| Drug class |
Atypical/atypical‑like antipsychotic (dopamine‑D₂/serotonin‑5‑HT₂A antagonist) |
| Approval status |
Approved by the FDA for Tourette’s syndrome and tic disorders. Off‑label use in schizophrenia is not formally approved, but it has been prescribed in certain settings. |
| Typical indications (off‑label) |
Schizophrenia (especially when other antipsychotics are ineffective or not tolerated), certain psychotic episodes, and severe agitation. |
| Common dosing |
• Adults: 1 mg orally once daily (start low) → titrate to 4 mg/day (max).
• Children: 0.25 mg/kg/day (max 4 mg), titrated slowly.
Note: Doses are highly individualized; always follow a prescriber's guidance. |
| Mechanism of action |
Pimozide competitively blocks dopamine D₂ receptors and serotonin 5‑HT₂A receptors. This reduces dopaminergic activity in the mesolimbic pathway (helping with positive symptoms) while maintaining some dopaminergic tone in the nigrostriatal pathway, which is why extrapyramidal side‑effects can be less pronounced than older antipsychotics. |
| Key pharmacokinetics |
• Oral bioavailability: ~50–60 %
• Peak plasma levels: 1–2 hours
• Half‑life: 18–30 hours (longer in chronic use)
• Metabolism: Primarily hepatic (CYP2D6, CYP3A4) |
| Major side‑effects |
• Extrapyramidal symptoms (EPS) – dystonia, tremor, tardive dyskinesia
• Anticholinergic effects – dry mouth, constipation, blurred vision
• QT‑interval prolongation (risk of torsades de pointes)
• Weight gain, hyperlipidemia, hyperglycemia
• Sedation, orthostatic hypotension |
| Contraindications |
• Known hypersensitivity to pimozide or its excipients
• Concomitant use of drugs that prolong the QT interval (e.g., quinidine, sotalol)
• Severe hepatic or renal impairment
• Pregnancy (category D; avoid unless benefits outweigh risks) |
| Drug interactions |
• QT‑prolonging agents (anti‑arrhythmics, macrolide antibiotics)
• CYP3A4 inhibitors (ketoconazole, clarithromycin) → ↑ pimozide levels
• CYP2D6 inhibitors (fluoxetine, paroxetine) may increase risk of EPS
• Alcohol and CNS depressants may enhance sedative effect |
| Monitoring recommendations |
• Baseline ECG to check QTc interval, repeat after dose titration or any dose >2 mg/day
• Periodic ECGs every 6–12 months (or more frequently if high dose, co‑administered QT‑prolonging drugs, or if the patient is on long‑term therapy)
• Baseline and periodic metabolic panel (glucose, lipids)
• Neurologic exam for EPS
• Weight, BMI, fasting glucose for metabolic monitoring |