Literature DB >> 28615787

Pimozide: An Old Wine in a New Bottle!

Ahmed Naguy1.   

Abstract

Entities:  

Year:  2017        PMID: 28615787      PMCID: PMC5461863          DOI: 10.4103/IJPSYM.IJPSYM_400_16

Source DB:  PubMed          Journal:  Indian J Psychol Med        ISSN: 0253-7176


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Sir, Pimozide is a high-potency conventional antipsychotic drug of the diphenylbutylpiperidine group (2 mg ≈ 2–3 mg haloperidol). It selectively blocks D1–D2 receptors and additionally calcium channels. It has a long half-life (55–66 h) allowing dosing q >24 h and metabolized mainly by CYP3A4. It is metabolic friendly. It caused 5 kg weight loss in a study by McCreadie et al.[1] in chronic schizophrenia. This would be advantageous given the current rampant use of atypical antipsychotics at the expense of metabolic syndrome and without demonstrable superior efficacy (e.g., in CATIE, CUtLASS studies). This holds true as shown in a recent Cochrane database systematic review of pimozide for schizophrenia or related psychoses.[2] Concerns over torsadogenicity might be tempered by close monitoring of serum, potassium, and magnesium, and surface electrocardiogram. QTc prolongation is dose dependent with heightened risk beyond 16 mg/day. Hence, keeping the maximum daily dose at 10 mg/day and avoiding polypharmacy (notably CYP3A4 inhibitors) would be more prudent. Risk is cumulative and multifactorial and this should never deter clinicians from prescribing pimozide out of this “QTc phobia.”[3] Of interest, Mendhekar et al.[4] have reported safe and effective pimozide augmentation to clozapine in resistant schizophrenia. Pimozide, an orphan drug, is FDA-approved for treating Tourette syndrome. Sallee et al.[5] have found it superior to haloperidol with less neurologic side effects. Pimozide is the European Medicines Agency-approved drug for treating schizophrenia and has long been the drug of choice in delusional disorders, notably somatic subtype as shown by Silva et al.[6] Puri and Singh.[7] have reported a successful pimozide treatment of a case of gender dysphoria superimposed on intellectual disability. Similarly, Martins et al.[8] described a case series of delusional parasitosis (Ekbom's syndrome) successfully treated with pimozide. Interestingly, pimozide helped in treating deficit-state schizophrenia as reported by Feinberg et al.[9] However, in a recent randomized controlled trial by Gunduz-Bruce et al.,[10] the efficacy of pimozide augmentation for clozapine partial responders in schizophrenia was questioned. Pimozide might also be used for treating Sydenham's chorea for its dopamine blockade actions. Similarly, McArthur et al.[11] reported its use in combination with tetrabenazine for treating Huntington's disease. Owing to calcium channel blockade, it confers antimanic properties as demonstrated by Cookson et al.[12] and Post et al.[13] Pimozide has been used for behavioral facets in autism spectrum disorder (ASD) as shown in an open pilot study by Ernst et al.[14] Naruse et al.[15] conducted a multi-center, double-blinded, placebo-controlled, cross-over study involving 87 patients (aged 6–13 years) with behavioral problems, 34 of whom had autism where pimozide was superior to placebo. Pimozide is the only drug approved for ASD in Japan.[16] Pimozide has also been used to augment selective serotonin reuptake inhibitor response in refractory obsessive-compulsive disorder (OCD) and obsessive-compulsive-related disorders. Delgado et al.[17] have reported on pimozide/fluvoxamine combination in resistant OCD with concurrent Tourette syndrome. It is similarly used, among others, for functional itch disorder.[18] All these would converge into a “resurrection” of pimozide use in clinical practice, given demonstrated high-potency, broad-spectrum indications, FDA-approval at age 12, and, above all benign side effects profile, notably metabolic syndrome.

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Conflicts of interest

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  18 in total

1.  The successful treatment of a gender dysphoric patient with pimozide.

Authors:  B K Puri; I Singh
Journal:  Aust N Z J Psychiatry       Date:  1996-06       Impact factor: 5.744

2.  Delusional infestation: a case series from a university dermatology center in São Paulo, Brazil.

Authors:  Ana Claudia G P Martins; Carolina P Mendes; Marcello M S Nico
Journal:  Int J Dermatol       Date:  2015-10-16       Impact factor: 2.736

3.  Fluvoxamine/pimozide treatment of concurrent Tourette's and obsessive-compulsive disorder.

Authors:  P L Delgado; W K Goodman; L H Price; G R Heninger; D S Charney
Journal:  Br J Psychiatry       Date:  1990-11       Impact factor: 9.319

4.  Relative efficacy of haloperidol and pimozide in children and adolescents with Tourette's disorder.

Authors:  F R Sallee; L Nesbitt; C Jackson; L Sine; G Sethuraman
Journal:  Am J Psychiatry       Date:  1997-08       Impact factor: 18.112

Review 5.  Psychogenic Itch Management.

Authors:  Jacek C Szepietowski; Radomir Reszke
Journal:  Curr Probl Dermatol       Date:  2016-08-23

Review 6.  Pimozide for schizophrenia or related psychoses.

Authors:  Meghana Mothi; Stephanie Sampson
Journal:  Cochrane Database Syst Rev       Date:  2013-11-05

7.  Once weekly pimozide versus fluphenazine decanoate as maintenance therapy in chronic schizophrenia.

Authors:  R McCreadie; M Mackie; D Morrison; J Kidd
Journal:  Br J Psychiatry       Date:  1982-03       Impact factor: 9.319

8.  Efficacy of pimozide augmentation for clozapine partial responders with schizophrenia.

Authors:  Handan Gunduz-Bruce; Stephen Oliver; Ralitza Gueorguieva; Kimberlee Forselius-Bielen; Deepak C D'Souza; Zoran Zimolo; Cenk Tek; Styliani Kaliora; Susan Ray; Georgios Petrides
Journal:  Schizophr Res       Date:  2012-12-06       Impact factor: 4.939

9.  Pimozide in autistic children.

Authors:  M Ernst; H J Magee; N M Gonzalez; J J Locascio; C R Rosenberg; M Campbell
Journal:  Psychopharmacol Bull       Date:  1992

10.  Prescription trends in children with pervasive developmental disorders: a claims data-based study in Japan.

Authors:  Michihiro Satoh; Taku Obara; Hidekazu Nishigori; Nobuhiro Ooba; Yoshihiko Morikawa; Mami Ishikuro; Hirohito Metoki; Masahiro Kikuya; Nariyasu Mano
Journal:  World J Pediatr       Date:  2016-06-10       Impact factor: 2.764

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  1 in total

Review 1.  Repurposing of Drug Candidates for Treatment of Skin Cancer.

Authors:  Hernán Cortés; Octavio D Reyes-Hernández; Sergio Alcalá-Alcalá; Sergio A Bernal-Chávez; Isaac H Caballero-Florán; Maykel González-Torres; Javad Sharifi-Rad; Manuel González-Del Carmen; Gabriela Figueroa-González; Gerardo Leyva-Gómez
Journal:  Front Oncol       Date:  2021-01-08       Impact factor: 6.244

  1 in total

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