Major Depressive Disorder

Key considerations: Suicidal ideation with plan, Bipolar disorder (screen before starting antidepressant), Medical causes: hypothyroidism, B12 deficiency, anemia, malignancy

Cannot miss

Suicidal ideation with plan
Bipolar disorder (screen before starting antidepressant)
Medical causes: hypothyroidism, B12 deficiency, anemia, malignancy
Postpartum depression

Likely diagnoses

Major depressive disorder
Persistent depressive disorder (dysthymia)
Adjustment disorder with depressed mood
Seasonal affective disorder

Red flags

Suicidal ideation (especially with plan or intent)
Psychotic features (hallucinations, delusions)
History of mania/hypomania (→ bipolar)
Rapid weight loss
Functional decline (unable to work, care for self)

Workup

history: PHQ-9 screening; Duration of symptoms (≥2 weeks for MDD diagnosis); Prior episodes and treatment response; Substance use; Family psychiatric history; Mania screen (MDQ or ask directly); exam: Mental status exam; Thyroid exam; General appearance (hygiene, psychomotor changes); labs: TSH; CBC (anemia); B12 (if risk factors); BMP; Urine drug screen if substance use suspected; imaging: ; bedside: PHQ-9; C-SSRS if SI present

Management

immediate: Assess suicide risk; Safety planning if SI present; general: Mild: psychotherapy alone (CBT, IPT) is first-line; Moderate-severe: pharmacotherapy + psychotherapy; First-line medications: SSRIs (sertraline, escitalopram) or SNRIs (venlafaxine, duloxetine); Allow 4-6 weeks for medication effect at adequate dose; specific: diagnosis: First Episode — Mild; steps: Psychotherapy referral (CBT most evidence); Lifestyle: exercise 150 min/week, sleep hygiene, social engagement; Follow-up in 2-4 weeks; diagnosis: First Episode — Moderate to Severe; steps: SSRI: sertraline 50mg or escitalopram 10mg; Titrate at 2-4 week intervals; Psychotherapy concurrent; Follow-up in 2 weeks initially; diagnosis: Treatment-Resistant; steps: Augment with bupropion, aripiprazole, or lithium; Switch SSRI class or to SNRI; Consider esketamine (Spravato) if 2+ adequate trials failed; Psychiatry referral

Disposition

admit: Active suicidal ideation with plan/intent; Psychotic depression; Unable to care for self; discharge: Outpatient management with follow-up in 1-2 weeks when starting medication; Safety plan if any SI; consults: Psychiatry for treatment-resistant depression, psychotic features, or complex comorbidity

Clinical pearls

Screen for bipolar BEFORE starting antidepressant — SSRI monotherapy can precipitate mania
Black box warning: monitor for suicidality in patients <25 during first weeks of antidepressant therapy
Exercise has evidence comparable to medication for mild-moderate depression
If SSRI causes sexual dysfunction: consider switching to bupropion, mirtazapine, or vortioxetine

Source and review

APA Practice Guidelines for MDD 2023; NICE Depression Guidelines 2022. Last reviewed: 2024-11-01