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Last Updated: 6/9/2014  

Depression

Diagnosis
  • Ask patients whether they have experienced depressed mood or anhedonia during the last month (PHQ-2).

  • Consider using the four “SALSA” questions to assess for the presence of four symptoms of depression: sleep disturbance, anhedonia, low self-esteem, and change in appetite in patients with a positive PHQ-2. Two of the four symptoms can confirm depression.

  • Use additional instruments, such as the PHQ-9, in patients with symptoms.

  • Recognize the elderly as a high-risk group for depression and screen them appropriately, generally using the Geriatric Depression Scale.

  • Assess the severity of depression and functional impairment using the PHQ-9.

  • Assess suicidal ideation, intent, and risk.

  • Consider screening for hypothyroidism in patients with depression; base other laboratory testing for secondary causes of depression on clinical evaluation.

  • Recognize that the syndrome of major depression can be a presenting feature of other major mental disorders and substance abuse.

Therapy
  • Refer patients to a psychiatrist when the diagnosis is uncertain or when complex comorbidities or significant suicidal ideation is present, or if a patient does not respond to treatment.

  • Offer psychotherapy to all patients with depression.

  • Consider single-agent antidepressant drug therapy in patients with major depressive disorder, persistent depressive disorder (dysthymia), or both (“double depression”). Treat patients with severe symptoms with an antidepressant.

  • Base choice of antidepressant on side-effect profile.

  • Treat first episodes of depression to achieve complete remission, and continue treatment for 4 to 9 months thereafter.

  • Treat recurrences of major depression with long-term maintenance therapy.

  • Provide patient and family education and inform patients about the expected response time. Create systems of care incorporating collaborative care and/or the chronic care model.

  • Assess patients at 1 to 2 weeks for medication side effects, and at 6 to 8 weeks and 12 weeks for therapeutic response.

Offer counseling to patients who have experienced stressful events, and encourage all patients to be physically active.  
  • Offer counseling to patients who have experienced stressful events, trauma, losses, anxiety, substance abuse, or acute medical events, such as stroke or MI.

  • Inquire about previous episodes of depression in patients currently without symptoms of depression, and stress the importance of early intervention.

  • Encourage physical activity for general health benefits as well as possible preventive effects on depression.

Evidence
  • A 2008 systematic review of the relationship between physical activity and the risk for depression in adults included 27 observational studies and 40 studies of interventions involving physical activity. Results were not pooled, but physical activity was associated with lower rates of depression; one study found that 20 to 30 minutes of exercise 2 to 3 times per week was optimal for depression prevention. Results regarding the optimal intensity of exercise were mixed (1).

  • A 2008 systematic review of the relationship between physical activity and the risk for depression in patients with type 2 diabetes included 16 studies. Inactivity was associated with depressed mood, with an adjusted RR ranging from 1.22 to 1.9 across studies (2).

  • A prospective study developed a risk algorithm for onset of major depression. The index included age, sex, educational level, history of depression, family history of psychological difficulties, poor physical or mental health on the Short Form-12, difficulties in work, and experiences of discrimination. The algorithm had an average C index of 0.79 (3).

Rationale
  • Stressful events, trauma, stroke, anxiety, substance abuse, and recent loss are associated with the onset of psychopathology, including mood and anxiety disorders; supportive counseling may help prevent or mitigate the severity of adverse effects.

  • About 30% of patients will experience further episodes of depression within 2 years of diagnosis and treatment, with a cumulative probability of recurrence of 13% after the first 6 months and 87% after 15 years.

  • The disability associated with depression is similar to that of other chronic medical conditions (4; 5).

Screen for depression using the PHQ-2 as a first step in the systematic detection and diagnosis of mood disorders in all adults. Use additional instruments, such as the PHQ-9, in patients with symptoms. 
  • Screen all adults by asking the following two questions (PHQ-2):

    • “Over the past 2 weeks, have you felt down, depressed, hopeless?”

    • “Over the past 2 weeks, have you felt little interest or pleasure in doing things?”

  • Consider using the four “SALSA” questions to assess for the presence of four symptoms of depression: sleep disturbance, anhedonia, low self-esteem, and change in appetite in patients with a positive PHQ-2. Two of the four symptoms can confirm depression.

  • If the patient has had symptoms, consider asking a single follow-up question: “Is this something with which you would like help?”

  • Initiate a full diagnostic assessment for mood disorders in patients with either depressed mood or anhedonia.

  • Assess symptoms directly using case-finding tools:

    • The 25-item Patient Questionnaire (PQ) component of the PRIME-MD, a two-component screening and diagnostic instrument for mental disorders

    • The 9-item Patient Health Questionnaire (PHQ-9), which is the mood (depression) section of the PQ

  • Use special screening tools in the elderly that account for their level of cognitive impairment and visual deficits.

  • Note that there is insufficient evidence to recommend for or against routine screening of children or adolescents for depression.

  • Although the optimal interval for screening is unknown, consider recurrent screening in patients with a history of depression, multiple unexplained or unrelated somatic complaints, comorbid psychological conditions (panic disorder or generalized anxiety), substance abuse, chronic pain, or lack of response to usually effective treatments for comorbid medical conditions.

  • See table Screening Measures for Depression in Adults and the Elderly.

Evidence
  • A 2013 clinical practice guideline from the Institute for Clinical Systems Improvement on depression in adults recommended screening all adult patients using the PHQ-2.

  • A 2009 guideline on screening for depression in adults from the U.S. Preventive Services Task Force recommended screening adults for depression when “staff-assisted depression care supports are in place” (6).

  • A 2012 systematic review of the optimal cutoff for the PHQ-9 for the diagnosis of depression included 18 studies of diagnostic accuracy. Overall, the PHQ-9 had a pooled sensitivity of 85% (CI, 75% to 91%) with a specificity of 89% (CI, 79% to 94%) at a cut-off score of 10; the specificity rose to 91% (CI, 84% to 95%) at a cut-off score of 12 and to 96% (CI, 94% to 97%) at a cut-off score of 15 (7).

  • A 2009 systematic review from the U.S. Preventive Services Task Force of screening for depression in primary care addressed four key questions. There was evidence that screening for depression increased rates of depression remission in systems with care management programs but not in systems without such programs. The review found no evidence addressing any adverse effects of screening (8).

  • A 2007 systematic review of the accuracy of the PHQ for depression screening in primary care included 14 studies of the PHQ-9 and 3 studies of the PHQ-2. Compared with a reference standard of DSM diagnosis by a psychiatrist. The PHQ-9 had a pooled sensitivity of 80% (CI, 71% to 87%) and a pooled specificity of 92% (CI, 88% to 95%). In primary care (one study), the PHQ-2 had a pooled sensitivity of 83% (CI, 68% to 93%) and a specificity of 83% (CI, 68% to 93%); in general medical outpatients (2 studies), the sensitivity was 87% (CI, 77% to 94%) with a specificity of 78% (CI, 74% to 82%) (9).

  • A 1995 systematic review of the accuracy of depression screening instruments in primary care included 18 studies with over 15,000 participants. The pooled sensitivity of the instruments was 84% (CI, 79% to 89%) and the specificity was 72% (CI, 67% to 77%), with no difference between instruments (10).

  • A cross-sectional study evaluated the diagnostic accuracy of a two-question depression screening test plus a question about the need for help in 1025 patients in primary care compared with a reference standard of a structured diagnostic interview. The “Is help needed today?” question alone had a sensitivity of 75% (CI, 60% to 85%) and a specificity of 94% (CI, 93% to 96%) for the diagnosis of depression. A positive response to either PHQ-2 question or the need-for-help question had a sensitivity of 96% (CI, 86% to 99%) and a specificity of 89% (CI, 87% to 91%) (11).

  • A cross-sectional study evaluated rates of appropriate therapy for depression among U.S. residents from different ethnic groups. Overall, the rate of depression was 8.9%, and about half of depressed people had received some treatment in the last year. Among African American, Mexican American, and Caribbean black individuals with depression, only 12.9% had received appropriate therapy in the past year (12).

Rationale
  • Depression is the second most common chronic disorder seen by primary care physicians.

  • In the absence of systematic screening, usual care by primary physicians fails to detect between 30% and 50% of depressed patients.

  • Use of case-finding procedures is low when initiation depends on physicians' decision to screen compared with automatic nonphysician-triggered screening protocols.

Comments
  • In a study of 2263 patients in a primary care clinic, use of a patient self-reported screening test was only 11% when initiated by physicians compared with 80% to 81% when administered systematically by other clinic staff. Use of the follow-up physician evaluation was higher with nonphysician initiation and staff prompting (OR, 9.7 to 24.7) (13).

  • Risk factors for depression include older age and associated neurologic conditions (14), female gender (15), alcohol dependence, comorbid medical conditions (16; 17), comorbid psychiatric diagnoses, personal or family history of depression (16), recent childbirth (18), and stressful life events (19).

  • Approximately 25% of patients in primary care have a mood disorder, 10% to 15% have major depressive disorder, and 8% to 10% have dysthymia, but rates can vary among clinical populations (20).

  • There is little evidence to recommend one screening method over another; physicians can choose the method that best suits their patient population and practice setting. The two-question instrument is more efficient and does as well as longer instruments.

Screen all women for depression during the postpartum period. 
  • Screen for postpartum depression during the 4 to 6 weeks after birth with special emphasis on women with previous psychiatric history or psychosocial stressors.

  • Consider using the PHQ-2 to screen women in the postpartum setting.

  • Consider using the Edinburgh Postnatal Depression Scale to screen postpartum women, especially those in whom there is suspicion of postpartum depression, noting that

    • The scale consists of 10 questions; each can receive between 0 and 3 points

    • A score of 9 or more or an affirmative response to question 10 (which asks about suicidal ideation) is considered a positive screen and should prompt further action

  • See module Postpartum Depression.

Evidence
  • A 2010 committee opinion from the American College of Obstetricians and Gynecologists on depression screening during and after pregnancy stated that evidence was insufficient to support universal screening but that depression is common during and after pregnancy and screening tools are effective.

  • A 2007 NICE guideline on antenatal and postnatal mental health recommended that all women be screened for depression at their routine postnatal visit using two questions about depressed mood and anhedonia (identical to the PHQ-2), and asking women who respond “yes” to either question whether they need or want help (21).

  • A 2009 systematic review of screening tests for postnatal depression included studies of a variety of instruments. The most commonly assessed tool was the Edinburgh Postnatal Depression Scale, which had a pooled sensitivity ranging from 60% to 96% with a specificity ranging from 45% to 97% for the diagnosis of major depression. No evidence was found regarding two- or three-question screening tests (22).

  • A 2001 systematic review of risk factors for postpartum depression from studies in the 1990s included 84 studies, 28 of which were unpublished. Postpartum depression was most strongly associated with social support, prenatal depression, life stress, marital relationship, general depression history, and child care stress (18).

  • A randomized trial compared routine screening for postpartum depression with usual care in 28 practices. All women were screened using a questionnaire outside of the care environment; 1897 women were included in the analysis. Overall, 34.5% had screening scores indicative of depression. Among women who had positive results for depression on screening, women in intervention practices were more likely to be diagnosed (66% vs. 41%; P=0.001) and treated with medication (56% vs. 35%; P<0.001) or counseling (20% vs. 11%; P=0.02) and were more likely to have a 5-point drop in their PHQ-9 score at 1 year (OR, 1.8 [CI, 1.1 to 2.9]) (23).

  • A 1987 cross-sectional study validated the Edinburgh Postnatal Depression Scale in 84 postpartum women who were considered by their physician to be potentially depressed and in 12 nondepressed women compared with a reference standard of a full diagnostic interview. The Edinburgh Postnatal Depression Scale had a sensitivity of 86% and a specificity of 78% (24).

Rationale
  • Depression is common during the postpartum period.

Comments
  • Women should be screened for depression in the first 4 to 6 weeks after giving birth, especially women with psychosocial stress during pregnancy and a history of psychiatric disorder (18; 25; 26; 27; 28).

  • Postpartum depression is undetected in approximately 50% of patients; screening tests are available and superior to usual care (29).

Recognize the elderly as a high-risk group for depression and screen them appropriately, generally using the Geriatric Depression Scale. 
Evidence
  • A 2009 guideline on screening for depression in adults from the U.S. Preventive Services Task Force recommended screening adults for depression when “staff-assisted depression care supports are in place.” The guideline did not differentiate older adults from the rest of the population (6).

  • A 2008 systematic review of the prevalence of depression in patients with Parkinson's disease included 36 studies of unique populations. Overall, the prevalence was 17% for major depression, 22% for minor depression, and 13% for dysthymia (30).

  • A 1999 systematic review of the prognosis of depression in elderly populations included 12 studies, all of which had methodologic limitations. Overall, among depressed elderly patients, 33% were well, 33% were still depressed, and 21% had died after a follow-up time of 2 years (31).

  • A cross-sectional study evaluated the diagnostic accuracy of the GDS in 66 older adults newly admitted to a nursing home, using full psychiatric assessment as the reference standard. The GDS had an overall sensitivity and specificity of 63% and 83%, respectively, with a sensitivity of 84% and a specificity of 91% in patients with an MMSE score >15 (32).

  • A cohort study in the Netherlands followed 3056 men and women aged 55 to 85 for 4 years. Major depression was seen in 2% of participants, and minor depression was seen in 12.8%. In the adjusted analysis, individuals with both minor (RR, 1.65 [CI, 1.33 to 2.04]) and major (RR, 2.32 [CI, 1.38 to 3.89]) depression were at increased risk for mortality (33).

  • A 1988 study validated the Cornell Scale for Depression in Dementia, a 19-item scale for use in patients with cognitive deficits (34).

Rationale
  • The prevalence of depression in adults older than age 65 ranges from 7% to 36% in medical outpatients and increases to 40% in hospitalized elderly.

  • Up to 50% of patients with Alzheimer's disease and Parkinson's disease develop a depressive disorder, and their caregivers, regardless of age, are at increased risk.

  • Major depression is associated with increased mortality in the elderly.

  • Early diagnosis and treatment of depression in the elderly improve quality of life and functional status and may help prevent premature death.

  • Signs of depression, such as diminished self-care, psychomotor retardation, and irritability, are sometimes more subtle in the elderly and require screening modalities for detection.

Comments
  • The validity of the GDS is maximal when the MMSE score is ≥15.

Use the PHQ-9 or another structured instrument to diagnose depression and to look for comorbid psychiatric conditions. 
  • Use the PHQ-9 to diagnose depression in most patients.

  • Use another validated instrument to assess for the presence of depression or other mood disorders:

    • The PRIME-MD to distinguish among depression, anxiety, eating disorder, alcohol abuse, and somatoform disorders

    • The SDDS-PC to assess for the presence of a variety of mental disorders

  • Consider using the “SALSA” questions in primary care to assess for the presence of four symptoms of depression: Sleep disturbance, Anhedonia, Low Self-esteem, and change in Appetite and confirm depression in patients with a positive initial two-question screen.

  • See table Diagnostic Instruments for Depression.

  • See table Accuracy of Symptoms and Diagnostic Instruments for Depression.

Evidence
  • A 2013 guideline from the Institute for Clinical Systems Improvement recommended using DSM-5 criteria to diagnose depression, assessing all patients with depression for safety and assessing for substance misuse and psychiatric comorbidity if suspected.

  • A 2009 NICE guideline on the management of depression recommended considering using a validated measure in patients with suspected depression to inform and evaluate treatment (35).

  • The 2013 DSM-5 presented diagnostic criteria for major depression, which are most often used in research settings but which may at times be clinically helpful (36).

  • A 2012 systematic review of the accuracy of the PHQ-9 for the diagnosis of depression included 18 validation studies. Pooled specificity was 73% (CI, 63% to 82%) at a cutoff score of 7, and 96% (CI, 94% to 97%) for a cutoff score of 15. At a cutoff score of 10, the pooled sensitivity was 85% (CI, 75% to 91%) and the pooled specificity was 89% (CI, 83% to 92%) (7).

  • A 1995 cross-sectional study validated the SDDS-PC in primary care settings for the diagnosis of a variety of mental illnesses. Compared with the reference standard of clinical diagnosis by a mental health professional, the sensitivity of the SDDS-PC was 90% and the specificity was 77% for the diagnosis of major depression (37).

  • A cross-sectional study compared the accuracy of the four SALSA questions, which assess sleep, anhedonia, self-esteem, and appetite, with PRIME-MD in the diagnosis of depression in a convenience sample of 1000 primary care patients who had a positive two-question screening. Having at least two SALSA symptoms had a sensitivity of 97.4% and a specificity of 94% for the diagnosis of depression (38).

  • A 1994 cross-sectional study evaluated the accuracy of the self-administered PRIME-MD questionnaire for the diagnosis of depression in a convenience sample of 1000 primary care patients compared with the reference standard of a diagnostic interview by a mental health professional. PRIME-MD had a sensitivity of 83% and a specificity of 88% for any psychiatric disorder, a sensitivity of 67% and a specificity of 92% for any mood disorder, and a sensitivity of 57% and a specificity of 98% for major depressive disorder. The average time to administer the questionnaire was 8.4 minutes (39).

Rationale
  • Clinical criteria for major depression predict treatment response and are useful prognostically.

  • The diagnostic accuracy of unaided primary care physicians is poor compared with results obtained with structured approaches.

  • Structured methods that assess anxiety, alcohol abuse, and other disorders are efficient because assessment of comorbidity is an essential component of evaluating the depressed patient.

Comments
  • The PRIME-MD, PHQ, and SDDS-PC have an additional benefit compared with other screening modalities because they assess a spectrum of psychiatric disorders in addition to the principal mood disorders.

Assess the severity of depression and functional impairment using the PHQ-9. 
Evidence
  • A 2010 systematic review of the accuracy of the PHQ scales for the diagnosis of depression noted that higher scores are diagnostic of increasing severity of depression. A score of 5 represents mild depression, a score of 10 represents moderate depression, a score of 15 represents moderately severe depression, and a score of 20 represents severe depression (40).

