Major depressive disorder (MDD) is a common, recurrent, and potentially debilitating mental health condition characterized by persistent low mood, diminished interest in pleasurable activities (anhedonia), and a constellation of cognitive, somatic, and behavioral symptoms that significantly impair functioning. Lifetime prevalence is approximately 17-20% with higher rates in women (2:1 female-to-male ratio). MDD is the leading cause of disability worldwide and contributes to significant morbidity, mortality (15% lifetime suicide risk in untreated cases), and economic burden. Pathophysiology involves disturbances in monoaminergic neurotransmitter systems (serotonin, norepinephrine, dopamine), HPA axis dysregulation, neuroinflammation, neuroplasticity deficits in hippocampus and prefrontal cortex, and genetic vulnerability (heritability ~40%).
DSM-5-TR diagnostic criteria require at least 5 of 9 symptoms during the same 2-week period (with at least one being depressed mood or anhedonia): (1) depressed mood most of the day, nearly every day; (2) markedly diminished interest or pleasure in all/almost all activities; (3) significant weight loss or gain (>5%) or appetite changes; (4) insomnia or hypersomnia; (5) psychomotor agitation or retardation; (6) fatigue or loss of energy; (7) feelings of worthlessness or excessive guilt; (8) diminished concentration or indecisiveness; (9) recurrent thoughts of death, suicidal ideation, or suicide attempt. Symptoms must cause clinically significant distress or impairment, not be attributable to substances or medical conditions, and not better explained by other psychiatric disorders. Severity specifiers (mild, moderate, severe), psychotic features, melancholic, atypical, peripartum, and seasonal patterns refine clinical characterization.
Treatment is multimodal and individualized: first-line includes selective serotonin reuptake inhibitors (sertraline 50-200 mg, escitalopram 10-20 mg, fluoxetine 20-80 mg, paroxetine, citalopram), serotonin-norepinephrine reuptake inhibitors (venlafaxine XR 75-225 mg, duloxetine 60-120 mg, desvenlafaxine), atypical antidepressants (bupropion 300-450 mg useful for fatigue/concentration without sexual side effects, mirtazapine 30-45 mg useful for insomnia/anorexia), and serotonin modulators (vortioxetine, vilazodone). Evidence-based psychotherapies include cognitive behavioral therapy (CBT), behavioral activation, interpersonal therapy (IPT), problem-solving therapy, and mindfulness-based cognitive therapy. Treatment-resistant depression (failure of >=2 adequate antidepressant trials) is managed with augmentation strategies (lithium, second-generation antipsychotics aripiprazole/quetiapine/olanzapine-fluoxetine, T3 thyroid hormone), switching antidepressants, ketamine/esketamine intranasal spray (rapid-acting NMDA antagonist), repetitive transcranial magnetic stimulation (rTMS), and electroconvulsive therapy (ECT) for severe/psychotic/catatonic depression. Maintenance treatment for 6-12 months after symptom remission is standard, with longer maintenance for recurrent episodes.