Behavioral Health

Major depressive disorder: outpatient diagnosis and treatment selection

Clinical Overview and When to Suspect Major Depressive Disorder

— 12-month US prevalence ~8%; lifetime ~20% in women, ~12% in men

— Peak onset late teens to mid-20s; second peak in older adults with medical comorbidity

— Leading cause of disability-adjusted life years among adults <50 in the US

— Vague somatic complaints: fatigue, insomnia/hypersomnia, weight change, low libido, chronic pain, GI distress

— Frequent no-shows, medication non-adherence, or unexplained worsening of chronic disease control (HbA1c, BP, asthma)

— Postpartum mood change, post-MI/stroke functional decline, new substance use

— Adolescents presenting with irritability or school failure rather than sadness

— Use PHQ-2 as initial screen; if positive (≥3), proceed to PHQ-9

— PHQ-9 ≥10 has ~88% sensitivity and specificity for MDD

Definition: Major depressive disorder (MDD) is a recurrent, episodic mood disorder defined by ≥2 weeks of depressed mood and/or anhedonia plus associated neurovegetative, cognitive, and psychomotor symptoms causing functional impairment.

Epidemiology and burden:

When to suspect in the outpatient clinic:

USPSTF screening (2023): Screen all adults including pregnant and postpartum patients for depression when systems are in place for accurate diagnosis, treatment, and follow-up. Screen adolescents 12–18. Insufficient evidence for children <12.

Step 3 management: A positive PHQ-2 in a primary care visit is not optional — you must complete a PHQ-9, assess suicidality (item 9 + direct questioning), and document a plan in the same encounter. Deferring to "next visit" is a wrong-answer pattern.

Board pearl: Anhedonia or depressed mood is required for MDD diagnosis — without one of these two cardinal symptoms, you cannot diagnose MDD regardless of how many other criteria are met. This is the single most tested gating concept on Step 3 mood-disorder questions.

Presentation Patterns and Key History

— Sleep disturbance (insomnia or hypersomnia)

— Interest loss (anhedonia)

— Guilt or worthlessness (excessive, inappropriate)

— Energy loss/fatigue

— Concentration impairment or indecisiveness

— Appetite or weight change (>5% body weight in a month)

— Psychomotor agitation or retardation (observable by others)

— Suicidal ideation, plan, or attempt

— Depressed mood

— With anxious distress — most common; predicts worse outcomes

— With melancholic features — early-morning awakening, diurnal mood variation (worse AM), profound anhedonia, weight loss, excessive guilt

— With atypical features — mood reactivity, hypersomnia, hyperphagia, leaden paralysis, rejection sensitivity

— With psychotic features — mood-congruent delusions (guilt, poverty, nihilism); requires antipsychotic + antidepressant or ECT

— With peripartum onset — during pregnancy or within 4 weeks postpartum (DSM); clinically extended to 12 months

— With seasonal pattern — fall/winter onset, full remission in spring

— Prior episodes, prior trials (dose, duration, response, side effects)

— Manic/hypomanic symptoms — must screen to rule out bipolar before starting an antidepressant

— Substance use, especially alcohol, cannabis, stimulants

— Trauma, recent losses, relationship/financial stressors

— Family history of mood disorder, suicide, response to specific agents

DSM-5 SIGECAPS criteria — ≥5 of 9 symptoms for ≥2 weeks, most of the day nearly every day, with at least one being depressed mood or anhedonia:

Required: Significant distress or impairment; not attributable to substance/medication or another medical condition.

MDD specifiers to recognize on stems:

History essentials to elicit:

Key distinction: Bereavement vs MDD — grief is wave-like, preserves self-esteem, and centers on the deceased; MDD is pervasive, with worthlessness and anhedonia. DSM-5 removed the bereavement exclusion — you can diagnose MDD within 2 weeks of a loss if criteria are met.

Physical Exam Findings and Mental Status Assessment

— Poor grooming, weight loss or gain, downcast gaze

— Psychomotor retardation: slow movements, delayed responses, paucity of gesture

— Psychomotor agitation: hand-wringing, pacing, hair-pulling

— Thyroid: goiter, dry skin, delayed reflex relaxation (hypothyroid); tremor, lid lag (hyperthyroid)

— Neurologic: focal deficits, parkinsonism (subcortical depression), cognitive slowing suggesting pseudodementia vs dementia

— Skin: pallor (anemia), hyperpigmentation (Addison), striae/moon facies (Cushing)

— Cardiopulmonary in post-MI or HF patients (depression doubles cardiac mortality)

— Appearance/Behavior: disheveled, poor eye contact, tearful

— Speech: soft, slow, decreased latency response, low volume

— Mood/Affect: "depressed," "empty"; affect constricted, dysphoric, congruent

— Thought process: linear but slowed; ruminative

— Thought content: hopelessness, worthlessness, guilt; assess suicidal ideation, intent, plan, access to means, homicidal ideation; mood-congruent delusions if psychotic features

— Perception: hallucinations (rare; auditory derogatory in psychotic depression)

— Cognition: MMSE/MoCA if pseudodementia suspected — typically poor effort with "I don't know" answers (vs confabulation in dementia)

— Insight/Judgment: often impaired

General appearance:

Vital signs: Usually normal; check for tachycardia (anxiety overlap, stimulant use, hyperthyroidism), bradycardia (hypothyroidism), orthostasis (anorexia, dehydration).

Targeted physical exam to exclude medical mimics:

Mental Status Exam (MSE) — the de facto "physical exam" of psychiatry:

Step 3 management: Every depression visit must include a documented suicide risk assessment: ideation, plan, intent, means, prior attempts, protective factors. Use the C-SSRS in higher-risk settings. Failure to document is a malpractice and board-exam trap.

Board pearl: In elderly patients, pseudodementia from depression improves with antidepressant treatment, while true dementia does not — this distinction drives management.