Rationale
  • Overall assessment of functional impairment and suicide risk will guide decisions about referral for psychiatric hospitalization and consultation.

Comments
  • The PHQ contains a single-item assessment of functional impairment secondary to problems with depression or anxiety, assessing difficulty at work, home, or with other people, using a four-point Likert-type scale ranging from not at all difficult to extremely difficult (41).

  • Current mild depression in patients with past major depression is consistent with DSM-5 criteria for major depression in partial remission or recurrence. Patients with MDPRR may be candidates for treatment similar to patients with current major depression because they are at risk for relapse and have significant current functional impairment.

Assess suicidal and homicidal ideation, intent, and risk. 
  • Ask all patients with suspected or diagnosed depression about thoughts of hurting or killing themselves or others.

  • Assess suicide risk in all patients with suicidal ideation, focusing on

    • Family and social support

    • Patient's ability to make a “contract” for actions if suicidal ideation intensifies

  • Determine the care plan. For patients with

    • Ideation but no plan or intent:

      • Initiate treatment

      • Monitor suicidal ideation closely

      • Consider referral to psychiatrist

    • A plan:

      • Refer to psychiatrist

      • Further stratify risk:

        • If good social support, able to make a contract for safety, able to express reasons for living, and in the absence of other exacerbating factors, proceed with outpatient treatment with close follow-up

        • If poor social support, unable to make a contract for safety, or current alcohol or drug disorders, choose emergency referral for hospitalization and psychiatric assessment

      • Stress the importance of family involvement and psychiatric consultation in all cases

  • Understand the legal and ethical foundation for hospitalization against the wishes of the patient when the patient is in imminent danger to self and others.

  • See table Assessment of Suicidal Ideation, Intent, and Risk.

  • See table Accuracy of Symptoms and Diagnostic Instruments for Depression.

Evidence
  • A 2013 guideline from the Institute for Clinical Systems Improvement recommended using DSM-5 criteria to diagnose depression, assessing all patients with depression for safety and assessing for substance misuse and psychiatric comorbidity if suspected.

  • A 2010 guideline from the American Psychiatric Association for the treatment of patients with major depressive disorder recommended that all patients be assessed for safety, including asking about suicidal ideation and plans, other psychiatric symptoms, social supports, impulsivity, and thoughts of hurting others.

  • A 2009 NICE guideline on the management of depression recommended referring patients who are a risk to themselves or others urgently for specialized mental health care (35).

  • A 2005 systematic review of suicide prevention strategies included cohort studies, population-based studies, and randomized trials. Overall, physician education and programs to reduce access to lethal means (especially firearms) were effective in reducing the risk for suicide (42).

  • A 2009 structured narrative review on contracts for safety noted that there was no evidence for the utility of safety contracts with suicidal patients and that they afford the physician little, if any, medicolegal protection (43).

  • A retrospective study described features of 6865 suicides across the U.S. from 2004 by race/ethnicity. Problems with alcohol were reported by family members of 17.4% to 19.1% of patients; rates of previously diagnosed depression ranged from 15.6% among Hispanics to 34.7% among whites (44).

  • A randomized trial compared telephone contact at 1 or 3 months with usual care in 605 adults discharged from the emergency department after attempted suicide. In the intention-to-treat analysis, there were no differences in outcomes among the groups, but patients who were successfully contacted at 1 month had lower rates of repeat suicide attempts compared with the usual care group (12% vs. 22%; P=0.03) (45).

  • A 1999 narrative review on the evaluation and treatment of patients with suicidal ideation noted that previous suicide attempts should be considered the best predictor of complete suicide (46).

Rationale
  • More than 90% of completed suicides are associated with psychiatric disorders.

  • Major depressive disorder, alcohol abuse, and especially the combination of depression and alcohol or substance abuse are strongly associated with suicide.

  • Most patients who commit suicide see their physicians in the preceding months, and thus careful assessment of suicidal intent at the time of diagnosis will significantly affect the outcome.

Comments
  • Clinicians should consult a psychiatrist if there is any uncertainty regarding suicidal risk. In the past, the “No Harm Contract” (47), which is a verbal or written agreement in which suicidal patients are asked to agree not to harm or kill themselves for a particular period and agree to seek immediate care if suicide is being seriously considered or planned, was commonly used by clinicians.

  • Suicide is consistently among the top-ten leading causes of death in the United States, with 11.2 per 100,000 persons in 1995 (48).

  • In the absence of exacerbating factors, if the patient has adequate social support and is able to voice reasons for living, the clinician can proceed with outpatient treatment and close follow-up. If the patient has poor social support, cannot give clear indication of alliance for treatment, or is currently intoxicated or abusing drugs or alcohol, the clinician should choose emergency referral for hospitalization and psychiatric assessment.

Consider screening for hypothyroidism in patients with depression; base other laboratory testing for secondary causes of depression on clinical evaluation. 
  • Ask patients with depression about symptoms of hypothyroidism and consider measuring a TSH level.

  • Focus laboratory testing on conditions associated with depression suspected after clinical evaluation for

    • Cortisol

    • Glucose

    • Vitamin B12

  • See module Hypothyroidism.

Evidence
  • A prospective study evaluated the rate of abnormal findings in 598 patients who were admitted to a psychiatric inpatient unit after being cleared in the emergency department. Diagnostic testing was performed in 155 (25.9%) patients, including for TSH level in 85 patients. Only 1 patient had an abnormal value that affected management (a positive toxicology screen for acetaminophen) (49).

  • A small cross-sectional study evaluated the relationship between hypothyroidism and depression in 31 volunteers. More patents who met the criteria for subclinical hypothyroidism had a lifetime history of depression compared with those with normal thyroid function (56% vs. 20%; P=0.04) (50).

  • A 2013 structured narrative review of subclinical hypothyroidism and mood and cognition in the elderly noted that evidence of a connection between hypothyroidism and depression is weak (51).

  • A 2012 narrative review discussed thyroid abnormalities in patients with psychiatric illness (52).

Rationale
  • Symptoms of hypothyroidism are similar to symptoms of depression, and hypothyroidism is common in women older than age 50.

  • Depression and hypothyroidism may be comorbid, and antidepressants may be required in addition to thyroid replacement.

  • Many medical conditions are associated with depression.

Differentiate other mood disorder syndromes from major depression. 
  • Differentiate major depression from other mood syndromes using DSM-5 criteria, including

    • Persistent depressive disorder (dysthymia)

    • Bipolar disorder

    • Minor depression

    • Adjustment disorder with depressed mood

    • Major depressive disorder in partial remission or recurrence (MDPRR)

    • Grief (which can be comorbid with a major depressive episode)

  • See table Differential Diagnosis of Major Depressive Disorder and Other Mood Disorders.

Evidence
  • A 2010 guideline from the American Psychiatric Association for the treatment of patients with major depressive disorder recommended that the initial assessment of patients with depression include an assessment for other mental health disorders.

Rationale
  • Prognosis and treatment decisions must be based on specific diagnoses.

  • Major depression and persistent depressive disorder are both responsive to drug therapy and psychotherapy.

  • MDPRR should be distinguished from minor depression because MDPRR is associated with significant functional impairment and should be treated as major depression.

  • Individuals experiencing normal grief may have symptoms of depression but should be treated for major depressive disorder if they meet criteria. Grief is no longer an exclusion criterion for the diagnosis of major depressive disorder.

  • Minor depression (depressive symptoms not meeting full criteria for major depressive disorder) and adjustment disorder with depressed mood should be differentiated from major depression because drug therapy has not been shown to be effective; supportive counseling and careful assessment over time are indicated.

  • Patients with bipolar disorder and depression require a mood-stabilizing medication before or concurrently with antidepressant medication to prevent precipitating a manic episode.

  • Major depressive disorder with seasonal pattern involves recurrent episodes of major depression, usually occurring in the fall and winter months, and may respond to light therapy.

Comments
  • In the DSM-5, there is no longer an exclusion criterion for grief (depressive symptoms lasting less than 2 months following the death of a loved one).

Recognize that the syndrome of major depression can be a presenting feature of substance abuse and prescription drug use, and that depression is more common among patients with many chronic medical conditions.  
  • Recognize that there is an increased prevalence of depression in the following conditions:

    • Prescription drug effects:

      • Glucocorticoids

      • Interferon

      • Reserpine and other centrally acting antihypertensives

    • Substance abuse:

      • Anabolic steroids

      • Ethyl alcohol

      • Cocaine or amphetamine withdrawal

    • Medical conditions:

      • Chronic pain syndromes

      • Hypothyroidism

      • Cushing's disease

      • Dementia

      • Parkinson's disease

      • Stroke

      • Multiple sclerosis

      • Cancer

      • Diabetes

      • Coronary heart disease

      • Chronic fatigue syndrome

      • Vitamin B12 deficiency

      • Infectious disease, such as tuberculosis and viral hepatitis

  • See table Differential Diagnosis of Major Depressive Disorder and Other Mood Disorders.

Evidence
  • A 2013 guideline from the Institute for Clinical Systems Improvement recommended using DSM-5 criteria to diagnose depression, assessing all patients with depression for safety and assessing for substance misuse and psychiatric comorbidity if suspected.

  • A 2012 systematic review of the relationship between diabetes and depression included 20 mostly cross-sectional studies. Overall, depression was more common in patients with type 1 diabetes than in those without type 1 diabetes (12% vs. 3.2%) and higher in patients with type 2 diabetes than in those without type 2 diabetes (19.1% vs. 10.7%) (53).

  • A 2006 systematic review of the prevalence of depression in patients after MI included 24 studies. Overall, depression was seen in 19.8% of patients (54).

  • A 2003 systematic review of the relationship between pain and depression included 14 studies addressing the prevalence of pain in patients with depression and 15 addressing the prevalence of depression in patients with pain. The mean prevalence of pain in patients with depression was 65%, and the prevalence of major depression among patients with chronic pain varied based on the setting, with a mean of 27% (CI, 5.9% to 46.0%) in primary care settings and 52% (CI, 1.5% to 100%) in pain clinics (55).

  • A report of 14 cases of steroid-induced psychiatric syndromes and a review of the literature found that severe psychiatric reactions occurred in approximately 5% of steroid-treated patients. Psychiatric disturbances usually occurred early in the course of steroid therapy. Female sex and high dose of steroids appeared to be risk factors for steroid-induced psychiatric problems. Treatment with tapering doses of steroid or neuroleptics was generally effective, although TCAs did not appear to be useful. Most patients recovered within several weeks (56).

  • A cross-sectional study compared rates of psychiatric and other symptoms in 160 athletes, 88 of whom used anabolic steroids. Overall, 23% of anabolic steroid users reported major mood syndromes of mania, hypomania, or major depression in association with steroid use; mood disorders were more common among steroid users than among nonusers (57).

  • A large body of epidemiologic literature associates depression with a variety of specific medical conditions after cerebrovascular accident, MI, depression, Cushing's disease, hypothyroidism (58; 59; 60), and diabetes (61; 60).

Rationale
  • Certain medications and comorbid conditions are associated with clinical depression.

  • It is important to rule out underlying causes of depression because treatment is directed toward the underlying condition, such as neuroleptics for psychosis, levothyroxine replacement for hypothyroidism, and counseling for bereavement.

Look for other underlying or comorbid mental disorders in patients with major depression.  
Evidence
  • A 2013 guideline from the Institute for Clinical Systems Improvement recommended using DSM-5 criteria to diagnose depression, assessing all patients with depression for safety and assessing for substance misuse and psychiatric comorbidity if suspected.

  • A 2013 guideline from the U.S. Preventive Services Task Force recommended that health care providers screen all adults aged 18 or older for alcohol misuse and provide brief behavioral counseling interventions to persons engaged in risky or hazardous drinking. The guideline recommended one of several screening instruments, including the AUDIT, AUDIT-C, and a single-question screen. The guideline recommended a brief behavioral counseling intervention to reduce at-risk drinking (62).

  • A retrospective, population-based cohort study evaluated the risk for depression in patients with other psychiatric disorders. Compared with patients without comorbid psychiatric disease, patients with generalized anxiety disorder (HR, 38.07 [CI, 28.93 to 50.09]), panic disorder (HR, 12.28 [CI, 6.76 to 22.32]), alcohol dependence (HR, 6.90 [CI, 5.61 to 8.50]), and phobia (HR, 4.99 [CI, 3.54 to 7.03] were at increased risk for depression during the same year (63).

  • A cross-sectional study evaluated rates of anxiety disorders in patients in primary care. Among patients with depression, the prevalence of panic disorder was 9.4%, with a lifetime prevalence of 10.9%. The prevalence of generalized anxiety disorder was 54% among patients with depression (64).

  • A retrospective study assessed the accuracy of the AUDIT-C in a representative population-based U.S. sample compared with DSM-4 criteria for alcohol use disorders. A score of three or more had a sensitivity of 92.5% and a specificity of 73.6%, and a score of four or more had a sensitivity of 83.7% and a specificity of 83.1% (65).

  • A 1992 narrative review on OCD noted that most patients have concurrent mood disorders (66).

Rationale
  • Depressed mood may be present in other psychiatric conditions and mood disorders that require different treatment and have different prognoses as compared with major depression.

  • Mood disturbance may respond to treatment of the primary psychiatric disorder.

Refer patients to a psychiatrist when the diagnosis is uncertain or when complex comorbidities or significant suicidal ideation is present. 
  • Refer patients for diagnostic consultation with a psychiatrist when

    • Psychotic symptoms are present or primary psychotic disorder is suspected

    • Significant suicidal ideation or intent occur, to confirm the diagnosis of a mood disorder and to assess the risk for suicide

    • A history of possible or diagnosed bipolar affective disorder, or a family history of bipolar disorder and symptoms suggesting mania, is present

    • Depression and complex comorbid mental conditions (psychotic disorder, bipolar disorder, PTSD, OCD) and substance abuse are present

    • When complex family or couple problems exist

Evidence
  • A 2009 NICE guideline on the management of depression recommended referring patients who are a risk to themselves or others urgently for specialized mental health care and also referring patients who have severe or moderately severe depression (35).

Rationale
  • The presence of psychotic symptoms in major depression is an indicator of severe disease or a primary psychotic disorder and is associated with greater risk for suicide and more severe functional impairment.

  • Accurate assessment of suicidal risk and consideration of hospitalization is a critical task in the management of depressed patients with suicidal ideation and intent.

  • Psychiatric hospitalization and other acute interventions in the management of actively suicidal patients will also usually require the intervention of a psychiatrist.

  • Patients with bipolar affective disorder who present with depressed mood may “flip” or convert to frank mania if they receive antidepressant medication without concurrently receiving a mood-stabilizing medication; this condition is relatively rare in primary care, and psychiatrists are more likely to have experience and expertise with the diagnosis.

Refer patients who do not respond to treatment to a psychiatrist. 
  • Refer patients to a psychiatrist if

    • Therapy with drugs familiar to the primary care provider fails

    • Therapy with different drug agents fails

    • They have suboptimal response to therapy and are more severely impaired

    • They are having difficult-to-control side effects

Evidence
  • Consensus.

Rationale
  • Patients who do not respond to an initial medication may respond well to another, from within that class or from another class.

  • Primary care providers who are comfortable with antidepressant medication management can do so without consultation.

  • If, however, the patient has not responded to agents familiar to the primary care provider, or after repeated failures, the patient should be referred to a psychiatrist for further diagnostic evaluation and management.

Refer patients to a psychiatrist for help in managing complex comorbidities or when significant suicidal ideation is present. 
  • Refer patients to a psychiatrist when

    • Psychotic symptoms are present or a primary psychotic disorder is suspected

    • There is significant suicidal ideation or intent and assessment and management of suicide risk are needed

    • There is a history of possible or diagnosed bipolar affective disorder or a family history of bipolar disorder and symptoms suggesting mania

    • They are depressed and have complex comorbid mental conditions and substance abuse problems

Evidence
  • Consensus.

  • A 1991 narrative review on depression and suicide noted that acute psychosis in the depressed patient, substance abuse, or both increases an individual's risk for suicide and should prompt psychiatric referral (67).

Rationale
  • The presence of psychotic symptoms in major depression is an indicator of severe disease or a primary psychotic disorder and is associated with greater risk for suicide and more severe functional impairment.

  • Accurate assessment of suicidal risk and consideration of hospitalization is a critical task in the management of depressed patients with suicidal ideation and intent; primary care physicians should consult a psychiatrist if there is uncertainty regarding suicidal risk.

  • Psychiatric hospitalization and other acute interventions in the management of actively suicidal patients will also usually require the intervention of a psychiatrist.

  • Patients with bipolar affective disorder who present with depressed mood may “flip” or convert to frank mania if they receive antidepressant medication without concurrently receiving a mood-stabilizing medication; this condition is relatively rare in primary care, and psychiatrists are more likely to have experience and expertise with the diagnosis

Consider hospitalization for patients with significant suicidal ideation or intent. 
  • Hospitalize patients

    • With significant suicidal ideation or intent who do not have adequate safeguards in their family environment

    • With intent to hurt others

    • To assess their ability to care for themselves and adhere to their treatment in light of the supports available in their home environment

    • Who are in need of detoxification or substance abuse treatment

    • Who are candidates for electroconvulsive therapy

    • With comorbid dysfunctional family systems that exacerbate their depressive disorder or interfere with treatment

Evidence
  • A 2009 guideline from the American Psychiatric Association for the treatment of patients with major depressive disorder recommended determining the optimal care setting for all patients and stated that hospitalization should be considered for patients who pose a serious threat to themselves or others.

Rationale
  • Hospitalization is usually necessary when suicidal intent is significant but may also be necessary with suicidal ideation alone when social support systems are not adequate to safeguard the patient.

