Elsevier LogoMental and Behavioral Health

    ThisiscontentfromClinicalKey

    Recurrent major depressive disorder with a seasonal pattern

    Sign up for your free ClinicalKey trial today!  Your first step in getting the right answers when you need them.

    Start Free Trial
    Nov.01.2022

    Recurrent Major Depressive Disorder With a Seasonal Pattern

    Synopsis

    Key Points

    • Recurrent major depressive disorder with a seasonal pattern is diagnosed in patients when symptoms of depression emerge at a particular time of year, usually in winter
    • Diagnosis is based on the recognition of major depressive episodes occurring at a specific time of the year, causing social or occupational impairment, with the presence of at least 5 of the following symptoms, necessarily including depressed/irritable mood or anhedonia: r1
      • Depressed mood or irritability for most of the day, and nearly every day, indicated via subjective report of the patient or via observation of others
      • Anhedonia
      • Sleep disturbance
      • Change in weight or appetite
      • Psychomotor retardation or agitation
      • Fatigue or loss of energy
      • Feelings of worthlessness or excessive or inappropriate guilt
      • Diminished ability to concentrate or indecisiveness
      • Recurrent thoughts of death, suicidal ideation, suicide attempt, or a specific plan for committing suicide
    • Must be differentiated from hypothyroidism, major depressive disorder, bipolar disorders I and II, cyclothymic disorder, and substance misuse
    • Principal treatment modalities consist of light therapy, cognitive behavioral therapy, and selective serotonin reuptake inhibitors
      • These treatment options can be used in concert as well as individually
      • In the case of fall/winter seasonality, light therapy is useful not only for treatment, but also as a prevention modality if begun in early fall

    Urgent Action

    • Recognition of suicidal or homicidal ideation is urgent; when present, this warrants immediate referral to a psychiatrist and admission to psychiatric unit

    Pitfalls

    • Failure to recognize the seasonality element of the condition can result in misdiagnosis (eg, cyclothymic disorder), leading to failure to implement effective treatment
    • Failure to recognize a patient’s suicidal or homicidal risk can lead to tragic consequences of an otherwise manageable condition

    Terminology

    Clinical Clarification

    • Recurrent major depressive disorder with a seasonal pattern is a major depressive disorder with a regular temporal relationship between symptomatic episodes and a particular time of the year r2

    Classification

    • DSM-5 TR considers seasonality as an episode specifier for recurrent major depressive disorder r1
      • Defining characteristic is the onset and remission of episodes of major depressive disorder at characteristic times of the year (usually beginning in fall or winter) r1
      • Major depressive disorder r1
        • At least 5 of the following symptoms are present nearly every day during the same 2-week period:
          • Depressed mood most of the day
          • Markedly reduced interest or pleasure in all or nearly all activities
          • Change in appetite or weight (increase or decrease)
          • Sleep disturbance (insomnia or hypersomnia)
          • Psychomotor agitation or retardation (observable by others)
          • Fatigue or lack of energy
          • Reduced ability to think or concentrate; indecisiveness
          • Feelings of worthlessness or excessive, inappropriate guilt
          • Recurrent thoughts of death or suicidal ideation or attempt
        • Symptoms represent a change from usual functioning
        • At least 1 of the symptoms is depressed mood or loss of interest or pleasure
        • Symptoms cause clinically significant distress or impairment in social, work, or other areas of functioning
        • Episode is not attributable to the physiologic effects of substance use or other medical disorder
      • Seasonal specifier r1
        • Depressive episodes must occur during a particular time of the year with predictable annual recurrence r3
        • This pattern of onset and remission of episodes must have occurred during at least a 2-year period (ie, 2 depressive episodes must have occurred in the previous 2 years) with no nonseasonal episodes occurring during this period
        • Seasonal major depressive episodes substantially outnumber the nonseasonal major depressive episodes that may have occurred during individual's life
        • The seasonal specifier does not apply to when the pattern is better explained by seasonally linked psychosocial stressors (eg, seasonal unemployment)
    • Recurrent major depressive disorder with a seasonal pattern can be further classified into 2 subtypes, based on the time of year in which episodes occur r2
      • Winter or fall/winter recurrence
        • Accounts for the vast majority of cases, especially in populations living at high latitudes
        • Certain ethnic groups who live at very high latitudes and their descendants may have adapted to long winters and therefore are less prone
      • Summer or spring/summer recurrence
        • Constitutes only a minority of cases r4
    • A subsyndromal type of seasonal depression, manifesting mostly with sleep disturbances, has been reported among individuals staying at Arctic and Antarctic sites r5