Diagnostic Workup — Initial Labs and Medical Mimic Exclusion

— TSH — hypothyroidism is the most commonly tested mimic

— CBC — anemia causes fatigue; baseline before mirtazapine (rare blood dyscrasias)

— CMP — Na+ (baseline before SSRIs due to SIADH risk), glucose, renal/hepatic function for drug dosing

— Vitamin B12 and 25-OH vitamin D in elderly, vegans, malabsorption, atypical features

— HbA1c if obesity, family hx, or planning agent with metabolic effects

— Urine pregnancy test in reproductive-age women before initiating any psychotropic

— Urine drug screen if substance use suspected

— HIV, RPR in at-risk patients with cognitive/mood changes

— AM cortisol or dexamethasone suppression only if Cushingoid features

— Ceruloplasmin in young patients with mood + movement disorder (Wilson)

— MRI brain only if focal neuro deficits, late-onset depression with cognitive change, or atypical course suggesting structural lesion (frontal tumor, NPH, stroke)

— Baseline ECG before citalopram or escitalopram in patients >60, on QT-prolonging drugs, with cardiac disease, or electrolyte disturbance

— Citalopram max dose: 40 mg (20 mg if >60 y/o or CYP2C19 poor metabolizer) due to dose-dependent QT prolongation

— Baseline ECG before TCAs (quinidine-like, prolong QRS/QT)

— Interferon-α, corticosteroids, isotretinoin, varenicline (warning relaxed but still review), β-blockers (propranolol > selective), reserpine, hormonal contraceptives in susceptible women, opioids, benzodiazepines (chronic)

MDD is a clinical diagnosis — no lab confirms it. Workup targets reversible medical contributors and baseline values before pharmacotherapy.

First-visit labs in new depression:

Targeted testing based on history:

ECG indications before/during therapy:

Medications that cause/worsen depression — review the med list:

CCS pearl: On a CCS case of new depression, order TSH, CBC, CMP, urine pregnancy (if applicable), urine tox at the index visit — not later. Skipping the pregnancy test before SSRI in a 28-year-old woman is a documented scoring deduction.

Board pearl: Apathy + cognitive slowing + bradycardia + constipation = check TSH before diagnosing MDD.

Diagnostic Workup — Severity Staging and Rating Scales

— 9 items, each 0–3, total 0–27

— 5–9 mild, 10–14 moderate, 15–19 moderately severe, 20–27 severe

— Use to confirm diagnosis, stratify severity, and track response longitudinally (measurement-based care)

— Response = ≥50% reduction in score; remission = PHQ-9 <5

— Recheck at 2, 4, 6, 8, 12 weeks after starting/changing therapy

— HAM-D (Hamilton) — clinician-administered, used in research/specialty

— BDI-II (Beck) — self-report, often in psychotherapy settings

— GDS (Geriatric Depression Scale) — 15-item version preferred in elderly; avoids somatic items that overlap with aging

— EPDS (Edinburgh Postnatal Depression Scale) — peripartum standard; score ≥10 prompts further assessment, ≥13 likely depression

— PHQ-A for adolescents

— Columbia Suicide Severity Rating Scale (C-SSRS) — structured ideation/behavior assessment

— Risk factors (SAD PERSONS legacy mnemonic; clinical judgment trumps any score):

— Male sex, age >65 or adolescent, prior attempt (strongest single predictor), psychiatric illness, substance use, hopelessness, access to firearms, recent loss, chronic illness

— MDQ (Mood Disorder Questionnaire) — sensitive screen

— Direct questions: episodes of decreased need for sleep with high energy, grandiosity, racing thoughts, impulsive spending/sex

— Antidepressant monotherapy in unrecognized bipolar can precipitate mania — a classic Step 3 vignette

PHQ-9 — the workhorse of outpatient depression care:

Other validated instruments:

Suicide risk stratification:

Bipolar screening before initiating an antidepressant:

Step 3 management: Implement measurement-based care: document PHQ-9 at every visit, adjust therapy if no ≥50% reduction by week 6–8 at therapeutic dose. "Watchful waiting" beyond 8 weeks without response is a wrong answer.

Board pearl: A patient with PHQ-9 of 22 + plan to overdose on stockpiled medications + lives alone = psychiatric emergency; arrange immediate evaluation, ensure means restriction, do not discharge home unmonitored.

Risk Stratification and First-Line Management Logic

— Mild MDD (PHQ-9 5–9): Psychotherapy alone (CBT or IPT) OR antidepressant; shared decision-making. Behavioral activation + exercise + sleep hygiene as adjuncts.

— Moderate MDD (10–19): Antidepressant or psychotherapy; combination superior to either alone for sustained remission.

— Severe MDD (≥20), psychotic, suicidal, or functionally incapacitated: Combination pharmacotherapy + psychotherapy; consider ECT if psychotic, catatonic, pregnant with severe symptoms, or treatment-resistant.

— Preference, prior response, pregnancy/lactation, medical comorbidities, drug interactions, cost/access, side-effect tolerance

— Psychotherapy preferred in mild illness, pregnancy, adolescents (initial), patient preference, substance use comorbidity

— Pharmacotherapy preferred in moderate–severe, melancholic, recurrent, prior med response, limited therapy access

— CBT — best evidence; addresses cognitive distortions and behavior

— IPT (Interpersonal Therapy) — role transitions, grief, interpersonal conflict

— Behavioral Activation — scheduled rewarding activities; effective and scalable

— Problem-Solving Therapy — older adults, primary care

— Mindfulness-Based Cognitive Therapy — relapse prevention after remission

— Aerobic exercise ≥150 min/week (effect size similar to SSRI in mild–moderate)

— Sleep regularization, alcohol reduction, light therapy (10,000 lux AM) for seasonal pattern

— Step 1: Recognition, watchful waiting if subthreshold + low risk, low-intensity psychosocial intervention

— Step 2: Antidepressant or structured psychotherapy

— Step 3: Combination, switch, augment

— Step 4: Specialty referral, ECT, TMS, esketamine

Severity-based treatment matching (APA, NICE-aligned):

Choosing between modalities — patient factors:

Evidence-based psychotherapies:

Lifestyle interventions with evidence:

Stepped care framework:

CCS pearl: For moderate MDD without contraindications, the highest-scoring order set is: SSRI + referral to CBT + PHQ-9 in 2 weeks + safety plan + lifestyle counseling, all at the index visit.

