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Typical (First-Generation) Antipsychotic

Pimozide | Orap

Clinical Overview

Pimozide is a diphenylbutylpiperidine antipsychotic specifically indicated for the suppression of motor and phonic tics in patients with Tourette’s disorder who have failed to respond adequately to standard treatment. It is reserved for severe cases due to its significant side effect profile and potential for serious cardiac complications.

Primary Clinical Applications

Pimozide is indicated exclusively for Tourette’s disorder in patients with severe symptoms who cannot take or have not responded to other medications. It is not approved for other psychotic conditions and should only be used when the potential benefits clearly outweigh the substantial risks.

Mechanism and Clinical Considerations

As a potent dopamine receptor antagonist, pimozide effectively suppresses tics but carries significant risks including QT prolongation, extrapyramidal symptoms, and tardive dyskinesia. The medication requires careful cardiac monitoring and should be used at the lowest effective dose.

Specialized Usage Requirements

Due to its narrow therapeutic indication and significant risk profile, pimozide requires specialized monitoring including baseline and periodic ECGs, and should only be prescribed by clinicians experienced in treating Tourette’s disorder.

Prescribing Information

Dosing & Administration

Tourette’s Disorder:

  • Initial: 0.05 mg/kg preferably at bedtime (or 1-2 mg daily)
  • Titration: Increase every other day as needed
  • Maximum: 0.2 mg/kg/day or 10 mg/day (whichever is less)

Pediatric (>12 years):

  • Same dosing as adults
  • Children <12 years: Not recommended

Indications

  • Tourette’s disorder (motor and phonic tics)
  • Reserved for severe cases unresponsive to standard treatment

Contraindications

  • History of cardiac arrhythmias
  • Congenital long QT syndrome
  • Concurrent use of drugs that prolong QT interval
  • Severe CNS depression
  • Comatose states
  • History of severe toxic CNS depression

Warnings & Precautions

  • Boxed Warning: QT prolongation and risk of sudden death
  • Cardiac monitoring: Baseline and periodic ECGs required
  • Tardive dyskinesia: Risk increases with duration of treatment
  • Neuroleptic malignant syndrome: Rare but potentially fatal
  • Electrolyte monitoring: Hypokalemia and hypomagnesemia increase QT risk

Drug Interactions

  • QT-prolonging drugs: Contraindicated (quinidine, procainamide, amiodarone)
  • CYP3A4 inhibitors: Increase pimozide levels
  • CNS depressants: Enhanced sedation
  • Phenothiazines: Additive anticholinergic effects

Adverse Reactions

Common:

  • Extrapyramidal symptoms, sedation, anticholinergic effects

Serious:

  • QT prolongation, cardiac arrhythmias, tardive dyskinesia

Special Populations

  • Pediatric: Not recommended under 12 years
  • Elderly: Increased sensitivity to adverse effects
  • Hepatic/Renal Impairment: Use with extreme caution
  • Pregnancy: Category C – use only if clearly needed
Medical Disclaimer: This information is for educational purposes only and is not intended as medical advice. Always consult with qualified healthcare professionals before making any treatment decisions. Individual patient circumstances may vary significantly.