DSM-5 Diagnostic Criteria
MDD: ≥5 of 9 SIGECAPS symptoms for ≥2 weeks (must include depressed mood or anhedonia): Sleep disturbance (insomnia or hypersomnia), Interest loss (anhedonia), Guilt/worthlessness, Energy decrease (fatigue), Concentration difficulty, Appetite/weight change (usually decreased), Psychomotor agitation or retardation, Suicidal ideation. Symptoms cause significant distress or functional impairment; not explained by substances, medical condition, or grief. Specifiers: with anxious distress, with melancholic features, with psychotic features (command hallucinations — emergency, needs antipsychotic + antidepressant), with seasonal pattern. PHQ-9 screening: 9-item validated tool scoring 0–27; score ≥10 = moderate depression requiring treatment. Screen annually in primary care. Distinguish from: Adjustment disorder (stressor-related, <2 months, symptoms don't meet full MDD criteria), Bipolar depression (prior manic/hypomanic episode), Persistent depressive disorder (dysthymia — chronic low-grade depression ≥2 years, fewer symptoms than MDD).
Antidepressant Pharmacology
First-line: SSRIs (selective serotonin reuptake inhibitors): sertraline, escitalopram, fluoxetine, paroxetine, citalopram. Mechanism: block SERT → increase synaptic serotonin. Side effects: GI upset (first 1–2 weeks), sexual dysfunction (most significant long-term issue), insomnia (especially fluoxetine — most activating), weight gain, discontinuation syndrome (especially paroxetine — short half-life), QTc prolongation (citalopram at high doses). Fluoxetine: longest half-life (active metabolite 1–2 weeks) — safest in overdose, best for non-adherent patients. SNRIs (serotonin-norepinephrine reuptake inhibitors): venlafaxine, duloxetine, desvenlafaxine. Advantages over SSRI: effective for comorbid chronic pain (duloxetine for diabetic neuropathy, fibromyalgia), anxiety, stress incontinence. Side effect: dose-dependent hypertension (norepinephrine). Bupropion (NDRI — norepinephrine-dopamine reuptake inhibitor): first-line for MDD + smoking cessation. Activating (good for fatigue/hypersomnia). Lowers seizure threshold — contraindicated in eating disorders (electrolyte disturbances → seizure risk), seizure disorder. No sexual dysfunction, may cause weight loss. Mirtazapine: antagonizes alpha-2 receptors + H1 + 5-HT2/3. Sedating (good for insomnia), increases appetite/weight. Used in elderly patients with insomnia + weight loss. TCAs (amitriptyline, nortriptyline): older class; significant anticholinergic toxicity; dangerous in overdose (QRS widening, seizures — treat with sodium bicarbonate). MAOIs: selegiline, phenelzine, tranylcypromine. Most dangerous class — tyramine interaction (hypertensive crisis from aged cheese, wine, cured meats). Reserve for treatment-resistant depression.
Treatment Timeline and ECT
Response timeline: therapeutic effect takes 2–4 weeks. Full effect may take 6–8 weeks. If no response at 4–6 weeks: increase dose, then switch drug class. Minimum treatment duration: 6–12 months after first MDD episode; ≥2 years or indefinite after recurrent episodes. Electroconvulsive therapy (ECT): most effective treatment for MDD — response rates 60–85% vs 40–60% for medications. Indications: treatment-resistant MDD (failed ≥2 antidepressant trials), psychotic depression, severe suicidality (fastest response), MDD in pregnancy (safe, no teratogenicity), catatonia, severe melancholic depression with refusal to eat. Mechanism: unknown — seizure activity modifies neurotransmitter systems. Short-term side effects: transient memory loss (anterograde > retrograde) and confusion. No absolute contraindications — high anesthesia risk is relative. Ketamine/esketamine (Spravato, intranasal): rapid-acting antidepressant (hours) for treatment-resistant depression or acute suicidality; approved for TRD.