    Diagnosis

    Clinical Presentation

    History

    • Seasonal pattern of symptoms r6
    • Any of the following symptoms or complaints are common:
      • Decline in performance at work or school c1c2
      • Change in sleep, appetite, or weight (gaining or losing more than 5% body weight within a month, as reported by patient or observed by others) r1c3c4c5
        • Hypersomnia with hyperphagia, craving for carbohydrates, and weight gain is typical of recurrent major depressive disorder with fall/winter seasonal pattern, as if patient were in a quasi-hibernation state r1c6c7c8
        • Opposite symptom profile is typical of spring/summer pattern (ie, patient sleeps less, eats less, loses weight) c9c10c11
        • Seasonal specifier does not apply to those situations in which the pattern is better explained by seasonally linked psychosocial stressors (eg, seasonal unemployment or school schedule)
      • Fatigue c12
      • Loss of interest in sexual activity c13
      • Headache or other pain c14c15
      • Concentration difficulty, indecisiveness, or memory impairment c16c17c18
      • Nausea c19
      • Change in bowel habits (constipation or diarrhea) c20c21c22
      • Craving for carbohydrates c23
      • Difficulty with morning awakening c24
    • Additional symptoms that may be present include:
      • Anxiety or worry c25c26
      • Suicidal ideation or thoughts of death c27
      • Feelings of guilt or worthlessness c28c29
      • Preoccupation with physical discomfort c30
      • Symptoms of psychosis (eg, delusions, hallucinations) c31c32c33

    Physical examination

    • Physical findings can include:
      • Weight changes or, in the case of children, not meeting expected weight gain c34
      • Signs of self-abuse (eg, scars, bruises, lacerations) c35c36c37c38
    • Psychiatric signs
      • Any of the following types of abnormal affect:
        • Blunted (flat) or constricted c39c40
        • Irritable c41
        • Labile c42
        • Inappropriate c43
      • Abnormal psychomotor activity is often seen
        • Psychomotor retardation c44
          • Indicated by slowed or absent spontaneous movement c45
          • Typical of the fall/winter pattern
        • Psychomotor agitation c46
          • Patient appears restless

    Causes and Risk Factors

    Causes

    • Condition is thought to be caused by combination of factors that likely include: r7
      • Circadian phase delay or advance, probably affecting depressive symptoms via changes in melatonin levels c47
      • Self prescribed medications that can be ineffective and/or cause side effects (such as melatonin) r8c48
      • Abnormal retinal sensitivity to light c49
      • Neurotransmitter dysfunction c50
      • Genetic variations affecting circadian rhythms c51
      • Abnormal serotonin levels c52

    Risk factors and/or associations

    Age
    • Higher risk from age 18 to 30 years r9c53
    • Younger people are at higher risk for winter depressive episodes than older people r1c54
    Sex
    • More common in women, with reported female to male ratio of 4 to 1 r7c55c56
    Genetics
    • Variants of the melanopsin gene (OPN4) could predispose some individuals r10c57
    • Having a first-degree relative who has experienced depressive symptoms increases the risk r9c58
    Other risk factors/associations
    • Residence at mid to high latitudes r11c59
    • Severe visual impairment r12c60
    • Chronic tinnitus r13c61

    Diagnostic Procedures

    Primary diagnostic tools

    • History and physical examination r7c62
    • Depression scales, inventories, and questionnaires r7
      • Hamilton Depression Rating Scale and Beck Depression Inventory are commonly used c63c64

    Laboratory

    • Laboratory tests play no role in diagnosing the condition, but are used to rule out common conditions, such as substance abuse (urine screen for drugs of abuse) and hypothyroidism (TSH and thyroxine levels) r1c65

    Other diagnostic tools

    • Hamilton Depression Rating Scale r14c66
      • Recurrent major depressive disorder with a seasonal pattern is designated seasonal affective disorder on this scale
      • Completed by examiner while observing patient
    • Beck Depression Inventory r15c67
      • Questionnaire answered by patient
      • Available in standard 21-question format, or as an abridged 7-question format appropriate for screening in the primary care setting
      • Elucidates severity, intensity, and depth of typical major depression symptoms

