North Carolina Neurological Foundation (NCNF)

Major Depressive Disorder With Psychotic Features

Major depressive disorder with psychotic features is a severe variant of MDD where patients experience delusions or hallucinations congruent or incongruent with depressive themes. Etiology involves genetic vulnerability, dysregulation of dopaminergic, serotonergic, and glutamatergic pathways, and often severe psychosocial stressors. Clinically, patients present with profound low mood, anhedonia, psychomotor retardation, and psychotic symptoms such as nihilistic delusions or auditory hallucinations. Diagnosis relies on DSM-5 or ICD-11 criteria, emphasizing differentiation from schizoaffective disorder, bipolar disorder with psychotic features, and primary psychotic disorders. Management requires a combination of antidepressants and antipsychotic medications, often supplemented with psychotherapy, hospitalization if necessary for safety, and careful monitoring due to elevated suicide risk.