Persistent depressed mood or anhedonia >=2 weeks with neurovegetative and cognitive symptoms causing functional impairment.
Also known as: MDD, depression, unipolar depression, clinical depression, major depression
Overview
A mood disorder defined by one or more major depressive episodes — >=2 weeks of depressed mood or anhedonia plus additional neurovegetative, cognitive, and psychomotor symptoms causing significant distress or functional impairment, without a history of mania or hypomania.
Epidemiology
Lifetime prevalence ~20% in US adults; 12-month prevalence ~8%. Female-to-male ratio ~2:1. Peak onset in 20s-30s but can occur at any age. Higher rates with chronic medical illness, perinatal period, and substance use.
Try two board-style Major Depressive Disorder questions
Real questions from the FirstPassPA bank, with the full explanation. Pick an answer — no signup, no email.
Question 1PsychiatryEasy
A 35-year-old woman presents with 3 weeks of persistent low mood, loss of interest in activities she previously enjoyed, fatigue, feelings of worthlessness, and difficulty sleeping, along with recurrent thoughts that she would be better off dead. She has no prior psychiatric history, no manic or hypomanic symptoms, and no substance use. She denies any specific plan or intent to harm herself. Which of the following is the most appropriate first-line pharmacotherapy?
ALithium carbonate
BAmitriptyline
CSertraline
DLorazepam
Reveal answer & full explanation
Correct answer: C — Sertraline
ALithium carbonate
BAmitriptyline
CSertraline✓
DLorazepam
Why Sertraline is correct
Depressed mood, anhedonia, fatigue, worthlessness, insomnia, and recurrent thoughts of death for more than 2 weeks meet criteria for major depressive disorder, with no manic history to suggest bipolar disorder.
Selective serotonin reuptake inhibitors such as sertraline are first-line pharmacotherapy for major depressive disorder per current APA guidance, owing to their favorable tolerability and safety, including low lethality in overdose when passive suicidal ideation is present.
SSRIs require 4-6 weeks for full effect and are continued 6-12 months after remission.
Why the others are wrong
Lithium carbonate — a mood stabilizer for bipolar disorder; with no manic or hypomanic history it is not indicated, a buzzword trap of matching 'mood' to a mood stabilizer.
Amitriptyline — a tricyclic antidepressant that is effective but not first-line because of anticholinergic side effects and high lethality in overdose, a particular concern given her thoughts of death (right-category-wrong-drug).
Lorazepam — a benzodiazepine that may transiently ease insomnia or anxiety but does not treat the underlying depression and carries dependence risk (symptomatic-anchoring trap).
Question 2PsychiatryMedium
A 65-year-old man has 3 months of insomnia, decreased appetite, and psychomotor slowing after losing his wife 4 months ago. He says, 'I wouldn't mind if I didn't wake up.' His son asks if this is 'normal grief.' Which of the following features most distinguishes major depressive disorder (MDD) from normal grief?
AExcessive crying and tearfulness
BPassive suicidal ideation
CYearning for the deceased
DInsomnia with reduced appetite
Reveal answer & full explanation
Correct answer: B — Passive suicidal ideation
AExcessive crying and tearfulness
BPassive suicidal ideation✓
CYearning for the deceased
DInsomnia with reduced appetite
Why Passive suicidal ideation is correct
Normal grief comes in waves, centers on yearning for the deceased, and preserves self-esteem, with any thoughts of death usually focused on joining or being with the lost person
Persistent passive suicidal ideation ('I wouldn't mind if I didn't wake up') reflects self-directed hopelessness and is a feature of major depressive disorder (MDD), not uncomplicated grief
Other features that flag MDD over grief: pervasive worthlessness/guilt, sustained (not wave-like) low mood, marked functional impairment, and meeting full MDD criteria for at least 2 weeks
This patient meets MDD criteria and warrants treatment, typically a selective serotonin reuptake inhibitor (SSRI) plus grief-focused psychotherapy
Why the others are wrong
Excessive crying and tearfulness — occurs in both normal grief and MDD, so it cannot discriminate between them; this is a buzzword-matching trap that picks the most emotionally salient symptom
Yearning for the deceased — the hallmark of normal grief (and prolonged grief disorder), not MDD, so it points away from the diagnosis; a confused-with-grief trap
Insomnia with reduced appetite — neurovegetative symptoms are equally common in uncomplicated grief and in MDD, so they do not separate the two; a trap that rewards picking the finding the patient obviously has
🔒 Free preview limit reached
Keep reading — start your free trial
You've read your 2 free diagnosis previews. Create your free account to unlock the full Major Depressive Disorder (MDD) outline — plus all 514 diagnoses, 6,500+ board-style questions, flashcards, and an AI tutor. Your 7-day free trial includes everything, and there's no credit card required.
Multifactorial. Dysregulation of monoaminergic neurotransmission (serotonin, norepinephrine, dopamine), HPA-axis hyperactivity with elevated cortisol, reduced hippocampal neurogenesis and BDNF, neuroinflammatory changes, and altered limbic-prefrontal connectivity. Genetic heritability ~40%.