Comments
  • Patients may be hospitalized against their wishes when their life is in jeopardy.

  • The conditions of involuntary hospitalization are governed by legal requirements for corroborated documentation of risk and judicial review.

  • Patients with suicidal or homicidal ideation, intention, or plans require close monitoring. Hospitalization, involuntary when indicated, should be considered for patients at significant risk. Severely ill patients who lack adequate social support outside of a hospital setting should be considered for admission to a hospital or intensive day program. In addition, patients who also have complicating psychiatric or general medical conditions or who have not responded adequately to outpatient treatment may need to be hospitalized.

Treat patients with depression using the collaborative care model. 
  • Use a collaborative care model to treat patients with depression in primary care.

  • Note that the collaborative care model includes

    • A team-based model of care with enhanced communication

    • A structured care plan with scheduled patient follow-up

    • Case management

    • Continued care of the primary care physician

    • Possible consultation by a mental health professional

Evidence
  • A 2012 Cochrane review of the collaborative care model for the treatment of depression and anxiety included 79 randomized trials with over 24,000 participants. The collaborative care model improved outcomes of depression in the short, medium, and long term but not in the very long term (>2 years). Patients receiving collaborative care were more likely to experience treatment response at 0 to 6 months (RR, 1.34 [CI, 1.23 to 1.45]) and more likely to take antidepressant medication at 0 to 6 months (RR, 1.47 [CI, 1.33 to 1.63]) (68).

Rationale
  • Collaborative interprofessional care can improve outcomes in patients with depression.

Offer psychotherapy to all patients with depression and consider psychotherapy alone in patients with mild to moderate depression. 
  • Offer psychotherapeutic options to all patients with depression, including

    • Cognitive therapy

    • Interpersonal therapy

    • Psychodynamic therapy

    • Problem-solving therapy

  • Offer patients with mild to moderate depression psychotherapeutic options as an alternative to drug therapy.

  • Consider psychotherapeutic options after drug therapy in some patient groups, including

    • Patients with dysthymia with residual symptoms after treatment with antidepressant medication

    • Patients with a history of major depression with current subsyndromal depression with residual symptoms after treatment with drug therapy

Evidence
  • A 2009 guideline from the American Psychiatric Association for the treatment of patients with major depressive disorder recommended psychotherapy as an option for the initial treatment of mild to moderate depression, specifically cognitive-behavioral therapy, interpersonal psychotherapy, psychodynamic therapy, or problem-solving therapy.

  • A 2009 NICE guideline on the management of depression recommended treating patients with subthreshold, mild, or moderate depression with individual guided self-help based on cognitive-behavioral therapy principles, computerized cognitive-behavioral therapy, a structured group physical activity program, or group cognitive-behavioral therapy. The guideline recommended more intense psychological interventions, such as individual cognitive-behavioral therapy, interpersonal therapy, or behavioral activation as an option for patients who do not improve with lower-intensity therapy (35).

  • A 2012 systematic review of cognitive therapy compared with interpersonal therapy for major depression included seven studies with 741 participants. There was no difference between the treatment groups in scores on either the Hamilton Rating Scale for Depression or the Beck Depression Inventory (69).

  • A 2011 Cochrane review of counseling for mental health problems compared with usual care in primary care settings included nine studies with 1384 participants. Counseling improved mental health outcomes in the short term but not the long term (70).

  • A 2011 systematic review of cognitive-behavioral therapy compared with no treatment for patients with depression included 12 trials with 669 participants; all trials had a high risk for bias. Overall, cognitive-behavioral therapy reduced depressive symptoms by 3.05 points on the Hamilton Rating Scale for Depression and by 4.86 points on the Beck Depression Inventory (71).

  • A 2008 systematic review of long-term psychodynamic psychotherapy in complex mental disorders (including depression complicated by chronicity or personality disorder) included 23 studies with 1053 participants. Long-term psychodynamic psychotherapy had significantly better outcomes in terms of overall effectiveness, target problems, and personality functioning than comparators (72).

  • A 2002 systematic review of psychotherapy, medication, and control for the treatment of depression included six randomized trials with 883 participants. Overall, both forms of active treatment were superior to control, but they did not differ from each other. The percentages of remission for all patients randomly assigned to medication, psychotherapy, and control conditions were 46.4%, 46.3%, and 24.0%, respectively (73).

Rationale
  • Patients with mild to moderate major depression will benefit equally from specific psychotherapies and medication; combined therapy offers no demonstrated short-term benefit.

Comments
  • The therapeutic equivalence of proven specific psychotherapies and drug therapy suggests that patient preference should influence choice of initial therapy.

  • Patient choice should be based on adequate understanding of the differences between treatments.

  • Cognitive therapy, interpersonal psychotherapy, and other forms of therapy require considerable training and therefore may have limited availability.

  • Web-based cognitive behavioral therapy and problem-solving therapy lessons are also effective and may provide another avenue through which patients can access psychotherapeutic interventions (74).

  • Psychotherapy may have theoretical benefit in relapse prevention.

Treat patients with severe depression with an antidepressant; base drug choice on the side-effect profile. 
  • Consider an antidepressant medication to treat major depressive disorder, persistent depressive disorder (dysthymia), or both (“double depression”).

  • Use an antidepressant to treat patients with severe symptoms and some patients with more mild symptoms:

    • Use an antidepressant in combination with psychotherapy (if available) for patients with severe depression

    • Use an antidepressant as an alternative to or in combination with psychotherapy for patients with moderate depression

    • Consider an antidepressant if psychotherapy is unavailable or based on patient preference for patients with mild depression

  • Base choice of agent on differences in the side-effect profile and other properties, such as

    • History of successful treatment with a particular agent

    • History of a first-degree relative successfully treated for depression with a particular agent

    • Differences in the role of cytochrome P450 2D6 metabolism that may influence the risk for drug interaction

    • Differences in SSRI half-life that may influence risk for withdrawal if medication is abruptly stopped

    • Risk for drug and food interactions with MAOIs

    • Potential lethality in overdose

    • The increased risk for death when paroxetine is used in patients taking tamoxifen for treatment of breast cancer

  • Start most patients on an SSRI, an SNRI, mirtazapine, or bupropion.

  • Note that electroconvulsive therapy may be used by psychiatrists to treat patients with life-threatening depression.

  • See table Characteristics of Selected Antidepressants.

  • See table Drug Treatment for Depression.

Evidence
  • A 2009 guideline from the American Psychiatric Association for the treatment of patients with major depressive disorder recommended pharmacotherapy for most patients with depression (particularly more severe forms) and stated that the choice of agent should depend on the side-effect profile and individual patient factors. The guideline stated that most patients should initially be treated with an SSRI, an SNRI, mirtazapine, or bupropion.

  • A 2009 NICE guideline on the management of depression recommended antidepressant medication, generally an SSRI, as an option in patients with moderate to severe depression and in those with milder depression who have inadequate response to lower-intensity psychological interventions (35).

  • A 2008 ACP guideline on using second-generation antidepressants to treat depressive disorders recommended using second-generation antidepressants for drug therapy for depression and choosing specific agents based on side-effect profile, cost, and patient preference (75).

  • A 2013 Cochrane review of fluoxetine compared with other antidepressants for the treatment of depression included 171 studies with over 24,000 participants. Most studies were industry sponsored and at high risk for bias. Fluoxetine resulted in similar response rates as TCAs and was better tolerated, but was less effective than sertraline (OR, 1.37 [CI, 1.08 to 1.74]), mirtazapine (OR, 1.46 [CI, 1.04 to 2.04]), venlafaxine (OR, 1.29 [CI, 1.10 to 1.51]), and some other less commonly prescribed drugs (76).

  • A 2012 Cochrane review of duloxetine compared with other antidepressants for the treatment of depression included 16 studies with 5735 participants. There were no differences in efficacy between duloxetine and paroxetine, escitalopram, fluoxetine, venlafaxine, or desvenlafaxine. There was a higher drop-out rate with duloxetine than with venlafaxine or escitalopram (77).

  • A 2012 Cochrane review of citalopram compared with other antidepressants for the treatment of depression included 37 studies. In terms of response to therapy, escitalopram was more effective than citalopram (OR, 1.47 [CI, 1.08 to 2.02]), but paroxetine (OR, 0.65 [CI, 0.44 to 0.96]) and reboxetine (OR, 0.63 [CI, 0.43 to 0.91]) were less effective than citalopram (78).

  • A 2011 AHRQ comparative effectiveness review of second-generation antidepressants for adults with depression included 92 studies. Drugs generally had similar effects; however, citalopram led to a higher response rate than escitalopram (OR, 1.47 [CI, 1.07 to 2.01]), sertraline led to a higher response rate than fluoxetine (OR, 1.42 [CI, 1.08 to 1.85]), and venlafaxine led to a higher response rate than fluoxetine (OR, 1.47 [CI, 1.16 to 1.86]) (79).

  • A 2011 systematic review of the effect of antidepressants and benzodiazepines in patients with minor depression included six studies of fluoxetine, amitriptyline, and isocarboxazid. The antidepressant group had similar rates of failure of response as the placebo group (RR, 0.94 [CI, 0.81 to 1.08]), and there was no difference in drug acceptability (80).

  • A 2010 Cochrane review of sertraline compared with other antidepressants included 59 studies that were mostly of low quality. Sertraline was similar to TCAs in terms of efficacy and therapy completion, although there was a trend toward better efficacy with TCAs. Compared with other SSRIs, sertraline resulted in higher response rates than fluoxetine (RR, 0.73 [CI, 0.59 to 0.92]), but was similar to other SSRIs (81).

  • A 2010 individual patient meta-analysis of the effect of antidepressant drugs compared with placebo by depression severity included data from six randomized trials with 718 participants. Overall, patients with more severe depression benefited more from antidepressant medication; the effect was minimal in patients with mild to moderate depressive, with a statistically significant effect only among patients with severe depression (82).

  • A 2008 Cochrane review of psychostimulants (dexamphetamine, methylphenidate, methylamphetamine, pemoline, modafinil) for moderate to severe depression included 24 studies of generally low quality. Three trials were included in the meta-analysis, which showed that psychostimulants reduced short-term symptoms and fatigue compared with placebo (83).

  • A 2000 Cochrane review of drugs compared with placebo for dysthymia included 15 randomized, controlled trials. Overall, the response rate was higher in medication groups than in placebo groups (NNT for TCAs, SSRIs, and MAOIs ranged from 2.9 to 4.7) (84).

  • A 2000 systematic review of newer vs. older antidepressants in primary care settings showed average response rates of 63% for newer agents and 60% for TCAs vs. 35% for placebo (85).

  • A 2009 structured review of the effect of methylphenidate in older and ill adults included 19 controlled trials. Methylphenidate was well tolerated, but data regarding efficacy was mixed (86).

  • A 2008 structured review of the use of thyroid hormone for the treatment of depression (in conjunction with antidepressants) included five studies. Results were mixed (87).

  • A population-based cohort study included women 66 years or older living in Canada and treated with tamoxifen for breast cancer between 1993 and 2005 who had overlapping treatment with a single SSRI. Absolute increases of 25%, 50%, and 75% in the proportion of time on tamoxifen with overlapping use of paroxetine (an irreversible inhibitor of CYP2D6) were associated with 24%, 54%, and 91% increases in the risk for death from breast cancer, respectively (P<0.05 for each comparison). By contrast, no such risk was seen with other antidepressants. The authors estimate that use of paroxetine for 41% of tamoxifen treatment (the median overlap in the sample) would result in one additional breast cancer death within 5 years of cessation of tamoxifen for every 19.7 (CI, 12.5 to 46.3) patients treated; the risk with more extensive overlap would be greater (88).

Rationale
  • Choice of antidepressant agent may be based on tolerability, safety, past evidence of effectiveness with the patient, and cost.

  • SSRIs are generally well tolerated.

  • Adverse-effect profiles differ among agents: dry mouth, constipation, and dizziness are more common with TCAs; nausea and headache are more common with SSRIs; and MAOIs are associated with greater risk for adverse drug and food interactions.

  • The risk for death from breast cancer has been reported to be increased with increasing time of concomitant paroxetine and tamoxifen treatments in patients with breast cancer.

Comments
  • The most commonly prescribed antidepressants are classified as second-generation antidepressants (SSRIs, SNRIs, bupropion, mirtazapine). First-generation antidepressants (TCAs and MAOIs) are less commonly used (75).

  • A novel drug, vilazodone, exhibiting both selective serotonin reuptake inhibition and 5-HT1a partial agonism was approved in 2011 by the FDA for the treatment of major depressive disorder. Long-term safety and efficacy are not known (89).

  • In postmarketing experience with venlafaxine, there have been reports of overdose characterized by mental status changes and arrhythmias. Epidemiologic evidence places the risk for serious overdose syndromes with venlafaxine somewhere between that of TCAs (high) and SSRIs (low).

  • SSRIs are associated with hyponatremia in elderly persons (90) and may promote osteoporosis (91).

  • The FDA released a drug safety communication in 2011 about the risk for QT prolongation in patients taking >40 mg per day of citalopram.

Offer patients with severe or chronic depression combination therapy with psychotherapy and antidepressants. 
  • Offer the combination of psychotherapy and antidepressant medications for patients

    • With severe depression

    • With moderate depression and other more complex psychosocial issues

    • With chronic depression for more than 2 years

    • With mild or moderate depression who do not improve with appropriate psychotherapy

Evidence
  • A 2009 guideline from the American Psychiatric Association for the treatment of patients with major depressive disorder stated that the combination of psychotherapy plus an antidepressant may be used in patients with moderate to severe depression or for patients with milder depression but more complex disease.

  • A 2009 NICE guideline on the management of depression recommended the combination of an antidepressant plus a high-intensity psychological therapy (generally cognitive-behavioral therapy) for patients with moderate or severe depression (35).

  • A 2012 systematic review of the combination of medication and psychotherapy compared with medication alone in the treatment of chronic depression included eight studies. Overall, there was a trend toward better response rates with combination therapy than with medication alone (RR, 1.20 [CI, 0.98 to 1.48]) and a trend toward higher rates of remission (RR, 1.25 [CI, 0.97 to 1.61]) (92).

  • A 2009 systematic review of adding psychotherapy to pharmacotherapy (compared with pharmacotherapy alone) for the treatment of depression included 25 studies with 2036 participants. Overall, combination therapy was slightly superior to pharmacotherapy, with an effect size of d=0.31 (CI, 0.20 to 0.43), which corresponded to an NNT of 6 for one additional treatment response (93).

Rationale
  • Combined psychotherapy and antidepressant medication treatment may be better than either modality alone in treating major depression, particularly for patients with severe depression.

Treat first episodes of depression to achieve complete remission, and continue treatment for 4 to 9 months thereafter. 
  • Aim for complete remission of symptoms and return to normal functioning.

  • If remission is not achieved with the initial antidepressant, switch to another agent, augment with a second agent, or consider adding or switching to cognitive therapy.

  • In first episodes, continue treatment with antidepressant medication for an additional 4 to 9 months at the same dosage required to achieve remission.

  • Consider long-term maintenance therapy beyond 9 months in patients older than age 70 and in those with diabetes.

  • Base duration of continuation therapy for a first episode of major depression or dysthymia on

    • Completeness of remission

    • Previous history of subsyndromal depression

    • Duration of depression before remission

    • Persistence of stressors

    • Recovery from precipitating events

  • See table Drug Treatment for Depression.

Evidence
  • A 2013 guideline from the Institute for Clinical Systems Improvement recommended treating for 4 to 9 months after remission is achieved, and considering maintenance therapy beyond that time in patients at high risk for relapse, including those with multiple previous episodes, severe episodes, or residual symptoms and older patients.

  • A 2009 guideline from the American Psychiatric Association for the treatment of patients with major depressive disorder recommended treatment for 4 to 9 months after therapeutic response.

  • A 2009 NICE guideline on the management of depression recommended treating with an antidepressant medication for at least 6 months after remission begins (35).

  • A small randomized, controlled trial (n=116) compared continued paroxetine for 2 years with placebo and continued counseling for 2 years compared with clinical management sessions, in a 2x2 factorial design in depressed older patients (aged 70 years or older) who responded to initial therapy. Recurrence of major depression occurred in 35% of patients receiving paroxetine and psychotherapy, 37% of those receiving paroxetine and clinical management, 68% of those receiving placebo and psychotherapy, and 58% of those receiving placebo and clinical management (P=0.02) (94).

  • A randomized trial compared sertraline for 1 year and for 16 weeks in 152 patients with diabetes and major depression after initial therapeutic response. The risk for relapse was lower in the group receiving medication for 1 year (34% vs. 52%; NNT, 6) (95).

Rationale
  • Up to half of patients with an initial episode of depression will have a recurrence of symptoms.

  • Treatment with medication and psychotherapy can prevent relapse.

  • Older patients and those with diabetes are at higher than average risk for recurrence and depression-related disability after successful treatment of a first episode of major depression.

Comments
  • Treatment to remission may take 1 to several months.

  • Some clinicians advocate total duration of treatment for 1 year to maintain remission during one occurrence of every major holiday and anniversary.

  • Augmentation with a second-generation antipsychotic has been shown in a number of studies (at least 28 trials with 8487 participants and five second-generation antipsychotic drugs) to be superior to augmentation with placebo in treating major depressive disorder. Only aripiprazole is FDA approved for augmentation in treating major depressive disorder. Side effects are more common in those treated with a second-generation antipsychotic (96).

  • Note that response to treatment is defined as a 50% reduction in depressive symptoms.

Provide long-term maintenance therapy for patients with recurrent major depression or very severe or complex depression. 
  • Treat patients who are suffering a first recurrence of major depression for longer than the initial episode.

  • For first recurrence, consider maintenance treatment for one to two times the interepisode interval (e.g., if the second episode occurs 18 months after the first episode, the treatment should be 18 to 36 months).

