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Apr.30.2019View related content

Major depressive disorder

Synopsis

Key Points

  • Major depressive disorder is a chronic and relapsing disease, characterized by a pervasive sad mood and the loss of pleasure in most activities (anhedonia)
  • Rule out underlying physical illnesses that may mimic major depressive disorder (eg, hypothyroidism, dementia)
  • Diagnosis relies on history and physical examination, as well as validated depression inventory toolsr1 such as Beck Depression Inventory,r2Hamilton Depression Rating Scale,r2 Major Depression Inventory,r3 and Patient Health Questionnaire-9r4
  • Psychotherapy is often adequate as initial therapy early in the course of the disease r5
  • Use antidepressant medications for more severe or chronic disease r5
  • Consider combination therapy (psychotherapy and medication) when the response to a single therapy is inadequate r5
  • For severe disease, drug therapy is required, and for most patients combined therapy is more effective than either psychotherapy or antidepressant medication alone r5
  • If patient has a high risk of suicide or if welfare is threatened (eg, lack of nutrition or fluid intake), electroconvulsive therapy will be necessary r5
  • Untreated depression increases the risk of self-inflicted injury or suicide

Urgent Action

  • Suicidal ideation or suicide attempts require hospitalization and urgent evaluation by a psychiatrist

Pitfalls

  • Even if major depressive disorder is diagnosed correctly, bipolar disorder may be present; treatment varies by disorder, so differentiation is required
  • Always consider substance abuse as a potential contributor to major depressive disorder and a potential consequence of it
  • Discontinuing medications that influence serotonin levels (particularly with short half-lives) can suddenly cause antidepressant discontinuation syndrome:
    • Flulike symptoms (eg, nausea, vomiting, diarrhea, headaches)
    • Sensory/movement disturbances (eg, vertigo, dizziness)
    • Cognitive symptoms (eg, hyperarousal, confusion)

Terminology

Clinical Clarification

  • Major depressive disorder is a chronic and relapsing disease, characterized by a pervasive sad mood and the loss of pleasure in most activities (anhedonia) persisting for at least 2 weeks r6

Classification

  • DSM-5 diagnostic classification states that major depressive disorder presents with at least 5 of the following 9 symptoms: r7
    • Depressed mood or anhedonia (patient must have at least 1; present most of the day nearly every day for a minimum of 2 consecutive weeks)
    • Sleep disturbance
    • Change in appetite or weight
    • Psychomotor problems
    • Lack of energy
    • Poor concentration
    • Feelings of worthlessness or guilt
    • Suicidal ideation
  • Symptoms cause clinically significant distress or impairment in social, work, or other areas of functioning
  • Episode is not attributable to the physiologic effects of a substance or other medical disorder

Diagnosis

Clinical Presentation

History

  • Patients do not always present with a straightforward complaint of feeling depressed r8
  • Vague somatic complaints or numerous complaints that do not fit any clear clinical pattern often occur, particularly in elderly patients and in patients for whom psychological symptoms are stigmatized r8
    • Fatigue c1
    • Poor concentration c2
    • Memory impairment c3
    • Difficulty making day-to-day decisions c4
    • Decline in school or work performance c5c6
    • Decreased sexual interest c7
    • Sleep disturbance c8
    • Appetite changes c9
    • Weight changes (gain or loss) c10c11c12
    • Headache c13
    • Nausea c14
    • Pain c15
    • Change in bowel habits (constipation or diarrhea) c16c17c18
  • Depressive symptoms r8
    • Loss of interest or pleasure in previously enjoyable things c19
    • Disproportionate feelings of guilt or thoughts of worthlessness c20c21c22
    • Suicidal thoughts or thoughts about dying c23c24
    • Psychotic symptoms (particularly in elderly patients) c25c26
    • Anxiety and worry c27c28
    • Preoccupation with physical complaints c29

Physical examination

  • Psychological findings r8
    • Depressed or flat affect c30c31
    • Appears withdrawn, with poor eye contact c32c33
    • Psychomotor agitation or retardation c34c35
    • Crying c36
    • Anxious behavior
    • Irritability c37
    • Evidence of self-neglect with poor personal hygiene c38c39
  • Dermatologic findings r8
    • Evidence of self-harm (eg, healed lacerations, scars on body or extremities) c40c41c42
  • Weight loss, weight gain, or evidence of poor nutrition r8

Causes and Risk Factors

Causes

Risk factors and/or associations

Age r6
  • Median age of onset is 32 years c44
  • Overall prevalence is low until early adolescence c45
Sex r6
  • Women are twice as likely as men to experience major depressive disorder, regardless of racial background, ethnic background, or socioeconomic status c46
    • Times of hormonal fluctuation convey the greatest risk
Genetics r6
  • Major depressive disorder is a multifactorial disorder with genetic susceptibility c47
    • Greatest risk for major depressive disorder is observed in families with early age at onset r9c48
Ethnicity/race r6
  • Higher incidence in black and Hispanic populations compared with white populations c49c50
Other risk factors/associations r6
  • History of childhood maltreatment in any form c51
  • Early parental loss (for women) c52c53

Diagnostic Procedures

Primary diagnostic tools

  • Depression screening tools (eg, Beck Depression Inventory, Patient Health Questionnaire-9) can be used initially to identify patients requiring full diagnostic interviews using standard diagnostic criteria r1r2r3r4
  • History and physical examination provide definitive diagnosis c54
  • Laboratory analyses (eg, hypothyroidism testing [TSH], urine or serum drug screen) can be used to exclude medical disorders that produce or exacerbate mood symptoms or screen for substance-induced mood symptoms r10c55c56

Other diagnostic tools

  • Standardized depression inventory tests c57
    • United States Preventive Services Task Force recommends the following: "All positive screening results should lead to additional assessment that considers severity of depression and comorbid psychological problems (eg, anxiety, panic attacks, or substance abuse), alternate diagnoses, and medical conditions" r1
    • Beck Depression Inventory r2c58
      • Self-rated questionnaire
      • Measures the intensity, severity, and depth of common depression symptoms
      • Standard test has 21 questions; a shorter 7-question version is optimized for screening use in the office setting
    • Hamilton Depression Rating Scale r2c59
      • Observer-rated scale designed to be administered by the health care professional
    • Major Depression Inventory r3c60
      • Self-rated questionnaire
      • Incorporates both the ICD‐10 symptoms of depression and the DSM-IV symptoms of major depression
    • Patient Health Questionnaire-9 r4r11c61
      • Self-rated questionnaire with 9 items

