Major Depressive Disorder
Psychiatry
Illness script · Psychiatry
Major Depressive Disorder
Mood disorder characterized by ≥2 weeks of depressed mood and/or anhedonia plus ≥4 additional neurovegetative symptoms causing functional impairment.
This illness script for Major Depressive Disorder covers predisposing factors, classic presentation, mechanism, workup, management, and the clinical pivots that separate it from look-alikes—written for USMLE Step 1 and clerkship reasoning.
01
Predisposing factors
- Peak onset: late teens–mid 20s; lifetime prevalence ~17%; 2× more common in women
- Strong genetic component; 50% heritability
- Prior depressive episodes, anxiety disorders, trauma/adverse childhood experiences
- Chronic medical illness (stroke, MI, hypothyroidism, cancer)
- Substance use disorder; social isolation; postpartum period
- Low socioeconomic status, recent major life stressors
02
Presentation
- Mnemonic SIG E CAPS: Sleep ↑/↓, Interest ↓ (anhedonia), Guilt/worthlessness, Energy ↓, Concentration ↓, Appetite ↑/↓, Psychomotor changes, Suicidal ideation
- Requires ≥5 symptoms for ≥2 weeks; depressed mood or anhedonia must be one
- Psychomotor retardation or agitation observable by others
- Diurnal variation: symptoms often worse in morning
- May present somatically (fatigue, pain, GI complaints) — common in older adults
- Always assess for suicidality, homicidality, and psychotic features
03
Pathophysiology
- Monoamine deficiency (↓serotonin, norepinephrine, dopamine) in limbic and prefrontal circuits
- HPA axis dysregulation → hypercortisolemia → hippocampal atrophy
- Neuroinflammatory cytokines (IL-6, TNF-α) implicated in anhedonia and fatigue
- Reduced neuroplasticity and BDNF levels; impaired synaptic remodeling
04
Diagnostics
- Clinical diagnosis via DSM-5 criteria — no lab test confirms MDD
- Rule out organic causes: TSH (hypothyroidism), CBC (anemia), BMP, RPR, B12
- PHQ-9 score ≥10 supports diagnosis; ≥20 = severe; use for monitoring treatment response
- Urine drug screen to exclude substance-induced mood disorder
- Distinguish from bipolar disorder: screen for prior manic/hypomanic episodes before prescribing antidepressants
05
Management
- Mild-moderate: psychotherapy (CBT is first-line) ± SSRI
- Moderate-severe: SSRI (sertraline, escitalopram) + CBT is gold standard combination
- Antidepressant full effect takes 4–6 weeks; reassess at 4 weeks; adequate trial = 6–8 weeks at therapeutic dose
- Treatment-resistant (failed ≥2 adequate trials): augment (lithium, atypical antipsychotic), switch, or refer for ECT
- ECT: fastest, most effective; indicated for severe refractory MDD, psychotic depression, catatonia, suicidal crisis
- Hospitalization if active suicidal ideation with plan/intent or inability to contract for safety
06
Clinical pivots
How to separate this script from the look-alikes that show up on exams and on the wards.
Bipolar disorder (depressed episode)
History of manic/hypomanic episode distinguishes bipolar; SSRIs alone can precipitate mania
Persistent depressive disorder (dysthymia)
Dysthymia is milder but chronic (≥2 years); MDD requires full symptom threshold for ≥2 weeks
Hypothyroidism
TSH elevated in hypothyroidism; both cause fatigue and low mood — always check TSH first
Adjustment disorder with depressed mood
Adjustment disorder is identifiable stressor-triggered, symptoms < 6 months, and does not meet full MDD criteria
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Educational use only. This illness script is a study framework, not medical advice. Confirm decisions with current guidelines and your clinical supervisors.