  • Consider lifetime maintenance therapy for patients with three or more recurrences or patients with a first recurrence and risk factors for further recurrences, including

    • Family history of bipolar disorder

    • Recurrence within 1 year of successful treatment of previous episode

    • Chronic major depression

    • Young age of onset (adolescent)

    • Severe (debilitating or suicidal attempt) and sudden onset of symptoms

  • See table Drug Treatment for Depression.

Evidence
  • A 2013 guideline from the Institute for Clinical Systems Improvement recommended treating for 4 to 9 months after remission is achieved and considering maintenance therapy beyond that time in patients at high risk for relapse, including those with multiple previous episodes, severe episodes, or residual symptoms and older patients.

  • A 2009 guideline from the American Psychiatric Association for the treatment of patients with major depressive disorder recommended that patients with chronic major depression or 3 or more prevous episodes of major depression be treated for a longer period, with the duration based on specific clinical factors.

Rationale
  • Risk for recurrence increases with each subsequent recurrence.

  • Patients with three recurrences have a 90% chance of having another.

  • Antidepressant medications are effective in preventing recurrence.

Counsel patients about antidepressant medication to improve adherence. 
  • Counsel patients in order to improve medication adherence, emphasizing

    • The importance of taking the medication daily

    • That symptomatic improvement may be noticed within 1 week but often takes 2 to 4 weeks

    • That they must continue to take medicine even if feeling better

    • That they must not stop taking the antidepressant without checking with their physician

    • How they can resolve questions regarding antidepressants

    • Potential side effects

Evidence
  • A retrospective cohort study evaluated correlates with adherence to antidepressants in 155 patients who started on antidepressants in primary care. Overall, 28% of patients stopped medication during the initial month of treatment, and 44% stopped within 3 months. Patients were more likely to adhere to therapy during the first month if they were told one of the following: take medication daily, antidepressants take 2 to 4 weeks to be effective, continue medication even if you feel better, or do not stop medication without checking with your doctor; patients given specific instructions about what to do if they had questions were also more likely to adhere (97).

  • A randomized trial compared drug counseling to information leaflets in 250 patients beginning treatment with a TCA. Adherence at 12 weeks was higher in the counseling group (63% vs. 39%) (98).

  • A 1997 narrative review on adherence noted that nonadherence is directly correlated to severe adverse side effects (99).

Rationale
  • Nonadherence to antidepressant medication often begins in the initial weeks of therapy.

  • Specific information about how antidepressant medications work and how to deal with medication questions and problems can improve adherence.

  • Adverse effects, especially severe ones, are associated with nonadherence.

Exercise caution in initiating antidepressant therapy in adolescents and young adults. 
  • Consider non-drug therapy or psychiatric consultation in depressed adolescents and young adults as an alternative to drug therapy.

  • Monitor patients carefully after initiation of antidepressant drug therapy, especially in adolescents and young adults.

    • Watch carefully for drug side effects

    • Assess continuously for risk of suicide

Evidence
  • A 2007 North American guideline for the treatment of depression in adolescents in primary care recommended active support for mild depression, and medical management, psychotherapy, or mental health referral for patients with moderate or severe depression. For patients receiving drug therapy, the guideline recommended SSRIs for most patients, with individualization of the choice of specific drug (100).

  • A 2012 Cochrane review of newer-generation antidepressants compared with placebo for children and adolescents with depression included 19 studies with 3335 participants. Overall, rates of remission were slightly higher in patients receiving antidepressants (44.8% vs. 38%), but the risk for suicide was increased (RR, 1.58 [CI, 1.02 to 2.45]) (101).

  • A 2009 systematic review of the risk for suicide with SSRIs included eight studies with over 200,000 participants with moderate or severe depression. Among adolescents, SSRIs increased the risk for suicide attempt (OR, 1.92 [CI, 1.51 to 2.44]) and completed suicide (OR, 5.81 [CI, 1.57 to 21.51]) (102).

Rationale
  • Antidepressants may be associated with an increased risk for suicidality in children, adolescents, and young adults.

  • Careful monitoring for suicidal ideation during the first weeks of therapy may identify patients who need additional support, more intensive observation, or a change in therapy.

Comments
  • Since 2005, the FDA has recommended close monitoring of all patients treated with antidepressants, particularly early during the course of treatment and has included a black box warning on antidepressants.

Consider offering St. John's wort as a potential treatment for patients with mild depression or subsyndromal depression who decline other therapies. 
  • Consider offering St. John's wort to patients with mild depression who decline other therapies.

  • Initiate St. John's wort at a dose of 0.3% hypericin, 300 mg three times daily.

  • See table Drug Treatment for Depression.

Evidence
  • A 2009 NICE guideline on the management of depression recommended against the use of St. John's wort, given concerns about dosing and product uncertainty, although it acknowledged that the substance may be effective (35).

  • A 2008 Cochrane review of St. John's wort (Hypericum extracts) for major depression included 29 studies with 5489 participants. Overall, there was heterogeneity in the results of placebo-controlled trials, but St. John's wort resulted in higher response rates in both larger trials (RR, 1.28 [CI,1.10 to 1.49]) and smaller trials (RR, 1.87 [CI, 1.22 to 2.87]). St. John's wort resulted in similar response rates to TCAs and SSRIs with fewer drop-outs due to side effects compared with SSRIs (OR, 0.53 [CI, 0.34 to 0.83]) (103).

Rationale
  • St. John's wort may be beneficial for patients who want to take something for subsyndromal depression or who are unwilling or unable to take conventional therapy for moderate depression.

  • Optimal doses are not established, but many trials with positive findings have used standardized doses of 0.3% hypericin, 300 mg three times daily.

  • Serious adverse effects with St. John's wort are uncommon.

Comments
  • St. John's wort should not be used in conjunction with SSRIs. There have been several cases reported in the elderly who have experienced symptoms of serotonin excess, including hyperthermia, tachycardia, diaphoresis, and rigidity when used in combination with St. John's wort (104).

  • St. John's wort activates the CYP P450 system and may reduce plasma concentration of certain coadministered drugs, such as digoxin, theophylline, simvastatin, and warfarin (105).

  • Severe drug interactions have been reported with antiretroviral therapy, including increased photosensitivity and alterations in pharmacokinetics. By activating the 3A4 isoform of CYP P450, St. John's wort can decrease concentrations of protease inhibitors and nonnucleoside reverse transcriptase inhibitors (106).

  • At high concentrations, St. John's wort has been shown to be harmful to sperm cells and may lead to decreased fertility (107).

  • Augmentation with other nontraditional agents have shown mixed results: adding omega-3 fatty acids to sertraline in patients with coronary heart disease has not improved depressive outcomes (108).

  • A 2005 systematic review of light therapy (6000 to 10,000 lux for 30 to 90 minutes each morning) for seasonal and nonseasonal depression found overall modest improvements in depressive symptoms (109).

  • A 2013 Cochrane review of exercise for depression included 39 trials. In the pooled analysis, exercise interventions improved depressive symptoms moderately (110).

  • Yoga, self-help books, relaxation therapy, and acupuncture may also be useful.

Consider the possible adverse effects of antidepressants on fetal development in pregnant women. 
  • Weigh the possible adverse effects of antidepressants on fetal development and well-being against the risk for depression relapse among pregnant women who discontinue them.

Evidence
  • A retrospective cohort study of 6976 offspring exposed to SSRIs during pregnancy showed an elevation in the risk for isolated ventricular septal defects with fluoxetine (OR, 2.03 [CI, 1.28 to 3.21]), right ventricular outflow tract defects with paroxetine (OR, 4.68 [CI, 1.48 to 14.74]), neural tube defects with citalopram (OR, 2.46 [CI, 1.20 to 5.07]), and fetal alcohol syndrome with any SSRI (OR, 9.6 [CI, 4.6 to 20.0]) (111).

  • A case-control study showed a six-fold increase in the incidence of persistent pulmonary hypertension of the newborn in mothers taking SSRIs (112).

  • A cohort study of 201 pregnant women with a history of depression showed a 68% relapse rate among the 65 women who discontinued their antidepressant medication compared with a 26% rate among the 82 women who maintained their medication throughout their pregnancy (113).

Rationale
  • Second-generation antidepressants may be associated with an increased risk for fetal malformations (first trimester) and pulmonary hypertension (third trimester).

  • However, the absolute risk for fetal harm is low and is counterbalanced by an increased risk for relapse among women who discontinue antidepressants during pregnancy.

Comments
  • In 2005 the FDA issued a Public Health Advisory concerning fetal malformations associated with paroxetine (Paxil) use in the first trimester. START HERE

Assess patient knowledge of illness and management. 
  • Assess patient beliefs about depression, antidepressant medication, and psychotherapy.

  • Ask about the beliefs and attitudes of family members as well, as they may also be relevant to the patient's acceptance of the diagnosis and subsequent treatment.

  • Personalize educational messages to the patient's actual beliefs in order to enhance the effect of patient education.

  • Recognize that a belief that depression is not an illness, that it is only a natural reaction to adverse events, can interfere with acceptance of the diagnosis and effective treatment.

Evidence
  • A retrospective cohort study evaluated correlates with adherence to antidepressants in 155 patients who started on antidepressants in primary care. Overall, 28% of patients stopped medication during the initial month of treatment, and 44% stopped within 3 months. Patients were more likely to adhere to therapy during the first month if they were told one of the following: take medication daily, antidepressants take 2 to 4 weeks to be effective, continue medication even if you feel better, or do not stop medication without checking with your doctor; patients given specific instructions about what to do if they had questions were also more likely to adhere to therapy (97).

Rationale
  • Personalized messages may improve adherence to therapy and satisfaction with care.

Comments
  • Reasons for noncompliance can include rational and intentional decisions based on beliefs about the illness, concerns over side effects, ineffectiveness of treatment, cost of medications, and many other cultural and attitudinal factors (99; 114).

Provide key messages to patients about medication use. 
  • Counsel patients in order to improve medication adherence, urging them to

    • Take the medication daily

    • Wait 2 to 4 weeks before expecting to see a noticeable effect

    • Continue to take medicine even if feeling better

    • Check with their physician first before stopping an antidepressant

    • Resolve with their physician any questions regarding antidepressants and possible side effects

  • Counsel patients about discontinuation-emergent symptoms.

Evidence
  • A retrospective cohort study evaluated correlates with adherence to antidepressants in 155 patients who started on antidepressants in primary care. Overall, 28% of patients stopped medication during the initial month of treatment, and 44% stopped within 3 months. Patients were more likely to adhere to therapy during the first month if they were told one of the following: take medication daily, antidepressants take 2 to 4 weeks to be effective, continue medication even if you feel better, or do not stop medication without checking with your doctor; patients given specific instructions about what to do if they had questions were also more likely to adhere (97).

  • A randomized trial compared drug counseling with information leaflets in 250 patients beginning treatment with a TCA. Adherence at 12 weeks was higher in the counseling group (63% vs. 39%) (98).

Rationale
  • Specific messages about antidepressant medication and use have an effect on adherence during the first, critical month of treatment.

Comments
  • Abrupt discontinuation of some antidepressant agents, such as SSRIs, is associated with such symptoms as dizziness, nausea, paresthesia, rhinitis, and headaches in some people. Such symptoms are probably more likely and more severe with drugs with a short half-life, such as paroxetine and sertraline (115; 116; 117).

  • Among patients with cardiovascular illness, both depression and nonadherence to depression treatment have been associated with nonadherence to cardiovascular medications. These findings underscore the importance of aggressive treatment of depression in patients with comorbid medical illness (118; (119).

Provide information about continuation therapy and the prevention of recurrence. 
  • Provide patients with information about the risks for relapse and recurrence and importance of monitoring their symptoms.

Evidence
  • Consensus.

Rationale
  • Depression commonly recurs.

  • Continuation therapy can prevent relapse.

  • Early intervention with reemergence of symptoms can prevent full-blown recurrence; maintenance medications and possibly psychotherapy can help prevent remission.

  • Patients should play an active role in identifying reemergence of symptoms and initiation of interventions to prevent recurrence.

Include patients' families in “psychoeducational” interventions whenever possible. 
  • Provide information about depression to patients and their families if patients consent to family involvement.

Evidence
  • A cohort study described outcomes in 132 older patients with depression and 182 of their family members, among whom 108 patients participated in a psychoeducational family workshop and 24 did not. Workshop participation was associated with lower rates of dropout during continuation therapy (120).

  • Descriptive studies have discussed psychoeducational approaches (121; 122).

Rationale
  • Psychoeducational models that provide information about illness and disease management to patients and their families appear to be helpful in chronic mental illnesses.

  • Families can be instrumental in enhancing patient adherence with treatment, and their involvement may improve acceptance of and support for patients' problems and the needs of their treatment regimens.

Comments
Provide written and electronic patient education materials that are appropriate for the patient's health literacy skills. 
  • Provide patients and their families with appropriate written and electronic patient education materials about depression and its management.

Evidence
  • A 1997 systematic review of bibliotherapy (providing educational material and advising patients to read them) for depression included seven studies in which bibliotherapy was compared with a wait-list control and with other active therapies. Overall, bibliotherapy was more effective than control and had a similar effect as individual and group therapy (123).

  • Mainly consensus.

Rationale
  • Written and electronic information may supplement individualized patient and family education efforts.

Comments
  • The average general literacy level of the U.S. population is between the 8th- and 9th-grade level (124), and functional health literacy is even lower: one third of English-speaking patients are unable to read basic health materials. Forty-two percent of patients cannot understand directions for taking medication on an empty stomach, 26% are unable to understand appointment slips, and 60% do not understand a standard informed-consent document (125).

  • Older patients and patients with low socioeconomic status have even more marginal health literacy skills.

Assess patients' experience with medication at 1 to 2 weeks. 
  • In the initial weeks of treatment, assess acceptance of medication, reinforce educational messages, and address adverse events.

Evidence
  • A 2009 NICE guideline on the management of depression recommended seeing patients 2 weeks after starting medication, and then at 2- to 4-week intervals for 3 months, and then at longer intervals if they have responded well to treatment (35).

  • A retrospective cohort study evaluated correlates with adherence to antidepressants in 155 patients who started on antidepressants in primary care. Overall, 28% of patients stopped medication during the initial month of treatment, and 44% stopped within 3 months. Patients were more likely to adhere to therapy during the first month if they were told one of the following: take medication daily, antidepressants take 2 to 4 weeks to be effective, continue medication even if you feel better, or do not stop medication without checking with your doctor; patients given specific instructions about what to do if they had questions were also more likely to adhere (97).

  • A randomized trial compared drug counseling with information leaflets in 250 patients beginning treatment with a TCA. Adherence at 12 weeks was higher in the counseling group (63% vs. 39%) (98).

  • A 1997 narrative review on adherence noted that increased frequency of contact and intensity of support during acute treatment can improve patient outcomes (99).

Rationale
  • Challenges to adherence specific to the initial phase of treatment include the pessimism and hopelessness intrinsic to depression and the relatively rapid onset of adverse effects before the benefits of treatment are noticed.

  • Addressing specific adverse effects as they emerge is critical to helping patients continue medication until they experience a response.

Assess patients at 6 to 8 weeks to determine response to treatment, and adjust or change medication as needed. 
  • Use a structured instrument, such as the PHQ-9 to assess changes in symptom severity by following changes in the score over time:

    • A 50% decrease in symptoms constitutes an adequate response

    • A 25% to 50% response may indicate the need to modify treatment by increasing the dose if there has been some response, or changing medication if response has been minimal

  • In patients who cannot tolerate or who do not respond to the initial choice of medication in 6 to 8 weeks, switch to another medication.

  • Note that although changing the class of antidepressant to avoid specific side effects (e.g., from an SSRI to bupropion because of anorgasmia) may be appropriate, it is usually not necessary to switch to a non-SSRI medication if the initial medication is an SSRI.

  • Note that patients who show no response to or are intolerant of one SSRI may successfully use another.

  • Use these strategies for specific SSRI adverse effects:

    • Sexual dysfunction: switch to bupropion, nefazodone, mirtazapine

    • Weight gain: switch to bupropion

    • Agitation or excessive activation: switch to another SSRI, a TCA, nefazodone, mirtazapine

  • When switching medications, ensure that both patient and physician distinguish discontinuation-emergent adverse effects from adverse effects from the new medication.

  • Note that with the exception of switches to or from MAOIs, a washout period is generally not required; however, simultaneously titrating the new medication on and the old off is also acceptable.

  • When switching to or from an MAOI, use a minimum of a 2-week washout.

  • When switching from fluoxetine to an MAOI, use a 6-week washout.

  • See table Characteristics of Selected Antidepressants.

  • See table Drug Treatment for Depression.

Evidence
  • A 2009 NICE guideline on the management of depression recommended seeing patients 2 weeks after starting medication, and then at 2- to 4-week intervals for 3 months, and then at longer intervals if they have responded well to treatment (35).

  • A retrospective cohort study described treatment approaches in 273 patients who did not respond to first-line antidepressant therapy. The most common strategies were switching to another antidepressant (40%), augmentation (generally with an atypical antipsychotic medication) (19%), and combination therapy (18%) (126).

  • A 1996 narrative review discussed treatment-resistant depression, noting that one study found between 29% and 46% of patients did not respond fully to antidepressant treatment of adequate dose and duration (6 weeks). Partial response, defined as symptomatic improvement that is at least 25% and less than 50%, occurred in 12% to 15%; and nonresponse, defined as less than 25% symptomatic improvement, occurred in 19% to 34% (127).

Rationale
  • The goal of treatment is complete remission of symptoms and return to normal functioning.

  • Because antidepressant medications take some time to be effective, specific response goals are helpful in ensuring appropriate and timely response.

  • A structured, quantitative assessment of symptom severity, such as provided by the PHQ-9, may make assessment of response easier and more accurate.