Board pearl: Combination therapy (med + therapy) yields the highest sustained remission rates and is the answer for moderate-to-severe MDD when offered.

Pharmacotherapy — First-Line Drug Regimen

— Sertraline — preferred in cardiac disease, pregnancy, lactation; minimal interactions

— Escitalopram — clean profile, few interactions; QT caution

— Fluoxetine — long half-life (good for non-adherent patients), activating, approved in pediatrics

— Citalopram — QT prolongation; max 40 mg (20 mg if >60)

— Paroxetine — most anticholinergic, sedating, weight gain, avoid in pregnancy (Category D — cardiac defects) and elderly

— SNRIs (venlafaxine, duloxetine): comorbid neuropathic pain, fibromyalgia, stress incontinence (duloxetine); venlafaxine raises BP dose-dependently

— Bupropion: activating, no sexual dysfunction, modest weight loss, helps smoking cessation; avoid in seizure disorder, active eating disorder, bulimia

— Mirtazapine: sedating, appetite-stimulating — useful in elderly with insomnia and weight loss; rare agranulocytosis

— Vortioxetine, vilazodone: newer, fewer sexual side effects, costly

— Start low (e.g., sertraline 25–50 mg, escitalopram 5–10 mg), titrate q1–2 weeks

— Therapeutic effect at 4–6 weeks at adequate dose; energy/sleep improve first, mood later

— Reassess at week 2 (tolerability, suicidality), week 4 (response), week 6–8 (response/remission)

— GI upset, headache, jitteriness in first 1–2 weeks (transient)

— Sexual dysfunction (30–50%) — most common reason for discontinuation

— Weight gain (paroxetine > others), insomnia or sedation, hyponatremia (especially elderly), bruising/bleeding (especially with NSAIDs/anticoagulants)

— FDA black-box warning: increased suicidal ideation in patients <25 in first weeks

— Partial response (25–50%): augment with bupropion, mirtazapine, atypical antipsychotic (aripiprazole, quetiapine XR, brexpiprazole), or lithium/T3

— No response: switch within class or to different class

— Treatment-resistant (≥2 failed adequate trials): refer; consider esketamine, TMS, ECT

First-line: SSRIs — equivalent efficacy across the class; choose by side-effect profile, interactions, and cost.

Second-line and alternative first-line agents:

Starting and titrating:

Side effects to counsel up front:

Switching/augmenting after inadequate response at 6–8 weeks:

Step 3 management: Treat first episode for 6–12 months after remission; ≥2 episodes or severe single episode → consider indefinite maintenance. Taper gradually over 2–4 weeks to avoid discontinuation syndrome (FINISH: Flu-like, Insomnia, Nausea, Imbalance, Sensory disturbance, Hyperarousal) — except fluoxetine (self-tapering).

Expanded Pharmacology — Switching, Augmentation, and Interventional Options

— Triad: mental status change + autonomic instability + neuromuscular hyperactivity (clonus, hyperreflexia, especially lower extremities)

— Triggers: SSRI/SNRI + MAOI, linezolid, methylene blue, tramadol, meperidine, triptans, dextromethorphan, St. John's wort, MDMA

— Washout: 2 weeks between SSRI and MAOI; 5 weeks for fluoxetine due to long half-life

— Treatment: stop agent, supportive care, benzodiazepines, cyproheptadine if severe

— Fluoxetine, paroxetine — strong CYP2D6 inhibitors → raise levels of tamoxifen (reduces efficacy — avoid), metoprolol, codeine

— Fluvoxamine — strong CYP1A2 inhibitor → theophylline, clozapine, caffeine

— SSRIs + NSAIDs/anticoagulants → GI bleed risk; consider PPI

— SSRIs + diuretics/elderly → hyponatremia

— Atypical antipsychotic: aripiprazole 2–15 mg, quetiapine XR 150–300 mg, brexpiprazole — FDA-approved for adjunctive MDD

— Bupropion — adds activation, mitigates sexual side effects

— Mirtazapine — "California rocket fuel" with venlafaxine

— Lithium, T3 (liothyronine 25–50 mcg) — classic augmenters

— Esketamine intranasal — adjunct to oral antidepressant; REMS program, monitor BP and sedation 2 h post-dose

— IV ketamine — off-label, rapid antisuicidal effect

— Repetitive TMS — non-invasive, outpatient, 4–6 weeks; no anesthesia

— ECT — gold standard for severe, psychotic, catatonic, pregnant with severe MDD, or imminently suicidal; main side effect is anterograde and retrograde amnesia

Serotonin syndrome — the can't-miss interaction:

Discontinuation syndrome: Worst with paroxetine and venlafaxine (short half-lives). Taper over weeks.

Drug interactions of note:

Augmentation strategies (STAR*D-derived):

Treatment-resistant depression (TRD): ≥2 adequate trials of different classes.

MAOIs (tranylcypromine, phenelzine, selegiline patch): Reserved for atypical or refractory MDD; tyramine-restricted diet (aged cheese, cured meats, fermented foods) to avoid hypertensive crisis.

CCS pearl: In a vignette of escalating depression on adequate SSRI dose for 8 weeks with PHQ-9 unchanged, the correct next action is to switch agent or augment, not "continue current dose and reassess in 4 weeks."

Board pearl: ECT is the single most effective treatment for severe MDD — remission rates 60–80%; do not withhold it because of age or pregnancy.

