Pimozide

Medical uses

Pimozide is used for Tourette syndrome, and resistant tics (Europe, United States, and Canada) and in Europe for schizophrenia, chronic psychosis, delusional disorder, and paranoid personality disorder.

Efficacy

A 2013 systematic review compared pimozide with other antipsychotics for schizophrenia or related psychoses: Pimozide versus any other antipsychotic

In one case a series of 33 patients with delusional parasitosis (median age, 60 years), pimozide was prescribed for 24 patients, 18 of whom took the drug. The dose ranged from 1 to 5 mg daily. No information regarding initial dosing was specified, although the dose was continued for 6 weeks prior to tapering. Of those patients receiving pimozide, 61% (11/18) experienced improvement in or full remission of symptoms. The use of pimozide for the treatment of delusional parasitosis is based primarily on data from case series/reports that demonstrate some efficacy in the majority of patients. Currently, atypical antipsychotics such as olanzapine or risperidone are used as first line treatment. However, patients who experience negative side-effects with the first line medications are typically given pimozide.

Contraindications

It is contraindicated in individuals with either acquired, congenital or a family history of QT interval prolongation. Its use is advised against in individuals with people with either a personal or a family history of arrhythmias or torsades de pointes. Likewise its use is also advised against in individuals with uncorrected hypokalaemia and hypomagnesaemia or clinical significant cardiac disorders (e.g. a recent myocardial infarction or bradycardia. It is also contraindicated in individuals being cotreated with selective serotonin reuptake inhibitors (SSRI) or in those with a known hypersensitivity to pimozide or other diphenylbutyl-piperidine derivatives. Likewise its use is contraindicated in individuals receiving treatment with CYP3A4, CYP1A2, or CYP2D6 inhibitors.

Side effects

Very common (10% frequency) side effects include:

• Akinesia
• Constipation
• Dizziness
• Dry mouth
• Hyperhidrosis
• Nocturia
• Somnolence
• Speech disorder

Overdose

Pimozide overdose presents with severe extrapyramidal symptoms, hypotension, sedation, QT interval prolongation and ventricular arrhythmias including torsades de pointes. Gastric lavage, establishment of a patent airway and, if necessary, mechanically assisted respiration is the recommended treatment for pimozide overdose. Cardiac monitoring should be continued for at least 4 days due to the long half-life of pimozide.

Pharmacology

Pimozide acts as an antagonist of the D2, D3, and D4 receptors and the 5-HT7 receptor. It is also a hERG blocker.

Similarly to other typical antipsychotics pimozide has a high affinity for the dopamine D2 receptor and this likely results in its sexual (due to prolactin hypersecretion) and extrapyramidal side effects as well as its therapeutic efficacy against the positive symptoms of schizophrenia.

History

In 1985 pimozide was approved by the FDA for marketing as an orphan drug for the treatment of Tourette's syndrome.

Notes

References

References

1. Anvisa. (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial". [[Diário Oficial da União]].
2. (1999). "Delusional disorder". Cambridge University Press.
3. (November 2013). "Pimozide for schizophrenia or related psychoses". The Cochrane Database of Systematic Reviews.
4. (February 2014). "Pimozide: parasitosis (delusional)". Hospital Pharmacy.
5. (March 2006). "Successful treatment of delusions of parasitosis with olanzapine". Archives of Dermatology.
6. (2012). "The Maudsley prescribing guidelines in psychiatry". Wiley-Blackwell.
7. (12 January 2011). "PDSP K_i Database". University of North Carolina at Chapel Hill and the United States National Institute of Mental Health.
8. (January–March 2011). "Anti-depressant like Effect of Pimozide in Acute and Chronic Animal Models of Depression". Indian Journal of Pharmaceutical Education and Research.
9. (2010). "Goodman and Gilman's The Pharmacological Basis of Therapeutics". McGraw-Hill Professional.
10. "Oral (pimozide) dosing, indications, interactions, adverse effects, and more". WebMD.
11. (2 April 2013). "Oral 4 mg tablets. - Summary of Product Characteristics". Janssen-Cilag Ltd.
12. (12 February 2013). "Pimozide". Pharmaceutical Press.
13. (July 2012). "ORAP (pimozide) tablet [Teva Select Brands]". Teva Select Brands.
14. (June 1985). "Pimozide: use in Tourette's syndrome". Drug Intelligence & Clinical Pharmacy.