Differential Diagnosis

Most common r12

  • Persistent depressive disorder (dysthymia) c62
    • Characterized by:
      • Changes in eating
      • Altered sleeping pattern (eg, insomnia, hypersomnia)
      • Low energy
      • Low self-esteem
      • Inability to concentrate or make decisions
      • Feelings of hopelessness or pessimism
    • Fewer symptoms than major depressive disorder
    • Involves feeling depressed for periods of variable duration, but without meeting DSM-5 criteria for major depressive disorder
    • Such patients often have major depressive disorder interspersed throughout their lifetime
    • Differentiated based on history and physical examination
  • Bipolar disorder r13c63d1
    • Mood disorder characterized by episodes of mania or hypomania
    • Carefully screen patients with major depression for bipolar disorder
      • 15% of patients with major depression have bipolar disorder r14
      • Patients with bipolar disorder do not respond to antidepressants; therefore, differentiation is crucial
    • Presence of mania or hypomania is the cardinal feature that distinguishes bipolar disorder from major depressive disorder
      • Mania
        • A period of mood change (happy, excited, or irritable) that causes impairment and is distinct and noted by others
        • At least 4 of the following symptoms are present:
          • Inflated self-esteem or grandiosity
          • Little need for sleep (without the development of fatigue)
          • Pressured or overly verbose speech
          • Racing thoughts
          • Distractibility
          • Irritability or agitation
          • Reckless or high-risk behavior
    • Differentiated based on history and physical examination
  • Adjustment disorder r15c64
    • Temporary, short-term, nonpsychotic response to an event or situation, such as a divorce, death in the family, a disappointment, or a failure
    • Symptoms can include sadness, anxiety, insomnia, poor concentration, poor performance in school
    • Symptoms persist for no longer than 6 months after termination of the stressor
    • Does not meet criteria for another mental disorder
    • Differentiated based on history and physical examination
  • Dementia r16c65
    • Especially in elderly patients, may be mistaken for major depressive disorder during early stages of the illness
    • The following features are more closely associated with dementia:
      • Impaired, inconsistent, and fluctuating orientation, mood, and behavior
      • Cognitive impairment that worsens over time
      • Neurologic deficits often present (eg, dysphasia, apraxia)
      • Disabilities concealed by the patient
      • Inability to remember recent events; often unaware of memory loss
      • Onset of memory loss occurs before mood change
      • Frequently uncooperative, confused, or disoriented
      • Demonstrated lack of concern about cognitive deficit
    • Differentiated based on history and physical examination
  • Parkinson disease r17c66d2
    • Progressive disorder of the central nervous system that often coexists with depression
    • Associated with symptoms of major depressive disorder, in addition to:
      • Increased muscle tone with cogwheel rigidity
      • Coarse resting tremor
      • Akinesia
      • Loss of facial expression
      • Shuffling gait
      • Flexed posture
    • Differentiated based on history and physical examination
  • Schizophrenia c67d3
    • Disorder that affects thoughts, feelings, and perceptions; primary symptom is psychosis with auditory hallucinations and delusions
    • Schizophrenic patients may develop secondary major depression r18
    • Distinguished from major depressive disorder by the following: r18
      • Severe personality deterioration
      • Thought disorder, including loose associations
      • Grandiose delusions
      • Hallucinations, which are typically auditory
      • Bizarre behavior
    • Differentiated based on history and physical examination
  • Hypothyroidism r19c68d4
    • Patients with hypothyroidism may have symptoms of major depressive disorder, in addition to signs and symptoms of slow metabolism (eg, dry skin, brittle hair, weight gain)
    • Differentiated by laboratory testing for hypothyroidism
  • Substance use disorders c69c70
    • May cause symptoms of depression with chronic use or from withdrawal
    • Causative substances include:
    • Differentiated from major depressive disorder by:
      • Positive result from urine or serum drug screen for the substance, if available
      • History of mood disorder that occurs temporally with substance use or withdrawal
  • Medication causes r11c85
    • Drug classes that are known to produce symptoms similar to depression include:
      • Benzodiazepines c86
      • Steroids c87
      • Levodopa c88
      • Oral contraceptives c89
      • Interferon c90
    • Differentiated based on history and physical examination

Treatment

Goals r11

  • Assess the patient for suicidality and take steps to protect the patient as needed
  • Reduce signs and symptoms, including residual symptoms r20r21r22
  • Relieve any complications, such as malnutrition and substance abuse
  • Restore prior level of psychosocial and occupational function
  • Prevent relapse and recurrence

Disposition

Admission criteria r22

  • Patients unable to take care of themselves at home
  • Patients undergoing electroconvulsive therapy
  • Suicidal/homicidal ideation with intention or overt suicide/homicide attempts
  • Psychosis

Recommendations for specialist referral

  • Consult psychiatrist if the patient exhibits any of the following:
    • Suicidal or homicidal ideation or attempts
    • Severe confusion, raising the question of dementia or delirium
    • Delusions or hallucinations
    • Substance abuse or dependence
    • Suspected bipolar disorder
    • Depression that has not responded to appropriate drug therapy

Treatment Options

Mild to moderate disease r5

  • Psychotherapy is often adequate as initial therapy early in the disease course r23
  • Use antidepressant medications for more severe or chronic disease
    • Antidepressant medications are first line treatment for depression of any severity that has persisted for 2 years or more r24
    • First line options include: r23r25r26
      • Selective serotonin reuptake inhibitors r27
      • Serotonin-norepinephrine reuptake inhibitors
      • Noradrenergic and specific serotonin antidepressants
      • Noradrenergic and dopaminergic antidepressants
    • Second line options include: r24
      • Tricyclic antidepressants
      • MAOIs
  • Consider combination therapy (ie, psychotherapy and medication) when the response to a single therapy is inadequate
    • For most patients, combination therapy is more effective than either psychotherapy or antidepressant medication alone; particularly for chronic or moderate to severe disease
    • Also consider for recurrent disease (with 3 or more episodes) r25

Severe disease r5

  • Drug therapy is required
  • For most patients, combination therapy (psychotherapy and medication) is more effective than either psychotherapy or antidepressant medication alone r25
  • If patient has a high risk of suicide or if welfare is threatened (eg, lack or nutrition or fluid intake), electroconvulsive therapy will be necessary
  • Electroconvulsive therapy may be used as first line therapy for patients who have psychotic depression or catatonia and patients who have previously responded to this treatment method

