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Pimozide: Use in dermatology

Published Web Location

https://doi.org/10.5070/D39mw0r7w7
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Pimozide: Use in Dermatology
Willem A.van Vloten, MD, PhD1
Dermatology Online Journal 9 (2): 3

1. Department of Dermatology, University Medical Center Utrecht, Post Box 85500, 3508 GA Utrecht, the Netherlands. w.a.vanvloten@wxs.nl

Abstract

Pimozide is widely used in psychiatry for chronic psychoses, schizophrenia, the syndrome of Gilles de la Tourette and to a certain extent, also in dermatology. The only dermatological indication is for delusions of parasitosis. Though there is a good rationale for using pimozide in this disease, the majority of the studies on pimozide in dermatology are uncontrolled trials and case reports.


Introduction

Pimozide is a neuroleptic and a selective blocker of dopamine D2 receptors.[1] In 1975 it was used for the first time in patients with monosymptomatic hypochondriacal psychoses (MHP's). In all five patients treated, there was disappearance or marked improvement of the symptoms.[2] Monosymptomatic hypochondriacal psychoses are defined as disorders in which a single delusion is present without other thought disorders and the delusions are not secondary to other psychiatric diseases.[3] Patients with MHP's generally appear normal in behavior. Since patients with delusions of parasitosis believe that the disease is a dermatological disease and not a psychiatric disorder they seek dermatological help.[4] "Folie a deux" is the term which describes the situation when the delusion is shared by another person, usually the spouse.


Chemistry

The chemical formula of pimozide is (C28 H 29 F2 N3O) is: 1- [1- [4,4- Bis(4- fluorphenyl) butyl] -4- piperidinyl] -1, 3- dihydro-2 H- benzimidazol -2-one. The molecular weight is 461.56


Pharmacology and toxicology

Pimozide is a highly selective blocker of dopamine D2 receptors in the limbic system, the corpus striatum and the pituitary. It also blocks the alpha-1-adrenoceptors and serotoninergic receptors, although to a lesser extent. The oral bioavailability of pimozide is about 50%. After oral administration the peak plasma concentration is reached in 6-8 hours. The plasma half-life of pimozide after a single oral dose is reported with a wide range of 29 - 150 hours. After ingestion pimozide is widely distributed in the body, but with increased concentrations in the liver. It is metabolized in the liver and the metabolites are excreted primarily in the urine and to lesser extent in the feces.

There is no direct correlation between the plasma concentration of pimozide and the clinical effect. In patients receiving 6 mg per day the plasma concentration may vary as much as 17 fold.[7] Therefore, the dosage to be given should be adapted individually. Generally, the effective dose range is from 2.8 to 11.4 mg/day. The action of pimozide lasts 24 - 48 hours, which allows it to be administered as a single daily dose in common practice.

As with other neuroleptic drugs pimozide in higher dosage may lead to a prolonged QT interval on the ECG. In the used dosage pimozide does not lead to sedation. Postural hypotension may result from blockage of the alpha-1-adrenoceptors. [5,6] Signs of acute toxicity include tremor, sedation and convulsions. Oral LD50 range from 10 g.kg-1 in guinea pigs to 40 mg.kg-1 in dogs. Chronic toxicity has not been reported.


Use in dermatology

Patients with delusions of parasitosis usually visit a dermatologist rather than a psychiatrist for the reason that they have a firm belief that they suffer from a dermatological disease, such as an infestation, and not a psychiatric disorder. For that reason most of the reports on delusions of parasitosis are published in dermatoloical journals. The diagnosis is often easy to make. Typical patients have a tendency to ramble in their descriptions. They generally disagree with or completely disregard even the slightest consideration of an alternative diagnosis. They relate histories of numerous previous evaluations and useless treatments. The so-called "proof" is the moment that the patient shows a matchbox in which he or she has gathered the "parasites." In fact, the contents of such a box are hairs, scales of skin, bits of wool, and crusts.

Prior to the use of pimozide the remission rate in this delusional disorder was about 30% as shown in a meta-analysis of 1223 case reports.[8] However, when pimozide was used for the first time in a double blind study of patients with delusions of parasitosis, after 6 weeks of pimozide medication, 10 out of 11 patients had improved markedly.[9] In addition, a 34 month follow-up study of 14 patients who were treated with pimozide 19 to 44 months earlier, revealed that 50% of these patients no longer suffered from delusions of parasitosis.[10] Zomer et al. studied 33 patients with delusions of parasitosis treated with pimozide. Of 18 patients treated with pimozide 11 obtained a remission. Of the 15 patients not treated with pimozide, only 3 showed a remission.[4]. Due to dramatic results such as these, pimozide is considered the drug of choice for the treatment of delusions of parasitosis.[11,12,13]

The lowest effective dosage of pimozide should be used to minimize side effects. The dosage used in delusions of parasitosis is 1-5 mg/d for about 6 weeks. Improvement is usually noticed after 3-4 weeks of medication.

The antipsychotic drug, risperidone, has also been shown to be effective in the treatment of delusions of parasitosis. Its much safer adverse effect profile compared to pimozide would make it a good alternative. However no large studies are available at present using risperidone in delusions of parasitosis.[14]


Psychiatric indications

  • Acute and chronic schizophrenia,
  • Syndrome of Gilles de la Tourette,
  • Mania and hypomania
  • Monosymptomatic hypochondrical psychoses,
  • Trigeminal neuralgia.