Clinical presentation
Symptoms
Depressed mood most of the day, nearly every day (self-reported or observed)
Markedly diminished interest or pleasure in nearly all activities (anhedonia)
Significant weight change or appetite disturbance
Insomnia (especially early-morning awakening) or hypersomnia
Psychomotor agitation or retardation observable by others
Fatigue or loss of energy
Feelings of worthlessness or excessive/inappropriate guilt
Diminished concentration or indecisiveness
Recurrent thoughts of death, suicidal ideation, plan, or attempt
Signs / physical exam
Flat or constricted affect, slowed speech, poor eye contact
Tearfulness; psychomotor retardation or agitation
Poor grooming in severe cases
Cognitive testing may reveal pseudodementia in older adults (reversible with treatment)
Classic findings
SIG E CAPS mnemonic — Sleep, Interest, Guilt, Energy, Concentration, Appetite, Psychomotor, Suicidality. Five of nine including depressed mood or anhedonia x 2 weeks.
Differential diagnosis
Bipolar depression — Screen for past hypomania/mania (elevated energy + decreased need for sleep + goal-directed activity); antidepressant monotherapy can precipitate mania
Persistent depressive disorder (dysthymia) — Chronic low-grade depressed mood >=2 years without meeting full MDE criteria; may co-exist as 'double depression'
Adjustment disorder with depressed mood — Identifiable stressor within 3 months, symptoms insufficient for MDD, resolves within 6 months of stressor end
Grief / bereavement — Waves of yearning, preserved self-esteem, ability to experience positive emotion; consider MDD if symptoms persist, involve worthlessness, or include active SI
Hypothyroidism — Fatigue, weight gain, cold intolerance, constipation; check TSH in every new presentation
Substance-induced mood disorder — Symptoms emerge in context of intoxication or withdrawal (alcohol, sedatives, stimulants, opioids); resolves with abstinence
Premenstrual dysphoric disorder — Mood symptoms confined to luteal phase, remitting with menses; prospective daily ratings confirm
Seasonal affective pattern — MDEs with onset in fall/winter and remission in spring; consider light therapy
Diagnostic workup
Diagnostic criteria
DSM-5-TR: >=5 of 9 symptoms present for >=2 weeks, with at least one being depressed mood OR anhedonia. Symptoms must cause clinically significant distress/impairment, not be attributable to a substance or medical condition, and not be better explained by a psychotic or bipolar disorder. PHQ-9 >=10 supports diagnosis and tracks severity (5-9 mild, 10-14 moderate, 15-19 moderately severe, >=20 severe).
Labs
TSH to exclude hypothyroidism
CBC, BMP, vitamin B12, vitamin D
Urine drug screen if substance use suspected
HIV, RPR in select populations
Imaging
Neuroimaging not routine; consider MRI brain if new focal neurologic findings, atypical features, or first episode after age 50
Diagnostic algorithm
Class
Examples
Strengths
Cautions
SSRI
sertraline, escitalopram, fluoxetine
First-line; broad efficacy; safe in overdose
GI upset, sexual dysfunction, hyponatremia, QT (citalopram)
SNRI
venlafaxine, duloxetine, desvenlafaxine
Comorbid pain, fatigue
BP elevation, discontinuation syndrome
Atypical (NDRI)
bupropion
No sexual side effects, activating
Lowers seizure threshold; avoid in eating disorders
Atypical (NaSSA)
mirtazapine
Sedation, appetite, weight gain
Sedation, weight gain
TCA
nortriptyline, amitriptyline
Refractory cases, neuropathic pain
Anticholinergic, cardiotoxic in overdose
MAOI
phenelzine, tranylcypromine
Atypical depression
Tyramine crisis, serotonin syndrome
Antidepressant class comparison — first-line vs second-line options with key trade-offs.
Treatment
First-line
Psychotherapy — cognitive behavioral therapy (CBT) or interpersonal therapy (IPT); comparable to medication for mild-moderate episodes
SSRI — sertraline, escitalopram, fluoxetine (first-line pharmacotherapy; start low, titrate after 2-4 weeks; full effect at 6-8 weeks)
SNRI — venlafaxine, duloxetine, desvenlafaxine (consider with comorbid pain or fatigue)
Combine medication + psychotherapy for moderate-to-severe MDD
Worsened outcomes in CAD, diabetes, and post-stroke recovery
Chronic course — 50% recurrence after first episode, 70% after second, 90% after third
PANCE pearls
Always screen for past hypomania/mania before starting an antidepressant — unopposed antidepressants in bipolar disorder can precipitate mania or rapid cycling.
FDA black box warning: increased suicidal ideation in patients <25 during initial weeks of antidepressant treatment. Monitor closely.
Allow 4-6 weeks at therapeutic dose before declaring treatment failure. Partial response by week 4 predicts remission.
After full remission, continue antidepressant for >=6-12 months (first episode) or indefinitely (>=3 episodes or severe episode) to prevent relapse.
Discontinuation syndrome: dizziness, flu-like symptoms, paresthesias ('brain zaps'), insomnia — worst with paroxetine and venlafaxine; taper slowly.
USPSTF recommends screening all adults including pregnant/postpartum for depression with adequate systems for diagnosis and follow-up.
References
APA 2010 — American Psychiatric Association Practice Guideline for the Treatment of Patients with Major Depressive Disorder, 3rd ed. (2010)
USPSTF 2023 — Screening for Depression and Suicide Risk in Adults: USPSTF Recommendation Statement, JAMA 2023
DSM-5-TR — American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed, Text Revision (2022)
STAR*D — Rush AJ et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR*D report. Am J Psychiatry 2006
Practice Psychiatry/Behavioral questions on FirstPassPA
Turn this outline into retention. 6,500+ board-style questions with an AI tutor that explains every answer — free to start, no card required.
Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.