Relapse prevention r24

  • Medication-responsive patients: continue medication at acute treatment dose after remission; use relapse risk to determine medication duration
    • Patients at lower risk of relapse (eg, experiencing first episode without other risk factors): continue medication at least 6 to 9 months after full remission r24r25
    • Other patients: tailor medication duration to individual relapse risk
      • Patients with any increased risk of relapse: continue medication at least 1 year after full remission r25
      • Higher risk patients (eg, having more than 5 lifetime episodes and/or 2 episodes in the past few years): continue medication for a minimum of 2 years; most will require long-term treatment
  • Patients with residual symptoms or at high risk of relapse: consider adding cognitive behavioral therapy to medication
  • Patients who respond well to acute-phase cognitive behavioral therapy: it is not routinely recommended to continue medication
  • Patients who are unstable or partial remitters (ie, patients in partial remission): continue cognitive behavioral therapy or antidepressants
  • Patients who respond to acute-phase electroconvulsive therapy: continue or initiate prophylactic medication; consider continuing electroconvulsive therapy in patients with frequent relapses who do not respond to prophylactic medication

Esketamine nasal spray—the first NMDA (N-methyl-D-aspartate) receptor antagonist to receive FDA approval for major depression—can be used as an adjunct to an oral antidepressant for treatment-resistant depression (those whose condition has failed to respond to 2 or more standard antidepressant treatments) r28