In acute psychoses the therapeutic dosage is 5-50 mg daily with a mean dose of 20 mg.[15] However due to reports of serious side effects a maximum daily dosage of 20 mg is now recommended. In the UK, the Committee of Safety for Medicines (CSM) recommends an ECG prior to treatment and follow-up ECG's periodically when dosages over 16 mg daily are used. In chronic psychotic conditions the effective dosage is 2-20 mg daily.


Contraindications

  • Hypersensitivity to pimozide
  • Cardiac arrythmic disorders and ECG abnormalities
  • Congenital prolonged QT interval
  • Severe CNS depression
  • Parkinson's disease (relatively contra-indicated)
  • Endogenous depression (relatively contra-indicated)
  • Age under 12 years

Pregnancy and lactation

Although no adverse effects have been reported in pregnancy, safety has not been demonstrated. Therefore, pimozide should be avoided in pregnant women. Pimozide is excreted in breast milk at the same or higher concentration of that in the plasma.


Interactions

Drugs which depress the central nervous system can be potentiated by pimozide. These drugs include alcohol, barbiturates, anesthetics, antihistamines and benzodiazepines. The use of pimozide together with any of these should be minimized.

QT wave lengthening will be greater in those patients already taking other medications that lenthen the QT interval, such as certain antiarrhythmics, other neuroleptics (eg. thioridazine), and antidepressants. The result of prolonged QT interval can be Q or T phenomenon or torsades de pointes (a polymorphic ventricular arrhythmia), both of which can degenerate into a fatal ventricular arrhythmia.[16]


Other potential adverse reactions

Pimozide may produce a number of other potential problems. It can cause a Parkinson's-like syndrome within the first few days. Tardive dyskinesia, like that seen with other neuroleptics, can occur with prolonged use.[12] Other dystonic manifestations can occur, the most common of which is torticollis. Tight binding to the dopamine D2 receptor appears to be the cause of these disturbing side effects.[17] Acute oculogyric crisis is a very frightening side effect that one should be familiar with if using this class of medications. Minor problems can be managed with concomitant benztropine, and acutely with with diphenhydramine, but oculogyric crisis is best managed by a psychiatrist.

Because of their effects on prolactin secretion, neuroleptics can precipitate amenorrhea, galactorrhea, and dysmenorrhea.[17]


Conclusion

Pimozide, a selective blocker of dopamine receptors, remains the drug of choice for treatment of delusions of parasitosis, though large, controlled studies are lacking. Smaller studies however, do show a significant, and often prolonged, benefit. However, though pimozide, with more published studies to attest to its efficacy, is currently the treatment of choice for patients with delusions of parasitosis, the much safer, atypical antipsychotics such as risperidone, may soon become more frequently used for this condition.

References

1. Carvey P. Drug action in the nervous system. New York, Oxford University Press, 1998

2. Riding BE, Munro A. Pimozide in monosymptomatic psychosis. Lancet 1975;1:400-401

3. Munro A. Monosymptomatic hypochondrical psychosis. Br J Hosp Med 1980;24:34-38

4. Zomer SF, de Wit RFE, van Bronswijk JE, Nabarro G, van Vloten WA. Delusions of parasitosis. A psychiatric disorder to be treated by dermatologists? An analysis of 32 patients. Br J Dermatol 1998;138:1030-1032

5. Dolery C ed. Therapeutic drugs. Churchill Livingstone 1999

6. Wielink PS van, Leysen JE. Choice of neuroleptic on the basis of in-vitro pharmacology. J Drug Res 1983;8:1984-1997

7. McCreadier RG, Heykants JJP, Chalmers A, Anderson AM. Plasma pimozide profilesin chronic schizophrenics. Br J Clin Pharmacol 1979;7:534-535

8. Trabert W. 100 years of delusion of parasitosis: meta-analysis of 1223 case reports. Psychopathology 1995;28:238-246

9. Hamann K, Avnstorp C, Delusions of infection treated by pimozide : a double-blind crossover clinical study. Acta Derm Venereol (Stockh) 1982;62:55-58

10. Lindskov R, Baadsgaard O. Delusions of infestation treated with pimozide: a follow up study. Acta Derm Venereol (Stockh) 1985;65:267-270

11. Driscoll MS, Rothe MJ, Grant-Kels JM, Hale MS. Delusions of parasitosis: a dermatologic, psychiatric and pharmacologic approach. J Am Acad Dermatol 1993;29:1023-1033

12. Koo J, Lee CS. Delusions of parasitosis. A dermatologist's guide to diagnosis and treatment. Am.J.Clin Dermatol 2001;2:285-290

13. Tennyson H, Levine N. Neurotropic and psychotropic drugs in dermatology. Sys Dermatol Ther 2001;19:179-197

14. Elmer KB, George RM, Peterson K. Therapeutic update:use of risperidone for the treatment of monosymptomatic hypochondriacal psychosis. J Am Acad Dermatol 2000;43:683-686

15. Silverstone T, Cookson J, Ball R et al.. The relationship of dopamine receptor blockade to clinical response in schizophrenic patients treated with pimozide or haloperidol. J Psychiatr Res 1984;18:255-268

16. Haddad PM, Andrews IM. Antipsychotic related QTc prolongation, torsades de pointes and sudden death. Drugs 2002;62:1649-1671.

17. Seeman P. Atypical antipsychotics: mechanisms of action. Can J Psychiatry 2002;47(1):27-38.

© 2003 Dermatology Online Journal




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