Special Populations — Elderly and Renal/Hepatic Impairment

— More somatic complaints, cognitive slowing ("pseudodementia"), anhedonia without sadness, irritability, social withdrawal

— Higher suicide risk — white men >85 have the highest suicide rate in the US

— Often missed: attributed to "normal aging," dementia, or medical illness

— Sertraline, escitalopram, mirtazapine are preferred

— Escitalopram max 10 mg/day if >60 (QT)

— Citalopram max 20 mg/day if >60

— Mirtazapine 7.5–15 mg qhs — bonus appetite/sleep effects

— Avoid: paroxetine (anticholinergic, Beers list), TCAs (anticholinergic, orthostasis, cardiac), benzodiazepines for "depression with anxiety" (falls, delirium)

— Watch for SIADH/hyponatremia — check Na at 2–4 weeks; risk highest in first month, in low-BMI elderly women on thiazides

— Bleeding risk if also on antiplatelet/anticoagulant

— Sertraline, fluoxetine — minimal dose adjustment

— Venlafaxine, desvenlafaxine — reduce dose in CrCl <50; check BP

— Paroxetine — reduce in severe CKD

— Avoid lithium augmentation in CKD (renal clearance, narrow window)

— Most antidepressants are hepatically metabolized — reduce dose by 50% in moderate impairment

— Sertraline preferred; avoid duloxetine in chronic liver disease/heavy alcohol use (hepatotoxicity)

— Bupropion — cirrhosis requires significant dose reduction

— Higher relapse rate; consider longer maintenance (≥2 years) after first episode, indefinite after recurrence

Geriatric depression — clinical features:

Screening: Use Geriatric Depression Scale (GDS-15) — avoids somatic overlap with aging/medical illness.

Workup additions: TSH, B12, folate, vitamin D, RPR if cognitive change, brain imaging if focal findings or late-onset (>60) first episode.

Pharmacology principles — "start low, go slow, but go":

Renal impairment:

Hepatic impairment:

Treatment duration in elderly:

Step 3 management: A 78-year-old on hydrochlorothiazide develops confusion 3 weeks after starting sertraline — check serum sodium first (SSRI-induced SIADH). Hold the SSRI, treat hyponatremia, switch to bupropion or mirtazapine.

Board pearl: Late-life depression with new cognitive deficits → treat depression first; if cognition normalizes, it was pseudodementia. If cognition persists, evaluate for underlying neurodegenerative disease.

Special Populations — Pregnancy, Postpartum, Adolescents

— Affects ~1 in 7 pregnancies; untreated maternal depression → preterm birth, low birth weight, impaired attachment, child developmental delay

— Screen at first prenatal visit, third trimester, and 6-week postpartum visit (and at well-child visits) with EPDS or PHQ-9

— Untreated depression carries fetal risks too — discuss risks of treating vs not

— Preferred SSRIs: sertraline, escitalopram (lowest placental transfer/exposure data favorable)

— Avoid paroxetine (cardiac malformations — VSD/ASD)

— Third-trimester SSRI use → transient neonatal adaptation syndrome (jitteriness, feeding difficulty) and small absolute risk of persistent pulmonary hypertension of the newborn (PPHN) — do not routinely discontinue, as relapse risk outweighs

— Avoid bupropion if seizure risk; valproate teratogenic (mood-stabilizer pitfall)

— ECT is safe in pregnancy for severe/psychotic depression or suicidality

— Sertraline is the preferred SSRI in breastfeeding (lowest infant serum levels)

— Paroxetine also acceptable; fluoxetine has long half-life and active metabolite — accumulates in infants

— Baby blues: 50–80%, days 2–14, self-limited, no impairment, supportive care only

— Postpartum depression: ≥2 weeks, functional impairment, treat as MDD

— Postpartum psychosis: abrupt, days–weeks postpartum, hallucinations/delusions, infanticidal/suicidal risk — psychiatric emergency, hospitalize, ECT or antipsychotic + mood stabilizer

— Brexanolone IV and zuranolone PO — neurosteroid GABA-A modulators FDA-approved specifically for postpartum depression

— Fluoxetine — FDA-approved for ages ≥8; escitalopram approved ≥12

— All antidepressants carry black-box warning for suicidal ideation <25 — does not preclude use; mandates close monitoring (weekly × 4 weeks, biweekly × 4, then monthly)

— Combination CBT + fluoxetine superior to either alone (TADS trial)

Perinatal depression:

Pharmacotherapy in pregnancy:

Lactation:

Postpartum depression vs blues vs psychosis:

Pediatric/adolescent MDD:

Step 3 management: A 22-year-old at 28 weeks gestation with severe MDD and active SI — admit, psychiatric consultation, continue or initiate sertraline, consider ECT if rapidly worsening. Do not withhold treatment because of pregnancy.

Board pearl: Postpartum psychosis = emergency; postpartum depression = treat aggressively but outpatient often feasible; baby blues = reassurance.

Complications and Adverse Outcomes

— ~50% of suicides have a mood disorder; MDD lifetime suicide rate ~4%

— Highest risk: prior attempt, hopelessness, active substance use, recent discharge from psychiatric hospitalization, access to firearms, severe insomnia, command auditory hallucinations

— Means restriction (firearm storage off-site, lockbox for medications) reduces suicide more than most clinical interventions

— Job loss, divorce, social isolation, financial decline

— Doubles cardiovascular mortality post-MI; worsens diabetes control (poor adherence, HPA dysregulation)

— Increased dementia risk in older adults with recurrent depression

— Higher rates of substance use disorders — bidirectional relationship

— Serotonin syndrome (see Chunk 8) — life-threatening

— SIADH/hyponatremia — especially elderly women on thiazides; first month

— GI bleeding — SSRI + NSAID + anticoagulant — add PPI

— Seizures — bupropion >400 mg/day, immediate-release formulation, eating disorders

— QT prolongation — citalopram, TCAs; check ECG, K+, Mg

— Sexual dysfunction — chronic, often persistent; consider bupropion add-on or switch

— Weight gain — mirtazapine, paroxetine; metabolic syndrome with antipsychotic augmentation

— Bone density loss and falls — SSRI use linked to increased fracture risk in elderly

— Bleeding/bruising — platelet serotonin depletion

— Patient with unrecognized bipolar started on antidepressant → manic switch

— Stop antidepressant, initiate mood stabilizer (lithium, valproate) or atypical antipsychotic

Suicide:

Self-harm without intent: Cutting, burning — assess function (regulation, communication); higher risk for future completed suicide.