Drug therapy

  • Selective serotonin reuptake inhibitors r29c91
    • Citalopram c92
      • Citalopram Hydrobromide Oral tablet; Children and Adolescents 7 to 17 years: 10 mg PO once daily initially. Some experts recommend initial doses of 20 mg/day PO in those 12 years and older. Clinical guidelines recommend to start with a low dose and titrate gradually, in 10 mg/day increments at 4-week intervals until clinical response is achieved. Some studies titrate as often as every week. A dose of 20 mg/day PO is considered effective. Max: 40 mg/day in the general population and 20 mg/day in poor metabolizers of CYP2C19 due to the potential for QT prolongation. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.Citalopram Hydrobromide Oral tablet; Children and Adolescents 7 to 17 years: 10 mg PO once daily initially. Some experts recommend initial doses of 20 mg/day PO in those 12 years and older. Clinical guidelines recommend to start with a low dose and titrate gradually, in 10 mg/day increments at 4-week intervals until clinical response is achieved. Some studies titrate as often as every week. A dose of 20 mg/day PO is considered effective. Max: 40 mg/day in the general population and 20 mg/day in poor metabolizers of CYP2C19 due to the potential for QT prolongation. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
      • Citalopram Hydrobromide Oral tablet; Adults 60 years and younger: Initially, 20 mg PO once daily; may increase to 40 mg PO once daily after 1 week. Max: 40 mg/day in the general population and 20 mg/day in poor metabolizers of CYP2C19 due to the potential for QT prolongation. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
      • Citalopram Hydrobromide Oral tablet; Adults older than 60 years: 20 mg PO once daily is the recommended and maximum daily dosage. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
    • Escitalopram r30r31c93
      • Escitalopram Oral tablet; Children and Adolescents 12 to 17 years: 10 mg PO once daily initially. Usual effective dose: 10 mg/day. May titrate in 5 mg increments every 3 to 4 weeks as needed. Max: 20 mg/day PO. Periodically reassess.
      • Escitalopram Oral tablet; Adults: 10 mg PO once daily initially.  May increase to 20 mg PO once daily after a minimum of 1 week if clinically indicated. Max: 20 mg/day PO. Periodically reassess to determine the need for ongoing maintenance treatment.
      • Escitalopram Oral tablet; Geriatric Adults: 10 mg PO once daily. Periodically reassess to determine the need for ongoing maintenance treatment.
    • Fluoxetine c94
      • Fluoxetine Hydrochloride Oral tablet [Depression/Mood Disorders]; Children and Adolescents 8 to 17 years: 10 to 20 mg PO once daily. An initial dose of 10 mg/day may be appropriate in lower weight children; increase to 20 mg/day after 1 week. Usual effective dose: 10 to 20 mg/day. Increase by 10 to 20 mg increments if clinical improvement is not sufficient; full effect may take 4 weeks or longer. Max: 60 mg/day. Periodically reassess to determine the need for maintenance treatment.
      • Fluoxetine Hydrochloride Oral tablet [Depression/Mood Disorders]; Adults: 20 mg/day PO initially. May increase dose after several weeks by 10 to 20 mg as needed and tolerated. A less frequent/lower dosage should be considered for geriatric adults. Doses above 20 mg/day may be given once daily or divided into 2 doses at morning and noon. Max: 80 mg/day PO. May divide into 2 doses if the dosage is 20 mg/day or more. Periodically re-evaluate to determine the need for continued treatment.
    • Paroxetine c95
      • Paroxetine Hydrochloride Oral tablet; Adults: 20 mg PO once daily initially, usually in the morning. May increase by 10 mg at weekly intervals. Max: 50 mg/day PO. DEBILITATED ADULTS: 10 mg PO once daily initially, with increases as needed by 10 mg at a minimum of weekly intervals up to a maximum of 40 mg/day PO. When discontinuing, taper the dose if possible.Paroxetine Hydrochloride Oral tablet; Adults: 20 mg PO once daily initially, usually in the morning. May increase by 10 mg at weekly intervals. Max: 50 mg/day PO. DEBILITATED ADULTS: 10 mg PO once daily initially, with increases as needed by 10 mg at a minimum of weekly intervals up to a maximum of 40 mg/day PO. When discontinuing, taper the dose if possible.
      • Paroxetine Hydrochloride Oral tablet; Geriatric Adults: 10 mg PO once daily initially. May increase by 10 mg at weekly intervals. Max: 40 mg/day PO. When discontinuing, taper the dose if possible.Paroxetine Hydrochloride Oral tablet; Geriatric Adults: 10 mg PO once daily initially. May increase by 10 mg at weekly intervals. Max: 40 mg/day PO. When discontinuing, taper the dose if possible.
    • Sertraline r32c96c97
      • Evidence recommends that physicians use caution when prescribing sertraline in pediatric patients (if at all)
        • For children 6 to 11 years with major depressive disorder: do not recommend off-label sertraline; the harms of the drug outweigh any benefits r33
        • For adolescents 12 to 17 years with major depressive disorder: r33
          • First line treatment: to achieve a clinical response with minimal risk of suicidality, recommend cognitive interventions first
          • Second line treatment: if cognitive interventions fail and adolescents are closely monitored for sertraline-associated harms, may recommend off-label sertraline
      • Sertraline Hydrochloride Oral tablet; Children 6 to 11 years†: 12.5 mg to 25 mg/day PO initially. Clinical guidelines recommend to start with a low dose and titrate gradually at 4-week intervals until clinical response is achieved; some studies report titration in 25 mg to 50 mg/day increments as often as every 1 to 2 weeks. A dose of 50 mg/day PO is considered effective. Max: 200 mg/day PO.Sertraline Hydrochloride Oral tablet; Children 6 to 11 years†: 12.5 mg to 25 mg/day PO initially. Clinical guidelines recommend to start with a low dose and titrate gradually at 4-week intervals until clinical response is achieved; some studies report titration in 25 mg to 50 mg/day increments as often as every 1 to 2 weeks. A dose of 50 mg/day PO is considered effective. Max: 200 mg/day PO.
      • Sertraline Hydrochloride Oral tablet; Children and Adolescents 12 to 17 years†: 25 to 50 mg/day PO initially. Clinical guidelines recommend to start with a low dose and titrate gradually at 4-week intervals until clinical response is achieved; some studies report titration in 25 mg to 50 mg/day increments as often as every 1 to 2 weeks. A dose of 50 mg/day PO is considered effective. Max: 200 mg/day PO.Sertraline Hydrochloride Oral tablet; Children and Adolescents 12 to 17 years†: 25 to 50 mg/day PO initially. Clinical guidelines recommend to start with a low dose and titrate gradually at 4-week intervals until clinical response is achieved; some studies report titration in 25 mg to 50 mg/day increments as often as every 1 to 2 weeks. A dose of 50 mg/day PO is considered effective. Max: 200 mg/day PO.
      • Sertraline Hydrochloride Oral tablet; Adults: 50 mg PO once daily. A lower initial dose (25 mg PO once daily) may be used to minimize adverse effects. If necessary, increase at intervals of not less than 1 week. Max: 200 mg/day PO. Continuation of medication for 6 to 12 months after symptom remission is recommended; periodically reassess the need for ongoing treatment.Sertraline Hydrochloride Oral tablet; Adults: 50 mg PO once daily. A lower initial dose (25 mg PO once daily) may be used to minimize adverse effects. If necessary, increase at intervals of not less than 1 week. Max: 200 mg/day PO. Continuation of medication for 6 to 12 months after symptom remission is recommended; periodically reassess the need for ongoing treatment.
  • Serotonin-norepinephrine reuptake inhibitors c98
    • Duloxetine c99
