpatient setting. However, we hope that providing a mnemonic that suggests an extensive differential for a depressed phenotype may improve identification and management of these issues.

Table 1

Psychological crises that may look like depression

Table 2

Differentiating patients with social challenges from those with depression

Table 3

Substance abuse and delirium can mimic depression

Related Resources

• Stern TA, Fricchione GL, Cassem NH, et al, eds. Massachusetts General Hospital handbook of general hospital psychiatry, 6th ed. Philadelphia, PA: Saunders Elsevier; 2010.
• Levenson JL, ed. The American Psychiatric Publishing textbook of psychosomatic medicine. 2nd ed. Arlington, VA: American Psychiatric Publishing, Inc.; 2011.
• Academy of Psychosomatic Medicine. www.apm.org.
• Caplan JP, Stern TA. Mnemonics in a mnutshell: 32 aids to psychiatric diagnosis. Current Psychiatry. 2008;7(10):27-33.

Drug Brand Names

• Bupropion • Wellbutrin, Zyban
• Duloxetine • Cymbalta
• Fluoxetine • Prozac
• Linezolid • Zyvox
• Paroxetine • Paxil
• Sertraline • Zoloft
• Tamoxifen • Nolvadex
• Tramadol • Ultracet

Disclosures

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

Dr. Rackley receives research/grant support from the Maternal and Child Health Bureau, Health Resources and Services Administration, U.S. Department of Health and Human Services, for a Collaborative Office Rounds program with primary care pediatricians.

Discuss this article at www.facebook.com/CurrentPsychiatry

Although depression affects nearly 2% of children (age ≤12) and up to 10% of adolescents (age 13 to 18),¹ the disorder often is underdiagnosed and undertreated in pediatric patients.² Treating depression in young patients is challenging. Only 30% to 40% of depressed children and adolescents who receive evidence-based treatment achieve remission.³ In addition, 50% to 70% of those who initially achieve remission will experience recurrence within 5 years.⁴ Suicide is the third leading cause of death among children and adolescents, and depression greatly increases the likelihood of suicide.^5,6

This article reviews assessing and treating depression in children and adolescents, and how to lower suicide risk in pediatric patients.

Symptoms vary with age

Depressive symptoms vary as a function of the child’s cognitive development and social functioning. Hopelessness and vegetative and motivational symptoms may be more frequent in adolescents than in children.⁷

In preschool-age children, depression manifests indirectly through somatic symptoms and behavioral disturbances. In this age group, sadness or irritability are sensitive and predominant symptoms of depression.⁸ In older children, sadness and loss of interest in social activities may indicate depression. In adolescents, feelings of mental and physical weariness, aloneness, disconnectedness, uncertainty, vulnerability, anger, irritability, and ambivalence toward friends suggest a depressive disorder.⁹

Genetic predisposition to depression, poor family support, dysfunctional parenting, and individual vulnerabilities such as poor self-esteem or emotional dysregulation may increase young patients’ risk for depression.¹⁰ Peer and family support may protect against depression. Personal competence stemming from social acceptance and body image satisfaction also may be protective factors. A sense of religious and existential well-being (finding meaning and purpose in life) are significantly associated with lower rates of depression among adolescents.¹¹

A persistent illness

The mean duration of a depressive episode in children and adolescents is 7 to 8 months.¹² However, subsyndromal depressive symptoms—as well as relapse and recurrence—are common. Long-term studies indicate that many depressed adolescents experience depressive episodes into adulthood.¹² Factors that may predict recurrence in adulthood include:

• severity of depressive episodes
• concurrent psychotic symptoms
• suicidal thoughts
• history of recurrent depressive episodes
• threshold residual symptoms
• recent stressful life events
• adverse family environment
• family history of depression.¹²

Early symptom onset, greater depression severity, suicidality, presence of comorbid anxiety, disruptive disorders, and an adverse family environment also predict longer recovery time.¹² A study of depressed adolescents found that a history of recurrent depression, family history of recurrent depression, personality disorder traits, and (for girls only) conflict with parents predicted recurrence of depression in young adulthood.⁴Table 1 summarizes factors that affect depression outcomes in children and adolescents.

Table 1

What affects depression outcomes in children and adolescents?

Assessment strategies

Semi-structured interviews such as the Child and Adolescent Psychiatric Assessment, the Diagnostic Interview for Children and Adolescents, and the Kiddie Schedule for Affective Disorder and Schizophrenia are useful for assessing depression in pediatric patients (Table 2).^13-16 These tools can be used to assess depression criteria based on information gathered from several sources. Many instruments can be used to assess and monitor pediatric depression, including the Children’s Depression Inventory, the Reynolds Child Depression Scales and Adolescent Depression Scales, and the Child Depression Rating Scale.

To assess suicide risk in depressed younger patients:

• ask about emotional difficulties
• identify lack of developmental progress
• estimate their level of distress
• detect impairment in functioning
• estimate the level of danger to themselves and others.¹⁷

The best way to assess for suicidal ideation is to ask about it directly while interviewing the patient and his or her parents. Simple questions such as “Have you ever thought about killing yourself or wish you were dead?” and “Have you ever done anything on purpose to hurt or kill yourself?” can be effective.¹⁰ These questions are best placed in the middle or toward the end of a list of questions about depressive symptoms.

Adolescents may be more likely than adults to disclose information about suicidality on self-reports.⁶ However, self-assessment suicide scales are not a substitute for clinical assessment because they tend to be oversensitive and non-specific and lack predictive value. A positive response to either of these questions should prompt a more detailed clinical investigation. There is no evidence that asking about suicide risk increases suicidal behavior, even in high-risk youths.

Table 2

Assessing children and adolescents: 3 semi-structured interviews

Treatment options

Psychotherapy. Several controlled studies and meta-analyses support the efficacy of cognitive-behavioral therapy (CBT) for mild depression in pediatric patients.^18-20 Two recent meta-analyses of CBT studies in depressed adolescents found the mean effect size of CBT was 0.34 to 0.35.^19,21 However, a separate analysis found CBT did not have long-term benefits for depressed adolescents, particularly patients with a history of abuse.²²

Interpersonal therapy also can be effective in adolescent outpatients with mild to moderate depression. One study found the effect size of psychotherapy was modest (0.36).¹⁹

Pharmacotherapy. Two meta-analyses support selective serotonin reuptake inhibitors (SSRIs) for treating mild to moderate depression in children and adolescents. One found 61% of depressed patients age <19 who received an SSRI were “much improved” or “very much improved.”²³ Another meta-analysis that compared SSRIs and placebo found fluoxetine was more effective than sertraline or citalopram for depressed adolescents.²⁴ Other studies have shown that for severe depression, the effect size of antidepressants (0.69) is higher than that of placebo (0.39).²⁵ Antidepressants are more effective in adolescents than in children.²⁵

Fluoxetine is the only FDA-approved medication for treating depression in children age ≥8. In 2007 the FDA extended to all antidepressants its “black-box” warning about increased risk of suicidality in patients up to age 24. The results of studies that analyzed data about the safety of antidepressants in children and adolescents have been mixed—some found evidence of increased suicidality with antidepressant use,^26,27 whereas others showed no increased risk.^28,29Table 3 summarizes steps to minimize the risk of antidepressant-induced suicidality.¹⁷

Psychotherapy plus pharmacotherapy. Researchers who compared fluoxetine to CBT and to a combination of the 2 in adolescents with moderate to severe depression found that fluoxetine was most effective in the first 12 weeks of treatment.³⁰ Surprisingly, CBT’s effectiveness was not different from placebo.³⁰ However, studies have shown that combining psychotherapy and medication results in greater symptom improvement,³⁰ faster clinical response,³¹ improvement of global functioning and quality of life,³² and reduced suicidality.³³ At 6 months, the difference in response between medication and psychotherapy was small.²⁵ The Treatment of Resistant Depression in Adolescents study found that for chronic adolescent depression, pharmacotherapy (fluoxetine and venlafaxine) combined with CBT produced a higher response rate than pharmacotherapy alone (54% vs 41%).³⁴

Table 3

Protecting against antidepressant-induced suicidality

Lowering suicide risk

Up to 60% of adolescents who commit suicide had a depressive disorder. Risk factors for child and adolescent suicide attempts include:

• self-harm behaviors
• psychiatric disorders
• family disturbances
• substance abuse
• physical/sexual abuse.¹⁷

How to best manage suicidal youths depends on an adequate assessment of the severity of the patient’s current problems and conflicts and the degree of suicidal intent. Assessment of coping resources, access to support systems, and the attitude of the patient and family toward intervention and follow-up also is important.

Children and adolescents at high risk for suicide—those with a plan or recent suicide attempt with high probability of lethality, stated current intent to kill themselves, or recent suicidal ideation or behavior—may need inpatient psychiatric admission. Although no studies have shown that admitting high-risk suicidal patients prevents suicide, hospitalization often is the safest course of action. Develop ing a comprehensive outpatient treatment plan before discharge is essential. Patients with fewer risk factors, especially those who want help and have social support, hope for the future, and a desire to resolve conflicts, may require only a brief crisis-oriented intervention.

The following recommendations for managing suicidality in children and adolescents are based on clinical experience and have not been empirically validated.