    Differential Diagnosis

    Most common

    • Hypothyroidism c68d1
      • Disorder characterized by inadequate synthesis and secretion of thyroid hormones r16
      • Similarities r16
        • Patient has low energy or fatigue and may have depressed mood
        • Hypophagia
        • Weight gain
        • Hypersomnia
      • Differences
        • TSH level is elevated r16
        • Free thyroid hormones (especially free thyroxine) are decreased r16
        • Usually there is no seasonal pattern or predictable annual occurrence, although seasonal course with summertime improvement has been seen with hypothyroidism r7
      • Definitive diagnosis is made via thyroid panel (TSH and thyroxine levels) r16
    • Major depressive disorder without a seasonal pattern r1c69d2
      • Major depressive disorder is defined by following symptoms, least 5 of which are present nearly every day during the same 2-week period:
        • Depressed mood most of the day
        • Markedly reduced interest or pleasure in all or nearly all activities
        • Change in appetite or weight (increase or decrease)
        • Sleep disturbance (insomnia or hypersomnia)
        • Psychomotor agitation or retardation (observable by others)
        • Fatigue or lack of energy
        • Reduced ability to think or concentrate; indecisiveness
        • Feelings of worthlessness or excessive, inappropriate guilt
        • Recurrent thoughts of death or suicidal ideation or attempt
      • Symptoms represent a change from usual functioning and cause clinically significant distress or impairment in social, work, or other areas
      • At least 1 of the symptoms is depressed mood or loss of interest or pleasure
      • Similar to recurrent major depressive disorder with a seasonal pattern in the history of major depressive episodes defined by presence of 5 or more of the same features; different in that there is no seasonal pattern or predictable annual occurrence
      • Diagnosis is entirely clinical, based mostly on history
    • Bipolar disorder r1c70d3
      • Mood disorder characterized by cycling between depressive and manic or hypomanic episodes
        • Bipolar I disorder
          • Criteria have been met for at least 1 manic episode in patient's lifetime
          • Manic episode may have been preceded by or followed by hypomanic or major depressive episodes
          • Occurrence of the manic and major depressive episode(s) cannot be better explained by schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or other schizophrenia spectrum or psychotic disorders
        • Bipolar II disorder
          • Criteria have been met for at least 1 hypomanic episode and at least 1 major depressive episode in patient's lifetime
          • No history of manic episodes
          • Occurrence of the hypomanic and major depressive episode(s) cannot be better explained by schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or other schizophrenia spectrum or psychotic disorders
          • Depressive symptoms or unpredictability caused by frequent alternation between periods of hypomania and depression causes clinically significant distress or impairment in social, occupational, or other important areas of functioning
      • Similar to recurrent major depressive disorder with a seasonal pattern in that patient meets criteria for at least 1 major depressive episode; different in that there is no seasonal pattern or predictable annual occurrence
      • Diagnosis is entirely clinical, based mostly on history
    • Cyclothymic disorder r17c71
      • Characterized by mood cycling that does not meet diagnostic criteria for major depressive disorder or bipolar disorders I or II
      • Similar to recurrent major depressive disorder with a seasonal pattern in that major depressive disorder symptoms come and go; different in that there is no seasonal pattern or predictable annual occurrence
      • Diagnosis is entirely clinical, based mostly on history
    • Substance-related disorder r18c72
      • Condition resulting from misuse of alcohol or drugs
      • Similar to recurrent major depressive disorder with a seasonal pattern in that both can manifest with changes in mood, social and occupational impairment, and other similar symptoms
      • Different in that use of a substance can be identified and established via admission by patient, observation of others, or medical tests (eg, urine screening for drugs of abuse)
      • Definitive diagnosis is based on history, physical examination, and appropriate substance abuse work-up, which includes:
        • Questioning regarding quantity of alcohol consumed and/or types and quantities of drugs used
        • Assays on urine samples for alcohol, opioids, benzodiazepines, cocaine/stimulants, cannabis, and other drugs of abuse
      • After a positive screening test result, conversation with patient is focused on the substance use to elicit DSM-5 symptoms of a substance use disorder, which include:
        • Tolerance
        • Withdrawal
        • Using more drugs than intended
        • Failed efforts to cut down or quit
        • Spending a lot of time related to use
        • Craving
        • Failure to fulfill important life roles
        • Giving up important life activities
        • Use in hazardous situations
        • Continued use in spite of either negative physical/psychological problems, or social/interpersonal consequences

