Pimozide
ORAP
What it isHigh-potency D2/D3-antagonist antipsychotic; severe motor and vocal tics in Tourette syndrome.
Why this oneIts narrow niche is disabling Tourette tics after safer alpha-2 agonists and newer antipsychotics fail.
What limits itQT prolongation and sudden death require ECG monitoring; CYP3A4 or CYP2D6 inhibition can make exposure dangerous.
FDA-approved for
- Tourette syndrome (1984)
Off-label
- delusional disorder
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Tourette's Disorder (tic suppression) | Adult | 1-2 mg/day in divided doses | <0.2 mg/kg/day or 10 mg/day (whichever less) | 0.2 mg/kg/day or 10 mg/day; 4 mg/day if poor CYP2D6 metabolizer |
| Tourette's Disorder (tic suppression) | Children ≥12 yr | 0.05 mg/kg QHS | Titrate to effect | 0.2 mg/kg/day, not to exceed 10 mg/day; 0.05 mg/kg/day if poor CYP2D6 metabolizer |
Titration Adults: increase every other day; children: increase every 3rd day (poor CYP2D6 metabolizers: not earlier than 14 days)
Renal Undefined
Hepatic Undefined
Instructions
- ECG at baseline and periodically, especially during dose adjustment
- CYP2D6 genotyping at doses >4 mg/day (adults) or >0.05 mg/kg/day (children)
- Gradual withdrawal recommended
Contraindications
- Simple tics or tics other than those of Tourette's Disorder
- Drugs that may cause tics (pemoline, methylphenidate, amphetamines) until patient withdrawn to determine cause
- Congenital long QT syndrome, history of cardiac arrhythmias, other QT-prolonging drugs, or hypokalemia/hypomagnesemia
- Severe toxic CNS depression or comatose states
- Macrolide antibiotics (clarithromycin, erythromycin, azithromycin, dirithromycin, troleandomycin) — CYP3A4/QT risk
- Strong CYP2D6 inhibitors and concomitant citalopram, escitalopram, paroxetine, or sertraline — CYP/QT risk
- Azole antifungals (itraconazole, ketoconazole), protease inhibitors, and nefazodone — CYP3A4 inhibition
Cautions
- Tardive dyskinesia (may be irreversible)
- Neuroleptic malignant syndrome
- ECG changes/QT prolongation; sudden deaths and seizures reported at doses >20 mg/day
- Extrapyramidal reactions, often early in treatment
Adverse reactions
- Sedation
- Drowsiness
- Akathisia
- Akinesia
- Dry mouth
- Visual disturbance
- Somnolence and behavioral effects (children)
Pregnancy Use only if benefit outweighs risk; third-trimester exposure risks neonatal extrapyramidal/withdrawal symptoms.
Lactation Undefined
⚠ BOXED WARNING
- QT prolongation and sudden death
Cost, est. cash$10–$300/month
Generic entry2015
Classes and tags
Clinical profile
Legacy pregnancy categoryC
Defining liabilityMetabolic effects, extrapyramidal symptoms/tardive dyskinesia and agent-specific QT or orthostatic risk.
Mechanism of action: Pimozide ballicule
Open Pimozide in the interactive console ↗
Memory aids: mascots and interaction avatars
Spooky greyscale mascot → high-potency first generation antipsychotic (FGA)
Cursing → approved for Tourette’s only (vocal tics may manifest as coprolalia)
QT prolongation