Develop a safety plan to direct the patient’s behavior under various situations. For example, the patient would agree in writing that “If I feel depressed, I will do X, Y, and Z to address it,” or “If I find myself having suicidal thoughts, I will contact ABC.” Having a safety plan lowers the risk of a suicide attempt more than having a suicide contract, which does not give the patient any tools.³⁵

Create a ‘hope box.’ This is a box in which the patient collects mementos and other objects that remind him or her of hope and reasons to live. The patient should be able to access it at all times, so he or she can tap into it during crisis periods to avert suicidal acts.³⁵

Counteract alienation. A sense of social isolation and burdensomeness may be “tipping factors” for suicidal acts when adolescents feel depressed.³⁵ Clinicians should try to help connect patients to meaningful social activities, even in small doses.

Manage overarousal. Overarousal in depressed children and adolescents is manifested as agitation. Insomnia is a clinically modifiable risk factor. Insomnia initially responds well to behavioral interventions such as sleep hygiene, sleep restriction, and stimulus control techniques.³⁵

Related Resources

• National Suicide Prevention Lifeline. 800-273-TALK (8255). www.suicidepreventionlifeline.org.
• Suicide Prevention Resource Center. www.sprc.org.

Drug Brand Names

• Citalopram • Celexa
• Fluoxetine • Prozac
• Sertraline • Zoloft
• Venlafaxine • Effexor

Disclosures

Drs. Shailesh Jain and Islam report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Rakesh Jain is a consultant to or has received research/grant support from Eli Lilly and Company, Merck, Pfizer Inc., Shionogi Pharmaceuticals, and Shire.

Discuss this article at www.facebook.com/CurrentPsychiatry

Although depression affects nearly 2% of children (age ≤12) and up to 10% of adolescents (age 13 to 18),¹ the disorder often is underdiagnosed and undertreated in pediatric patients.² Treating depression in young patients is challenging. Only 30% to 40% of depressed children and adolescents who receive evidence-based treatment achieve remission.³ In addition, 50% to 70% of those who initially achieve remission will experience recurrence within 5 years.⁴ Suicide is the third leading cause of death among children and adolescents, and depression greatly increases the likelihood of suicide.^5,6

This article reviews assessing and treating depression in children and adolescents, and how to lower suicide risk in pediatric patients.

Symptoms vary with age

Depressive symptoms vary as a function of the child’s cognitive development and social functioning. Hopelessness and vegetative and motivational symptoms may be more frequent in adolescents than in children.⁷

In preschool-age children, depression manifests indirectly through somatic symptoms and behavioral disturbances. In this age group, sadness or irritability are sensitive and predominant symptoms of depression.⁸ In older children, sadness and loss of interest in social activities may indicate depression. In adolescents, feelings of mental and physical weariness, aloneness, disconnectedness, uncertainty, vulnerability, anger, irritability, and ambivalence toward friends suggest a depressive disorder.⁹

Genetic predisposition to depression, poor family support, dysfunctional parenting, and individual vulnerabilities such as poor self-esteem or emotional dysregulation may increase young patients’ risk for depression.¹⁰ Peer and family support may protect against depression. Personal competence stemming from social acceptance and body image satisfaction also may be protective factors. A sense of religious and existential well-being (finding meaning and purpose in life) are significantly associated with lower rates of depression among adolescents.¹¹

A persistent illness

The mean duration of a depressive episode in children and adolescents is 7 to 8 months.¹² However, subsyndromal depressive symptoms—as well as relapse and recurrence—are common. Long-term studies indicate that many depressed adolescents experience depressive episodes into adulthood.¹² Factors that may predict recurrence in adulthood include:

• severity of depressive episodes
• concurrent psychotic symptoms
• suicidal thoughts
• history of recurrent depressive episodes
• threshold residual symptoms
• recent stressful life events
• adverse family environment
• family history of depression.¹²

Early symptom onset, greater depression severity, suicidality, presence of comorbid anxiety, disruptive disorders, and an adverse family environment also predict longer recovery time.¹² A study of depressed adolescents found that a history of recurrent depression, family history of recurrent depression, personality disorder traits, and (for girls only) conflict with parents predicted recurrence of depression in young adulthood.⁴Table 1 summarizes factors that affect depression outcomes in children and adolescents.

Table 1

What affects depression outcomes in children and adolescents?

Assessment strategies

Semi-structured interviews such as the Child and Adolescent Psychiatric Assessment, the Diagnostic Interview for Children and Adolescents, and the Kiddie Schedule for Affective Disorder and Schizophrenia are useful for assessing depression in pediatric patients (Table 2).^13-16 These tools can be used to assess depression criteria based on information gathered from several sources. Many instruments can be used to assess and monitor pediatric depression, including the Children’s Depression Inventory, the Reynolds Child Depression Scales and Adolescent Depression Scales, and the Child Depression Rating Scale.

To assess suicide risk in depressed younger patients:

• ask about emotional difficulties
• identify lack of developmental progress
• estimate their level of distress
• detect impairment in functioning
• estimate the level of danger to themselves and others.¹⁷

The best way to assess for suicidal ideation is to ask about it directly while interviewing the patient and his or her parents. Simple questions such as “Have you ever thought about killing yourself or wish you were dead?” and “Have you ever done anything on purpose to hurt or kill yourself?” can be effective.¹⁰ These questions are best placed in the middle or toward the end of a list of questions about depressive symptoms.

Adolescents may be more likely than adults to disclose information about suicidality on self-reports.⁶ However, self-assessment suicide scales are not a substitute for clinical assessment because they tend to be oversensitive and non-specific and lack predictive value. A positive response to either of these questions should prompt a more detailed clinical investigation. There is no evidence that asking about suicide risk increases suicidal behavior, even in high-risk youths.

Table 2

Assessing children and adolescents: 3 semi-structured interviews

Treatment options

Psychotherapy. Several controlled studies and meta-analyses support the efficacy of cognitive-behavioral therapy (CBT) for mild depression in pediatric patients.^18-20 Two recent meta-analyses of CBT studies in depressed adolescents found the mean effect size of CBT was 0.34 to 0.35.^19,21 However, a separate analysis found CBT did not have long-term benefits for depressed adolescents, particularly patients with a history of abuse.²²

Interpersonal therapy also can be effective in adolescent outpatients with mild to moderate depression. One study found the effect size of psychotherapy was modest (0.36).¹⁹

Pharmacotherapy. Two meta-analyses support selective serotonin reuptake inhibitors (SSRIs) for treating mild to moderate depression in children and adolescents. One found 61% of depressed patients age <19 who received an SSRI were “much improved” or “very much improved.”²³ Another meta-analysis that compared SSRIs and placebo found fluoxetine was more effective than sertraline or citalopram for depressed adolescents.²⁴ Other studies have shown that for severe depression, the effect size of antidepressants (0.69) is higher than that of placebo (0.39).²⁵ Antidepressants are more effective in adolescents than in children.²⁵

Fluoxetine is the only FDA-approved medication for treating depression in children age ≥8. In 2007 the FDA extended to all antidepressants its “black-box” warning about increased risk of suicidality in patients up to age 24. The results of studies that analyzed data about the safety of antidepressants in children and adolescents have been mixed—some found evidence of increased suicidality with antidepressant use,^26,27 whereas others showed no increased risk.^28,29Table 3 summarizes steps to minimize the risk of antidepressant-induced suicidality.¹⁷

Psychotherapy plus pharmacotherapy. Researchers who compared fluoxetine to CBT and to a combination of the 2 in adolescents with moderate to severe depression found that fluoxetine was most effective in the first 12 weeks of treatment.³⁰ Surprisingly, CBT’s effectiveness was not different from placebo.³⁰ However, studies have shown that combining psychotherapy and medication results in greater symptom improvement,³⁰ faster clinical response,³¹ improvement of global functioning and quality of life,³² and reduced suicidality.³³ At 6 months, the difference in response between medication and psychotherapy was small.²⁵ The Treatment of Resistant Depression in Adolescents study found that for chronic adolescent depression, pharmacotherapy (fluoxetine and venlafaxine) combined with CBT produced a higher response rate than pharmacotherapy alone (54% vs 41%).³⁴

Table 3

Protecting against antidepressant-induced suicidality

Lowering suicide risk

Up to 60% of adolescents who commit suicide had a depressive disorder. Risk factors for child and adolescent suicide attempts include:

• self-harm behaviors
• psychiatric disorders
• family disturbances
• substance abuse
• physical/sexual abuse.¹⁷

How to best manage suicidal youths depends on an adequate assessment of the severity of the patient’s current problems and conflicts and the degree of suicidal intent. Assessment of coping resources, access to support systems, and the attitude of the patient and family toward intervention and follow-up also is important.

Children and adolescents at high risk for suicide—those with a plan or recent suicide attempt with high probability of lethality, stated current intent to kill themselves, or recent suicidal ideation or behavior—may need inpatient psychiatric admission. Although no studies have shown that admitting high-risk suicidal patients prevents suicide, hospitalization often is the safest course of action. Develop ing a comprehensive outpatient treatment plan before discharge is essential. Patients with fewer risk factors, especially those who want help and have social support, hope for the future, and a desire to resolve conflicts, may require only a brief crisis-oriented intervention.