    Treatment

    Goals

    • Abatement of depression symptoms
    • Recognition of any suicidal or homicidal potential r6
    • Identification and management of medical complications of depression, such as malnutrition and nonadherence to medical treatment
    • Return of patient to normal social/occupational activities and function
    • Prevention of recurrent episodes

    Disposition

    Admission criteria

    • Admission to an inpatient psychiatric unit is warranted when patient cannot care for self or is a danger to self or others, owing to either of the following: r19
      • Suicidal or homicidal ideation
        • Previous suicide attempts or violence can strengthen the case for admission when case is equivocal
      • Presence of psychotic symptoms

    Recommendations for specialist referral

    • Consult psychiatrist for any of the following:
      • Suicidal or homicidal ideation or attempts
      • Alcohol or drug dependence or misuse
      • Comorbid psychosis, suspected bipolar disorder, or personality or developmental disorders
      • Dementia, delirium, or confusion
      • Lack of response to light therapy

    Treatment Options

    Principal treatment modalities consist of the following:

    • Light therapy (also called bright light therapy) r20
      • Primary treatment modality
    • Cognitive behavioral therapy r21
      • Efficacy is comparable with light therapy
      • Acceptable treatment option; may have prophylactic benefits for subsequent years
    • Second generation antidepressant drugs, especially selective serotonergic reuptake inhibitors r22
      • Second line treatment
      • Some evidence, albeit limited in quality and quantity, shows effectiveness for fluoxetine and sertraline r22
        • Light therapy and fluoxetine are comparably effective and well tolerated; other clinical factors, such as patient preference, might guide the selection of treatment r22

    Drug therapy

    • Selective serotonin reuptake inhibitors r9c73
      • Bupropion (extended-release bupropion hydrochloride tablets; e.g., Wellbutrin XL): r23c74
        • Bupropion Hydrochloride Oral tablet, extended release 24 hour [Depression/Mood Disorders]; Adults: Initiate in the autumn with 150 mg PO once daily in the AM; titrate after 7 days to target dose of 300 mg PO once daily in the AM. Continue through winter, then taper and discontinue in early spring. Individualize regimen to patient's historical pattern of SAD episodes. For those receiving 300 mg/day, taper to 150 mg/day prior to discontinuation. Total daily doses above 300 mg/day were not evaluated in SAD clinical trials.
      • Fluoxetine r9c75
        • Fluoxetine Hydrochloride Oral tablet [Depression/Mood Disorders]; Adults: 20 mg PO once daily, initially. May increase dose after several weeks if insufficient clinical improvement is observed. May divide doses of 20 mg/day or more in 2 doses. Max: 80 mg/day.
      • Sertraline r9c76
        • Sertraline Hydrochloride Oral tablet; Adults: 50 mg PO once daily, initially. May increase dose by 25 to 50 mg/day at intervals of at least 1 week as needed. Usual dose: 50 to 200 mg/day. Max: 200 mg/day.

    Nondrug and supportive care

    The following nondrug therapies have been used to treat this condition: r7

    • Light therapy
    • Cognitive behavioral therapy
    Procedures
    Light therapy r20c77
    General explanation
    • Just after awakening, patient is positioned next to a special light-emitting device to receive 5000 lux hours per day
      • Usually, this is achieved using a 10,000 lux device for 30 minutes
      • Patient can engage in any activity while receiving treatment, but must keep eyes within the needed distance from the light source as indicated by the instructions for the particular device
      • Abatement of major depressive symptoms within a few weeks (usually within 2 weeks) indicates that treatment is effective
    Indication
    • Recurrent major depressive disorder with fall/winter seasonal pattern
    Contraindications
    • Patients with bipolar disorder receiving light therapy are at greater risk of developing manic or hypomanic episodes; however, light therapy is not a contraindication for these patients
    Psychological therapy can include counseling or mindfulness based cognitive therapy r24c78
    General explanation
    • Mindfulness based cognitive therapy is highly structured, focused, short-term, and therapist-patient collaborative; consists of the following principal components:
      • Functional analysis
        • Patients are taught to recognize irrational thoughts and assumptions, and irrational connections between assumptions, thoughts, and behaviors that underlie, exacerbate, and perpetuate depression
        • Patients are taught to track, stop, and redirect thoughts with the aim of different behaviors, thereby changing the emotional response that underlies the depression
      • Skills training
        • Patients are taught to unlearn behaviors that underlie and exacerbate depression and to learn new behaviors via a variety of techniques, including:
          • Exposure and desensitization
          • Learning exercises and home assignments
          • Adoption of pleasurable activities during the problematic time of the year
    • Generally, cognitive behavioral therapy shows results in a few weeks or a few months; resolution of depressive symptoms within that time period suggests the treatment has been effective
    Indication
    • Recurrent major depressive disorder with seasonal pattern in any of the following scenarios:
      • Light therapy is inadequate in abating symptoms
      • Patient refuses light therapy or is not adherent
      • Light therapy is not appropriate, owing to nonwinter seasonality of the recurrent depression
      • Patient is eager to begin cognitive behavioral therapy alongside light therapy