      • Duloxetine Oral capsule, gastro-resistant pellets; Adults: Initially, 20 mg PO twice daily (40 mg/day) or 60 mg/day PO as a single dose or in 2 divided doses (i.e., 30 mg PO twice daily). An alternate regimen is 30 mg/day PO for 1 week, then increase to 60 mg/day. Target maintenance dose: 60 mg/day; dividing doses may increase tolerability; Max: 120 mg/day PO, but greater than 60 mg/day has not shown additional benefit.Duloxetine Oral capsule, gastro-resistant pellets; Adults: Initially, 20 mg PO twice daily (40 mg/day) or 60 mg/day PO as a single dose or in 2 divided doses (i.e., 30 mg PO twice daily). An alternate regimen is 30 mg/day PO for 1 week, then increase to 60 mg/day. Target maintenance dose: 60 mg/day; dividing doses may increase tolerability; Max: 120 mg/day PO, but greater than 60 mg/day has not shown additional benefit.
    • Milnacipran c100
      • Milnacipran Hydrochloride Oral tablet; Adults: Initially, 12.5 to 25 mg PO twice daily. Based on individual response, the dose may be titrated to 100 mg PO twice daily. Max: 200 mg/day. In one trial of adult patients with diabetes mellitus type 2 and co-morbid depression, 72.6% of treated patients fulfilled criteria for antidepressant response according to the Beck Depression Inventory scale.Milnacipran Hydrochloride Oral tablet; Adults: Initially, 12.5 to 25 mg PO twice daily. Based on individual response, the dose may be titrated to 100 mg PO twice daily. Max: 200 mg/day. In one trial of adult patients with diabetes mellitus type 2 and co-morbid depression, 72.6% of treated patients fulfilled criteria for antidepressant response according to the Beck Depression Inventory scale.
    • Venlafaxine c101
      • Venlafaxine Hydrochloride Oral tablet; Adults: Initially, 75 mg/day PO, given in 2 or 3 divided doses. If needed, daily dose may be increased by 75 mg/day no less than every 4 days. Outpatient Max: 225 mg/day PO in divided doses. Institutional Max: 375 mg/day PO, given in 3 divided doses.Venlafaxine Hydrochloride Oral tablet; Adults: Initially, 75 mg/day PO, given in 2 or 3 divided doses. If needed, daily dose may be increased by 75 mg/day no less than every 4 days. Outpatient Max: 225 mg/day PO in divided doses. Institutional Max: 375 mg/day PO, given in 3 divided doses.
  • Noradrenergic and specific serotonin antidepressants c102
    • Mirtazapine r30c103
      • Do not use concomitantly with MAOIs
      • Mirtazapine Oral tablet; Adults: Initially, 15 mg PO at bedtime. The effective dose range is 15 mg/day to 45 mg/day. Dosage adjustments should not be made more often than every 1 to 2 weeks. Geriatric patients may require a slower titration schedule.Mirtazapine Oral tablet; Adults: Initially, 15 mg PO at bedtime. The effective dose range is 15 mg/day to 45 mg/day. Dosage adjustments should not be made more often than every 1 to 2 weeks. Geriatric patients may require a slower titration schedule.
  • Noradrenergic and dopaminergic antidepressants c104
    • Bupropion c105
      • Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]; Children† and Adolescents† 6 years and older: Dosage not established. Suggested dosage ranges from 1.4 to 6 mg/kg/day PO, titrated upward slowly and administered in divided doses. In trials, the average effective dose is roughly 3 mg/kg/day PO; the maximum dosage is generally 250 to 300 mg/day PO. Safety data are not extensive; most patients have also been diagnosed with ADHD.Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]; Children† and Adolescents† 6 years and older: Dosage not established. Suggested dosage ranges from 1.4 to 6 mg/kg/day PO, titrated upward slowly and administered in divided doses. In trials, the average effective dose is roughly 3 mg/kg/day PO; the maximum dosage is generally 250 to 300 mg/day PO. Safety data are not extensive; most patients have also been diagnosed with ADHD.
      • Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]; Adults: Initially, 100 mg PO twice daily; titrate after 3 days to 100 mg PO 3 times per day if needed; no single dose should exceed 150 mg.Bupropion Hydrochloride Oral tablet [Depression/Mood Disorders]; Adults: Initially, 100 mg PO twice daily; titrate after 3 days to 100 mg PO 3 times per day if needed; no single dose should exceed 150 mg.
  • Tricyclic antidepressants r29c106
    • Amitriptyline c107
      • Amitriptyline Hydrochloride Oral tablet; Adolescents: Begin at a low daily dosage, usually at bedtime, and titrate as needed and tolerated. Lower doses are used compared to young adults; 10 mg PO 3 times per day with 20 mg PO at bedtime may be satisfactory in adolescents who do not tolerate higher dosages. When satisfactory improvement has occurred, reduce to the lowest effective dose. Weight-based dosing has been used in clinical trials in adolescents for other indications. TCAs are not drugs of choice for pediatric patients with depression; there is lack of high-quality data to support efficacy and safety.Amitriptyline Hydrochloride Oral tablet; Adolescents: Begin at a low daily dosage, usually at bedtime, and titrate as needed and tolerated. Lower doses are used compared to young adults; 10 mg PO 3 times per day with 20 mg PO at bedtime may be satisfactory in adolescents who do not tolerate higher dosages. When satisfactory improvement has occurred, reduce to the lowest effective dose. Weight-based dosing has been used in clinical trials in adolescents for other indications. TCAs are not drugs of choice for pediatric patients with depression; there is lack of high-quality data to support efficacy and safety.
      • Amitriptyline Hydrochloride Oral tablet; Adults: Initially, 75 mg/day PO, given in divided doses, or, 50 mg to 100 mg PO once daily at bedtime. Hospitalized patients may require 100 mg/day PO initially. Titrate if needed, up to 150 mg/day PO, by increasing the daily dose 25 to 50 mg at weekly intervals, to response and tolerance. Max (hospitalized patients): 300 mg/day PO. Usual maintenance dose: 50 to 100 mg PO per day. In some patients, 40 mg/day PO is sufficient. For maintenance, give as a single dose, preferably at bedtime. Use lowest effective dose. It is appropriate to continue maintenance therapy 3 months or longer to lessen the possibility of relapse.Amitriptyline Hydrochloride Oral tablet; Adults: Initially, 75 mg/day PO, given in divided doses, or, 50 mg to 100 mg PO once daily at bedtime. Hospitalized patients may require 100 mg/day PO initially. Titrate if needed, up to 150 mg/day PO, by increasing the daily dose 25 to 50 mg at weekly intervals, to response and tolerance. Max (hospitalized patients): 300 mg/day PO. Usual maintenance dose: 50 to 100 mg PO per day. In some patients, 40 mg/day PO is sufficient. For maintenance, give as a single dose, preferably at bedtime. Use lowest effective dose. It is appropriate to continue maintenance therapy 3 months or longer to lessen the possibility of relapse.
      • Amitriptyline Hydrochloride Oral tablet; Geriatric: 10 to 25 mg PO at bedtime initially. Titrate as needed and tolerated. Max: 150 mg/day PO, but such doses are not typically tolerated in the geriatric adult. Usual adult maintenance dosage: 50 to 100 mg per day. In some patients, 40 mg/day is sufficient. For maintenance therapy, give as a single dose, preferably at bedtime. Use lowest effective dose. It is appropriate to continue maintenance therapy 3 months or longer to lessen the possibility of relapse.Amitriptyline Hydrochloride Oral tablet; Geriatric: 10 to 25 mg PO at bedtime initially. Titrate as needed and tolerated. Max: 150 mg/day PO, but such doses are not typically tolerated in the geriatric adult. Usual adult maintenance dosage: 50 to 100 mg per day. In some patients, 40 mg/day is sufficient. For maintenance therapy, give as a single dose, preferably at bedtime. Use lowest effective dose. It is appropriate to continue maintenance therapy 3 months or longer to lessen the possibility of relapse.
    • Clomipramine c108