  • Although partial response may be treated with an increase in dose or introduction of a second agent while maintaining the initial agent, complete intolerance or nonresponse should be treated by a complete change in medication.

  • Intolerance and lack of response to any particular antidepressant is common but not predictive of response to another antidepressant.

  • Some specific side effects are more common with particular drugs and should guide choice of replacement medication.

Assess patients at 10 to 12 weeks to determine response to treatment. 
  • Use a structured procedure to assess changes in symptom severity.

  • Assess patients at 10 to 12 weeks to determine if response to treatment has been complete; if not, consider

    • Increasing the dose of the current agent

    • Switching to a different antidepressant

    • Adding a second antidepressant (combination therapy):

      • Bupropion plus SSRI

      • TCA plus SSRI, carefully monitoring TCA levels

      • Mirtazapine plus SSRI

    • Adding an agent not typically used for depression (augmentation therapy):

      • Lithium

      • Liothyronine

      • Second-generation antipsychotic (only aripiprazole has an FDA indication)

      • Pindolol

      • Buspirone

    • Adding psychotherapy

    • Adding light therapy, especially in patients with seasonal depression

  • See table Drug Treatment for Depression.

Evidence
  • A 2009 NICE guideline on the management of depression recommended seeing patients 2 weeks after starting medication, and then at 2- to 4-week intervals for 3 months, and then at longer intervals if they have responded well to treatment (35).

  • A 2012 AHRQ comparative effectiveness report on the efficacy of treatments for depression after incomplete response to an SSRI included 44 primary studies; the overall quality of the evidence was low. Overall, compared with monotherapy, combination therapy did not result in superior rates of response. However, augmentation with atypical antipsychotic medications were slightly superior to monotherapy (128).

  • A randomized trial compared bright-light therapy with placebo in 89 patients aged 60 or older with nonseasonal depression. Scores on the Hamilton Scale for Depression improved more in the light therapy group (129).

  • A 2008 structured review of the use of thyroid hormone for the treatment of depression (in conjunction with antidepressants) included five studies. Results were mixed (87).

Rationale
  • The goal of treatment is complete remission of symptoms and return to normal functioning.

  • Because antidepressant medications take some time to be effective, specific response goals are helpful in ensuring a timely response.

  • A structured, quantitative assessment of symptom severity, such as provided by the PHQ-9, may make assessment of response easier and more accurate.

  • Before adding or switching medication, the dose of the initial agent should be maximized as tolerated if a partial response was observed.

  • The advantages of combination or augmentation therapy include a relatively rapid effect compared with withdrawing one medication and then starting another, potential for synergistic or complementary effect, and avoidance of withdrawal symptoms when the first agent is stopped.

  • The disadvantages of combination or augmentation therapy include the increasing complexity of the regimen and increased opportunities for drug interactions and adverse effects.

  • Fluoxetine and paroxetine are P450 (CYP) 2D6 inhibitors and may raise blood levels of TCAs metabolized by that system; drug levels of TCAs should be carefully monitored.

Comments
  • Consider referring patients in whom multiple different antidepressants fail despite appropriate adherence counseling.

  • Although the combined use of MAOIs and TCAs has been reported, this combination is fraught with hazard and is not recommended. When employed by physicians with experience in their combined use, MAOIs should be added to existing TCA therapy and never used in the opposite sequence.

  • Although they have been used, there are no controlled studies of the use of stimulants for augmentation (130).

  • Incidence of side effects with lithium is greater in the elderly.

Monitor patients in person or by phone monthly while they are on medication during the initial 6 months after symptom relief and periodically during maintenance. 
  • Assess adherence to medication and psychotherapy, emergence of adverse effects, symptom breakthrough, and level of psychosocial stress at monthly intervals.

  • Educate patients and their families to self-assess for symptoms and risk for depression.

  • In patients who have completed successful treatment for an initial episode of depression, address the problem of recurrence, early warning signs, and proper evaluation of stressors.

Evidence
  • A 2009 NICE guideline on the management of depression recommended seeing patients 2 weeks after starting medication, and then at 2- to 4-week intervals for 3 months, and then at longer intervals if they have responded well to treatment (35).

Rationale
  • Continuation of treatment is important to ensure remission, and adherence to treatments may deteriorate when patients are feeling better.

  • Patients may fail to bring reemerging or persistent symptoms to attention without active monitoring.

  • Patients and family who are vigilant can detect reemergence of symptoms or anticipate recurrence when levels of stress that have precipitated depressive episodes are present.

  • Recurrence of depression after a first episode is common.

Use disease management care pathways to address the multiple needs of patients with depression throughout the course of the illness. 
  • Use depression disease management programs that include

    • Coordination of care by care managers

    • Telephone or telemedicine interventions

    • Provider education and feedback on performance

    • Structured systematic assessment of patient response to treatment with feedback to the provider

    • Stepped-care referrals for psychiatric consultation based upon structured systematic assessment of patient progress

    • Nurse-administered telephone support and education calls

    • Peer support

Evidence
  • A 2012 Cochrane review of the collaborative care model for the treatment of depression and anxiety included 79 randomized trials with over 24,000 participants. The collaborative care model improved outcomes of depression in the short, medium, and long term but not in the very long term (>2 years). Patients receiving collaborative care were more likely to experience treatment response at 0 to 6 months (RR, 1.34 [CI, 1.23 to 1.45]) and more likely to take antidepressant medication at 0 to 6 months (RR, 1.47 [CI, 1.33 to 1.63]) (68).

Rationale
  • Patients with depression benefit from ongoing, personalized education, support, and access to resources for resolving difficulties with medication.

  • Cognitive therapy can be effectively delivered by telephone.

  • Usual physician practice has been shown to be inadequate based on guideline standards.

  • Structured practices that automate the utilization of treatment assessment, patient education, and support eliminate variability in physician practice and can ensure adherence to best practices.

  • Efforts to improve primary care treatment of depression have implemented collaborative care models, nurse telehealth services, and therapy groups.

  • Nurse telehealth care improves clinical outcomes of antidepressant drug treatment and patient satisfaction.

Comments
  • Changing physician behavior requires structured interventions that operate independently of physician initiation. Most require additional resources, but costs seem commensurate with demonstrated benefit. Implementation of these approaches requires initiative at the health care delivery system level rather than in individual doctor-patient relationships.

Table Grahic Jump Location
 Accuracy of Symptoms and Diagnostic Instruments for Depression

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ElementSensitivity (%)Specificity (%)Notes
Depressed mood or anhedonia (PHQ-2)8778Differs in different populations; this is the accuracy in general outpatients
PRIME-MD for major depressive disorder5794Requires 8.4 minutes of physician time in patients who trigger evaluation
PHQ-9 criterion diagnosis for major depressive disorder
PHQ-9 score ≥15 for major depression
PHQ-9 score ≥10 for major depression
73
68
88
98
95
88
The entire PHQ: about 3 minutes to administer; the PHQ-9 for depression: about 1 minute to administer
SDDC-PC9077Assesses multiple mental disorders common in primary care; this is accuracy for major depression

PHQ = Patient Health Questionnaire; PRIME-MD = Primary Care Evaluation of Mental Disorders; SDDS-PC = Symptom-Driven Diagnostic System for Primary Care.

Table Grahic Jump Location
 Differential Diagnosis of Major Depressive Disorder and Other Mood Disorders

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DiseaseCharacteristics
Major depressive disorderDepressed mood or loss of interest or pleasure in almost all activities; symptoms must occur nearly every day for at least 2 weeks and a total of five DSM symptoms must be present.
Drug therapy and psychosocial interventions are effective
Persistent depressive disorder (dysthymia)A chronic mood disorder characterized by depressed mood or anhedonia at least half the time for at least 2 years accompanied by two or more vegetative or psychological symptoms and functional impairment.
Drug therapy is effective
Subsyndromal (minor) depressionsAn acute depression that is less symptomatic than major depression, causing less impairment in social or occupational functioning than major depression.
Unclear if drug therapy or psychotherapy improves patient outcomes
MDPRRFewer than five symptoms of major depression but past history consistent with major depressive episode.
Natural history of depression and risk for full relapse suggest that patient be treated with medication, therapy, or both
Adjustment disorder with depressed moodSubsyndromal depression with clear precipitant. Usually resolves with resolution of acute stressor without medication.
Careful brief observation may be indicated in patients with mild syndrome of major depression associated with clear stressful precipitant. Supportive counseling should also be initiated
Bipolar disorderCharacterized by one or more manic or mixed episodes, usually accompanied by major depressive disorder.
Requires mood-stabilizing medication in addition to and usually before antidepressant medication. Usually requires referral to psychiatrist
Major depressive disorder with seasonal patternOccurs with seasonal change, typically fall or winter onset and seasonal remission; rarely, onset is in the spring with remission in the fall or winter. Has occurred in the two previous years, without nonseasonal depression. More common in northern latitudes.
Responds to bright-light therapy and adjuvant therapy with SSRIs
Premenstrual dysphoric disorderCharacterized by depressed mood, anxiety, and irritability during the week before menses, resolving with menses.
May respond to SSRI treatment; intermittent treatment during part of the menstrual cycle may be effective
Secondary depressionEvidence of specific metabolic disturbance, recent drug or substance use or withdrawal, remission with treatment of disorder or removal of drug or substance, or recovery from withdrawal.
Treat underlying condition
DementiaCharacterized by impairment of memory, judgment, and other higher cortical functions; usually has insidious onset.
Assess mini-mental status or conduct neuropsychiatric testing if diagnosis uncertain. Consider trial of antidepressant therapy. The Memory Impairment Screen may be particularly useful in suggesting pseudodementia of depression vs. true dementia
Anxiety disorders (generalized anxiety disorder, panic disorder, PTSD, OCD)Generalized anxiety disorder is characterized by excessive worry, muscular tension, fatigue, autonomic hyperactivity, and increased vigilance. Specific anxiety disorders (panic disorder, social anxiety disorder, OCD, PTSD) should also be considered.
Occur frequently with depression
Alcohol abuseCharacterized by loss of control of drinking, adverse consequences as a result of alcohol use, evidence of tolerance, and drinking in quantities and at a frequency that is excessive.
Patients often may complain of insomnia, nightmares, poor memory, and nervousness
Eating disorderAnorexia nervosa characterized by refusal to maintain body weight over 85% of expected; intense fear of gaining weight, even though underweight; disturbance in the way body weight, size, or shape is perceived; and absence of at least three consecutive menstrual periods in postmenarchal females
Psychotic disorderThought disorder, in the case of schizophrenia a chronic progressive disorder. Patients with major depression may have psychotic symptoms during acute episodes.
Mood congruent hallucinations and delusions are classic for depression with psychotic features, whereas mood incongruent hallucinations or delusions typify other psychotic disorders
HypothyroidismSymptoms that overlap with depression include fatigue, decreased cognitive function, and depressive symptoms.
Laboratory testing is confirmatory
Medication adverse effectMay have a temporal relationship to medication initiation.
These include glucocorticoids, interferon, propranolol, levodopa, oral contraceptives

DSM = Diagnostic and Statistical Manual of Mental Disorders; MDPRR = major depression in partial remission or recurrence; OCD = obsessive-compulsive disorder; PTSD = posttraumatic stress disorder; SSRI = selective serotonin reuptake inhibitor.

Table Grahic Jump Location
 Drug Treatment for Depression

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Drug or Drug ClassDosingSide EffectsPrecautionsClinical Use
blackboxiconSelective serotonin reuptake inhibitorsPlatelet dysfunction, GI side effects, xerostomia, insomnia, anxiety, agitation, asthenia, drowsiness, headache, sexual dysfunction, hyponatremia, rare serotonin syndrome or NMSblackboxicon Suicidality, particularly in young adults. Avoid abrupt discontinuation, other serotonergic drugs and MAOI therapy. Drug interactions due to CYP450 metabolismAn option for first-line therapy. Use side effects to choose a specific agent
blackboxiconCitalopram (Celexa)20 mg qd. Maximum 40 mg qdDose-dependent QT prolongationAvoid with drugs that prolong QT interval. Maximum dose 20 mg qd with hepatic disease, age >60 years, poor metabolizers of CYP2C19 or receiving a CYP2C19 inhibitor. Caution with CrCl <20Low rate of anxiety and activation
blackboxiconEscitalopram (Lexapro)10 mg qd. Maximum 20 mg qdCNS depressionMaximum dose 10 mg qd with hepatic disease, elderly. Caution with CrCl < 20Low risk for drug interactions. Low rate of anxiety and activation
blackboxiconFluoxetine (Prozac, Prozac Weekly)Daily: 20 mg qd. Maximum 80 mg qd. Weekly: 90 mg once weeklyMay need to decrease dose with hepatic disease. Significant inhibitor of CYP isoenzymesLong half-life. Highest rate of anxiety and agitation
blackboxiconParoxetine (Paxil, Paxil CR, Pexeva)Regular-release: 20 mg qd in AM. Maximum 50 mg qd. Controlled-release: 25 mg qd in AM. Maximum 62.5 mg qdAvoid with pregnancy. Decrease starting dose and maximum dose with hepatic disease, elderly, CrCl <60. Potent inhibitor of CYP2D6. May decrease efficacy of tamoxifenMore anticholinergic side effects than other agents; high rate of drowsiness
blackboxiconSertraline (Zoloft)50 mg qd. Maximum 200 mg qdMay need to decrease dose with hepatic disease. Mild inhibitor of CYPs 2D6 and 3A4Higher rate of diarrhea and headache
blackboxiconSerotonin-norepinephrine reuptake inhibitorsPlatelet dysfunction, nausea, constipation, anorexia, weight loss, xerostomia, insomnia, anxiety, asthenia, dizziness, drowsiness, headache, hypertension, tachycardia, hyperhidrosis, sexual dysfunction, hyponatremia, serotonin syndrome, rare NMSblackboxicon Suicidality, particularly in young adults. Avoid abrupt discontinuation. Avoid other serotonergic drugs and MAOI therapy
blackboxiconVenlafaxine (Effexor, Effexor XR)Immediate-release: 25 mg tid. Maximum 75 mg tid. Extended-release: 37.5-75 mg qd. Maximum 225 mg qdDecrease initial dose by 50% with moderate hepatic disease. Decrease dose by 25%-50% if CrCl <70. Caution with CYP2D6 inhibitorsHigh rate of nausea and vomiting. May increase HR and BP
blackboxiconDesvenlafaxine (Pristiq)50 mg qd. Maximum 400 mg qd, although may be no benefit above 50 mg qdMaximum dose 100 mg qd with hepatic disease. If CrCl <50, maximum dose 50 mg qd. If CrCl <30, maximum dose 50 mg qodMay increase BP
blackboxiconDuloxetine (Cymbalta)40-60 mg total daily dose, dosed qd-bidUrinary retention, hepatotoxicity, musculoskeletal pain, muscle spasmsAvoid with hepatic disease, severe CKD, closed-angle glaucoma. Substrate and moderate inhibitor of CYP2D6. Caution with diabeticsMay increase BP
blackboxiconLevomilnacipran (Fetzima)Starting dose: 20 mg daily for two days, then increase to 40 mg daily. Recommended dose: 40-120 mg qdVomiting, palpitations, urinary hesitancyAvoid with severe CKD. If CrCl 30-59, or receiving potent CYP3A4 inhibitor, maximum dose 80 mg/day; if CrCl 15-29, maximum dose 40 mg/day. Caution with glaucomaMeasure Cr, BP, HR at baseline, then periodically
Tricyclic antidepressantsDue to sedation, bedtime dosing may be preferredDrowsiness and other CNS side effects, anticholinergic side effects (such as constipation, xerostomia, urinary retention, visual impairment), orthostatic hypotension, ECG abnormalities, tremor, nausea, weight gain, sexual dysfunctionblackboxicon Suicidality, particularly in young adults. Avoid abrupt discontinuation, MAOI therapy. Decrease dose with hepatic disease, elderly. Caution with decreased GI motility, cardiac disease, closed-angle glaucoma, BPH, urinary retention, seizure disorder, thyroid disease, diabetes, sunlight
blackboxiconAmitriptyline25-75 mg qhs, up to 200 mg total daily dose, qhs or in divided dosesMost anticholinergic effects
blackboxiconDesipramine (Norpramin)50-75 mg total daily dose, dosed qd-qid. Maximum 200 mg total daily doseMore dangerous than other TCAs in overdoseFewer anticholinergic effects; less weight gain
blackboxiconDoxepin (Silenor)50-75 mg total daily dose, dosed bid-tid or qhs. Usual 75-150 mg total daily doseCaution with potent CYP2C19 or 2D6 inhibitors
blackboxiconImipramine (Tofranil, Tofranil-PM)75 mg total daily dose, dosed qd-qid. Maximum 150 mg total daily dose. Tofranil-PM: 75 mg qhs, up to 150 mg qhs
blackboxiconNortriptyline (Pamelor)25-50 mg total daily dose, dosed qhs or in divided doses. Maximum 150 mg total daily doseFewer anticholinergic effects; less weight gain and fewer GI and sexual side effects
blackboxiconProtriptyline (Vivactil)5-10 mg tid. Maximum 20 mg tidMay be less sedating than other TCAs
blackboxiconTrimipramine (Surmontil)75 mg total daily dose, dosed qhs or in divided doses. Maximum 200 mg total daily dose
Monoamine oxidase inhibitorsHypertensive crisis, particularly with certain drugs or foods. Orthostatic hypotension, peripheral edema, hepatitis, insomnia, anticholinergic side effects, tremor, weight gain, sexual dysfunctionblackboxicon Suicidality, particularly in young adults. Avoid abrupt discontinuation. Avoid alcohol, excessive caffeine, foods* containing tyramine. Avoid with hypertension, cardiac disease, CV disease, history of headache. Caution with asthma, diabetes, seizure disorder, hyperthyroidism. Many drug interactionsSecond-line due to serious adverse reactions. Interacting drugs must be discontinued 1-2 weeks before start
blackboxiconIsocarboxazid (Marplan)10 mg bid. Maximum 60 mg total daily dose, dosed bid-qidAvoid with hepatic disease, severe CKD. Caution with CKD
blackboxiconPhenelzine (Nardil)15 mg tid, up to 60 mg total daily doseAvoid with hepatic disease, severe CKD. Caution with CKD
blackboxiconSelegiline transdermal (Emsam)6 mg applied qd, up to 12 mg qdApplication site reaction or rashTransdermal formulation makes adverse reactions less likely than with other MAOIs
blackboxiconTranylcypromine (Parnate)30 mg total daily dose, in divided doses. Maximum 60 mg total daily doseAvoid with hepatic disease, severe CKD. Caution with CKD
Otherblackboxicon Suicidality, particularly in young adults. Avoid abrupt discontinuation, MAOI therapy
blackboxiconAmoxapine50-100 mg bid-tid. Maximum total daily dose, 400 mgDrowsiness and other CNS side effects, anticholinergic side effects (such as constipation, xerostomia, urinary retention, visual impairment), orthostatic hypotension, ECG abnormalities, tremor, nausea, weight gain, sexual dysfunction, NMS, TD, AGEPDecrease dose with elderly. Caution with hepatic disease, decreased GI motility, cardiac disease, closed-angle glaucoma, BPH, urinary retention, seizure disorder, thyroid disease, diabetes, sunlight
blackboxiconBupropion (Wellbutrin, Wellbutrin SR, Wellbutrin XL, Aplenzin, Forfivo XL)Immediate-release: 100 mg bid-tid. Sustained-release (SR): 150 mg qd-bid. Maximum 200 mg bid. Extended-release (XL): 150-300 mg qd. Maximum 450 mg qd. Aplenzin: 174-348 mg qd. Maximum 522 mg qd. Forfivo XL: Not for initial use. 450 mg qdDose-dependent seizures. Insomnia, dizziness, tremor, agitation, anxiety, confusion, weight loss, hyperhidrosisAvoid with seizure disorder, eating disorder. Decrease dose with severe hepatic disease, moderate-severe CKD. Caution with mild-moderate hepatic disease. Inhibitor of CYP2D6 and substrate of CYP2B6Lowest rates of sexual side effects and weight gain
blackboxiconMaprotiline25 mg tid. Maximum 150-225 mg total daily dose, dosed qd or tidDrowsiness and other CNS side effects, anticholinergic side effects (such as constipation, xerostomia, urinary retention, visual impairment), orthostatic hypotension, ECG abnormalities, tremor, nausea, weight gain, sexual dysfunctionConsider decreased dose with hepatic disease, elderly. Caution with decreased GI motility, cardiac disease, closed-angle glaucoma, BPH, urinary retention, seizure disorder, thyroid disease, diabetes, sunlight
blackboxiconMirtazapine (Remeron)15 mg qhs. Usual dose 15-45 mg qdDrowsiness, dizziness, nausea, vomiting, increased appetite, weight gain, constipation, xerostomia, rare agranulocytosis or severe neutropeniaDecrease dose with elderly, CrCl <40. Caution with seizure disorder, inhibitors of CYPs 2D6, 1A2, or 3A4More drowsiness; can stimulate appetite and cause weight gain
blackboxiconNefazodone100 mg bid. Usual dose 150-300 mg bidDrowsiness, dizziness, nausea, vomiting, increased appetite, weight gain, constipation, xerostomia, asthenia, confusion, blurred vision, orthostatic hypotension, rare agranulocytosis or severe neutropeniablackboxicon Hepatic failure. Avoid with hepatic disease. Decrease initial dose if elderly. Inhibitor of CYP3A4
blackboxiconTrazodone (Oleptro)Immediate-release: 150 mg total daily dose, given in divided doses. Maximum 400 mg total daily dose. Extended-release: 150 mg qhs, on an empty stomach. Maximum 375 mg qdDrowsiness, dizziness, hypotension, anxiety, insomnia, xerostomia, constipation, nausea, blurred vision, priapismDecrease dose with elderly, hepatic disease, potent CYP3A4 inhibitors. Caution with cardiac disease, CKDDrowsiness
blackboxiconVilazodone (Viibryd)Starting dose: 10 mg qd for 7 days, then 20 mg qd for 7 days, then 40 mg qdDiarrhea, vomiting, insomnia, dizziness, sexual dysfunction, platelet dysfunctionDecrease dose with potent CYP3A4 inhibitors, consider increasing dose with potent CYP3A4 inducers
blackboxiconVortioxetine (Brintellix)Starting dose: 10 mg qd. Typical dose: 10-20 mg qdNausea, diarrhea, dizziness, xerostomia, constipation, abnormal dreams, pruritus, sexual dysfunction, platelet dysfunction, hyponatremiaAvoid with severe hepatic disease. Maximum dose of 10 mg qd in CYP2D6 poor metabolizers. Decrease dose with potent CYP2D6 inhibitors. Consider increasing dose with potent CYP2D6 inducers
Nutritional supplement
St. John's wort0.3% hypericin, 300 mg tidAbdominal pain, headache, xerostomia, insomnia, sexual dysfunction, photosensitivity reactions, possible male infertilityAvoid MAOI therapy, SSRIs. Drug interactions due to induction of CYP3A4 and P-gp (including oral contraceptives and antiretroviral protease inhibitors)Not FDA approved. Option for mild-moderate depression