    Comorbidities

    • Major psychiatric disorders c79
      • Bipolar disorders I and II c80c81d3
        • Typically require additional treatment alongside light therapy or cognitive behavioral therapy
      • Cyclothymic disorders c82
        • Patients can have a seasonal element (treatable with light therapy) plus depressive features throughout the year, requiring continuous psychotherapy or medication
      • Anxiety disorders, including obsessive-compulsive disorder c83c84
        • May alter the plan for any cognitive behavioral therapy, requiring it to be longer or more intense
      • Eating disorders c85
        • Can exacerbate or hide the changes in appetite of recurrent major depressive disorder with a seasonal pattern, thereby making the diagnosis more challenging
      • Depression during pregnancy or the postpartum period c86c87d4
        • Symptoms of depression are common in the postpartum period, and this period may correlate with the season during which a patient with recurrent depressive disorder suffers symptoms d5
        • Cognitive behavioral therapy may be the best first option; effects of light therapy during pregnancy are largely unknown
        • Selective serotonin reuptake inhibitors entail a treatment dilemma: some data show neurobehavioral and long-term cognitive problems among children of women who were treated with those drugs during pregnancy, but untreated maternal depression also carries serious risks for both mother and child
    • Personality and developmental disorders c88c89d6
      • May alter the plan for any cognitive behavioral therapy, requiring it to be longer or more intense
      • In the case of certain personality disorders, such as borderline personality disorder, presence as a comorbid condition may require dialectic behavioral therapy d6
        • Dialectic behavioral therapy is a modified form of cognitive behavioral therapy that is focused on changing behaviors that are particularly common in borderline personality disorder (eg, suicidal ideation, self-harm, substance misuse)

    Monitoring

    • Schedule patients for regular follow-up and use a standardized scale to measure response to therapy, as this has been shown to improve outcomes r25
      • Hamilton Depression Rating Scale or Beck Depression Inventory are useful for monitoring, as are other standardized depression scales (eg, the Patient Health Questionnaire [PHQ-9])

    Complications and Prognosis

    Complications

    • Suicide r6c90
    • Impaired social and occupational performance c91c92
    • Disrupted interpersonal relations c93
    • Substance misuse c94

    Prognosis

    • Response to light therapy within 2 weeks of initiation predicts a favorable outcome r14
    • A meta-analysis supported the efficacy of light therapy in both seasonal and nonseasonal depression, and reported effect sizes that were equivalent to those in most trials of antidepressants r26
    • Improvement of atypical symptoms (eg, hypersomnolence, increased appetite, carbohydrate craving) after 1 hour of light therapy correlates with improvement of disorder after 2 weeks of therapy r14