The following recommendations for managing suicidality in children and adolescents are based on clinical experience and have not been empirically validated.

Develop a safety plan to direct the patient’s behavior under various situations. For example, the patient would agree in writing that “If I feel depressed, I will do X, Y, and Z to address it,” or “If I find myself having suicidal thoughts, I will contact ABC.” Having a safety plan lowers the risk of a suicide attempt more than having a suicide contract, which does not give the patient any tools.³⁵

Create a ‘hope box.’ This is a box in which the patient collects mementos and other objects that remind him or her of hope and reasons to live. The patient should be able to access it at all times, so he or she can tap into it during crisis periods to avert suicidal acts.³⁵

Counteract alienation. A sense of social isolation and burdensomeness may be “tipping factors” for suicidal acts when adolescents feel depressed.³⁵ Clinicians should try to help connect patients to meaningful social activities, even in small doses.

Manage overarousal. Overarousal in depressed children and adolescents is manifested as agitation. Insomnia is a clinically modifiable risk factor. Insomnia initially responds well to behavioral interventions such as sleep hygiene, sleep restriction, and stimulus control techniques.³⁵

Related Resources

• National Suicide Prevention Lifeline. 800-273-TALK (8255). www.suicidepreventionlifeline.org.
• Suicide Prevention Resource Center. www.sprc.org.

Drug Brand Names

• Citalopram • Celexa
• Fluoxetine • Prozac
• Sertraline • Zoloft
• Venlafaxine • Effexor

Disclosures

Drs. Shailesh Jain and Islam report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Rakesh Jain is a consultant to or has received research/grant support from Eli Lilly and Company, Merck, Pfizer Inc., Shionogi Pharmaceuticals, and Shire.

Discuss this article at www.facebook.com/CurrentPsychiatry

Although depression affects nearly 2% of children (age ≤12) and up to 10% of adolescents (age 13 to 18),¹ the disorder often is underdiagnosed and undertreated in pediatric patients.² Treating depression in young patients is challenging. Only 30% to 40% of depressed children and adolescents who receive evidence-based treatment achieve remission.³ In addition, 50% to 70% of those who initially achieve remission will experience recurrence within 5 years.⁴ Suicide is the third leading cause of death among children and adolescents, and depression greatly increases the likelihood of suicide.^5,6

This article reviews assessing and treating depression in children and adolescents, and how to lower suicide risk in pediatric patients.

Symptoms vary with age

Depressive symptoms vary as a function of the child’s cognitive development and social functioning. Hopelessness and vegetative and motivational symptoms may be more frequent in adolescents than in children.⁷

In preschool-age children, depression manifests indirectly through somatic symptoms and behavioral disturbances. In this age group, sadness or irritability are sensitive and predominant symptoms of depression.⁸ In older children, sadness and loss of interest in social activities may indicate depression. In adolescents, feelings of mental and physical weariness, aloneness, disconnectedness, uncertainty, vulnerability, anger, irritability, and ambivalence toward friends suggest a depressive disorder.⁹

Genetic predisposition to depression, poor family support, dysfunctional parenting, and individual vulnerabilities such as poor self-esteem or emotional dysregulation may increase young patients’ risk for depression.¹⁰ Peer and family support may protect against depression. Personal competence stemming from social acceptance and body image satisfaction also may be protective factors. A sense of religious and existential well-being (finding meaning and purpose in life) are significantly associated with lower rates of depression among adolescents.¹¹

A persistent illness

The mean duration of a depressive episode in children and adolescents is 7 to 8 months.¹² However, subsyndromal depressive symptoms—as well as relapse and recurrence—are common. Long-term studies indicate that many depressed adolescents experience depressive episodes into adulthood.¹² Factors that may predict recurrence in adulthood include:

• severity of depressive episodes
• concurrent psychotic symptoms
• suicidal thoughts
• history of recurrent depressive episodes
• threshold residual symptoms
• recent stressful life events
• adverse family environment
• family history of depression.¹²

Early symptom onset, greater depression severity, suicidality, presence of comorbid anxiety, disruptive disorders, and an adverse family environment also predict longer recovery time.¹² A study of depressed adolescents found that a history of recurrent depression, family history of recurrent depression, personality disorder traits, and (for girls only) conflict with parents predicted recurrence of depression in young adulthood.⁴Table 1 summarizes factors that affect depression outcomes in children and adolescents.

Table 1

What affects depression outcomes in children and adolescents?

Assessment strategies

Semi-structured interviews such as the Child and Adolescent Psychiatric Assessment, the Diagnostic Interview for Children and Adolescents, and the Kiddie Schedule for Affective Disorder and Schizophrenia are useful for assessing depression in pediatric patients (Table 2).^13-16 These tools can be used to assess depression criteria based on information gathered from several sources. Many instruments can be used to assess and monitor pediatric depression, including the Children’s Depression Inventory, the Reynolds Child Depression Scales and Adolescent Depression Scales, and the Child Depression Rating Scale.

To assess suicide risk in depressed younger patients:

• ask about emotional difficulties
• identify lack of developmental progress
• estimate their level of distress
• detect impairment in functioning
• estimate the level of danger to themselves and others.¹⁷

The best way to assess for suicidal ideation is to ask about it directly while interviewing the patient and his or her parents. Simple questions such as “Have you ever thought about killing yourself or wish you were dead?” and “Have you ever done anything on purpose to hurt or kill yourself?” can be effective.¹⁰ These questions are best placed in the middle or toward the end of a list of questions about depressive symptoms.

Adolescents may be more likely than adults to disclose information about suicidality on self-reports.⁶ However, self-assessment suicide scales are not a substitute for clinical assessment because they tend to be oversensitive and non-specific and lack predictive value. A positive response to either of these questions should prompt a more detailed clinical investigation. There is no evidence that asking about suicide risk increases suicidal behavior, even in high-risk youths.

Table 2

Assessing children and adolescents: 3 semi-structured interviews

Treatment options

Psychotherapy. Several controlled studies and meta-analyses support the efficacy of cognitive-behavioral therapy (CBT) for mild depression in pediatric patients.^18-20 Two recent meta-analyses of CBT studies in depressed adolescents found the mean effect size of CBT was 0.34 to 0.35.^19,21 However, a separate analysis found CBT did not have long-term benefits for depressed adolescents, particularly patients with a history of abuse.²²

Interpersonal therapy also can be effective in adolescent outpatients with mild to moderate depression. One study found the effect size of psychotherapy was modest (0.36).¹⁹

Pharmacotherapy. Two meta-analyses support selective serotonin reuptake inhibitors (SSRIs) for treating mild to moderate depression in children and adolescents. One found 61% of depressed patients age <19 who received an SSRI were “much improved” or “very much improved.”²³ Another meta-analysis that compared SSRIs and placebo found fluoxetine was more effective than sertraline or citalopram for depressed adolescents.²⁴ Other studies have shown that for severe depression, the effect size of antidepressants (0.69) is higher than that of placebo (0.39).²⁵ Antidepressants are more effective in adolescents than in children.²⁵

Fluoxetine is the only FDA-approved medication for treating depression in children age ≥8. In 2007 the FDA extended to all antidepressants its “black-box” warning about increased risk of suicidality in patients up to age 24. The results of studies that analyzed data about the safety of antidepressants in children and adolescents have been mixed—some found evidence of increased suicidality with antidepressant use,^26,27 whereas others showed no increased risk.^28,29Table 3 summarizes steps to minimize the risk of antidepressant-induced suicidality.¹⁷

Psychotherapy plus pharmacotherapy. Researchers who compared fluoxetine to CBT and to a combination of the 2 in adolescents with moderate to severe depression found that fluoxetine was most effective in the first 12 weeks of treatment.³⁰ Surprisingly, CBT’s effectiveness was not different from placebo.³⁰ However, studies have shown that combining psychotherapy and medication results in greater symptom improvement,³⁰ faster clinical response,³¹ improvement of global functioning and quality of life,³² and reduced suicidality.³³ At 6 months, the difference in response between medication and psychotherapy was small.²⁵ The Treatment of Resistant Depression in Adolescents study found that for chronic adolescent depression, pharmacotherapy (fluoxetine and venlafaxine) combined with CBT produced a higher response rate than pharmacotherapy alone (54% vs 41%).³⁴

Table 3

Protecting against antidepressant-induced suicidality

Lowering suicide risk

Up to 60% of adolescents who commit suicide had a depressive disorder. Risk factors for child and adolescent suicide attempts include:

• self-harm behaviors
• psychiatric disorders
• family disturbances
• substance abuse
• physical/sexual abuse.¹⁷

How to best manage suicidal youths depends on an adequate assessment of the severity of the patient’s current problems and conflicts and the degree of suicidal intent. Assessment of coping resources, access to support systems, and the attitude of the patient and family toward intervention and follow-up also is important.

Children and adolescents at high risk for suicide—those with a plan or recent suicide attempt with high probability of lethality, stated current intent to kill themselves, or recent suicidal ideation or behavior—may need inpatient psychiatric admission. Although no studies have shown that admitting high-risk suicidal patients prevents suicide, hospitalization often is the safest course of action. Develop ing a comprehensive outpatient treatment plan before discharge is essential. Patients with fewer risk factors, especially those who want help and have social support, hope for the future, and a desire to resolve conflicts, may require only a brief crisis-oriented intervention.