      • Clomipramine Hydrochloride Oral capsule; Children and Adolescents 10 years and older: Initially, 25 mg PO once daily, gradually increasing up to a total of 100 mg/day PO given in divided doses; or 3 mg/kg/day given in divided doses, whichever is the smaller, over the first 2 weeks. In clinical trials in pediatric patients for OCD, the average effective dose range was 100 to 200 mg/day.Clomipramine Hydrochloride Oral capsule; Children and Adolescents 10 years and older: Initially, 25 mg PO once daily, gradually increasing up to a total of 100 mg/day PO given in divided doses; or 3 mg/kg/day given in divided doses, whichever is the smaller, over the first 2 weeks. In clinical trials in pediatric patients for OCD, the average effective dose range was 100 to 200 mg/day.
      • Clomipramine Hydrochloride Oral capsule; Adults: Initially, 25 mg PO once daily, may gradually increase in the first 2 weeks to 100 mg/day PO, given in divided doses. Max: 250 mg/day. After titration, the total daily dose may be given every night at bedtime to minimize daytime sedation.Clomipramine Hydrochloride Oral capsule; Adults: Initially, 25 mg PO once daily, may gradually increase in the first 2 weeks to 100 mg/day PO, given in divided doses. Max: 250 mg/day. After titration, the total daily dose may be given every night at bedtime to minimize daytime sedation.
    • Desipramine c109
      • Desipramine Hydrochloride Oral tablet; Adolescents: 25 to 50 mg PO at bedtime initially. May titrate at weekly intervals by 25to 50 mg, depending on response and tolerance. Usual Max: 100 mg/day PO, in single or divided doses. Max (hospitalized patients): 150 mg/day PO. Once at a maintenance dosage, administering the total daily dose at bedtime may minimize daytime sedation and improve compliance. TCAs are not drugs of choice for pediatric patients with depression; there is lack of high-quality data to support efficacy and safety.Desipramine Hydrochloride Oral tablet; Adolescents: 25 to 50 mg PO at bedtime initially. May titrate at weekly intervals by 25to 50 mg, depending on response and tolerance. Usual Max: 100 mg/day PO, in single or divided doses. Max (hospitalized patients): 150 mg/day PO. Once at a maintenance dosage, administering the total daily dose at bedtime may minimize daytime sedation and improve compliance. TCAs are not drugs of choice for pediatric patients with depression; there is lack of high-quality data to support efficacy and safety.
      • Desipramine Hydrochloride Oral tablet; Adults: 50 to 75 mg/day PO initially, in single or divided doses. Titrate by 25 to 50 mg at weekly intervals according to response and tolerance. The usual adult dose is 100 mg to 200 mg PO per day, in single or divided doses. Max: 300 mg/day PO. Patients requiring up to 300 mg/day should generally be hospitalized for therapy initiation. Once at a maintenance dosage, administering the total daily dose at bedtime may minimize daytime sedation and improve compliance.Desipramine Hydrochloride Oral tablet; Adults: 50 to 75 mg/day PO initially, in single or divided doses. Titrate by 25 to 50 mg at weekly intervals according to response and tolerance. The usual adult dose is 100 mg to 200 mg PO per day, in single or divided doses. Max: 300 mg/day PO. Patients requiring up to 300 mg/day should generally be hospitalized for therapy initiation. Once at a maintenance dosage, administering the total daily dose at bedtime may minimize daytime sedation and improve compliance.
      • Desipramine Hydrochloride Oral tablet; Geriatric: 25 mg PO at bedtime initially. May titrate at weekly intervals by 25 to 50 mg, depending on response and tolerance. Usual max: 100 mg/day PO, in single or divided doses. Max (hospitalized patients): 150 mg/day PO. Once at a maintenance dosage, administering the total daily dose at bedtime may minimize daytime sedation and improve compliance.Desipramine Hydrochloride Oral tablet; Geriatric: 25 mg PO at bedtime initially. May titrate at weekly intervals by 25 to 50 mg, depending on response and tolerance. Usual max: 100 mg/day PO, in single or divided doses. Max (hospitalized patients): 150 mg/day PO. Once at a maintenance dosage, administering the total daily dose at bedtime may minimize daytime sedation and improve compliance.
    • Imipramine c110
      • Imipramine Hydrochloride Oral tablet; Adolescents: Initially, 30 mg to 40 mg/day PO once daily at bedtime to help minimize daytime sedation. If necessary, titrate upward based on response and tolerability. Usual Max: 100 mg/day PO. Use the lowest effective dose that maintains remission. TCAs are not drugs of choice for pediatric patients with depression; there is lack of high-quality data to support efficacy and safety.Imipramine Hydrochloride Oral tablet; Adolescents: Initially, 30 mg to 40 mg/day PO once daily at bedtime to help minimize daytime sedation. If necessary, titrate upward based on response and tolerability. Usual Max: 100 mg/day PO. Use the lowest effective dose that maintains remission. TCAs are not drugs of choice for pediatric patients with depression; there is lack of high-quality data to support efficacy and safety.
      • Imipramine Hydrochloride Oral tablet; Adults: OUTPATIENTS: Initially, 75 mg/day PO; bedtime dosing may reduce daytime sedation. The, titrate to 150 mg/day as a single dose or divided doses based on response and tolerability. Optimal response may take 1 to 3 weeks of treatment at a given dose. Maintenance: 50 to 150 mg/day. Outpatient Max: 200 mg/day PO. HOSPITALIZED ADULTS: Initially, 100 mg/day PO in divided doses, gradually increased to 200 mg/day PO in divided doses as required. If no response after 2 weeks, increase to 250 mg/day to 300 mg/day PO. Hospitalized patient Max: 300 mg/day PO. Use lowest effective dose that maintains remission.Imipramine Hydrochloride Oral tablet; Adults: OUTPATIENTS: Initially, 75 mg/day PO; bedtime dosing may reduce daytime sedation. The, titrate to 150 mg/day as a single dose or divided doses based on response and tolerability. Optimal response may take 1 to 3 weeks of treatment at a given dose. Maintenance: 50 to 150 mg/day. Outpatient Max: 200 mg/day PO. HOSPITALIZED ADULTS: Initially, 100 mg/day PO in divided doses, gradually increased to 200 mg/day PO in divided doses as required. If no response after 2 weeks, increase to 250 mg/day to 300 mg/day PO. Hospitalized patient Max: 300 mg/day PO. Use lowest effective dose that maintains remission.
      • Imipramine Hydrochloride Oral tablet; Geriatric Adults: Initially, 30 mg to 40 mg/day PO once daily at bedtime to help minimize daytime sedation. If necessary, titrate to response and tolerability. Usual Max: 100 mg/day. Use the lowest effective dose that maintains remission.Imipramine Hydrochloride Oral tablet; Geriatric Adults: Initially, 30 mg to 40 mg/day PO once daily at bedtime to help minimize daytime sedation. If necessary, titrate to response and tolerability. Usual Max: 100 mg/day. Use the lowest effective dose that maintains remission.
    • Nortriptyline c111
      • Nortriptyline Hydrochloride Oral capsule; Adolescents: Initially, 10 mg or 25 mg PO at bedtime.May increase as tolerated to 30 mg to 50 mg per day, given in divided doses or once daily at bedtime. TCAs are not drugs of choice for pediatric patients with depression; the quality of data to support efficacy and safety in adolescents is considered marginal.Nortriptyline Hydrochloride Oral capsule; Adolescents: Initially, 10 mg or 25 mg PO at bedtime.May increase as tolerated to 30 mg to 50 mg per day, given in divided doses or once daily at bedtime. TCAs are not drugs of choice for pediatric patients with depression; the quality of data to support efficacy and safety in adolescents is considered marginal.
      • Nortriptyline Hydrochloride Oral capsule; Adults: Initially, 25 mg to 50 mg PO per day, given in divided doses or at bedtime. May increase as needed and tolerated. Max: 150 mg/day PO.Nortriptyline Hydrochloride Oral capsule; Adults: Initially, 25 mg to 50 mg PO per day, given in divided doses or at bedtime. May increase as needed and tolerated. Max: 150 mg/day PO.