*Foods to avoid include aged cheese, yeast or protein extract, soy sauce, beans, smoked or pickled meat or fish, liver, fermented sausage or other meat, bananas, avocados, any overripe fruit, anchovies, sauerkraut, canned figs, raisins, raspberries, yogurt, and sour cream.

AGEP = acute generalized exanthematous pustulosis; BBW = black box warning; bid = twice daily; BP = blood pressure; BPH = benign prostatic hypertrophy; BUN = blood urea nitrogen; CKD = chronic kidney disease; CNS = central nervous system; Cr= creatinine; CrCl = creatinine clearance; CYP = cytochrome P450 isoenzyme; ECG = electrocardiogram; GI = gastrointestinal; HR = heart rate; IM = intramuscular; IV = intravenous; MAOI = monoamine oxidase inhibitor; NMS = neuroleptic malignant syndrome; P-gp = P-glycoprotein; PO = oral; prn = as needed; q12hr = every 12 hours; q3-4hr = every 3 to 4 hours; qd = once daily; qhs = once daily at bedtime; qid = four times daily; qod = every other day; SC = subcutaneous; SCr = serum creatinine; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant; TD = tardive dyskinesia; tid = three times daily

ACP Smart Medicine provides key prescribing information for practitioners but is not intended to be a source of comprehensive drug information.

Table Grahic Jump Location
 Screening Measures for Depression in Adults and the Elderly

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AdultsNo. of ItemsTime FrameAvailable in SpanishAdministration Time
Beck Depression Inventory (BDI)21TodayYes5-10 minutes
Center for Epidemiologic Studies Depression Screen (CES-D)20Past weekYes5-10 minutes
General Health Questionnaire (GHQ)28Past few weeksN/A5-10 minutes
Medical Outcomes Study Depression Screen (MOS-D)8Past weekN/A<2 minutes
Patient Health Questionnaire Short Form (PHQ-9)9Past 2 weeksYes5 minutes
Patient Health Questionnaire Short Form (PHQ-2)2Past 2 weeksYes1 minute
Symptom-Driven Diagnostic System—Primary Care (SDDS-PC)5Past monthN/A< 2 minutes
Zung Self-Rating Depression Scale (SDS)20RecentlyNo5-10 minutes
Depression Scale10Past monthNo<2 minutes
ElderlyNo. of ItemsTime FrameAvailable in SpanishAdministration Time
Beck Depression Inventory (BDI)21TodayYes5-10 minutes
Center for Epidemiologic Studies Depression Screen (CES-D)20Past weekYes5-10 minutes
Geriatric Depression Scale (GDS)30Past weekYes10-15 minutes
Cornell Scale for Depression in Dementia19Past weekNo10-15 minutes

Adapted from 10 and 131. Overall sensitivity for instruments was 84% (CI, 79%-89%); overall specificity was 72% (CI, 67%-77%). There were no significant differences found among instruments.

Table Grahic Jump Location
 Assessment of Suicidal Ideation, Intent, and Risk

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Assess the presence of suicidal ideation:
Ask patients if they have had thoughts that they would be better off dead, or that life was not worth living, or of hurting themselves, or ending their life
It may be helpful to precede the initial question about suicidal ideation with a statement normalizing such thoughts in the setting of depression, e.g., “It is common for people who are feeling sad and depressed to feel that life is not worth living or to have thoughts of ending their life. Have you had thoughts that you would . . .”
Assess content of suicidal thoughts:
Duration, frequency
Precipitants and exacerbating factors, factors that decrease suicidal ideation
Associated feelings of hopelessness, being a burden, feeling worthless
Ability to control suicidal thoughts and/or ask for help
Does the patient have a plan?
Assess the patient's plan, if any:
What is the method, and how lethal is the method?
For patients with significant suicidal ideation, determine access to common methods of suicide in addition to those required for the patient's specific plans. Does the patient have access to
Firearms?
Medicines?
High windows, bridges, cliffs?
A car or vehicle?
Has the patient obtained the methods, rehearsed physically or mentally?
Has the patient made any other preparations for death, e.g., wills, notes, given away possessions?
Has the patient almost acted on a plan and had to hold themselves back?
Has the patient ever experienced command hallucinations?
Assess risk factors for suicide:
A history of suicide attempt, or family history of suicide
Comorbid alcohol and other substance abuse, anxiety or panic disorders, borderline personality, (schizophrenia is associated with suicide but precludes diagnosis of major depressive disorder)
Impulsivity, antisocial behavior, domestic violence, acute family dysfunction
Male gender associated with successful suicide, female with suicide attempts
Single, white, male, age older than 65
A history of feeling hopeless

Reprinted from 127.

Table Grahic Jump Location
 Diagnostic Instruments for Depression

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The PRIME-MD is a two-stage, modular instrument that assesses common mood, anxiety, eating, alcohol, and somatoform disorders. The Patient Questionnaire (PQ) is a 25-item patient self-report based on PRIME-MD that identifies patients for further assessment using the Clinician Evaluation Guide (CEG). PQ items may also be asked verbally by the physician or other personnel. Two specific PQ items regarding depressed mood and anhedonia are used for depression case-finding. The CEG contains one module consisting of a semi-structured, branching-logic interview for each category of disorder. The average CEG interview (addressing modules for all triggered disorders, not depression alone) takes an average of 8.5 minutes in the 80% of patients who screen positive for at least one module (39).
The Patient Health Questionnaire (PHQ) is a patient self-report version of the PRIME-MD with equivalent diagnostic accuracy that takes less than 3 minutes of physician time in 85% of patients (41; 132). Its utility may be limited by patient literacy, and it may have less effect on physician behavior in comparison to the original PRIME-MD. The mood module can be used to assess and follow symptom severity over time.
The PHQ-9 is the mood module of the PHQ. It consists of items assessing the presence and severity of the nine symptoms of major depression. It is diagnostically accurate compared with mental health professional structured assessment and can be used to assess and follow severity of depressive symptoms over time. PHQ-9 score ranges can be used as guides for treatment (133).
The brief PHQ includes the mood module portion of the PHQ and assesses for anxiety. It also contains a section exclusive to women with questions pertaining to menstruation, pregnancy, and childbirth issues.
The Symptom Driven Diagnostic System for Primary Care is an alternative structured diagnostic tool (37; 134). The SDDS-PC assesses multiple mental disorders that are common to primary care: alcohol abuse or dependence, generalized anxiety disorder, major depression, obsessive compulsive disorder, panic disorder, and suicidal ideation.
An alternative strategy for diagnosing major depressive disorder is to follow the two-item (depressed mood and anhedonia) case-finding questions with assessment of so-called SALSA score symptoms of depression:
Sleep disturbance
Anhedonia
Low Self-esteem
Appetite disturbance
Patients with 2 of these 4 symptoms present nearly every day for at least 2 weeks are virtually identical with patients diagnosed using the 5 out of 9 symptom algorithm. Over 97% of patients with major depression will have at least 2 of the SALSA symptoms. Only 6% without major depression will have ≥2 of the SALSA symptoms (38).

CEG = Clinical Evaluation Guide; PQ = Patient Questionnaire; PHQ = Patient Health Questionnaire; PRIME-MD = Primary care evaluation of mental disorders.

Table Grahic Jump Location
 The CAGE Questionnaire

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CHave you ever felt you should cut down on your drinking?
AHave people annoyed you by criticizing your drinking?
GHave you ever felt bad or guilty about your drinking?
EHave you ever had a drink first thing in the morning to steady your nerves or get rid of a hangover (eye opener)?

Scoring: Item responses on the CAGE questionnaire are scored 0 or 1, with a higher score being an indication of alcohol problems. A total score of 2 or greater is considered clinically significant. However, the cut point used is determined by the test characteristics required (e.g., high sensitivity for screening purposes; a cut point ≥1 should be used).

Time required: 1 minute.

American Journal of Psychiatry, 131, 1121-1123, 1974. Copyright © 2002, the American Psychiatric Association; http://ajp.psychiatryonline.org. Reprinted with permission. 135.

Table Grahic Jump Location
 Characteristics of Selected Antidepressants

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DrugAdvantagesDisadvantages
SSRIs
CitalopramFew drug interactionsGastrointestinal, sexual side effects
EscitalopramFew drug interactionsGastrointestinal, sexual side effects
FluoxetineLong half-life reduces risk for withdrawal syndrome; effective for anxiety disorders, OCD, PMDDLong half-life can lead to accumulation, drug interactions common (cytochrome P-450 inhibitor)
ParoxetineEffective for anxiety disorders, panic disorder, PTSD, OCDHigh risk in pregnancy (class D), drug interactions (cytochrome P-450 inhibitor), weight gain; high risk for withdrawal syndrome
SertralineFew drug interactions; effective for panic disorder, PTSD, OCD, PMDD
SNRIs
VenlafaxineEffective in anxiety disordersNausea, can increase blood pressure
DesvenlafaxineEffective in anxiety disordersNausea, can increase blood pressure
DuloxetineEffective in pain conditions, generalized anxiety disorderNausea, urinary retention
Tricyclic antidepressants
NortriptylineDrug level monitoring possible, analgesic effectCardiac toxicity with overdose, anticholinergic effects
AmitriptylineAnalgesic effect, sedating effectCardiac toxicity with overdose, anticholinergic effects, sedation, weight gain
Serotonin antagonist/norepinephrine agonist
MirtazapineSedating, increased appetite; available as orally disintegrating tabletWeight gain, sedation
Norepinephrine and dopamine reuptake inhibitor
BupropionFewer sexual side effects than SSRIs, improved concentration, less weight gainSeizure risk
MAOIsOral formulation can cause hypertensive crisis, serotonin syndrome
TranylcypromineGood for atypical symptomsDietary restrictions, hypertensive crisis, hypotension, serotonin syndrome
Selegiline transdermal systemFewer dietary restrictions than other MAOIs, transdermalHypotension, serotonin syndrome

MAOI = monoamine oxidase inhibitor; OCD = obsessive-compulsive disorder; PMDD = premenstrual dysphoric disorder; PTSD = posttraumatic stress disorder; SNRI = serotonin-norepinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitor.

Reproduced with permission from: American College of Physicians. General Internal Medicine section. Medical Knowledge Self-Assessment Program 16. Part B. 16th ed. Philadelphia, PA: American College of Physicians; 2012.