The following recommendations for managing suicidality in children and adolescents are based on clinical experience and have not been empirically validated.

Develop a safety plan to direct the patient’s behavior under various situations. For example, the patient would agree in writing that “If I feel depressed, I will do X, Y, and Z to address it,” or “If I find myself having suicidal thoughts, I will contact ABC.” Having a safety plan lowers the risk of a suicide attempt more than having a suicide contract, which does not give the patient any tools.³⁵

Create a ‘hope box.’ This is a box in which the patient collects mementos and other objects that remind him or her of hope and reasons to live. The patient should be able to access it at all times, so he or she can tap into it during crisis periods to avert suicidal acts.³⁵

Counteract alienation. A sense of social isolation and burdensomeness may be “tipping factors” for suicidal acts when adolescents feel depressed.³⁵ Clinicians should try to help connect patients to meaningful social activities, even in small doses.

Manage overarousal. Overarousal in depressed children and adolescents is manifested as agitation. Insomnia is a clinically modifiable risk factor. Insomnia initially responds well to behavioral interventions such as sleep hygiene, sleep restriction, and stimulus control techniques.³⁵

Related Resources

• National Suicide Prevention Lifeline. 800-273-TALK (8255). www.suicidepreventionlifeline.org.
• Suicide Prevention Resource Center. www.sprc.org.

Drug Brand Names

• Citalopram • Celexa
• Fluoxetine • Prozac
• Sertraline • Zoloft
• Venlafaxine • Effexor

Disclosures

Drs. Shailesh Jain and Islam report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Rakesh Jain is a consultant to or has received research/grant support from Eli Lilly and Company, Merck, Pfizer Inc., Shionogi Pharmaceuticals, and Shire.

Discuss this article at www.facebook.com/CurrentPsychiatry

Although forensic psychiatrists typically are consulted in complex legal matters, geriatric, consultation-liaison, and general psychiatrists are on the front lines of assessing capacity to give informed consent and need for guardianship. Psychiatrists often find such consultations daunting because residency training usually includes little to no formal training in performing psycho-legal assessments. Evaluating issues such as decision-making capacity, guardianship, and capacity to give informed consent requires a delicate balance between autonomy and beneficence. This article reviews 4 common legal issues in geriatric consultation—capacity evaluations, informed consent, guardianship, and elder abuse—and suggests a systematic approach to psycho-legal consultations in older adults.

Confidentiality and dual agency

Every psychiatrist should be familiar with basic principles of medical ethics as well as key aspects of local mental health law. Relevant ethical principles include autonomy, beneficence, confidentiality, and dual agency. A review of all these ethical issues is beyond the scope of this article, so here I highlight confidentiality and dual agency.

Confidentiality—the clinician’s obligation not to disclose private medical information—is a legal as well as an ethical requirement. A psychiatrist who performs a psycho-legal evaluation must disclose to the patient the purpose of the evaluation, that a report will be prepared, and to whom it will be submitted. Exceptions to confidentiality include medical emergencies, mandatory reporting of abuse and infectious diseases, and the duty to protect (warning police and the intended victim when a patient makes a threat).

Dual agency or dual role refers to serving as both a treating physician and a forensic evaluator. Although it is ideal to avoid serving in a dual role, sometimes it is impractical or impossible to avoid doing so, such as in guardianship or civil commitment evaluations, or in state forensic hospitals. In such cases, the psychiatrist must be aware of potential conflicts between clinical and forensic evaluations. A treating psychiatrist primarily serves his or her patient’s best interest, whereas a forensic psychiatrist primarily seeks truth.¹ A treating psychiatrist is at risk of consciously or unconsciously biasing his or her psycho-legal evaluation in favor of or against the patient/litigant, depending upon the psychiatrist’s countertransference. Further, performing a psycho-legal evaluation can cause problems in ongoing treatment. A psychiatrist who testifies that his or her fiercely independent patient needs a guardian or nursing home placement will experience significant challenges in continuing to work with that patient.

4 common issues for older adults

Decision-making capacity. Although “capacity” and “competence” often are used interchangeably, “capacity” broadly refers to the ability to perform a specific task, whereas “competence” refers to the legally defined standard for performing a specific task such as making a will. “Competence” is legally determined, whereas “capacity” may be determined clinically.

Capacity usually is task-specific rather than a general construct. The existence of physical or mental illness per se does not mean that a patient lacks capacity. Rather, capacity is determined by whether an individual has specific abilities, regardless of diagnosis. Specific capacities include the ability to give informed consent, manage finances, make a will, or enter into contracts (Table 1).^2-4 Appelbaum and Gutheil describe 4 components for assessing specific capacity:

• communication of a choice
• factual understanding of the issues
• appreciation of the situation and its consequences
• rational manipulation of information.^5,6

Table 1

Criteria of 3 specific capacities

Ability to communicate a choice refers to a patient’s ability to express his or her wishes in a reasonably stable manner. Factual understanding of the issues refers to an individual’s ability to understand the relevant facts before making a decision. Appreciation of the situation and its consequences refers to a person’s ability to rationally understand the effect of decisions. Appreciation is a higher level of understanding than mere factual understanding—eg, a delusional patient who believes himself immortal may intellectually understand that a surgical procedure carries a 50% mortality risk, but may be unable to appreciate the information as it relates to him because he believes he is immortal. Rational manipulation of information refers to a patient’s reasoning process and how the patient integrates data into his or her decision-making process.⁵

Informed consent. In my experience, capacity to give informed consent is the most commonly requested specific capacity assessment in general medical settings. Informed consent must be knowing, voluntary, and competent. All material information—information that would cause a reasonable person to accept or reject a proposed treatment—should be communicated to the patient. Informed consent requires an understanding of the patient’s condition and indication for treatment, risks and benefits of and alternatives to treatment, and risks of declining treatment.^2,3 Exceptions to informed consent include incompetence, medical emergencies, patient waiver of informed consent, and a limited therapeutic privilege (when a physician determines that the information would harm the patient).³

Several instruments can help clinicians assess patients’ capacity to give informed consent. The benefits of using a structured instrument include:

• ensuring that specific information is covered during each evaluation
• systematically recording a patient’s response.⁵

Disadvantages of using instruments include the fact that no instrument can take into account all aspects of a particular case, and some instruments are time-consuming and require training. Structured instruments can be a useful adjunct to the clinical interview in some cases, but should not substitute for it. In a review of 23 instruments for assessing decisional capacity to consent to treatment or clinical research, the MacArthur Competence Assessment Tool for Clinical Research and the MacArthur Competence Assessment Tool for Treatment had the most empirical support, although the authors noted that other instruments might be better suited to specific situations.⁷

Psychiatrists may be consulted when a patient refuses treatment or decides to leave the hospital against medical advice. The key issue in both situations is whether the patient has capacity to refuse treatment.⁸ If there is evidence that the patient is mentally ill and poses an imminent risk of suicide or violence or is unable to provide for his or her basic needs, the psychiatrist should assess whether the patient meets criteria for civil commitment.

Many clinicians employ a “sliding scale” approach to competence, requiring a lower degree of competence for consenting to low-risk, high-benefit interventions and a greater degree of competence for higher-risk procedures.^5,9 Family members often serve as informal surrogate decision makers for incapacitated patients, except when there is significant family discord or no family members are available.⁵

Guardianship. Guardians are appointed by courts to make decisions for individuals who have been found incompetent (wards). Although its purposes are beneficent, the guardianship system could do significant harm.¹⁰ Determining that an individual is incompetent is tantamount to depriving him or her of basic personhood. In many cases, the ward loses the ability to consent to or refuse medical care, manage his or her finances, enter into contracts, marry, and determine where he or she will live. On the other hand, failing to recognize incompetence can leave a vulnerable person in danger of physical deterioration, abuse, neglect, or exploitation.

It is critical that guardianship evaluations be conducted carefully. In a review of 298 guardianship cases from 3 states, Moye and colleagues¹¹ found that the quality of the reports was significantly better in Colorado, a state with guardianship reforms, but documentation of functional strengths and weaknesses was “particularly rare” in guardianship evaluations and prognosis often was not included. This information is relevant to judges, who need to determine which areas of function are impaired and how long the impairment is likely to last.

Guardianship evaluations often focus on general rather than specific capacity. In other words, often there is not a specific task such as consenting to surgery that the alleged incompetent person needs to perform. Rather, the question is whether an individual can manage his or her finances or make treatment decisions in general. Appelbaum and Gutheil suggest considering 6 factors when assessing general capacity:

• awareness of the situation
• factual understanding of the issues
• appreciation of the likely consequences
• rational manipulation of information
• functioning in one’s environment
• extent of demands on patient.⁵

The first 4 are closely related to the elements of specific capacity described above. Functioning in one’s environment and extent of demands on the patient attempt to anticipate the tasks that an individual will need to perform. A patient with mild dementia may be unable to manage a complex estate but can handle a bank account and a fixed income. Similarly, it is important to consider the patient’s support system. An impaired patient may function adequately with his wife’s help but may lose the capacity to live independently if his wife dies or becomes impaired.