      • Nortriptyline Hydrochloride Oral capsule; Geriatric Adults: Initially, 10 mg to 25 mg PO at bedtime. May increase as tolerated to 30 mg to 50 mg per day, in divided doses or at bedtime.Nortriptyline Hydrochloride Oral capsule; Geriatric Adults: Initially, 10 mg to 25 mg PO at bedtime. May increase as tolerated to 30 mg to 50 mg per day, in divided doses or at bedtime.
  • MAOIs r34c112
    • Avoid alcohol, tobacco, caffeine, and tyramine-containing foods (eg, aged cheeses, cured meats, fermented cabbage, soy sauce, fava beans) except when taking selegiline at the lowest dosage
    • Isocarboxazid c113
      • Isocarboxazid Oral tablet; Adolescents 16 years and older: In patients receiving contraindicated drugs known to interact with MAOIs, the interacting drug should be discontinued for at least 1 to 2 weeks before initiating isocarboxazid therapy. INITIAL DOSAGE: 10 mg PO twice daily. Carefully assess for drug efficacy and safety to individualize dosage. May increase by 10 mg/day PO every 2 to 4 days, up to 40 mg/day PO by end of first week. May increase further by up to 20 mg/week, if needed and tolerated. Max: 60 mg/day PO, given in 2 to 4 divided doses. Use caution if receiving more than 40 mg/day PO. MAINTENANCE DOSAGE: After maximum clinical response is achieved, reduce the dosage over several weeks to the lowest dosage that maintains effectiveness to limit cumulative MAOI effects and serious dose-related toxicity. Periodically re-evaluate for drug effectiveness and safety.Isocarboxazid Oral tablet; Adolescents 16 years and older: In patients receiving contraindicated drugs known to interact with MAOIs, the interacting drug should be discontinued for at least 1 to 2 weeks before initiating isocarboxazid therapy. INITIAL DOSAGE: 10 mg PO twice daily. Carefully assess for drug efficacy and safety to individualize dosage. May increase by 10 mg/day PO every 2 to 4 days, up to 40 mg/day PO by end of first week. May increase further by up to 20 mg/week, if needed and tolerated. Max: 60 mg/day PO, given in 2 to 4 divided doses. Use caution if receiving more than 40 mg/day PO. MAINTENANCE DOSAGE: After maximum clinical response is achieved, reduce the dosage over several weeks to the lowest dosage that maintains effectiveness to limit cumulative MAOI effects and serious dose-related toxicity. Periodically re-evaluate for drug effectiveness and safety.
      • Isocarboxazid Oral tablet; Adults: In patients receiving contraindicated drugs known to interact with MAOIs, the interacting drug should be discontinued for at least 1 to 2 weeks before initiating isocarboxazid therapy. INITIAL DOSAGE: 10 mg PO twice daily. Carefully assess for drug efficacy and safety to individualize dosage. May increase by 10 mg/day PO every 2 to 4 days, up to 40 mg/day PO by end of first week. May increase further by up to 20 mg/week, if needed and tolerated. Max: 60 mg/day PO, given in 2 to 4 divided doses. Use caution if receiving more than 40 mg/day PO. MAINTENANCE DOSAGE: After maximum clinical response is achieved, reduce the dosage over several weeks to the lowest dosage that maintains effectiveness to limit cumulative MAOI effects and serious dose-related toxicity. Periodically re-evaluate for drug effectiveness and safety.Isocarboxazid Oral tablet; Adults: In patients receiving contraindicated drugs known to interact with MAOIs, the interacting drug should be discontinued for at least 1 to 2 weeks before initiating isocarboxazid therapy. INITIAL DOSAGE: 10 mg PO twice daily. Carefully assess for drug efficacy and safety to individualize dosage. May increase by 10 mg/day PO every 2 to 4 days, up to 40 mg/day PO by end of first week. May increase further by up to 20 mg/week, if needed and tolerated. Max: 60 mg/day PO, given in 2 to 4 divided doses. Use caution if receiving more than 40 mg/day PO. MAINTENANCE DOSAGE: After maximum clinical response is achieved, reduce the dosage over several weeks to the lowest dosage that maintains effectiveness to limit cumulative MAOI effects and serious dose-related toxicity. Periodically re-evaluate for drug effectiveness and safety.
    • Phenelzine c114
      • Phenelzine Sulfate Oral tablet; Adults: 15 mg PO 3 times daily; may rapidly increase to 60 mg/day if tolerated. Individualize dosage based on careful observation. For some, an increase up to 90 mg/day may be necessary. Onset of maximum effect is 2 to 6 weeks. After the maximum benefit is achieved, reduce dosage slowly over several weeks to the lowest dose that maintains effectiveness. Maintenance dose may be as low as 15 mg/day PO or 15 mg PO every other day, continued as long as required. NOTE: In patients requiring a contraindicated drug known to interact with MAOIs, phenelzine should be discontinued for at least 2 weeks before initiating the interacting drug.Phenelzine Sulfate Oral tablet; Adults: 15 mg PO 3 times daily; may rapidly increase to 60 mg/day if tolerated. Individualize dosage based on careful observation. For some, an increase up to 90 mg/day may be necessary. Onset of maximum effect is 2 to 6 weeks. After the maximum benefit is achieved, reduce dosage slowly over several weeks to the lowest dose that maintains effectiveness. Maintenance dose may be as low as 15 mg/day PO or 15 mg PO every other day, continued as long as required. NOTE: In patients requiring a contraindicated drug known to interact with MAOIs, phenelzine should be discontinued for at least 2 weeks before initiating the interacting drug.
    • Selegiline c115
      • Selegiline Hydrochloride Transdermal patch - 24 hour; Adults: Initially, 6 mg/24 hours transdermally once daily. If clinically indicated, increase by 3 mg/24 hour at intervals of no less than 2 weeks. Effective dose range: 6 to 12 mg/24 hours. Max: 12 mg/24 hours. Inform patients to avoid tyramine-containing foods/beverages/dietary supplements beginning on the first day of selegiline 9 mg or 12 mg/24 hours treatment. Avoid tyramine for 2 weeks after dose reduction (to 6 mg/24 hours) or discontinuation of 9 mg/24 hours or 12 mg/24 hours.Selegiline Hydrochloride Transdermal patch - 24 hour; Adults: Initially, 6 mg/24 hours transdermally once daily. If clinically indicated, increase by 3 mg/24 hour at intervals of no less than 2 weeks. Effective dose range: 6 to 12 mg/24 hours. Max: 12 mg/24 hours. Inform patients to avoid tyramine-containing foods/beverages/dietary supplements beginning on the first day of selegiline 9 mg or 12 mg/24 hours treatment. Avoid tyramine for 2 weeks after dose reduction (to 6 mg/24 hours) or discontinuation of 9 mg/24 hours or 12 mg/24 hours.
  • NMDA (N-methyl-D-aspartate) receptor antagonists
    • Esketamine nasal spray r28
      • First NMDA antagonist to receive FDA approval for major depression
      • Used as an adjunct to an oral antidepressant for treatment-resistant depression (those who have failed 2 or more standard antidepressant treatments)
      • Only available through a restricted distribution system, under a Risk Evaluation and Mitigation Strategy, owing to risk of serious adverse outcomes resulting from sedation and dissociation and the potential for drug misuse
      • Esketamine intranasal dosage (ie, Spravato nasal spray containing 28 mg per device); Adults: INDUCTION PHASE: On day 1, administer 56 mg intranasally. For subsequent doses during Weeks 1 through 4, administer 56 mg or 84 mg twice per week. Use 2 devices for the 56 mg dose and 3 devices for the 84 mg dose with a 5-minute rest between use of each device. MAINTENANCE PHASE: During Weeks 5 through 8, administer 56 mg or 84 mg once weekly. During Week 9 and thereafter, administer 56 mg or 84 mg every 2 weeks or once weekly. The dosing frequency should be individualized to the least frequent dosing to maintain remission/response. r35