  • AUDIT Questionnaire (Alcohol Use Disorders Identification Test) * Scoring the AUDIT: Score to give for answer in column. Questions 1 to 8 are scored 0, 1, 2, 3, or 4. Questions 9 and 10 are scored 0, 2, or 4 only. The minimum score (for nondrinkers) is 0 and the maximum possible score is 40. A score of 8 or more indicates a strong likelihood of hazardous or harmful alcohol consumption. Time required: 2 minutes. Reprinted with permission from 136.
Teychenne M, Ball K, Salmon J. Physical activity and likelihood of depression in adults: a review. Prev Med. 2008;46:397-411. (PMID: 18289655)
 
Lysy Z, Da Costa D, Dasgupta K. The association of physical activity and depression in Type 2 diabetes. Diabet Med. 2008;25:1133-41. (PMID: 19046190)
 
King M, Walker C, Levy G, Bottomley C, Royston P, Weich S, et al. Development and validation of an international risk prediction algorithm for episodes of major depression in general practice attendees: the PredictD study. Arch Gen Psychiatry. 2008;65:1368-76. (PMID: 19047523)
 
Hays RD, Wells KB, Sherbourne CD, Rogers W, Spritzer K. Functioning and well-being outcomes of patients with depression compared with chronic general medical illnesses. Arch Gen Psychiatry. 1995;52:11-9. (PMID: 7811158)
 
Remick RA. Diagnosis and management of depression in primary care: a clinical update and review. CMAJ. 2002;167:1253-60. (PMID: 12451082)
 
U.S. Preventive Services Task Force. Screening for depression in adults: U.S. preventive services task force recommendation statement. Ann Intern Med. 2009;151:784-92. [Full Text] (PMID: 19949144)
 
Manea L, Gilbody S, McMillan D. Optimal cut-off score for diagnosing depression with the Patient Health Questionnaire (PHQ-9): a meta-analysis. CMAJ. 2012;184:E191-6. (PMID: 22184363)
 
O’Connor EA, Whitlock EP, Beil TL, Gaynes BN. Screening for depression in adult patients in primary care settings: a systematic evidence review. Ann Intern Med. 2009;151:793-803. [Full Text] (PMID: 19949145)
 
Gilbody S, Richards D, Brealey S, Hewitt C. Screening for depression in medical settings with the Patient Health Questionnaire (PHQ): a diagnostic meta-analysis. J Gen Intern Med. 2007;22:1596-602. (PMID: 17874169)
 
Mulrow CD, Williams JW Jr, Gerety MB, Ramirez G, Montiel OM, Kerber C. Case-finding instruments for depression in primary care settings. Ann Intern Med. 1995;122:913-21. [Full Text] (PMID: 7755226)
 
Arroll B, Goodyear-Smith F, Kerse N, Fishman T, Gunn J. Effect of the addition of a “help” question to two screening questions on specificity for diagnosis of depression in general practice: diagnostic validity study. BMJ. 2005;331:884. (PMID: 16166106)
 
González HM, Vega WA, Williams DR, Tarraf W, West BT, Neighbors HW. Depression care in the United States: too little for too few. Arch Gen Psychiatry. 2010;67:37-46. (PMID: 20048221)
 
Valenstein M, Dalack G, Blow F, Figueroa S, Standiford C, Douglass A. Screening for psychiatric illness with a combined screening and diagnostic instrument. J Gen Intern Med. 1997;12:679-85. (PMID: 9383136)
 
McDonald WM, Richard IH, DeLong MR. Prevalence, etiology, and treatment of depression in Parkinson's disease. Biol Psychiatry. 2003;54:363-75. (PMID: 12893111)
 
Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62:593-602. (PMID: 15939837)
 
Kendler KS, Gardner CO, Prescott CA. Clinical characteristics of major depression that predict risk of depression in relatives. Arch Gen Psychiatry. 1999;56:322-7. (PMID: 10197826)
 
Runeson B, Asberg M. Family history of suicide among suicide victims. Am J Psychiatry. 2003;160:1525-6. (PMID: 12900320)
 
Beck CT. Predictors of postpartum depression: an update. Nurs Res. ;50:275-85. (PMID: 11570712)
 
Person C, Tracy M, Galea S. Risk factors for depression after a disaster. J Nerv Ment Dis. 2006;194:659-66. (PMID: 16971817)
 
Miranda J, Chung JY, Green BL, Krupnick J, Siddique J, Revicki DA, et al. Treating depression in predominantly low-income young minority women: a randomized controlled trial. JAMA. 2003;290:57-65. (PMID: 12837712)
 
National Collaborating Centre for Mental Health (UK). 2007;:. (PMID: 21678630)
 
Hewitt C, Gilbody S, Brealey S, Paulden M, Palmer S, Mann R, et al. Methods to identify postnatal depression in primary care: an integrated evidence synthesis and value of information analysis. Health Technol Assess. 2009;13:1-145, 147-230. (PMID: 19624978)
 
Yawn BP, Dietrich AJ, Wollan P, Bertram S, Graham D, Huff J, et al.; TRIPPD practices. TRIPPD: a practice-based network effectiveness study of postpartum depression screening and management. Ann Fam Med. ;10:320-9. (PMID: 22778120)
 
Cox JL, Holden JM, Sagovsky R. Detection of postnatal depression. Development of the 10-item Edinburgh Postnatal Depression Scale. Br J Psychiatry. 1987;150:782-6. (PMID: 3651732)
 
Georgiopoulos AM, Bryan TL, Yawn BP, Houston MS, Rummans TA, Therneau TM. Population-based screening for postpartum depression. Obstet Gynecol. 1999;93:653-7. (PMID: 10912961)
 
Nielsen Forman D, Videbech P, Hedegaard M, Dalby Salvig J, Secher NJ. Postpartum depression: identification of women at risk. BJOG. 2000;107:1210-7. (PMID: 11028570)
 
Gaynes BN, Gavin N, Meltzer-Brody S, Lohr KN, Swinson T, Gartlehner G, et al. Perinatal depression: prevalence, screening accuracy, and screening outcomes. Evid Rep Technol Assess (Summ). 2005;:1-8. (PMID: 15760246)
 
Driscoll JW. Postpartum depression: the state of the science. J Perinat Neonatal Nurs. ;20:40-2. (PMID: 16508460)
 
Evins GG, Theofrastous JP, Galvin SL. Postpartum depression: a comparison of screening and routine clinical evaluation. Am J Obstet Gynecol. 2000;182:1080-2. (PMID: 10819833)
 
Reijnders JS, Ehrt U, Weber WE, Aarsland D, Leentjens AF. A systematic review of prevalence studies of depression in Parkinson's disease. Mov Disord. 2008;23:183-9; quiz 313. (PMID: 17987654)
 
Cole MG, Bellavance F, Mansour A. Prognosis of depression in elderly community and primary care populations: a systematic review and meta-analysis. Am J Psychiatry. 1999;156:1182-9. (PMID: 10450258)
 
McGivney SA, Mulvihill M, Taylor B. Validating the GDS depression screen in the nursing home. J Am Geriatr Soc. 1994;42:490-2. (PMID: 8176142)
 
Penninx BW, Geerlings SW, Deeg DJ, van Eijk JT, van Tilburg W, Beekman AT. Minor and major depression and the risk of death in older persons. Arch Gen Psychiatry. 1999;56:889-95. (PMID: 10530630)
 
Alexopoulos GS, Abrams RC, Young RC, Shamoian CA. Cornell Scale for Depression in Dementia. Biol Psychiatry. 1988;23:271-84. (PMID: 3337862)
 
National Collaborating Centre for Mental Health (UK). 2010;:. (PMID: 22132433)
 
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA, American Psychiatric Association, 2013. Web. [access date: 1 June 2013]. dsm.psychiatryonline.org.
 
Broadhead WE, Leon AC, Weissman MM, Barrett JE, Blacklow RS, Gilbert TT, et al. Development and validation of the SDDS-PC screen for multiple mental disorders in primary care. Arch Fam Med. 1995;4:211-9. (PMID: 7881602)
 
Brody DS, Hahn SR, Spitzer RL, Kroenke K, Linzer M, deGruy FV, et al. Identifying patients with depression in the primary care setting: a more efficient method. Arch Intern Med. 1998;158:2469-75. (PMID: 9855385)
 
Spitzer RL, Williams JB, Kroenke K, Linzer M, deGruy FV 3rd, Hahn SR, et al. Utility of a new procedure for diagnosing mental disorders in primary care. The PRIME-MD 1000 study. JAMA. 1994;272:1749-56. (PMID: 7966923)
 
Kroenke K, Spitzer RL, Williams JB, Löwe B. The Patient Health Questionnaire Somatic, Anxiety, and Depressive Symptom Scales: a systematic review. Gen Hosp Psychiatry. 2010;32:345-59. (PMID: 20633738)
 
Spitzer RL, Kroenke K, Williams JB. Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. Primary Care Evaluation of Mental Disorders. Patient Health Questionnaire. JAMA. 1999;282:1737-44. (PMID: 10568646)
 
Mann JJ, Apter A, Bertolote J, Beautrais A, Currier D, Haas A, et al. Suicide prevention strategies: a systematic review. JAMA. 2005;294:2064-74. (PMID: 16249421)
 
Garvey KA, Penn JV, Campbell AL, Esposito-Smythers C, Spirito A. Contracting for safety with patients: clinical practice and forensic implications. J Am Acad Psychiatry Law. 2009;37:363-70. (PMID: 19767501)
 
Karch DL, Barker L, Strine TW. Race/ethnicity, substance abuse, and mental illness among suicide victims in 13 US states: 2004 data from the National Violent Death Reporting System. Inj Prev. 2006;12 Suppl 2:ii22-ii27. (PMID: 17170166)
 
Vaiva G, Vaiva G, Ducrocq F, Meyer P, Mathieu D, Philippe A, et al. Effect of telephone contact on further suicide attempts in patients discharged from an emergency department: randomised controlled study. BMJ. 2006;332:1241-5. (PMID: 16735333)
 
Gliatto MF, Rai AK. Evaluation and treatment of patients with suicidal ideation. Am Fam Physician. 1999;59:1500-6. (PMID: 10193592)
 
Stanford EJ, Goetz RR, Bloom JD. The No Harm Contract in the emergency assessment of suicidal risk. J Clin Psychiatry. 1994;55:344-8. (PMID: 8071303)
 
Anderson RN, Kochanek KD, Murphy SL. Report of final mortality statistics, 1995. Monthly Vital Statistics Report. Hyattsville, MD. National Center for Health Statistics, 1997;45 (suppl 2).
 
Parmar P, Goolsby CA, Udompanyanan K, Matesick LD, Burgamy KP, Mower WR. Value of mandatory screening studies in emergency department patients cleared for psychiatric admission. West J Emerg Med. 2012;13:388-93. (PMID: 23359831)
 
Haggerty JJ Jr, Stern RA, Mason GA, Beckwith J, Morey CE, Prange AJ Jr. Subclinical hypothyroidism: a modifiable risk factor for depression? Am J Psychiatry. 1993;150:508-10. (PMID: 8434671)
 
Joffe RT, Pearce EN, Hennessey JV, Ryan JJ, Stern RA. Subclinical hypothyroidism, mood, and cognition in older adults: a review. Int J Geriatr Psychiatry. 2013;28:111-8. (PMID: 22410877)
 
Dickerman AL, Barnhill JW. Abnormal thyroid function tests in psychiatric patients: a red herring? Am J Psychiatry. 2012;169:127-33. (PMID: 22318794)
 
Roy T, Lloyd CE. Epidemiology of depression and diabetes: a systematic review. J Affect Disord. 2012;142 Suppl:S8-21. (PMID: 23062861)
 
Thombs BD, Bass EB, Ford DE, Stewart KJ, Tsilidis KK, Patel U, et al. Prevalence of depression in survivors of acute myocardial infarction. J Gen Intern Med. 2006;21:30-8. (PMID: 16423120)
 
Bair MJ, Robinson RL, Katon W, Kroenke K. Depression and pain comorbidity: a literature review. Arch Intern Med. 2003;163:2433-45. (PMID: 14609780)
 
Lewis DA, Smith RE. Steroid-induced psychiatric syndromes. A report of 14 cases and a review of the literature. J Affect Disord. 1983;5:319-32. (PMID: 6319464)
 
Pope HG Jr, Katz DL. Psychiatric and medical effects of anabolic-androgenic steroid use. A controlled study of 160 athletes. Arch Gen Psychiatry. 1994;51:375-82. (PMID: 8179461)
 
Depression in primary care: Volume 1: Detection and diagnosis. Clinical practice guideline, number 5. Rockville, MD. U.S. Department of Health Human Services, Public Health Service, Agency for Health Care Policy and Research. 1993; AHCPR Publication No. 93-0550.
 
House A, Dennis M, Mogridge L, Warlow C, Hawton K, Jones L. Mood disorders in the year after first stroke. Br J Psychiatry. 1991;158:83-92. (PMID: 2015456)
 
Geringer ES, Perlmuter LC, Stern TA, Nathan DM. Depression and diabetic neuropathy: a complex relationship. J Geriatr Psychiatry Neurol. 1988;1:11-5. (PMID: 3252874)
 
Hirschfeld RM, Calabrese JR, Weissman MM, Reed M, Davies MA, Frye MA, et al. Screening for bipolar disorder in the community. J Clin Psychiatry. 2003;64:53-9. (PMID: 12590624)
 
Moyer VA; Preventive Services Task Force. Screening and behavioral counseling interventions in primary care to reduce alcohol misuse: U.S. preventive services task force recommendation statement. Ann Intern Med. 2013;159:210-8. [Full Text] (PMID: 23698791)
 
Hettema JM, Prescott CA, Kendler KS. The effects of anxiety, substance use and conduct disorders on risk of major depressive disorder. Psychol Med. 2003;33:1423-32. (PMID: 14672251)
 
Sherbourne CD, Jackson CA, Meredith LS, Camp P, Wells KB. Prevalence of comorbid anxiety disorders in primary care outpatients. Arch Fam Med. 1996;5:27-34; discussion 35. (PMID: 8542051)
 
Dawson DA, Grant BF, Stinson FS, Zhou Y. Effectiveness of the derived Alcohol Use Disorders Identification Test (AUDIT-C) in screening for alcohol use disorders and risk drinking in the US general population. Alcohol Clin Exp Res. 2005;29:844-54. (PMID: 15897730)
 
Rasmussen SA, Eisen JL. The epidemiology and differential diagnosis of obsessive compulsive disorder. J Clin Psychiatry. 1992;53 Suppl:4-10. (PMID: 1564054)
 
Hofmann DP, Dubovsky SL. Depression and suicide assessment. Emerg Med Clin North Am. 1991;9:107-21. (PMID: 2001661)
 
Archer J, Bower P, Gilbody S, Lovell K, Richards D, Gask L, et al. Collaborative care for depression and anxiety problems. Cochrane Database Syst Rev. 2012;:CD006525. (PMID: 23076925)
 
Jakobsen JC, Hansen JL, Simonsen S, Simonsen E, Gluud C. Effects of cognitive therapy versus interpersonal psychotherapy in patients with major depressive disorder: a systematic review of randomized clinical trials with meta-analyses and trial sequential analyses. Psychol Med. 2012;42:1343-57. (PMID: 22051174)
 
Bower P, Knowles S, Coventry PA, Rowland N. Counselling for mental health and psychosocial problems in primary care. Cochrane Database Syst Rev. 2011;(9):CD001025. (PMID: 21901675)
 
Jakobsen JC, Hansen JL, Storebø OJ, Simonsen E, Gluud C. The effects of cognitive therapy versus ‘no intervention’ for major depressive disorder. PLoS One. 2011;6:e28299. (PMID: 22174786)
 
Leichsenring F, Rabung S. Effectiveness of long-term psychodynamic psychotherapy: a meta-analysis. JAMA. 2008;300:1551-65. (PMID: 18827212)
 
Casacalenda N, Perry JC, Looper K. Remission in major depressive disorder: a comparison of pharmacotherapy, psychotherapy, and control conditions. Am J Psychiatry. 2002;159:1354-60. (PMID: 12153828)
 
Warmerdam L, van Straten A, Twisk J, Riper H, Cuijpers P. Internet-based treatment for adults with depressive symptoms: randomized controlled trial. J Med Internet Res. 2008;10:e44. (PMID: 19033149)
 
Qaseem A, Snow V, Denberg TD, Forciea MA, Owens DK; Clinical Efficacy Assessment Subcommittee of American College of Physicians. Using second-generation antidepressants to treat depressive disorders: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2008;149:725-33. [Full Text] (PMID: 19017591)
 
Magni LR, Purgato M, Gastaldon C, Papola D, Furukawa TA, Cipriani A, et al. Fluoxetine versus other types of pharmacotherapy for depression. Cochrane Database Syst Rev. 2013;(7):CD004185. (PMID: 24353997)
 
Cipriani A, Koesters M, Furukawa TA, Nosè M, Purgato M, Omori IM, et al. Duloxetine versus other anti-depressive agents for depression. Cochrane Database Syst Rev. 2012;:CD006533. (PMID: 23076926)
 
Cipriani A, Purgato M, Furukawa TA, Trespidi C, Imperadore G, Signoretti A, et al. Citalopram versus other anti-depressive agents for depression. Cochrane Database Syst Rev. 2012;:CD006534. (PMID: 22786497)
 
Gartlehner G, Hansen RA, Morgan LC, Thaler K, Lux LJ, Van Noord M, et al. 2011;:. (PMID: 22299185)
 
Barbui C, Cipriani A, Patel V, Ayuso-Mateos JL, van Ommeren M. Efficacy of antidepressants and benzodiazepines in minor depression: systematic review and meta-analysis. Br J Psychiatry. 2011;198:11-6, sup 1. (PMID: 21200071)
 
Cipriani A, La Ferla T, Furukawa TA, Signoretti A, Nakagawa A, Churchill R, et al. Sertraline versus other antidepressive agents for depression. Cochrane Database Syst Rev. 2010;(4):CD006117. (PMID: 20393946)
 
Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC, et al. Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA. 2010;303:47-53. (PMID: 20051569)
 
Candy M, Jones L, Williams R, Tookman A, King M. Psychostimulants for depression. Cochrane Database Syst Rev. 2008;(2):CD006722. (PMID: 18425966)
 
Lima MS, Moncrieff J. Drugs versus placebo for dysthymia. Cochrane Database Syst Rev. 2000;(4):CD001130. (PMID: 11034701)
 
Williams JW Jr, Mulrow CD, Chiquette E, Noël PH, Aguilar C, Cornell J. A systematic review of newer pharmacotherapies for depression in adults: evidence report summary. Ann Intern Med. 2000;132:743-56. [Full Text] (PMID: 10787370)
 
Hardy SE. Methylphenidate for the treatment of depressive symptoms, including fatigue and apathy, in medically ill older adults and terminally ill adults. Am J Geriatr Pharmacother. 2009;7:34-59. (PMID: 19281939)
 
Cooper-Kazaz R, Lerer B. Efficacy and safety of triiodothyronine supplementation in patients with major depressive disorder treated with specific serotonin reuptake inhibitors. Int J Neuropsychopharmacol. 2008;11:685-99. (PMID: 18047754)
 
Kelly CM, Juurlink DN, Gomes T, Duong-Hua M, Pritchard KI, Austin PC, et al. Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study. BMJ. 2010;340:c693. (PMID: 20142325)
 
Citrome L. Vilazodone for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antidepressant - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? Int J Clin Pract. 2012;66:356-68. (PMID: 22284853)
 
Wright SK, Schroeter S. Hyponatremia as a complication of selective serotonin reuptake inhibitors. J Am Acad Nurse Pract. 2008;20:47-51. (PMID: 18184165)
 