Functional and medical complications:

Pharmacotherapy complications:

Treatment-emergent mania:

Discontinuation syndrome (FINISH): Flu-like, Insomnia, Nausea, Imbalance, Sensory (electric "zaps"), Hyperarousal — emerges within days of stopping short half-life agents.

Step 3 management: Patient on SSRI develops tremor, diarrhea, hyperreflexia, agitation after starting tramadol for back pain — diagnose serotonin syndrome, stop tramadol and SSRI, give IV fluids, benzodiazepine, consider cyproheptadine if severe.

Board pearl: Suicide rates may transiently increase in the first 1–2 weeks of antidepressant therapy as psychomotor retardation lifts before mood improves — counsel patient and family, schedule close follow-up.

When to Escalate Care — Inpatient Triage and Referral

— Active suicidal ideation with plan, intent, or means

— Recent suicide attempt

— Active homicidal ideation

— Psychotic features (delusions, hallucinations, especially command type)

— Catatonia

— Severe self-neglect — not eating, drinking, or caring for self

— Severe functional impairment without outpatient support

— Failed outpatient management with deterioration

— Mental illness AND

— Danger to self, danger to others, OR grave disability

— Initial hold typically 72 hours; extension requires court hearing

— Patient retains right to refuse treatment until adjudicated, except in emergencies

— Treatment resistance (≥2 failed trials) — for ECT/TMS/esketamine evaluation

— Bipolar disorder confirmed or strongly suspected

— Psychotic features

— Pregnancy or postpartum with severe symptoms

— Comorbid eating disorder or severe substance use

— Diagnostic uncertainty (personality disorder, PTSD, OCD overlap)

— Severe SIADH/hyponatremia, serotonin syndrome, TCA overdose, lithium toxicity

— Refeeding considerations in severely malnourished patient

— Suicide attempt with medical complications (overdose, trauma) — medically stabilize first, then transfer to psychiatry

— Stanley-Brown safety plan: warning signs, internal coping strategies, social supports, professional contacts, means restriction

— 988 Suicide and Crisis Lifeline (US, since 2022)

— Follow-up scheduled within 7 days of ED visit or hospital discharge (the highest-risk window)

— Firearm and medication safety counseling documented

Indications for psychiatric hospitalization (voluntary or involuntary):

Involuntary commitment criteria (state-dependent but core principles):

Indications for urgent psychiatric consult/referral (not necessarily hospitalization):

Indications for medical hospitalization:

Safety planning if discharging home from ED/clinic:

CCS pearl: Patient with PHQ-9 of 24, plan to overdose, lives alone — order: psychiatric consult, place on suicide precautions (1:1 sit), remove access to means, do not discharge. "Schedule outpatient follow-up tomorrow" is wrong.

Board pearl: Post-hospitalization, the first 30 days carry the highest suicide risk of any period — ensure follow-up within 7 days and bridge appointments.

Key Differentials — Within Mood and Anxiety Spectrum

— Depressed mood most days for ≥2 years (≥1 year in children/adolescents) with ≥2 of: appetite change, sleep change, low energy, low self-esteem, poor concentration, hopelessness

— Can coexist with MDD ("double depression")

— Same treatments; often more chronic course

— Must screen every depressed patient for prior mania (Bipolar I) or hypomania (Bipolar II)

— Hypomanic episode: ≥4 days of elevated/irritable mood + DIGFAST symptoms, no marked impairment, no psychosis

— Treatment differs fundamentally — mood stabilizer (lithium, lamotrigine for bipolar depression, lurasidone, quetiapine) ± antidepressant cautiously

— Antidepressant monotherapy contraindicated → induces mania, rapid cycling

— Symptoms within 3 months of identifiable stressor, resolving within 6 months of stressor end; do not meet full MDD criteria

— Treatment: psychotherapy, watchful support; medications usually unnecessary

Persistent depressive disorder (dysthymia):

Bipolar I and II disorder:

Cyclothymic disorder: Subthreshold mood fluctuations ≥2 years; treat with mood stabilizer.

Disruptive mood dysregulation disorder (DMDD): Pediatric (6–18); chronic irritability + temper outbursts; distinct from bipolar.

Premenstrual dysphoric disorder (PMDD): Cyclical luteal-phase depression/irritability; SSRIs (continuous or luteal-phase dosing) first-line.

Adjustment disorder with depressed mood:

Generalized anxiety disorder: Excessive worry ≥6 months + somatic symptoms; high comorbidity with MDD (~60%); SSRI/SNRI first-line.

PTSD: Trauma exposure + intrusion, avoidance, negative cognitions, hyperarousal ≥1 month; SSRI (sertraline, paroxetine FDA-approved) + trauma-focused therapy.

Substance-induced depressive disorder: Mood symptoms during intoxication/withdrawal (alcohol, opioids, stimulants, cannabis, sedative withdrawal); require 4 weeks of sobriety before diagnosing primary MDD when possible.

Bereavement (uncomplicated grief): Wave-like, intact self-esteem, focus on deceased; transitions to prolonged grief disorder if ≥12 months impairing grief.