Nondrug and supportive care

Music therapy

  • Music therapy (provided by a music therapist) has been found to decrease depressive symptoms, improve anxiety associated with major depressive disorder, and improve functioning r36c116

Acupuncture r37c117

  • Small to moderate reduction in the severity of depressive symptoms has been reported

Exercise r38c118

  • Exercise has been shown to have significant effect in reducing depressive symptoms in patients with major depressive disorder,r39 especially regular, moderate-level, aerobic exercise
Procedures
Psychotherapy c119c120c121
General explanation
  • Includes cognitive behavioral therapy, behavioral activation therapy, interpersonal psychotherapy, problem-solving therapy, nondirective counseling, and psychodynamic therapy r11
  • First line recommendations for acute major depressive disorder include cognitive-behavioral therapy, interpersonal psychotherapy, and behavioral activation therapy r40
  • All types are known to be effective options r11r41
  • May be used as the initial treatment modality for patients with major depressive disorder, with or without concomitant medication therapy; often adequate as initial therapy, early in the course of the disease r11
  • Cognitive behavioral therapy administered concurrently with medication may increase the rate of patient response r40r42
  • Cognitive behavioral therapy administered after medication is withdrawn may impart a protective effect against relapse r42
Indication
  • Significant psychological stressors, intrapsychic conflict, or interpersonal difficulties
  • Mild to moderate depression r24
    • Patients are more likely to respond to psychotherapy than to medication
Electroconvulsive therapy r43c122c123c124c125c126
General explanation
  • Generalized seizures are intentionally induced using electrical impulses
  • Typically performed 2 to 3 times per week until clinical response is seen
  • Average course is 6 to 12 treatments, which are administered under anesthesia and with muscle relaxants
Indication r24r44
  • May be used as first line therapy for patients who have:
    • Psychotic depression
    • Catatonia
    • Previous response to this treatment method
    • Severe suicidality
    • Anorexia/rapidly deteriorating physical status
    • Treatment-resistant depression
    • Repeated medication intolerance
Contraindications
  • Relative contraindications
    • Age younger than 18 years
    • Space-occupying brain lesions
    • Elevated intracranial pressure
    • Recent myocardial infarction
    • History of retinal detachment
    • Pheochromocytoma
Complications
  • Associated with transient postictal confusion and a period of antegrade and retrograde memory loss
  • Can cause a transient rise in heart rate, in cardiac workload, and in blood pressure
Repetitive transcranial magnetic stimulation r45c127
General explanation
  • Magnetic fields stimulate nerve cells in the brain to improve symptoms of depression
    • Evaluate patients for seizure risk before repetitive transcranial magnetic stimulation, including: r23r46
      • Personal/family history of seizures or epilepsy
      • Previous head injury or stroke with neurologic sequelae
      • Current use of medications/substances that lower seizure threshold (eg, psychostimulants) or reduction in dose of medication with antiseizure properties (eg, benzodiazepine)
      • Presence of medical condition or neurologic disorder that may lower seizure threshold (eg, electrolyte imbalance, sleep deprivation, drug withdrawal)
  • Electromagnetic coil is held against the forehead and short electromagnetic pulses are administered through the coil
  • Left prefrontal repetitive transcranial magnetic stimulation repeated daily for 4 to 6 weeks is an effective and safe treatment in adult patients with unipolar major depressive disorder that has failed 1 or more antidepressant trials r47
    • Typical session lasts 30 to 60 minutes and does not require anesthesia r46
Indication
  • First line treatment for patients with major depression who have not responded to antidepressant drug therapy r25r44
Contraindications
  • Pregnancy
  • Aneurysm clips
  • Presence of other ferromagnetic material in the head, with the exception of the mouth
  • Deep brain stimulator use (unintended currents can result)
Complications r48
  • Headache
  • Scalp discomfort
  • Seizures

Comorbidities

  • Anxiety disorder c128
    • Approximately one-half of patients with anxiety disorders have other mood disorders (typically dysthymia or depression) r49
  • Obsessive-compulsive disorder c129
    • Often produces additional depression symptoms r50
  • Substance abuse disorder (eg, alcohol, opioids, amphetamine, cocaine, cannabis) c130
    • Associated with depression and suicide attempts
    • Impulsivity is heightened when under the influence of substances r51
  • Coronary artery disease c131
    • Risk of future cardiac events is 2 to 3 times higher in patients with coronary artery disease and depression when compared to patients without depression r52
  • Diabetes mellitus c132
    • Patients with diabetes and depression experience worse glycemic control and an increased risk of diabetic complications r53
  • Obesity c133
    • Depression-associated low motivation, poor adherence, negative thinking, fatigue, and sleep problems reduce the success of early-treatment weight loss programs r54

Special populations

  • Pregnant women
    • Untreated major depressive disorder in pregnancy poses a risk to the mother and fetus (potential harm from malnutrition, poor prenatal care, substance abuse, or suicide attempts)
    • Treatment can include psychotherapy and medications determined by the patient's obstetrician and psychiatrist
      • Given the potential harms to the fetus and newborn child from certain pharmacologic agents, clinicians are encouraged to consider cognitive behavioral therapy or other evidence-based counseling interventions when managing depression in pregnant or breastfeeding women r1r25

Monitoring

  • During the initial phase of treatment, monitoring can vary from once per week to multiple times per week depending on severity
  • American Academy of Pediatrics guidelines recommend that adolescents are assessed in person within 1 week of treatment initiation r27
  • Frequency of monitoring can be based on severity, presence of suicidal ideation, patient adherence to treatment, social supports, and coexisting medical conditions

Complications and Prognosis

Complications

  • Suicide c134
    • Majority of patients with completed suicide have major depression
  • Substance abuse c135

Prognosis

  • There is a high risk of relapse after a depressive episode, especially in the first 6 months; risk declines with time in remission r24
    • Risk factors for relapse include presence of residual symptoms, number of previous episodes, severity, duration, and degree of treatment resistance of the most recent episode
  • Untreated depression increases the risk of self-inflicted injury or suicide
  • Prognosis of major depressive disorder in elderly patients is poor, as the majority of cases remain undetected r1

Screening and Prevention

Screening

At-risk populations

  • United States Preventive Services Task Force recommends screening adults for major depression; the optimum interval for screening is unknown r1c136c137c138c139
  • United States Preventive Services Task Force recommends screening adolescents aged 12 to 18 years for major depressive disorder r55
  • American Academy of Pediatrics guidelines recommend that adolescent patients aged 12 years and older should be screened annually for depression with a formal self-report screening tool r56
  • United States Department of Veterans Affairs recommends screening for major depression annually r11c140c141c142c143
  • American College of Obstetricians and Gynecologists recommends patients be screened for depression and anxiety symptoms at least once during the perinatal period, using a standardized, validated tool; screening for postpartum depression and anxiety is also recommended, using a validated instrument r57

Screening tests

  • Standardized depression inventory tests include Beck Depression Inventory, Major Depression Inventory, Hamilton Depression Rating Scale, and Patient Health Questionnaire-9 r1r2r3r11c144c145c146c147

Prevention c148

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