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Psychiatr Danub. 2010 Mar;22(1):112-6.

The role of CYP2D6 and TaqI A polymorphisms in malignant neuroleptic syndrome: two case reports with three episodes.

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  • 1Neuropsychiatric Hospital Dr. Ivan Barbot, Popovaca, Croatia. maja.zivkovic@zg.t-com.hr

Abstract

Malignant neuroleptic syndrome (MNS) is a serious and potentially fatal side-effect of neuroleptic treatment. Beside antipsychotic drugs, other psychotropic drugs such as antidepressants and lithium carbonate can cause this life threatening side-effect. Underlying mechanism of this side-effect is still unknown and debated. So far some risk factors have been identified, with clinical observations and recent pharmacogenetic research suggesting (with inconsistent findings) correlation between genetic mechanisms and predisposition to MNS. Polymorphisms of CYP2D6 enzyme through which most psychotropic drugs are metabolized and TaqIA DRD2 which is target for antipsychotic drugs could be the link between pharmacogenetic factors and potential for development of MNS. In this paper we present two case reports with clinical presentation of three consecutive MNS. One patient developed MNS while he was taking combination of drugs: first time haloperidol, promazine and fluphenazine, second time fluphenazine and perazine and third time clozapine, promazine and valproic acid consecutively. The other patient developed MNS while taking following combination of drugs: first time haloperidol and lithium carbonate, second time risperidone and third time clozapine consecutively. Pharmacogenetic analysis for CYP2D6 and TaqI A DRD2 polymorphisms for both patients was done. Genotypisation of CYP2D6*1*3*4*5*6 in both patients showed no evidence of poor metabolizer phenotype. On the other hand, first patient was heterozygous for CYP2D6*4 (genotype *1/*4). CYP2D6 polymorphisms could have clinical significance because may lead to toxicity and unwanted side-effects in standard usual antipsychotic dose ranges. Analysis Taql A DRD2 polymorphism for first patient showed that he is heterozygous for A1 allele (genotype A1A2) which is commonly associated with predisposition to MNS. According to our literature three consecutive MNS are rarely described, and incidence of MNS generally is too low to perform clinical research. Many patophysiological mechanisms may probably underlie this complex and potentially fatal syndrome, still unknown etiology. But, genetic mechanisms could be significant. Further pharmacogenetic research, findings and analysis in patients who develop single or repeated MNS are strongly recommended. In long term, pharmacogenetic analysis, implemented in daily clinical practice, could help in prevention of this extremely serious side-effect.

PMID:
20305604
[PubMed - indexed for MEDLINE]
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