Traditionally, guardianship has resulted in a complete loss of decision-making ability. Several state legislatures have passed laws allowing for limited guardianship, although orders for limited guardianship remain underutilized.¹⁰ Limited guardianship delineates specific areas of incompetence and limits the guardian’s decision-making authority to those areas while leaving intact the ward’s ability to make all other decisions for himself or herself.

The use of less-restrictive alternatives to guardianship—such as powers of attorney, durable powers of attorney, living wills, payees, and trusts—is increasing. A power of attorney allows a patient to authorize a specific individual to act on his or her behalf. The scope of the power of attorney can be limited, such as to manage finances or even to a specific transaction, such as selling a home or car. A durable power of attorney also allows an agent to make decisions on the patient’s behalf but becomes active only when the patient becomes incompetent. It often is used to appoint an individual to make medical decisions on behalf of an incompetent patient. Living wills allow patients to determine what treatment they would like in the event they become incompetent.

Elder abuse. An estimated 1 to 2 million adults age >65 have been abused, exploited, or neglected.¹² Elder abuse includes physical abuse, neglect, emotional abuse, sexual abuse, and financial exploitation (including undue influence). Most states have mandatory reporting of elder abuse, although they vary regarding who must report and what the report must entail. Psychiatrists should be vigilant in looking for signs of elder abuse (Table 2),¹³ regardless of the reason for the consult.

Table 2

Signs of elder abuse: What to wlook for

10 tips for thorough evaluations

1. Consider the context of the consultation. This includes medical factors (such as the patient’s condition, prognosis, relationship with the treatment team, and recommended course of treatment), legal factors (eg, pending litigation and relevant legal standards for issues such as guardianship), and psychosocial issues (eg, the patient’s current support structure and family conflicts).

2. Identify the legal issue and any relevant legal standards. The legal standard will inform you of the issues you need to address in the evaluation. If an attorney has consulted you, ask him or her to provide the legal standard.

3. Gather relevant collateral information, which may include interviews with family members or a review of financial or medical records.

4. Explain the purpose of the examination and the limits of confidentiality.

5. Perform a focused psychiatric evaluation, paying special attention to cognitive functioning, reasoning, and unusual thought content such as delusional beliefs.

6. Perform an interview specific to the referral issue.

7. Consider using a relevant assessment instrument.

8. Consider psychological testing, laboratory testing, imaging, or further medical evaluation. These assessments can help determine the diagnosis, the cause of any deficits in capacity, and whether any deficits are reversible.

9. Determine what opinions you are able to render. Limit opinions and remember that it may be appropriate to decline to address certain issues if there is insufficient information or if the issue is outside your area of expertise.

10. Prepare a written report. Consider the audience. Minimize the use of medical jargon and define all medical terms. State your opinions clearly and with reasonable medical certainty (in most jurisdictions, this means more likely than not). State the basis for all opinions.

For a case study that provides an example of a psycho-legal evaluation of a geriatric patient, see the Box.

Box

Related Resources

• American Academy of Psychiatry and the Law. www.aapl.org.
• American Bar Association Commission on Law and Aging. www.americanbar.org/groups/law_aging.html.
• National Center on Elder Abuse. www.ncea.aoa.gov.

Disclosure

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

Acknowledgement

The author thanks forensic psychiatry fellow Abhishek Jain, MD for reviewing the article and offering editorial suggestions.

Discuss this article at www.facebook.com/CurrentPsychiatry

Although forensic psychiatrists typically are consulted in complex legal matters, geriatric, consultation-liaison, and general psychiatrists are on the front lines of assessing capacity to give informed consent and need for guardianship. Psychiatrists often find such consultations daunting because residency training usually includes little to no formal training in performing psycho-legal assessments. Evaluating issues such as decision-making capacity, guardianship, and capacity to give informed consent requires a delicate balance between autonomy and beneficence. This article reviews 4 common legal issues in geriatric consultation—capacity evaluations, informed consent, guardianship, and elder abuse—and suggests a systematic approach to psycho-legal consultations in older adults.

Confidentiality and dual agency

Every psychiatrist should be familiar with basic principles of medical ethics as well as key aspects of local mental health law. Relevant ethical principles include autonomy, beneficence, confidentiality, and dual agency. A review of all these ethical issues is beyond the scope of this article, so here I highlight confidentiality and dual agency.

Confidentiality—the clinician’s obligation not to disclose private medical information—is a legal as well as an ethical requirement. A psychiatrist who performs a psycho-legal evaluation must disclose to the patient the purpose of the evaluation, that a report will be prepared, and to whom it will be submitted. Exceptions to confidentiality include medical emergencies, mandatory reporting of abuse and infectious diseases, and the duty to protect (warning police and the intended victim when a patient makes a threat).

Dual agency or dual role refers to serving as both a treating physician and a forensic evaluator. Although it is ideal to avoid serving in a dual role, sometimes it is impractical or impossible to avoid doing so, such as in guardianship or civil commitment evaluations, or in state forensic hospitals. In such cases, the psychiatrist must be aware of potential conflicts between clinical and forensic evaluations. A treating psychiatrist primarily serves his or her patient’s best interest, whereas a forensic psychiatrist primarily seeks truth.¹ A treating psychiatrist is at risk of consciously or unconsciously biasing his or her psycho-legal evaluation in favor of or against the patient/litigant, depending upon the psychiatrist’s countertransference. Further, performing a psycho-legal evaluation can cause problems in ongoing treatment. A psychiatrist who testifies that his or her fiercely independent patient needs a guardian or nursing home placement will experience significant challenges in continuing to work with that patient.

4 common issues for older adults

Decision-making capacity. Although “capacity” and “competence” often are used interchangeably, “capacity” broadly refers to the ability to perform a specific task, whereas “competence” refers to the legally defined standard for performing a specific task such as making a will. “Competence” is legally determined, whereas “capacity” may be determined clinically.

Capacity usually is task-specific rather than a general construct. The existence of physical or mental illness per se does not mean that a patient lacks capacity. Rather, capacity is determined by whether an individual has specific abilities, regardless of diagnosis. Specific capacities include the ability to give informed consent, manage finances, make a will, or enter into contracts (Table 1).^2-4 Appelbaum and Gutheil describe 4 components for assessing specific capacity:

• communication of a choice
• factual understanding of the issues
• appreciation of the situation and its consequences
• rational manipulation of information.^5,6

Table 1

Criteria of 3 specific capacities

Ability to communicate a choice refers to a patient’s ability to express his or her wishes in a reasonably stable manner. Factual understanding of the issues refers to an individual’s ability to understand the relevant facts before making a decision. Appreciation of the situation and its consequences refers to a person’s ability to rationally understand the effect of decisions. Appreciation is a higher level of understanding than mere factual understanding—eg, a delusional patient who believes himself immortal may intellectually understand that a surgical procedure carries a 50% mortality risk, but may be unable to appreciate the information as it relates to him because he believes he is immortal. Rational manipulation of information refers to a patient’s reasoning process and how the patient integrates data into his or her decision-making process.⁵

Informed consent. In my experience, capacity to give informed consent is the most commonly requested specific capacity assessment in general medical settings. Informed consent must be knowing, voluntary, and competent. All material information—information that would cause a reasonable person to accept or reject a proposed treatment—should be communicated to the patient. Informed consent requires an understanding of the patient’s condition and indication for treatment, risks and benefits of and alternatives to treatment, and risks of declining treatment.^2,3 Exceptions to informed consent include incompetence, medical emergencies, patient waiver of informed consent, and a limited therapeutic privilege (when a physician determines that the information would harm the patient).³

Several instruments can help clinicians assess patients’ capacity to give informed consent. The benefits of using a structured instrument include:

• ensuring that specific information is covered during each evaluation
• systematically recording a patient’s response.⁵

Disadvantages of using instruments include the fact that no instrument can take into account all aspects of a particular case, and some instruments are time-consuming and require training. Structured instruments can be a useful adjunct to the clinical interview in some cases, but should not substitute for it. In a review of 23 instruments for assessing decisional capacity to consent to treatment or clinical research, the MacArthur Competence Assessment Tool for Clinical Research and the MacArthur Competence Assessment Tool for Treatment had the most empirical support, although the authors noted that other instruments might be better suited to specific situations.⁷

Psychiatrists may be consulted when a patient refuses treatment or decides to leave the hospital against medical advice. The key issue in both situations is whether the patient has capacity to refuse treatment.⁸ If there is evidence that the patient is mentally ill and poses an imminent risk of suicide or violence or is unable to provide for his or her basic needs, the psychiatrist should assess whether the patient meets criteria for civil commitment.

Many clinicians employ a “sliding scale” approach to competence, requiring a lower degree of competence for consenting to low-risk, high-benefit interventions and a greater degree of competence for higher-risk procedures.^5,9 Family members often serve as informal surrogate decision makers for incapacitated patients, except when there is significant family discord or no family members are available.⁵

Guardianship. Guardians are appointed by courts to make decisions for individuals who have been found incompetent (wards). Although its purposes are beneficent, the guardianship system could do significant harm.¹⁰ Determining that an individual is incompetent is tantamount to depriving him or her of basic personhood. In many cases, the ward loses the ability to consent to or refuse medical care, manage his or her finances, enter into contracts, marry, and determine where he or she will live. On the other hand, failing to recognize incompetence can leave a vulnerable person in danger of physical deterioration, abuse, neglect, or exploitation.