    Screening and Prevention

    Screening c95

    Prevention

    • Consider initiating light therapy in early fall for patients with fall/winter seasonality r7c96
      • Evidence supporting light therapy for prevention is limited owing to small studies and methodologic flaws; requires discussion with patient r3
    • Bupropion is the only medication shown to be effective in preventing recurrence of seasonal affective disorder, but adverse effects, such as headaches, nausea, and insomnia, are commonly observed r9
    • Lifestyle adjustments are recommended by some experts, including: r7c97
      • Exercising more often c98
      • Increasing light in the home c99
      • Practicing relaxation and stress management techniques c100c101
      • Spending more time outside c102
      • Visiting sunnier, warmer climates c103
    American Psychiatric Association: Depressive disorders. In: Diagnostic and Statistical Manual of Mental Disorders. 5th ed Text Revision (DSM-5 TR). American Psychiatric Association; 2022:177-214Danilenko KV et al: Seasonal affective disorder. Handb Clin Neurol. 106:279-89, 201222608628Nussbaumer-Streit B et al: Light therapy for preventing seasonal affective disorder. Cochrane Database Syst Rev. 3:CD011269, 201930883670Meesters Y et al: Seasonal affective disorder, winter type: current insights and treatment options. Psychol Res Behav Manag. 9:317-27, 201627942239Arendt J: Biological rhythms during residence in polar regions. Chronobiol Int. 29(4):379-94, 201222497433American Psychiatric Association. Seasonal affective disorder. American Psychiatric Association website. Reviewed October 2020. Accessed October 22, 2022. https://psychiatry.org/patients-families/seasonal-affective-disorderhttps://psychiatry.org/patients-families/seasonal-affective-disorderKurlansik SL et al: Seasonal affective disorder. Am Fam Physician. 86(11):1037-41, 201223198671Nussbaumer-Streit B et al: Melatonin and agomelatine for preventing seasonal affective disorder. Cochrane Database Syst Rev. 6:CD011271, 201931206585Galima SV et al: Seasonal affective disorder: common questions and answers. Am Fam Physician. 102(11):668-72, 202033252911Roecklein KA et al: A missense variant (P10L) of the melanopsin (OPN4) gene in seasonal affective disorder. J Affect Disord. 114(1-3):279-85, 200918804284Øverland S et al: Seasonality and symptoms of depression: A systematic review of the literature. Epidemiol Psychiatr Sci. 29:e31, 201931006406Madsen HØ et al: High prevalence of seasonal affective disorder among persons with severe visual impairment. Br J Psychiatry. ePub, 201526338990Kim YH: Seasonal affective disorder in patients with chronic tinnitus. Laryngoscope. ePub, 201526154998Sher L et al: Early response to light therapy partially predicts long-term antidepressant effects in patients with seasonal affective disorder. J Psychiatry Neurosci. 26(4):336-8, 200111590974Schneibel R et al: Sensitivity to detect change and the correlation of clinical factors with the Hamilton Depression Rating Scale and the Beck Depression Inventory in depressed inpatients. Psychiatry Res. 198(1):62-7, 201222445070Gaitonde D et al: Hypothyroidism: an update. Am Fam Physician. 86(3):244-51, 201222962987Perugi G et al: Cyclothymia reloaded: a reappraisal of the most misconceived affective disorder. J Affect Disord. 183:119-33, 201526005206Merrill JO et al: Addiction disorders. Med Clin North Am. 98(5):1097-122, 201425134875Schoepf D et al: Comorbidity and its relevance on general hospital-based mortality in major depressive disorder: a naturalistic 12-year follow-up in general hospital admissions. J Psychiatr Res. 52:28-35, 201424513499May IC: Light therapy for preventing seasonal affective disorder: summary of a Cochrane review. Explore (NY). 16(2):133-4, 202032111489Rohan KJ et al: Randomized trial of cognitive-behavioral therapy versus light therapy for seasonal affective disorder: acute outcomes. Am J Psychiatry. 172(9):862-9, 201525859764Nussbaumer-Streit B et al: Second-generation antidepressants for treatment of seasonal affective disorder. Cochrane Database Syst Rev. 3:CD008591, 202133661528Cools O et al: Pharmacotherapy and nutritional supplements for seasonal affective disorders: a systematic review. Expert Opin Pharmacother. 19(11):1221-33, 201830048159Forneris CA et al: Psychological therapies for preventing seasonal affective disorder. Cochrane Database Syst Rev. 5:CD011270, 201931124141Guo T et al: Measurement-based care versus standard care for major depression: a randomized controlled trial with blind raters. Am J Psychiatry. 172(10):1004-13, 201526315978Golden RN et al: The efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidence. Am J Psychiatry. 162(4):656-62, 200515800134
    Small Elsevier Logo

    Cookies are used by this site. To decline or learn more, visit our cookie notice.


    Copyright © 2025 Elsevier, its licensors, and contributors. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

    Small Elsevier Logo
    RELX Group