Psychotic depression, formally classified as Major Depressive Disorder with Psychotic Features in DSM-5-TR or Severe Depression with Psychotic Symptoms in ICD-11, is a severe and distinct subtype of major depression characterized by the presence of delusions and/or hallucinations during a major depressive episode. Affects 14-20% of patients hospitalized for major depressive disorder and 30-50% of older adults with severe depression. Distinguished from schizophrenia and schizoaffective disorder by the temporal relationship of psychotic symptoms occurring exclusively during mood episodes.
Clinical features include severe major depressive episode plus psychotic features. Mood-congruent psychotic features are most common (consistent with depressive themes): delusions of guilt (responsible for catastrophes), worthlessness, nihilism (Cotard syndrome with belief that body parts or self do not exist), poverty, somatic delusions (incurable disease, internal decay), persecution (deserved punishment), and auditory hallucinations (derogatory voices, commands to harm self). Mood-incongruent features (less common, possibly worse prognosis): grandiose, persecutory unrelated to depressive themes. Severe psychomotor retardation or agitation, profound anhedonia, marked guilt, somatic complaints, and high suicide rates (3-5x higher than non-psychotic MDD) are characteristic.
Diagnosis is clinical based on DSM-5-TR criteria for major depressive episode plus psychotic features specifier. Differential diagnosis includes bipolar I depression with psychotic features (history of mania), schizoaffective disorder (psychosis without mood symptoms for ≥2 weeks), schizophrenia (chronic psychosis), substance/medication-induced, medical (thyroid, B12, neurological), and dementia. Workup: comprehensive history, mental status examination including suicide risk assessment, screening labs (TSH, B12, folate, vitamin D, RPR, HIV), urine toxicology, brain imaging if indicated. First-line treatment per APA/NICE guidelines: combination antidepressant + antipsychotic (e.g., venlafaxine + olanzapine; sertraline + risperidone; bupropion + quetiapine; not antidepressant alone). Specific evidence: STOP-PD trial supported sertraline + olanzapine. Treatment duration: continue combination for at least 6-12 months, gradual antipsychotic taper before antidepressant. Electroconvulsive therapy (ECT) is highly effective (response 80-95%) and considered first-line for severe, life-threatening, treatment-resistant, catatonic, geriatric, or pregnant patients; response is rapid (1-3 weeks) and acceptability is high; acute course typically 6-12 sessions, maintenance ECT for relapse prevention. Hospitalization is often required for safety. Suicide prevention is paramount: close monitoring, means restriction, family education. Comorbidities (medical, anxiety, substance) are addressed concurrently. Long-term: maintenance therapy, relapse prevention, psychotherapy (CBT for depression after acute resolution), and lithium augmentation as adjunct.