About This Page
This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- MDD requires >=5 depressive symptoms for >=2 weeks, including depressed mood or anhedonia
- Always assess suicide risk, psychosis, mania history, substance use, medications, hypothyroidism, and bereavement context
- First-line: psychotherapy and/or SSRI/SNRI; combine both for moderate-severe disease
- ECT is first-line for life-threatening depression: psychosis, catatonia, refusal to eat/drink, severe suicidality, or pregnancy when rapid response is needed
- Screen for bipolar disorder before starting antidepressants — antidepressant monotherapy can precipitate mania
Overview
Major depressive disorder is diagnosed clinically using DSM-5-TR criteria: at least 5 symptoms during the same 2-week period, representing a change from baseline, with at least one symptom being depressed mood or loss of interest/pleasure. Symptoms include sleep disturbance, guilt or worthlessness, low energy, impaired concentration, appetite or weight change, psychomotor change, and recurrent thoughts of death. Symptoms must cause distress or impairment, cannot be attributable to substances or another medical condition, and must not be better explained by bipolar disorder or a psychotic disorder.
Epidemiology
MDD is one of the most common psychiatric disorders in the United States and a leading cause of disability. Risk increases with family history, prior depressive episodes, trauma, chronic medical illness, postpartum state, substance use disorders, and comorbid anxiety disorders. Suicide risk is highest with prior attempts, active plan, access to lethal means, intoxication, psychosis, severe hopelessness, and recent major loss.
Clinical Features
Symptoms
Depressed mood most of the day nearly every day
Markedly diminished interest or pleasure in almost all activities
Insomnia or hypersomnia, fatigue, appetite or weight change
Poor concentration, guilt, worthlessness, psychomotor slowing or agitation
Recurrent thoughts of death, suicidal ideation, plan, or attempt
Psychotic depression: mood-congruent delusions, hallucinations, or severe functional impairment
Signs
Flat or tearful affect, reduced eye contact, slowed speech, psychomotor retardation
Poor grooming, weight loss or gain, reduced activity
Catatonia: mutism, negativism, posturing, waxy flexibility, refusal to eat/drink
Signs of self-harm, intoxication, delirium, hypothyroidism, or neurological disease
Investigations
First-line
DSM-5-TR clinical assessmentConfirm symptoms, duration, impairment, exclusion of mania/hypomania, psychosis, substances, and medical mimics
Suicide risk assessmentAsk directly about ideation, intent, plan, prior attempts, access to firearms/medications, intoxication, psychosis, and protective factors
Targeted medical screenTSH, CBC, CMP, B12/folate, pregnancy test, urine toxicology when new-onset, atypical, severe, or treatment-resistant
Second-line
PHQ-9Severity and response monitoring; item 9 prompts but does not replace full suicide assessment
Medication/substance reviewSteroids, interferon, isotretinoin, levetiracetam, alcohol, stimulants, and sedatives can worsen depression
Bipolar screenAsk about decreased need for sleep, grandiosity, impulsivity, pressured speech, family history, and antidepressant activation
Specialist
Psychiatry referralPsychosis, catatonia, high suicide risk, treatment resistance, pregnancy complexity, diagnostic uncertainty, or ECT/TMS/ketamine consideration
1
Immediate safety
- Hospitalize or obtain emergency psychiatric evaluation for active suicidal intent/plan, psychosis, catatonia, inability to care for self, or lack of safe supervision
- Remove or secure lethal means; involve supports when appropriate; create a safety plan and crisis pathway
- Treat intoxication, withdrawal, delirium, pain, insomnia, and medical contributors urgently
2
First-line treatment
- Mild depression: psychotherapy, behavioral activation, exercise, sleep regularity, and close follow-up
- Moderate-severe depression: SSRI or SNRI plus psychotherapy; common first choices include sertraline, escitalopram, fluoxetine, venlafaxine, or duloxetine
- Allow 4-6 weeks at therapeutic dose before judging response; continue 6-12 months after remission, longer for recurrent disease
3
Special situations
- Psychotic depression: antidepressant + antipsychotic or ECT
- Catatonia: lorazepam challenge and/or ECT
- Treatment resistance: confirm diagnosis/adherence/substances, then switch or augment with bupropion, mirtazapine, lithium, atypical antipsychotic, psychotherapy, ECT, TMS, or ketamine/esketamine
Complications
- Suicide and self-harm:
- Functional decline in work, school, relationships, and self-care:
- Substance use worsening mood and suicide risk:
- Psychotic depression with severe morbidity:
- Recurrent episodes with progressively higher relapse risk:
- Depressive pseudodementia in older adults:
USMLE Step 2 CK Exam Tips
- 1>=5 symptoms for >=2 weeks + depressed mood or anhedonia = MDD
- 2Best next step with suicidal thoughts is direct suicide risk assessment, not reassurance
- 3Depression + decreased need for sleep/grandiosity = bipolar disorder until proven otherwise
- 4Psychotic depression or refusal to eat/drink = ECT is the fastest effective treatment
- 5Normal grief comes in waves; MDD is suggested by persistent anhedonia, worthlessness, psychomotor change, or suicidal intent
- 6SSRIs can cause SIADH/hyponatremia, especially in older adults
practicetest your knowledge on major depressive disorderApply what you've learnt with USMLE Step 2 CK-style questions from the iatroX Q-Bank — psychiatry and beyond.
open q-bank