It is critical that guardianship evaluations be conducted carefully. In a review of 298 guardianship cases from 3 states, Moye and colleagues¹¹ found that the quality of the reports was significantly better in Colorado, a state with guardianship reforms, but documentation of functional strengths and weaknesses was “particularly rare” in guardianship evaluations and prognosis often was not included. This information is relevant to judges, who need to determine which areas of function are impaired and how long the impairment is likely to last.

Guardianship evaluations often focus on general rather than specific capacity. In other words, often there is not a specific task such as consenting to surgery that the alleged incompetent person needs to perform. Rather, the question is whether an individual can manage his or her finances or make treatment decisions in general. Appelbaum and Gutheil suggest considering 6 factors when assessing general capacity:

• awareness of the situation
• factual understanding of the issues
• appreciation of the likely consequences
• rational manipulation of information
• functioning in one’s environment
• extent of demands on patient.⁵

The first 4 are closely related to the elements of specific capacity described above. Functioning in one’s environment and extent of demands on the patient attempt to anticipate the tasks that an individual will need to perform. A patient with mild dementia may be unable to manage a complex estate but can handle a bank account and a fixed income. Similarly, it is important to consider the patient’s support system. An impaired patient may function adequately with his wife’s help but may lose the capacity to live independently if his wife dies or becomes impaired.

Traditionally, guardianship has resulted in a complete loss of decision-making ability. Several state legislatures have passed laws allowing for limited guardianship, although orders for limited guardianship remain underutilized.¹⁰ Limited guardianship delineates specific areas of incompetence and limits the guardian’s decision-making authority to those areas while leaving intact the ward’s ability to make all other decisions for himself or herself.

The use of less-restrictive alternatives to guardianship—such as powers of attorney, durable powers of attorney, living wills, payees, and trusts—is increasing. A power of attorney allows a patient to authorize a specific individual to act on his or her behalf. The scope of the power of attorney can be limited, such as to manage finances or even to a specific transaction, such as selling a home or car. A durable power of attorney also allows an agent to make decisions on the patient’s behalf but becomes active only when the patient becomes incompetent. It often is used to appoint an individual to make medical decisions on behalf of an incompetent patient. Living wills allow patients to determine what treatment they would like in the event they become incompetent.

Elder abuse. An estimated 1 to 2 million adults age >65 have been abused, exploited, or neglected.¹² Elder abuse includes physical abuse, neglect, emotional abuse, sexual abuse, and financial exploitation (including undue influence). Most states have mandatory reporting of elder abuse, although they vary regarding who must report and what the report must entail. Psychiatrists should be vigilant in looking for signs of elder abuse (Table 2),¹³ regardless of the reason for the consult.

Table 2

Signs of elder abuse: What to wlook for

10 tips for thorough evaluations

1. Consider the context of the consultation. This includes medical factors (such as the patient’s condition, prognosis, relationship with the treatment team, and recommended course of treatment), legal factors (eg, pending litigation and relevant legal standards for issues such as guardianship), and psychosocial issues (eg, the patient’s current support structure and family conflicts).

2. Identify the legal issue and any relevant legal standards. The legal standard will inform you of the issues you need to address in the evaluation. If an attorney has consulted you, ask him or her to provide the legal standard.

3. Gather relevant collateral information, which may include interviews with family members or a review of financial or medical records.

4. Explain the purpose of the examination and the limits of confidentiality.

5. Perform a focused psychiatric evaluation, paying special attention to cognitive functioning, reasoning, and unusual thought content such as delusional beliefs.

6. Perform an interview specific to the referral issue.

7. Consider using a relevant assessment instrument.

8. Consider psychological testing, laboratory testing, imaging, or further medical evaluation. These assessments can help determine the diagnosis, the cause of any deficits in capacity, and whether any deficits are reversible.

9. Determine what opinions you are able to render. Limit opinions and remember that it may be appropriate to decline to address certain issues if there is insufficient information or if the issue is outside your area of expertise.

10. Prepare a written report. Consider the audience. Minimize the use of medical jargon and define all medical terms. State your opinions clearly and with reasonable medical certainty (in most jurisdictions, this means more likely than not). State the basis for all opinions.

For a case study that provides an example of a psycho-legal evaluation of a geriatric patient, see the Box.

Box

Related Resources

• American Academy of Psychiatry and the Law. www.aapl.org.
• American Bar Association Commission on Law and Aging. www.americanbar.org/groups/law_aging.html.
• National Center on Elder Abuse. www.ncea.aoa.gov.

Disclosure

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

Acknowledgement

The author thanks forensic psychiatry fellow Abhishek Jain, MD for reviewing the article and offering editorial suggestions.

Discuss this article at www.facebook.com/CurrentPsychiatry

Although forensic psychiatrists typically are consulted in complex legal matters, geriatric, consultation-liaison, and general psychiatrists are on the front lines of assessing capacity to give informed consent and need for guardianship. Psychiatrists often find such consultations daunting because residency training usually includes little to no formal training in performing psycho-legal assessments. Evaluating issues such as decision-making capacity, guardianship, and capacity to give informed consent requires a delicate balance between autonomy and beneficence. This article reviews 4 common legal issues in geriatric consultation—capacity evaluations, informed consent, guardianship, and elder abuse—and suggests a systematic approach to psycho-legal consultations in older adults.

Confidentiality and dual agency

Every psychiatrist should be familiar with basic principles of medical ethics as well as key aspects of local mental health law. Relevant ethical principles include autonomy, beneficence, confidentiality, and dual agency. A review of all these ethical issues is beyond the scope of this article, so here I highlight confidentiality and dual agency.

Confidentiality—the clinician’s obligation not to disclose private medical information—is a legal as well as an ethical requirement. A psychiatrist who performs a psycho-legal evaluation must disclose to the patient the purpose of the evaluation, that a report will be prepared, and to whom it will be submitted. Exceptions to confidentiality include medical emergencies, mandatory reporting of abuse and infectious diseases, and the duty to protect (warning police and the intended victim when a patient makes a threat).

Dual agency or dual role refers to serving as both a treating physician and a forensic evaluator. Although it is ideal to avoid serving in a dual role, sometimes it is impractical or impossible to avoid doing so, such as in guardianship or civil commitment evaluations, or in state forensic hospitals. In such cases, the psychiatrist must be aware of potential conflicts between clinical and forensic evaluations. A treating psychiatrist primarily serves his or her patient’s best interest, whereas a forensic psychiatrist primarily seeks truth.¹ A treating psychiatrist is at risk of consciously or unconsciously biasing his or her psycho-legal evaluation in favor of or against the patient/litigant, depending upon the psychiatrist’s countertransference. Further, performing a psycho-legal evaluation can cause problems in ongoing treatment. A psychiatrist who testifies that his or her fiercely independent patient needs a guardian or nursing home placement will experience significant challenges in continuing to work with that patient.

4 common issues for older adults

Decision-making capacity. Although “capacity” and “competence” often are used interchangeably, “capacity” broadly refers to the ability to perform a specific task, whereas “competence” refers to the legally defined standard for performing a specific task such as making a will. “Competence” is legally determined, whereas “capacity” may be determined clinically.

Capacity usually is task-specific rather than a general construct. The existence of physical or mental illness per se does not mean that a patient lacks capacity. Rather, capacity is determined by whether an individual has specific abilities, regardless of diagnosis. Specific capacities include the ability to give informed consent, manage finances, make a will, or enter into contracts (Table 1).^2-4 Appelbaum and Gutheil describe 4 components for assessing specific capacity:

• communication of a choice
• factual understanding of the issues
• appreciation of the situation and its consequences
• rational manipulation of information.^5,6

Table 1

Criteria of 3 specific capacities

Ability to communicate a choice refers to a patient’s ability to express his or her wishes in a reasonably stable manner. Factual understanding of the issues refers to an individual’s ability to understand the relevant facts before making a decision. Appreciation of the situation and its consequences refers to a person’s ability to rationally understand the effect of decisions. Appreciation is a higher level of understanding than mere factual understanding—eg, a delusional patient who believes himself immortal may intellectually understand that a surgical procedure carries a 50% mortality risk, but may be unable to appreciate the information as it relates to him because he believes he is immortal. Rational manipulation of information refers to a patient’s reasoning process and how the patient integrates data into his or her decision-making process.⁵

Informed consent. In my experience, capacity to give informed consent is the most commonly requested specific capacity assessment in general medical settings. Informed consent must be knowing, voluntary, and competent. All material information—information that would cause a reasonable person to accept or reject a proposed treatment—should be communicated to the patient. Informed consent requires an understanding of the patient’s condition and indication for treatment, risks and benefits of and alternatives to treatment, and risks of declining treatment.^2,3 Exceptions to informed consent include incompetence, medical emergencies, patient waiver of informed consent, and a limited therapeutic privilege (when a physician determines that the information would harm the patient).³

Several instruments can help clinicians assess patients’ capacity to give informed consent. The benefits of using a structured instrument include:

• ensuring that specific information is covered during each evaluation
• systematically recording a patient’s response.⁵

Disadvantages of using instruments include the fact that no instrument can take into account all aspects of a particular case, and some instruments are time-consuming and require training. Structured instruments can be a useful adjunct to the clinical interview in some cases, but should not substitute for it. In a review of 23 instruments for assessing decisional capacity to consent to treatment or clinical research, the MacArthur Competence Assessment Tool for Clinical Research and the MacArthur Competence Assessment Tool for Treatment had the most empirical support, although the authors noted that other instruments might be better suited to specific situations.⁷

Psychiatrists may be consulted when a patient refuses treatment or decides to leave the hospital against medical advice. The key issue in both situations is whether the patient has capacity to refuse treatment.⁸ If there is evidence that the patient is mentally ill and poses an imminent risk of suicide or violence or is unable to provide for his or her basic needs, the psychiatrist should assess whether the patient meets criteria for civil commitment.