Key distinction: Bipolar depression looks identical cross-sectionally to MDD — diagnosis hinges on longitudinal history of mania/hypomania. Family history of bipolar, early onset, atypical features, psychotic features, postpartum onset, and antidepressant-induced switch raise suspicion.

Board pearl: The single most important question to ask a new depressed patient before prescribing an antidepressant: "Have you ever had a period of several days when you needed less sleep but had unusually high energy, racing thoughts, or did impulsive things?"

Key Differentials — Medical and Substance-Related Mimics

— Hypothyroidism — most commonly tested; fatigue, weight gain, cold intolerance, bradycardia, constipation; check TSH

— Hyperthyroidism — anxiety/irritability, can mimic agitated depression in elderly (apathetic hyperthyroidism)

— Cushing syndrome — depression in 50–80%; central obesity, striae, hyperglycemia, hypertension

— Addison disease — fatigue, weight loss, hyperpigmentation, hyponatremia

— Hyperparathyroidism — "stones, bones, groans, psychiatric overtones"

— Diabetes — bidirectional with depression

— Parkinson disease — depression in ~40%, often precedes motor symptoms

— Stroke — particularly left frontal; post-stroke depression in ~30%

— Multiple sclerosis — depression and pseudobulbar affect

— Dementia (Alzheimer, frontotemporal, Lewy body) — overlap with depression; pseudodementia consideration

— Traumatic brain injury, NPH, brain tumor (frontal) — late-onset personality/mood change

— Sleep apnea — fatigue, irritability, cognitive complaints; screen with STOP-BANG

— HIV, neurosyphilis, Lyme, hepatitis C, mononucleosis, post-COVID

— Autoimmune: SLE (neuropsychiatric lupus), Sjögren, paraneoplastic encephalitis

— B12, folate, vitamin D deficiency, iron deficiency anemia

— Pancreatic cancer classically presents with depression preceding diagnosis

— Any chronic/occult malignancy → fatigue, weight loss, anhedonia

— Alcohol use disorder — depressant; assess all depressed patients for alcohol use

— Cannabis — amotivational syndrome

— Stimulant withdrawal (cocaine, methamphetamine) — crash with intense dysphoria

— Opioids, benzodiazepines — chronic use depressogenic

— Withdrawal from caffeine, nicotine — irritability, low mood

— Interferon-α (chronic HCV), corticosteroids, isotretinoin, β-blockers (less than thought), reserpine, varenicline, hormonal contraceptives in susceptible women, anticonvulsants (topiramate, levetiracetam)

Endocrine causes:

Neurologic causes:

Infectious/inflammatory:

Nutritional:

Malignancy:

Substance-induced:

Medication-induced:

Key distinction: Order TSH, CBC, CMP, B12 at minimum in every new depression workup. New-onset depression in a patient >60 with weight loss and back pain warrants imaging to rule out pancreatic malignancy.

Board pearl: A patient with depression + new-onset glucose intolerance + central obesity + easy bruising + proximal muscle weakness → check 24-h urine free cortisol or overnight dexamethasone suppression before treating as primary MDD.

Continuation Phase, Maintenance, and Relapse Prevention

— Acute (6–12 weeks): achieve response then remission (PHQ-9 <5)

— Continuation (4–9 months after remission): prevent relapse of current episode

— Maintenance (1 year to indefinite): prevent new recurrence

— First episode: treat for 6–12 months after remission, then consider taper

— Second episode: consider 2+ years

— Third episode, severe, psychotic, suicidal, family history, residual symptoms, or chronic course: indefinite maintenance

— Residual symptoms at remission, prior recurrence, family history, comorbid anxiety/substance use, ongoing psychosocial stressors, early age of onset, severe index episode

— Gradual taper over 2–4 weeks minimum (longer for short half-life agents)

— Paroxetine, venlafaxine — taper slowly over weeks to months

— Fluoxetine self-tapers (long half-life); can usually stop without taper

— Counsel about discontinuation symptoms vs relapse

— Use the same dose that achieved remission — "the dose that gets you well keeps you well"

— Do not reduce dose for maintenance; this increases relapse risk

— MBCT (Mindfulness-Based Cognitive Therapy) — strong evidence for relapse prevention after remission, especially in recurrent MDD

— Maintenance CBT or IPT sessions

— Continued exercise, sleep regularity, alcohol moderation

— Bright light therapy for seasonal pattern recurrence

— Antidepressant at effective dose with refills

— PRN sleep aid if needed (avoid chronic benzodiazepines)

— Smoking cessation, substance-use treatment referral

— Reconcile interacting meds (NSAIDs, tramadol, MAOIs)

— Lockbox/limited quantities if any suicide risk

— Safety plan in writing, copy to patient

Phases of MDD treatment:

Duration recommendations:

Risk factors for relapse driving longer treatment:

Tapering antidepressants:

Maintenance pharmacotherapy principle:

Relapse prevention strategies:

Discharge medication list checklist (after MDD-related hospitalization):

Step 3 management: A patient in remission for 8 months on sertraline 100 mg asks to stop. If first episode and no risk factors, taper after total 9–12 months of treatment, monitor monthly × 6 months for relapse signs. If second episode, continue at least 2 years.

Board pearl: The most common reason for MDD relapse is premature discontinuation of an effective antidepressant — patient stops once feeling better. Anticipate and counsel at every visit.

