First-generation (typical) antipsychotic; piperazine phenothiazine derivative
Dopamine D₂ receptor antagonist with moderate anticholinergic and antihistaminic properties; also has antiemetic effects via dopamine blockade in the chemoreceptor trigger zone
Schizophrenia, severe nausea and vomiting
Augmentation in treatment-resistant depression (especially in tricyclic antidepressant [TCA] combinations), acute agitation, and behavioral dysregulation in neuropsychiatric conditions
Oral tablet, oral solution, short-acting intramuscular (IM) injection
Typically initiated at 4–8 mg p.o. twice daily, titrated gradually based on response and tolerability
8–64 mg/day, divided BID to QID
Hepatic metabolism via CYP2D6 with variable half-life (~8–12 hours); steady state reached in several days
Extrapyramidal symptoms (EPS), sedation, dry mouth, constipation, blurred vision, and weight gain
Tardive dyskinesia, neuroleptic malignant syndrome (NMS), QTc prolongation, cholestatic jaundice, and seizure threshold lowering
Monitor for EPS (e.g., AIMS every 6–12 months), weight and metabolic parameters periodically, and ECG if cardiac risk factors or polypharmacy. Consider prolactin or liver enzymes if symptomatic.
Increased mortality in elderly patients with dementia-related psychosis
Use caution in older adults and individuals with cognitive impairment, Parkinson’s disease (PD), or traumatic brain injury (TBI) due to heightened risk of rigidity, sedation, and falls. Perphenazine is not typically used first-line for psychosis in dementia due to increased sensitivity to EPS and anticholinergic burden. Lower doses and close monitoring may be considered if used in medically complex patients.