Haney EM, Chan BK, Diem SJ, Ensrud KE, Cauley JA, Barrett-Connor E, et al.; Osteoporotic Fractures in Men Study Group. Association of low bone mineral density with selective serotonin reuptake inhibitor use by older men. Arch Intern Med. 2007;167:1246-51. (PMID: 17592097)
 
von Wolff A, Hölzel LP, Westphal A, Härter M, Kriston L. Combination of pharmacotherapy and psychotherapy in the treatment of chronic depression: a systematic review and meta-analysis. BMC Psychiatry. 2012;12:61. (PMID: 22694751)
 
Cuijpers P, Dekker J, Hollon SD, Andersson G. Adding psychotherapy to pharmacotherapy in the treatment of depressive disorders in adults: a meta-analysis. J Clin Psychiatry. 2009;70:1219-29. (PMID: 19818243)
 
Reynolds CF 3rd, Dew MA, Pollock BG, Mulsant BH, Frank E, Miller MD, et al. Maintenance treatment of major depression in old age. N Engl J Med. 2006;354:1130-8. (PMID: 16540613)
 
Lustman PJ, Clouse RE, Nix BD, Freedland KE, Rubin EH, McGill JB, et al. Sertraline for prevention of depression recurrence in diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Arch Gen Psychiatry. 2006;63:521-9. (PMID: 16651509)
 
Komossa K, Depping AM, Gaudchau A, Kissling W, Leucht S. Second-generation antipsychotics for major depressive disorder and dysthymia. Cochrane Database Syst Rev. 2010;(12):CD008121. (PMID: 21154393)
 
Lin EH, Von Korff M, Katon W, Bush T, Simon GE, Walker E, et al. The role of the primary care physician in patients' adherence to antidepressant therapy. Med Care. 1995;33:67-74. (PMID: 7823648)
 
Peveler R, George C, Kinmonth AL, Campbell M, Thompson C. Effect of antidepressant drug counselling and information leaflets on adherence to drug treatment in primary care: randomised controlled trial. BMJ. 1999;319:612-5. (PMID: 10473477)
 
Frank E. Enhancing patient outcomes: treatment adherence. J Clin Psychiatry. 1997;58 Suppl 1:11-4. (PMID: 9054903)
 
Cheung AH, Zuckerbrot RA, Jensen PS, Ghalib K, Laraque D, Stein RE; GLAD-PC Steering Group. Guidelines for Adolescent Depression in Primary Care (GLAD-PC): II. Treatment and ongoing management. Pediatrics. 2007;120:e1313-26. (PMID: 17974724)
 
Hetrick SE, McKenzie JE, Cox GR, Simmons MB, Merry SN. Newer generation antidepressants for depressive disorders in children and adolescents. Cochrane Database Syst Rev. 2012;:CD004851. (PMID: 23152227)
 
Barbui C, Esposito E, Cipriani A. Selective serotonin reuptake inhibitors and risk of suicide: a systematic review of observational studies. CMAJ. 2009;180:291-7. (PMID: 19188627)
 
Linde K, Berner MM, Kriston L. St John's wort for major depression. Cochrane Database Syst Rev. 2008:CD000448. (PMID: 18843608)
 
Lantz MS, Buchalter E, Giambanco V. St. John's wort and antidepressant drug interactions in the elderly. J Geriatr Psychiatry Neurol. 1999;12:7-10. (PMID: 10447148)
 
Obach RS. Inhibition of human cytochrome P450 enzymes by constituents of St. John's Wort, an herbal preparation used in the treatment of depression. J Pharmacol Exp Ther. 2000;294:88-95. (PMID: 10871299)
 
de Maat MM, Hoetelmans RM, Math t RA, van Gorp EC, Meenhorst PL, Mulder JW, et al. Drug interaction between St John's wort and nevirapine. AIDS. 2001;15:420-1. (PMID: 11273226)
 
Ondrizek RR, Chan PJ, Patton WC, King A. An alternative medicine study of herbal effects on the penetration of zona-free hamster oocytes and the integrity of sperm deoxyribonucleic acid. Fertil Steril. 1999;71:517-22. (PMID: 10065791)
 
Carney RM, Freedland KE, Rubin EH, Rich MW, Steinmeyer BC, Harris WS. Omega-3 augmentation of sertraline in treatment of depression in patients with coronary heart disease: a randomized controlled trial. JAMA. 2009;302:1651-7. (PMID: 19843899)
 
Golden RN, Gaynes BN, Ekstrom RD, Hamer RM, Jacobsen FM, Suppes T, et al. The efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidence. Am J Psychiatry. 2005;162:656-62. (PMID: 15800134)
 
Cooney GM, Dwan K, Greig CA, Lawlor DA, Rimer J, Waugh FR, et al. Exercise for depression. Cochrane Database Syst Rev. 2013;(9):CD004366. (PMID: 24026850)
 
Malm H, Artama M, Gissler M, Ritvanen A. Selective serotonin reuptake inhibitors and risk for major congenital anomalies. Obstet Gynecol. 2011;118:111-20. (PMID: 21646927)
 
Chambers CD, Hernandez-Diaz S, Van Marter LJ, Werler MM, Louik C, Jones KL, et al. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. N Engl J Med. 2006;354:579-87. (PMID: 16467545)
 
Cohen LS, Altshuler LL, Harlow BL, Nonacs R, Newport DJ, Viguera AC, et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA. 2006;295:499-507. (PMID: 16449615)
 
Delgado PL. Approaches to the enhancement of patient adherence to antidepressant medication treatment. J Clin Psychiatry. 2000;61 Suppl 2:6-9. (PMID: 10714617)
 
Geddes J, Butler R. Depressive disorders. In: Clinical Evidence. London: BMJ Publishing Group; 2001:726-742.
 
Zajecka J, Fawcett J, Amsterdam J, Quitkin F, Reimherr F, Rosenbaum J, et al. Safety of abrupt discontinuation of fluoxetine: a randomized, placebo-controlled study. J Clin Psychopharmacol. 1998;18:193-7. (PMID: 9617977)
 
Stahl MM, Lindquist M, Pettersson M, Edwards IR, Sanderson JH, Taylor NF, et al. Withdrawal reactions with selective serotonin re-uptake inhibitors as reported to the WHO system. Eur J Clin Pharmacol. 1997;53:163-9. (PMID: 9476026)
 
Gehi A, Haas D, Pipkin S, Whooley MA. Depression and medication adherence in outpatients with coronary heart disease: findings from the Heart and Soul Study. Arch Intern Med. 2005;165:2508-13. (PMID: 16314548)
 
Katon W, Cantrell CR, Sokol MC, Chiao E, Gdovin JM. Impact of antidepressant drug adherence on comorbid medication use and resource utilization. Arch Intern Med. 2005;165:2497-503. (PMID: 16314547)
 
Sherrill JT, Frank E, Geary M, Stack JA, Reynolds CF 3rd. Psychoeducational workshops for elderly patients with recurrent major depression and their families. Psychiatr Serv. 1997;48:76-81. (PMID: 9117505)
 
Maynard C. A psychoeducational approach to depression in women. J Psychosoc Nurs Ment Health Serv. 1993;31:9-14. (PMID: 8114028)
 
Jacob M, Frank E, Kupfer DJ, Cornes C, Carpenter LL. A psychoeducational workshop for depressed patients, family, and friends: description and evaluation. Hosp Community Psychiatry. 1987;38:968-72. (PMID: 3679103)
 
Cuijpers P. Bibliotherapy in unipolar depression: a meta-analysis. J Behav Ther Exp Psychiatry. 1997;28:139-47. (PMID: 9194011)
 
Stedman L, Kaestle C. Literacy and reading performance in the United States from 1880 to present. In: Kaestle C, ed. Literacy in the United States: readers and readings since 1880. New Haven (CT): Yale University Press; 1991. p. 75-128.
 
Williams MV, Parker RM, Baker DW, Parikh NS, Pitkin K, Coates WC, et al. Inadequate functional health literacy among patients at two public hospitals. JAMA. 1995;274:1677-82. (PMID: 7474271)
 
Garcia-Toro M, Medina E, Galan JL, Gonzalez MA, Maurino J. Treatment patterns in major depressive disorder after an inadequate response to first-line antidepressant treatment. BMC Psychiatry. 2012;12:143. (PMID: 22988986)
 
Fava M, Davidson KG. Definition and epidemiology of treatment-resistant depression. Psychiatr Clin North Am. 1996;19:179-200. (PMID: 8827185)
 
Santaguida PL, MacQueen G, Keshavarz H, Levine M, Beyene J, Raina P. 2012;:. (PMID: 22696777)
 
Lieverse R, Van Someren EJ, Nielen MM, Uitdehaag BM, Smit JH, Hoogendijk WJ. Bright light treatment in elderly patients with nonseasonal major depressive disorder: a randomized placebo-controlled trial. Arch Gen Psychiatry. 2011;68:61-70. (PMID: 21199966)
 
Nelson JC. Augmentation strategies in depression 2000. J Clin Psychiatry. 2000;61 Suppl 2:13-9. (PMID: 10714619)
 
Sharp LK, Lipsky MS. Screening for depression across the lifespan: a review of measures for use in primary care settings. Am Fam Physician. 2002;66:1001-8. (PMID: 12358212)
 
Spitzer RL, Williams JB, Kroenke K, Hornyak R, McMurray J. Validity and utility of the PRIME-MD patient health questionnaire in assessment of 3000 obstetric-gynecologic patients: the PRIME-MD Patient Health Questionnaire Obstetrics-Gynecology Study. Am J Obstet Gynecol. 2000;183:759-69. (PMID: 10992206)
 
Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16:606-13. (PMID: 11556941)
 
Weissman MM, Olfson M, Leon AC, Broadhead WE, Gilbert TT, Higgins ES, et al. Brief diagnostic interviews (SDDS-PC) for multiple mental disorders in primary care. A pilot study. Arch Fam Med. 1995;4:220-7. (PMID: 7881603)
 
Mayfield D, McLeod G, Hall P. The CAGE questionnaire: validation of a new alcoholism screening instrument. Am J Psychiatry. 1974;131:1121-3. (PMID: 4416585)
 
Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M. Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption—II. Addiction. 1993;88:791-804. (PMID: 8329970)
 
5-HT

5-hydroxytryptamine

ACP

American College of Physicians

AHRQ

Agency for Healthcare Research and Quality

AUDIT

Alcohol Use Disorder Identification Test

CAGE

screening test for alcoholism

CI

confidence interval

CYP

cytochrome

DSM

Diagnostic and Statistical Manual of Mental Disorders

FDA

Food and Drug Administration

GDS

Geriatric Depression Scale

HR

hazard ratio

MAOI

monoamine oxidase inhibitors

MDPRR

major depression in partial remission or recurrence

MI

myocardial infarction

MMSE

Mini-Mental State Examination

NICE

National Institute for Health and Care Excellence (UK)

NNT

number needed to treat

OCD

obsessive-compulsive disorder

OR

odds ratio

PHQ

Patient Health Questionnaire (the self-administered version of the PRIME-MD PQ)

PRIME-MD

Primary Care Evaluation of Mental Disorders

PQ

Patient Questionnaire (the patient questionnaire component of the PRIME-MD)

PTSD

posttraumatic stress disorder

RR

risk ratio

SALSA

Sleep disturbance, Anhedonia, Low Self-esteem, and change in Appetite (four symptoms of depression)

SDDS-PC

Symptom-Driven Diagnostic System for Primary Care

SNRI

serotonin norepinephrine reuptake inhibitor

SSRI

selective serotonin reuptake inhibitor

TCA

tricyclic antidepressant

TSH

thyrotropin (thyroid-stimulating hormone)


Terms
Anhedonia

Lack of interest or pleasure in activities

Brief Patient Health Questionnaire

Includes the mood module portion of the PHQ and assesses for anxiety. It also contains a section exclusive to women with questions pertaining to menstruation, pregnancy, and childbirth issues

Clinician Evaluation Guide (CEG)

Guides the second stage of the PRIME-MD (the evaluation or interview stage). The CEG consists of a semi-structured, branching-logic interview for each category of disorder

Euthymia

Normal mood

Patient Health Questionnaire (PHQ)

The entirely self-administered version of the PRIME-MD PQ. There are many variations on the PHQ, including the PHQ-9, PHQ-2, and brief PHQ

Patient Health Questionnaire-2 (PHQ-2)

The two-item (depressed mood and anhedonia) version of the PHQ. Consists of the first two questions: 1) “Over the past 2 weeks, have you felt down, depressed, hopeless?” and 2) “Over the past 2 weeks have you felt little interest or pleasure in doing things?”

Patient Health Questionnaire-9 (PHQ-9)

The 9-item mood (depression) module of the PHQ. The PHQ-9 consists of items assessing the presence and severity of the 9 symptoms of major depression, as identified in the DSM-5

Patient Questionnaire (PQ)

The 25-item patient questionnaire component of the PRIME-MD. It screens and identifies patients who require further evaluation with the Clinician Evaluation Guide. Only two PQ items (depressed mood and anhedonia) are required for depression case-finding

Primary Care Evaluation of Mental Disorders (PRIME-MD)

A two-stage, modular instrument that assesses common mood, anxiety, eating, alcohol, and somatoform disorders. The two stages or components are the Patient Questionnaire (PQ) and the clinician interview using the Clinician Evaluation Guide (CEG)

Symptom Driven Diagnostic System for Primary Care (SDDS-PC)

Assesses multiple mental disorders that are common to primary care: alcohol abuse or dependence, generalized anxiety disorder, major depression, obsessive compulsive disorder, panic disorder, and suicidal ideation. An alternative to the PRIME-MD system


Guidelines

Guidelines for adolescent depression in primary care (GLAD-PC): II. Treatment and ongoing management

Using second-generation antidepressants to treat depressive disorders: a clinical practice guideline from the American College of Physicians

Screening and behavioral counseling interventions in primary care to reduce alcohol misuse: U.S. Preventive Services Task Force recommendation statement

National Institute for Health Care and Excellence: Depression in adults: The treatment and management of depression in adults

Screening for depression in adults: U.S. Preventive Services Task Force recommendation statement

National Institute for Health and Clinical Excellence: Antenatal and postnatal mental health

American College of Obstetricians and Gynecologists: Screening for depression during and after pregnancy

ICSI: Adult depression in primary care

Screening for depression in adults: U.S. Preventive Services Task Force recommendation statement

American Psychiatric Association: Practice guideline for the treatment of patients with major depressive disorder, 3rd edition (2010)

Systematic Reviews

Treatment for depression after unsatisfactory response to SSRIs

Exercise for depression (Cochrane review)

The efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidence

Selective serotonin reuptake inhibitors and risk of suicide: a systematic review of observational studies

Newer generation antidepressants for depressive disorders in children and adolescents (Cochrane review)

Psychostimulants for depression (Cochrane review)

A systematic review of newer pharmacotherapies for depression in adults: evidence report summary

Drugs versus placebo for dysthymia (Cochrane review)

Efficacy of antidepressants and benzodiazepines in minor depression: systematic review and meta-analysis

Sertraline versus other antidepressive agents for depression (Cochrane review)

Second-generation antidepressants in the pharmacologic treatment of adult depression: an update of the 2007 comparative effectiveness review

Citalopram versus other anti-depressive agents for depression (Cochrane review)

Duloxetine versus other anti-depressive agents for depression (Cochrane review)

Fluoxetine versus other types of pharmacotherapy for depression (Cochrane review)

Adding psychotherapy to pharmacotherapy in the treatment of depressive disorders in adults: a meta-analysis

Combination of pharmacotherapy and psychotherapy in the treatment of chronic depression: a systematic review and meta-analysis

Remission in major depressive disorder: a comparison of pharmacotherapy, psychotherapy, and control conditions

Effectiveness of long-term psychodynamic psychotherapy: a meta-analysis

The effects of cognitive therapy versus 'no intervention' for major depressive disorder

Effects of cognitive therapy versus interpersonal psychotherapy in patients with major depressive disorder: a systematic review of randomized clinical trials with meta-analyses and trial sequential analyses

Collaborative care for depression and anxiety problems (Cochrane review)

Depression and pain comorbidity: a literature review

Prevalence of depression in survivors of acute myocardial infarction

Epidemiology of depression and diabetes: a systematic review

Suicide prevention strategies: a systematic review

The Patient Health Questionnaire Somatic, Anxiety, and Depressive Symptom Scales: a systematic review

Prognosis of depression in elderly community and primary care populations: a systematic review and meta-analysis

A systematic review of prevalence studies of depression in Parkinson's disease

Predictors of postpartum depression: an update

Methods to identify postnatal depression in primary care: an integrated evidence synthesis and value of information analysis

Optimal cut-off score for diagnosing depression with the Patient Health Questionnaire (PHQ-9): a meta-analysis

Case-finding instruments for depression in primary care settings

Screening for depression in medical settings with the Patient Health Questionnaire (PHQ): a diagnostic meta-analysis

Screening for depression in adult patients in primary care settings: a systematic evidence review

The association of physical activity and depression in Type 2 diabetes

Physical activity and likelihood of depression in adults: a review

Counselling for mental health and psychosocial problems in primary care

St John's wort for major depression (Cochrane Review)

Antidepressant drug effects and depression severity: a patient-level meta-analysis

DOI: 10.7326/d954
The information included herein should never be used as a substitute for clinical judgment and does not represent an official position of ACP.
Disclosures:
Elana Sydney, MD has no financial relationships with pharmaceutical companies, biomedical device manufacturers, or health-care related organizations. Steven Hahn, MD is a consultant for Pfizer, received honorarium from Pfizer, received grant from Lilly. Robert McCarron, DO has no financial relationships with pharmaceutical companies, biomedical device manufacturers, or health-care related organizations. Matthew Reed, MD, MSPH has no financial relationships with pharmaceutical companies, biomedical device manufacturers, or health-care related organizations.
Deborah Korenstein, MD, FACP, Editor in Chief, ACP Smart Medicine, has no relationships with any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients. Richard B. Lynn, MD, FACP, Editor, ACP Smart Medicine, has no relationships with any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients.
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