Major Depressive Disorder (MDD): High-Yield USMLE Review

Major depressive disorder (MDD) is a syndromic diagnosis defined by a cluster of depressive symptoms present for at least 2 weeks with functional impairment. It is one of the most heavily tested psychiatric conditions on the USMLE because of its diagnostic criteria, its first-line management with SSRIs, and the essential pre-treatment step of screening for bipolar disorder.

Presentation

• Depressed mood (feeling like a 'failure,' crying) — at least one of depressed mood or anhedonia must be present
• Anhedonia — loss of interest or pleasure in activities
• Sleep disturbance, classically insomnia with early morning awakening (a melancholic feature)
• Loss of energy or fatigue
• Difficulty concentrating
• Appetite or weight change (e.g., decreased appetite with weight loss)
• Psychomotor agitation or retardation (observable by others)
• Excessive guilt or feelings of worthlessness (feeling of letting everyone down)
• Suicidal ideation — may be passive ('I wish I didn't wake up' / 'better off without me')
• Symptoms persist for ≥2 weeks and cause functional impairment

Diagnosis

• Clinical diagnosis by DSM-5 criteria: ≥5 of 9 symptoms present for ≥2 weeks, at least one of which must be depressed mood or anhedonia. Use SIG E CAPS to recall the 9 symptoms: Sleep changes, loss of Interest (anhedonia), Guilt/worthlessness, loss of Energy/fatigue, Concentration difficulty, Appetite/weight change, Psychomotor agitation/retardation, Suicidal ideation, plus depressed mood
• Symptoms must cause clinically significant functional impairment and not be attributable to a substance or another medical condition
• Always take a careful mood history (including collateral) for prior manic or hypomanic episodes and family history of bipolar disorder before diagnosing MDD
• Suicide risk assessment in every patient: ask about ideation, plan, intent/means, and protective factors
• Rule out organic/medical causes before attributing symptoms to primary depression — e.g., TSH and free T4 should be reflexive, since hypothyroidism can mimic depression (weight gain, cold intolerance, bradycardia, delayed reflex relaxation)

Management

• Mild-to-moderate depression: psychotherapy (CBT or interpersonal therapy) alone may be sufficient; SSRIs are first-line pharmacotherapy
• Moderate-to-severe depression: combination of psychotherapy plus an SSRI is most effective
• Severe depression with psychosis or suicidality: hospitalize for safety if needed; ECT is highly effective for severe, treatment-resistant, or psychotic depression
• Counsel patients that antidepressants take 2–4 weeks for full effect, must not be stopped abruptly, and carry a black box warning for suicidal ideation in patients under 25 — monitor closely early in treatment
• Ensure an adequate trial (therapeutic dose for 4–6 weeks) before switching agents or labeling as treatment-resistant

High-yield

• SIG E CAPS — MDD requires ≥5 of 9 symptoms for ≥2 weeks, at least one being depressed mood or anhedonia
• The 9 symptoms: Sleep, Interest (anhedonia), Guilt, Energy, Concentration, Appetite, Psychomotor changes, Suicidality, and depressed mood
• SSRIs (e.g., sertraline, escitalopram) are first-line for depression; know side effects: sexual dysfunction, GI upset, and serotonin syndrome
• Always ask about mania before starting an antidepressant — antidepressant monotherapy can trigger mania in bipolar disorder
• Prior suicide attempt is the strongest predictor of completed suicide; other risk factors include male sex, older age, living alone, substance abuse, hopelessness, and access to lethal means
• SSRI + MAOI causes serotonin syndrome — wait 2 weeks to switch (5 weeks for fluoxetine due to its long half-life); triptans and tramadol also raise the risk
• ECT is highly effective for severe, psychotic, or treatment-resistant depression

Pitfalls

• Starting an antidepressant without screening for prior hypomanic/manic episodes — this risks precipitating mania in an undiagnosed bipolar patient; family history of bipolar disorder is a Bayesian prior, not a verdict
• Forgetting the quantitative threshold — a diagnosis of MDD requires ≥5 of the 9 symptoms, not just any depressive symptom; fewer than 5 (or duration <2 weeks) does not meet criteria
• False medical-psychiatric dichotomy: labeling a presentation as depression without ruling out medical mimics — vegetative features inconsistent with depression (weight gain rather than loss, bradycardia rather than tachycardia) point to hypothyroidism and demand medical workup
• The recurrence reflex: assuming a new episode in a patient with prior MDD is 'the depression coming back' without reconfirming the diagnosis, screening for new medical contributors, substance use, or an intervening hypomanic episode
• Premature labeling of treatment resistance — declaring non-response before an adequate dose and 4–6-week duration; a 3-week trial is undertreatment, not failure