Many clinicians employ a “sliding scale” approach to competence, requiring a lower degree of competence for consenting to low-risk, high-benefit interventions and a greater degree of competence for higher-risk procedures.^5,9 Family members often serve as informal surrogate decision makers for incapacitated patients, except when there is significant family discord or no family members are available.⁵

Guardianship. Guardians are appointed by courts to make decisions for individuals who have been found incompetent (wards). Although its purposes are beneficent, the guardianship system could do significant harm.¹⁰ Determining that an individual is incompetent is tantamount to depriving him or her of basic personhood. In many cases, the ward loses the ability to consent to or refuse medical care, manage his or her finances, enter into contracts, marry, and determine where he or she will live. On the other hand, failing to recognize incompetence can leave a vulnerable person in danger of physical deterioration, abuse, neglect, or exploitation.

It is critical that guardianship evaluations be conducted carefully. In a review of 298 guardianship cases from 3 states, Moye and colleagues¹¹ found that the quality of the reports was significantly better in Colorado, a state with guardianship reforms, but documentation of functional strengths and weaknesses was “particularly rare” in guardianship evaluations and prognosis often was not included. This information is relevant to judges, who need to determine which areas of function are impaired and how long the impairment is likely to last.

Guardianship evaluations often focus on general rather than specific capacity. In other words, often there is not a specific task such as consenting to surgery that the alleged incompetent person needs to perform. Rather, the question is whether an individual can manage his or her finances or make treatment decisions in general. Appelbaum and Gutheil suggest considering 6 factors when assessing general capacity:

• awareness of the situation
• factual understanding of the issues
• appreciation of the likely consequences
• rational manipulation of information
• functioning in one’s environment
• extent of demands on patient.⁵

The first 4 are closely related to the elements of specific capacity described above. Functioning in one’s environment and extent of demands on the patient attempt to anticipate the tasks that an individual will need to perform. A patient with mild dementia may be unable to manage a complex estate but can handle a bank account and a fixed income. Similarly, it is important to consider the patient’s support system. An impaired patient may function adequately with his wife’s help but may lose the capacity to live independently if his wife dies or becomes impaired.

Traditionally, guardianship has resulted in a complete loss of decision-making ability. Several state legislatures have passed laws allowing for limited guardianship, although orders for limited guardianship remain underutilized.¹⁰ Limited guardianship delineates specific areas of incompetence and limits the guardian’s decision-making authority to those areas while leaving intact the ward’s ability to make all other decisions for himself or herself.

The use of less-restrictive alternatives to guardianship—such as powers of attorney, durable powers of attorney, living wills, payees, and trusts—is increasing. A power of attorney allows a patient to authorize a specific individual to act on his or her behalf. The scope of the power of attorney can be limited, such as to manage finances or even to a specific transaction, such as selling a home or car. A durable power of attorney also allows an agent to make decisions on the patient’s behalf but becomes active only when the patient becomes incompetent. It often is used to appoint an individual to make medical decisions on behalf of an incompetent patient. Living wills allow patients to determine what treatment they would like in the event they become incompetent.

Elder abuse. An estimated 1 to 2 million adults age >65 have been abused, exploited, or neglected.¹² Elder abuse includes physical abuse, neglect, emotional abuse, sexual abuse, and financial exploitation (including undue influence). Most states have mandatory reporting of elder abuse, although they vary regarding who must report and what the report must entail. Psychiatrists should be vigilant in looking for signs of elder abuse (Table 2),¹³ regardless of the reason for the consult.

Table 2

Signs of elder abuse: What to wlook for

10 tips for thorough evaluations

1. Consider the context of the consultation. This includes medical factors (such as the patient’s condition, prognosis, relationship with the treatment team, and recommended course of treatment), legal factors (eg, pending litigation and relevant legal standards for issues such as guardianship), and psychosocial issues (eg, the patient’s current support structure and family conflicts).

2. Identify the legal issue and any relevant legal standards. The legal standard will inform you of the issues you need to address in the evaluation. If an attorney has consulted you, ask him or her to provide the legal standard.

3. Gather relevant collateral information, which may include interviews with family members or a review of financial or medical records.

4. Explain the purpose of the examination and the limits of confidentiality.

5. Perform a focused psychiatric evaluation, paying special attention to cognitive functioning, reasoning, and unusual thought content such as delusional beliefs.

6. Perform an interview specific to the referral issue.

7. Consider using a relevant assessment instrument.

8. Consider psychological testing, laboratory testing, imaging, or further medical evaluation. These assessments can help determine the diagnosis, the cause of any deficits in capacity, and whether any deficits are reversible.

9. Determine what opinions you are able to render. Limit opinions and remember that it may be appropriate to decline to address certain issues if there is insufficient information or if the issue is outside your area of expertise.

10. Prepare a written report. Consider the audience. Minimize the use of medical jargon and define all medical terms. State your opinions clearly and with reasonable medical certainty (in most jurisdictions, this means more likely than not). State the basis for all opinions.

For a case study that provides an example of a psycho-legal evaluation of a geriatric patient, see the Box.

Box

Related Resources

• American Academy of Psychiatry and the Law. www.aapl.org.
• American Bar Association Commission on Law and Aging. www.americanbar.org/groups/law_aging.html.
• National Center on Elder Abuse. www.ncea.aoa.gov.

Disclosure

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

Acknowledgement

The author thanks forensic psychiatry fellow Abhishek Jain, MD for reviewing the article and offering editorial suggestions.

Approximately 75% of women experience a premenstrual change in emotional or physical symptoms commonly referred to as premenstrual syndrome (PMS). These symptoms—including increased irritability, tension, depressed mood, and somatic complaints such as breast tenderness and bloating—often are mild to moderate and cause minimal distress.¹ However, approximately 3% to 9% of women experience moderate to severe premenstrual mood symptoms that meet criteria for premenstrual dysphoric disorder (PMDD).²

PMDD includes depressed or labile mood, anxiety, irritability, anger, insomnia, difficulty concentrating, and other symptoms that occur exclusively during the 2 weeks before menses and cause significant deterioration in daily functioning. Women with PMDD use general and mental health services more often than women without the condition.³ They may experience impairment in marital and parental relationships as severe as that experienced by women with recurrent or chronic major depression.²

PMDD often responds to treatment. Unfortunately, many women with PMDD do not seek treatment, and up to 90% may go undiagnosed.⁴ In this article, we review the prevalence, etiology, diagnosis, and treatment of PMDD.

A complex disorder

A distinguishing characteristic of PMDD is the timing of symptom onset. In women with PMDD, mood symptoms occur only during the luteal phase of the menstrual cycle (ovulation until onset of menses) and resolve after menstruation onset. Women with PMDD report normal mood and functioning during the follicular phase of the menstrual cycle (first day of the menstrual cycle until ovulation).

Although PMS and PMDD criteria share affective and somatic symptoms, more symptoms are required for a PMDD diagnosis, and symptoms often are more severe.⁵ As defined in DSM-IV-TR (Table),⁶ PMDD has a broader range of symptoms than PMS and includes symptoms not included in the American College of Obstetrics and Gynecology criteria for PMS,⁷ such as impaired concentration, appetite, and sleep (hypersomnia or insomnia); and mood lability. PMDD symptoms must occur only during the 2 weeks preceding menses, although on average symptoms last 6 days and severity usually peaks in the 2 days before menses.¹ The prevalence of subthreshold PMDD is fairly common; approximately 19% of women will meet some—but not all—DSM-IV-TR criteria for PMDD.³

In a revision proposed for DSM-5, PMDD would be included as a mood disorder, which represents a significant change from DSM-IV-TR, where it is listed in the appendix as “research criteria.”⁸ In addition, in oral contraceptive users, a PMDD diagnosis should not be made unless the premenstrual symptoms are reported to be present and as severe when the woman is not taking the oral contraceptive.⁸

Comorbidity with other axis I disorders such as major depressive disorder (MDD), bipolar disorder (BD), and anxiety disorders is high.^9-11 Women with an MDD history have the highest correlation with PMDD,⁹ and worsening premenstrual mood symptoms are more common in women with BD.¹² Payne et al¹¹ found that premenstrual symptoms were reported by twice as many women diagnosed with mood disorders (68%) than women without a psychiatric diagnosis (34%). Moreover, 38% to 46% of women with PMDD have comorbid seasonal affective disorder, and 11% to 38% report a comorbid anxiety disorder.¹² Women with PMDD and a history of MDD have lower cortisol concentrations than non-PMDD women.¹⁰ Although interventions for PMDD and a comorbid axis I disorder may be similar, it is important to consider both when planning treatment.

