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For further information, see CMDT Part 25-12: Mood Disorders (Depression & Mania)

Key Features

Essentials of Diagnosis

  • In most depressions

    • Mood varies from mild sadness to intense guilt, worthlessness, and hopelessness

    • Difficulty in thinking and concentration, with rumination and indecision

    • Loss of interest, with diminished involvement in activities

    • Somatic complaints

    • Disrupted, reduced, or excessive sleep

    • Loss of energy, appetite, and sex drive

  • In some severe depressions

    • Psychomotor disturbance: retardation or agitation

    • Delusions of a somatic or persecutory nature

    • Withdrawal from activities

    • Physical symptoms of major severity (eg, anorexia, insomnia, reduced sexual drive, weight loss)

    • Suicidal ideation

General Considerations

  • Sadness and grief are normal responses to loss; depression is not

  • Unlike grief, depression is marked by a disturbance of self-esteem, with a sense of guilt and worthlessness

  • Persistent depressive disorder (dysthymia) is a chronic depressive disturbance with symptoms generally milder than in a major depressive episode


  • Up to 30% of primary care patients have depressive symptoms

  • The COVID-19 pandemic has increased the risk of depression

    • One meta-analysis of studies of community-based prevalance of depression found a seven-fold increase in depression in some heavily impacted communities in Europe and Asia

    • US national surveys show a three-fold increase in the prevalence of depressive symptoms, with risk factors including lower income, < $5000 in savings, and exposure to stressors

Clinical Findings

Symptoms and Signs

  • Anhedonia

  • Withdrawal from activities

  • Feelings of guilt and worthlessness

  • Poor concentration and cognitive dysfunction

  • Anxiety

  • Chronic fatigue and somatic complaints

  • Loss of sexual drive

  • Thoughts of death

  • Diurnal variation with improvement as the day progresses

  • Vegetative signs

    • Insomnia

    • Anorexia

    • Constipation

  • Occasionally, severe agitation and psychotic ideation

  • Atypical features

    • Hypersomnia

    • Overeating

    • Lethargy

    • Mood reactivity

Differential Diagnosis

  • Depression may be a part of any illness, either reactively or as a secondary symptom

  • Schizophrenia

  • Partial complex seizures

  • Organic brain syndromes

  • Panic disorders

  • Anxiety disorders

  • Thyroid dysfunction and other endocrinopathies

  • Malignancies

  • Strokes, particularly dominant hemisphere lesions

  • Mood disorders

    • Bipolar disorder or cyclothymia

    • Adjustment disorder with depressed mood

    • Psychotic major depression

    • Major depression with atypical features

    • Melancholic major depression

    • Persistent depressive disorder (dysthymia)

    • Premenstrual dysphoric disorder

    • Major depression with peripartum onset: occurs during pregnancy or starts up to 4 weeks after delivery

    • Drug-induced depression

    • Seasonal affective disorder

      • Carbohydrate craving, lethargy, hyperphagia, hypersomnia


Laboratory Tests

  • Complete blood count

  • Serum thyroid-stimulating hormone

  • Serum folate

  • Toxicology screen may be indicated



  • See Table 25–6 and Figure 25–2

  • SSRIs, SNRIs, and atypical antidepressants

    • Generally lack anticholinergic or cardiovascular side effects

    • Most are activating and should be given in the morning

    • Some patients may experience sedation with paroxetine, ...

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