Follow-Up, Monitoring, and Longitudinal Care

— Week 1–2: check tolerability, adherence, suicidality (telephone or visit; in-person preferred <25 y/o)

— Week 4: PHQ-9, side effects, adherence

— Week 6–8: assess for response (≥50% PHQ-9 reduction); adjust if not

— Week 12: target remission

— Then every 1–3 months during continuation phase

— Every 3–6 months in maintenance phase

— PHQ-9 score (track trend)

— Suicide risk reassessment

— Side effects (sexual, GI, weight, sleep, sedation)

— Adherence (pill counts, refill history)

— Substance use, sleep, exercise, social function

— Serum Na+ at 2–4 weeks after starting SSRI in elderly or at risk

— ECG annually if on citalopram, TCA, or QT-prolonging combination

— Lipid panel, HbA1c, weight every 6 months if on antipsychotic augmentation (aripiprazole, quetiapine)

— Lithium level, TSH, Cr every 6 months if lithium augmentation

— Weekly CBT × 12–16 sessions typical for acute phase

— Monthly booster sessions during continuation

— Coordinate with prescribing clinician (collaborative care model improves outcomes)

— Primary care provider + care manager + consulting psychiatrist

— Population-based registry, measurement-based care, stepped intensification

— Best-evidence model for depression management in primary care; reimbursed under CMS codes (CoCM)

— Medications work over weeks, not days

— Side effects often transient

— Do not stop abruptly

— Avoid alcohol; review interacting OTC meds (St. John's wort, dextromethorphan, tramadol)

— Lifestyle: aerobic exercise 30 min × 5 days/week, sleep hygiene, social engagement

— When to call: suicidal thoughts, manic symptoms, severe side effects

— Short-term medical leave may aid acute recovery

— Prolonged disability worsens prognosis — facilitate graded return to function

Follow-up cadence after starting/changing antidepressant:

Measurement-based care monitoring at every visit:

Lab monitoring:

Psychotherapy follow-up:

Collaborative care model (Step 3 health-systems concept):

Patient education and counseling at every visit:

Return-to-work and disability planning:

Step 3 management: Document a PHQ-9 score at every depression follow-up. Adjust therapy if no ≥50% reduction by week 6–8. This is the cornerstone of measurement-based care and a frequent exam target.

Board pearl: The collaborative care model is the highest-evidence health-systems intervention for primary-care depression — favored answer on systems/quality questions.

Ethical, Legal, and Patient Safety Considerations

— Discuss black-box warning for suicidality in patients <25; document

— Discuss sexual side effects (highest treatment-discontinuation driver)

— Discuss discontinuation syndrome and need for tapering

— Discuss pregnancy implications in reproductive-age patients

— For ECT: detailed consent including memory effects; capacity assessment essential

— Severe depression can impair decision-making capacity, especially regarding refusal of life-sustaining treatment

— Capacity is decision-specific and time-specific; reassess when mental state changes

— Hopelessness alone does not eliminate capacity — but psychotic depression with nihilistic delusions ("I'm already dead") typically does

— Civil commitment requires mental illness + danger to self/others or grave disability

— Patient retains right to refuse medication unless emergency or court-ordered

— Document specific behaviors, statements, and risk factors — not just "suicidal"

— When a patient presents credible threat against an identifiable third party, clinicians have a duty to take reasonable steps (warn victim, notify police, hospitalize patient)

— Confidentiality yields to safety

— Child, elder, dependent-adult abuse — mandatory in all US states

— Some states require reporting of impaired drivers; clinician should know local law

— Reporting does not require certainty — reasonable suspicion suffices

— Generally confidential, with exceptions for suicidality, abuse, or homicidal ideation

— Discuss limits of confidentiality at treatment outset

— Post–ED discharge for SI: follow-up within 7 days, safety plan, means restriction, prescription quantity limited, family contact when consented

— Post–psychiatric hospitalization: bridge appointment scheduled before discharge; medication reconciliation; warm handoff to outpatient provider

— Failure to ensure follow-up after ED suicidality visit is a documented malpractice and Step 3 wrong-answer pattern

— Ask about firearm access in any depressed patient with SI or risk factors

— Recommend off-site storage, gun locks, or voluntary surrender during high-risk periods

— Most states permit clinician inquiry; some have Extreme Risk Protection Order ("red flag") laws

Informed consent for antidepressants:

Capacity and competency:

Involuntary treatment:

Duty to warn (Tarasoff):

Mandatory reporting:

Confidentiality and adolescents:

Transition-of-care safety (Step 3 favorite):

Firearm counseling:

Step 3 management: A 45-year-old discharged from the ED after passive SI must have a documented safety plan, means restriction (firearm/medication), and outpatient follow-up scheduled within 7 days. Anything less is the wrong answer.

High-Yield Associations and Rapid-Fire Clinical Facts

Cardinal symptom requirement: Depressed mood OR anhedonia — must have one.

PHQ-9 cutoffs: 5/10/15/20 = mild/moderate/mod-severe/severe.

Response = 50% reduction; remission = PHQ-9 <5.

Time to response: 4–6 weeks at therapeutic dose; sleep/energy improve first.

First-line: SSRI (sertraline, escitalopram preferred); + CBT/IPT for moderate–severe.

Avoid in pregnancy: Paroxetine (cardiac defects).

Preferred in pregnancy/lactation: Sertraline.

Pediatric FDA approvals: Fluoxetine (≥8), escitalopram (≥12).

Black-box warning: Suicidality <25 in first weeks.

Highest US suicide rate: White men >85.

Strongest single predictor of suicide: Prior attempt.

Most common cause of antidepressant non-adherence: Sexual dysfunction.

Bupropion contraindications: Seizure disorder, eating disorders, MAOI use.

Mirtazapine niche: Elderly with insomnia and poor appetite.

Citalopram cap: 40 mg (20 mg if >60) — QT prolongation.

Discontinuation syndrome worst with: Paroxetine, venlafaxine.

Fluoxetine washout to MAOI: 5 weeks; other SSRIs: 2 weeks.

Serotonin syndrome triad: AMS + autonomic instability + neuromuscular hyperactivity (clonus, hyperreflexia, lower extremity > upper).

NMS distinction: "Lead-pipe" rigidity + hyperthermia + bradyreflexia after antipsychotic.

ECT first-line: Severe psychotic depression, catatonia, pregnancy with severe MDD, imminent suicide, treatment resistance.

