pimozide

General Information

Pimozide is an antipsychotic-class dopamine receptor antagonist used primarily for tic suppression in Tourette’s disorder. The label states it is not intended as a first-choice treatment and is reserved for patients who have failed standard treatment and whose functioning is severely compromised by tics (label).

Cardiac safety is central: pimozide prolongs the QT interval and has extensive contraindicated drug interactions. Labeling calls for a baseline ECG and periodic ECG monitoring, especially during dose adjustment (label).

The AAN guideline summary for tic disorders emphasizes behavioral interventions and layered treatment selection; dopamine-blocking agents are typically reserved for more severe impairment or when other options are insufficient (Pringsheim 2019).

The pimozide compare view, evidence feed, and print page support interaction review and counseling.

Pimozide’s role is defined by two constraints: (1) it is reserved for clinically significant Tourette impairment after other options, and (2) its QT risk and interaction list require a careful medication review. Co-management with neurology is common (label/Pringsheim 2019).

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Dopamine receptor antagonism is thought to underlie tic suppression (label).

Dopamine blockade also explains antipsychotic-class risks (EPS and tardive dyskinesia).

• Dopamine receptor antagonism (tic suppression/antipsychotic-class effects).

Metabolism and Pharmacokinetics

• The label notes that pimozide is metabolized in part by CYP3A4 and that CYP3A4 inhibition (e.g., macrolides) can increase exposure; multiple macrolide antibiotics are contraindicated (label).
• The label includes CYP2D6 genotype-based dose limits at higher doses due to exposure differences and QT risk (label).

Dosing and Administration

• The label emphasizes slow, gradual titration to balance tic suppression with adverse effects. Baseline and periodic ECG monitoring is described as essential, particularly during dose adjustment (label).
• Adults: label describes starting 1–2 mg/day in divided doses and increasing every other day as needed. Most patients are maintained at <0.2 mg/kg/day or 10 mg/day (whichever is less); higher doses are not recommended (label).
• Children: label describes starting 0.05 mg/kg once daily (preferably at bedtime) and titrating every third day to a maximum of 0.2 mg/kg/day (not to exceed 10 mg/day). It also describes CYP2D6 genotyping requirements at higher doses (label).
• The label discusses periodic attempts to reduce dose to determine if tics persist, acknowledging that transient rebound tic worsening can occur after dose reduction (label).

Monitoring & Labs

• Baseline ECG and periodic ECGs during dose adjustment (label).
• Electrolytes (hypokalemia/hypomagnesemia increases torsades risk; label).
• Medication list review after any new prescription (QT and CYP interactions).
• Movement symptoms and tardive dyskinesia screening.
• Sedation and functional impairment when combined with other sedatives.

Adverse Effects

Interactions

• Extensive QT-prolonging contraindications are listed in labeling. The label highlights macrolides (clarithromycin, erythromycin, azithromycin, and others) as contraindicated due to QT and metabolism effects (label).
• Pimozide is contraindicated with citalopram and escitalopram due to QTc increases observed in controlled study (label).
• CYP3A4 or CYP2D6 inhibitors can increase exposure; interaction review is central before dose escalation (label).

Other Useful Information

• Tourette treatment selection is typically layered: behavioral interventions and lower-risk medications are often tried before dopamine-blocking agents; care teams weigh tic impairment against medication adverse effects (Pringsheim 2019).

References

1. Pimozide tablets prescribing information — DailyMed (2024)
2. Practice guideline recommendations summary: Treatment of tics in people with Tourette syndrome and chronic tic disorders — Neurology (PMC) (2019)
3. Torsade de Pointes (StatPearls) — StatPearls Publishing (NCBI Bookshelf) (2025)
4. AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology — Pharmacopsychiatry (2018)