Abuse, trauma, and PMDD. An association between PMS/PMDD and a history of sexual and physical abuse is well-documented.¹³ Studies have reported abuse histories among almost 60% of women with PMDD,¹⁴ although studies comparing abuse and trauma in PMDD vs non-PMDD women have been small. A recent study found that trauma and posttraumatic stress disorder are independently associated with PMDD and premenstrual symptoms.¹⁵

Evidence suggests that a history of abuse is associated with specific biological sequelae in PMDD women, particularly with respect to hypothalamic-pituitary-thyroid axis measures and noradrenergic activity.^16-18 Women with PMDD and a history of sexual abuse show:

• markedly elevated triiodothyronine (T3) concentrations (the more biologically potent thyroid hormone) that appear to result from increased conversion of thyroxine (T4) to T3¹⁶
• lower circulating plasma norepinephrine concentrations¹⁷
• greater resting and stress-induced heart rates and systolic blood pressure compared with non-abused PMDD women, an effect that is eliminated by clonidine (an α-2 adrenergic receptor agonist).¹⁸

One study showed that PMDD women with abuse histories had higher blood pressure measurements at rest and during stress and exhibited greater vascular tone than non-abused women; these effects were not seen in non-PMDD women with similar abuse histories.¹⁴ This body of evidence is consistent with the concept that PMDD is a stress-related disorder,¹⁹ and that a history of abuse is prevalent and may identify a clinically distinct subgroup of PMDD women with respect to thyroid axis and adrenergic physiology. Screening PMDD patients for abuse histories may help manage the disorder.

For a discussion of the etiology of PMDD, see Box 1.

Table

DSM-IV-TR research criteria for PMDD

Box 1

Mood charting aids diagnosis

A PMDD diagnosis requires prospective daily monitoring of symptoms for ≥2 consecutive months. Because only 25% to 35% of women who present with PMDD meet diagnostic criteria when prospective daily monitoring is used,²⁰ it is important for patients to keep a daily diary of PMDD symptoms to distinguish the disorder from PMS (Box 2). The Prospective Record of the Impact and Severity of Premenstrual Symptoms calendar and the Daily Record of Severity of Problems (DRSPP)²¹ may help make the diagnosis.

The widely used DRSPP allows clinicians to quantify the severity of physical, emotional, and behavioral symptoms and may be the easiest to use in clinical practice because it creates a graphic representation of cyclical symptom changes. The DRSPP includes all PMDD symptoms and severity ratings²¹ and is recognized as a valid instrument for diagnosing PMDD. Another option is a revised visual analogue scale. Lastly, a new revised Premenstrual Tension Syndrome (PMTS) rating scale, which combines the PMTS Observer rating scale plus multiple visual analogue scales, shows promise as a tool to assess PMDD symptoms.

Box 2

Treatment options

Hormonal interventions. Attempts to treat PMS with progesterone during the luteal phase have been largely unsuccessful, although progesterone is approved to treat PMS in the United Kingdom. Long-acting gonadotropin-releasing hormone (GnRH) agonists are effective but result in medical menopause with its accompanying symptoms, which puts women at risk for osteoporosis.²² Approximately 60% to 70% of women with PMDD respond to leuprolide (a GnRH agonist), but it is difficult to predict who will respond; daily mood self-ratings of sadness, anxiety, and irritability predict a positive response to leuprolide with high probability.²³ Side effects of GnRH agonists (hot flashes, night sweats, vaginal dryness, etc.) can be tempered by “adding back” some estrogen with a hormonal agent with progestational activity to reduce the risks of unopposed estrogen (ie, endometrial hyperplasia).²⁴

Surgical bilateral oophorectomy is effective but extremely invasive, especially in younger women in whom removal of ovaries generally is inadvisable. Patients should receive a trial of a GnRH agonist before a surgical intervention, because oophorectomy may not reduce symptoms and is irreversible. Oophorectomy also would require hormone replacement therapy.

High-dose estrogen as transdermal patches or subcutaneous implants to inhibit ovulation is effective, but because of the risks of unopposed estrogen, a progestin would be needed. Risks of estrogen therapy (alone and in combination with progestins) include increased risk of endometrial cancer, coronary heart disease, breast cancer, stroke, and pulmonary embolism.²⁵ Danazol, a synthetic androgen and gonadotropin inhibitor, effectively blocks ovulation, but side effects include hirsutism and possible teratogenicity.²⁶ Although these hormonal manipulations may effectively treat PMDD, none are considered practical.

The use of combined oral contraceptives (estrogen and progestin) is common. Although continuous cycle oral contraceptives often are recommended for PMDD, limited evidence supports their use; studies have been mostly negative.^27,28 A recent review of 4 studies of a continuous oral contraceptive (levonorgestrel 90 mcg/ethinyl estradiol 20 mcg) for PMDD and PMS had more promising results, although the results were highly variable among studies and a large placebo effect was observed.²⁹

A combination oral contraceptive, drospirenone/ethinyl estradiol, is FDA-approved for treating PMDD in women seeking hormonal contraception because it has shown efficacy compared with placebo, with reported improvements in perceived productivity, social activities, and interpersonal relationships.³⁰ The nature of hormone delivery (ie, a reduction in the pill-free interval from 7 to 4 days) in drospirenone/ethinyl estradiol may contribute to its efficacy because a reduced pill-free interval minimizes the degree of follicular recruitment and subsequent estrogen production and cyclicity seen with standard oral contraceptive.³¹

Antidepressants have been shown to effectively ameliorate affective and physical symptoms and improve quality of life and psychosocial function in patients with PMS and PMDD. The response rates for selective serotonin reuptake inhibitors (SSRIs) in PMDD treatment vary from 60% to 90%, vs 30% to 40% for placebo.³² A 2009 Cochrane review found SSRIs reduced premenstrual symptoms compared with placebo.³³ However, a literature review suggested that the percentage of women with PMDD who respond to SSRIs or continuous oral contraceptives is lower than the percentage of women who do not respond at all, once the placebo effect is taken into account, and that approximately 40% of women with PMDD do not respond to SSRIs.³⁴ A small study found that citalopram may be effective for women with PMDD who did not respond to a prior SSRI.³⁵

However, only antidepressants that affect serotonergic—not noradrenergic—transmission are effective in PMDD.²² These include:

• the tricyclic antidepressant clomipramine
• the SSRIs citalopram, escitalopram, fluoxetine, paroxetine, and sertraline
• the serotonin-noradrenergic reuptake inhibitor venlafaxine.

It appears that in PMDD, serotonergic agents play a role other than their antidepressant effect.³⁶ The effect of these agents is rapid in PMS/PMDD; women with PMDD who take antidepressants often experience reduced symptoms within the first menstrual cycle, whereas in MDD the onset of action can take weeks or months.³⁷

Although why onset of antidepressant action is quick in PMDD is unclear, rapid onset allows for several dosing options. Some women prefer continuous dosing throughout the month because they do not have to keep track of ovulation. Dosing antidepressants only in the luteal phase (taking the antidepressant from ovulation onset to the start of menses) is an effective treatment strategy.³⁸ Many women prefer to take medication for only 2 weeks per month, which can decrease side effects and lower treatment costs. Alternatively, symptom-onset dosing—initiating the antidepressant when PMDD symptoms begin and stopping at menses onset or within 3 days thereafter—has shown promising results.^39,40 Paroxetine, sertraline, and fluoxetine are FDA-approved for PMDD as continuous or intermittent regimens, although using fluoxetine intermittently may not make sense because its biologically active metabolite has an extended half-life.³⁷

Other treatments. Dietary interventions, psychotherapy, vitamins, bright light treatment, and spironolactone have been assessed for PMS/PMDD, although for many evidence-based findings are lacking (Box 3).

See the Bibliography below for studies that support using antidepressants to treat PMDD

Box 3

Bibliography

Treatment selection

To enhance compliance and improve the likelihood of successful treatment, tailor treatment decisions to your patient’s needs. Carefully discuss with your patient the evidence-based literature to select the best option for her. Factors to consider when counseling patients include:

• the patient’s age, cigarette smoking habits, and body mass index, which may contraindicate oral contraceptives
• does the patient have regular cycle lengths?
• can she adhere to an on-off schedule? If so, intermittent SSRI dosing may be a good treatment option
• does the patient have irregular cycles?
• is there evidence that symptoms persist into the follicular phase, albeit at a lower level? If so, continuous SSRI dosing may be the best option.

Related Resources

• American Psychiatric Association. DSM-5 development: D 04 Premenstrual dysphoric disorder. www.dsm5.org/proposedrevision/pages/proposedrevision.aspx?rid=484.

Drug Brand Names

• Citalopram • Celexa
• Clomipramine • Anafranil
• Clonidine • Catapres, others
• Danazol • Danocrine
• Drospirenone/ethinyl estradiol • Yaz
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Leuprolide • Lupron
• Levonorgestrel/ethinyl estradiol • Seasonale, others
• Paroxetine • Paxil
• Progesterone • Prometrium
• Sertraline • Zoloft
• Spironolactone • Aldactone
• Venlafaxine • Effexor

Disclosures