TMS: Outpatient, no anesthesia, 4–6 weeks; for TRD.

Esketamine: Intranasal, REMS, adjunct for TRD; monitor BP and sedation 2 h.

Bipolar screen: Always before SSRI — antidepressant monotherapy can trigger mania.

Postpartum psychosis: Emergency, hospitalize, antipsychotic + mood stabilizer; ECT highly effective.

Pancreatic cancer: Classic mimic; new depression + weight loss + back pain in older adult → image.

Sleep apnea: Treatable mimic — screen with STOP-BANG.

Collaborative care model: Best primary-care depression delivery system; CMS reimbursable.

Maintenance duration: 1st episode 6–12 mo post-remission; 2nd 2 yr; 3rd+ indefinite.

988: US Suicide and Crisis Lifeline.

Means restriction: Firearm and medication lockbox — single highest-impact suicide prevention intervention.

Board pearl: When two answer choices both look reasonable, the one that includes follow-up within 7 days and a safety plan usually wins on Step 3.

Board Question Stem Patterns

Stem 1 — The bipolar trap: 24-year-old woman with 3 weeks of depression, history of "a really productive month" with little sleep and impulsive credit-card spending last year → screen for bipolar; do not start SSRI alone; refer/initiate mood stabilizer.

Stem 2 — Citalopram QT: 70-year-old man on citalopram 40 mg with new dizziness; ECG QTc 510 ms → reduce/discontinue citalopram, correct electrolytes, switch to sertraline or escitalopram (with care).

Stem 3 — SSRI + NSAID GI bleed: Elderly patient on SSRI plus ibuprofen for arthritis with melena → SSRI-NSAID bleed; add PPI, reassess NSAID, consider acetaminophen.

Stem 4 — Hyponatremia: Elderly woman 3 weeks after starting sertraline with confusion, Na 122 → SIADH; hold sertraline, treat hyponatremia.

Stem 5 — Serotonin syndrome: Patient on fluoxetine starts tramadol; develops agitation, clonus, hyperreflexia, hyperthermia → stop both, supportive care, benzos, cyproheptadine.

Stem 6 — Postpartum psychosis: 6 days postpartum with paranoid delusions about the baby → hospitalize; antipsychotic + mood stabilizer; assess infanticidal risk.

Stem 7 — Pseudodementia: 75-year-old man with cognitive complaints, "I don't know" answers on MoCA, prominent anhedonia → treat depression first; expect cognitive improvement.

Stem 8 — Paroxetine in pregnancy: Pregnant patient with MDD asks about paroxetine continuation → switch to sertraline (paroxetine teratogenic).

Stem 9 — STAR*D step: Patient on adequate SSRI dose × 8 weeks with PHQ-9 still 18 → switch agent or augment, not "continue and wait."

Stem 10 — Adjustment vs MDD: Depressed mood after job loss for 1 month, partial criteria met, mild functional impact → adjustment disorder with depressed mood; therapy alone reasonable.

Stem 11 — Bereavement vs MDD: Widow at 3 weeks post-loss with anhedonia, worthlessness, SI, functional impairment → MDD (DSM-5 removed bereavement exclusion); treat as MDD.

Stem 12 — ECT indication: Severely depressed pregnant patient with active SI refusing oral medication → ECT is appropriate and safe.

Stem 13 — Pediatric: 14-year-old with moderate MDD → fluoxetine + CBT (TADS); weekly follow-up × 4 weeks.

Stem 14 — Post-ED discharge: Patient seen in ED for SI, denies plan, discharged → must have safety plan + follow-up within 7 days.

Stem 15 — Collaborative care: Primary care system question → answer mentions care manager + measurement-based care + psychiatric consultant.

Step 3 management: When a vignette describes 6–8 weeks at adequate SSRI dose with partial response, the right answer is augment or switch, not extend the trial.

One-Line Recap

Major depressive disorder is a clinical diagnosis requiring ≥2 weeks of depressed mood or anhedonia plus ≥4 SIGECAPS symptoms with functional impairment, treated with an SSRI (sertraline/escitalopram first-line) plus evidence-based psychotherapy (CBT/IPT) for moderate–severe disease, monitored with PHQ-9 every visit to remission, continued 6–12 months after a first episode and indefinitely after recurrent or severe episodes, with mandatory bipolar screening, suicide-risk assessment, and safety planning at every encounter.

High-yield bullet recap 1 — Diagnosis: SIGECAPS ≥5 for ≥2 weeks, one of which must be depressed mood or anhedonia; always screen for prior mania/hypomania and substance use before labeling as MDD; rule out medical mimics with TSH, CBC, CMP, B12, and urine pregnancy.

High-yield bullet recap 2 — First-line treatment: SSRI (sertraline or escitalopram) titrated to therapeutic dose; expect 4–6 weeks for response; combine with CBT or IPT for moderate–severe disease; aim for PHQ-9 <5 (remission), not just improvement.

High-yield bullet recap 3 — Special populations and safety: Sertraline preferred in pregnancy/lactation; avoid paroxetine in pregnancy; fluoxetine and escitalopram FDA-approved for adolescents with black-box monitoring; ECT for severe, psychotic, catatonic, pregnant, or treatment-resistant cases; reassess suicidality every visit; restrict means (firearms, medications) for at-risk patients.

High-yield bullet recap 4 — Longitudinal care: Treat first episode 6–12 months after remission, recurrent/severe indefinitely; taper slowly to avoid discontinuation syndrome (worst with paroxetine, venlafaxine); ensure follow-up within 7 days after any ED suicidality visit; use measurement-based care with PHQ-9 at every visit; collaborative care model is the highest-evidence delivery system in primary care.

Board pearl: The two most decisive Step 3 questions to ask every depressed patient — "Have you ever had a manic/hypomanic episode?" and "Do you have access to firearms or stockpiled medications?" — drive both correct treatment selection and correct disposition.