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THE ROLE OF CYP2D6 AND TAQI A POLYMORPHISMS IN MALIGNANT NEUROLEPTIC SYNDROME: TWO CASE REPORTS WITH THREE EPISODES

Maja Živković ; Neuropsychiatric Hospital Dr. Ivan Barbot, Jelengradska 1, Popovača, Croatia
Alma Mihaljević-Peleš ; Department of Psychiatry, Zagreb University Hospital Center, Kišpatićeva 12, Zagreb, Croatia
Marina Šagud ; Department of Psychiatry, Zagreb University Hospital Center, Kišpatićeva 12, Zagreb, Croatia
Ante Silić ; Psychiatric Hospital “Sveti Ivan”, Jankomir 11, Zagreb, Croatia
Mate Mihanović ; Psychiatric Hospital “Sveti Ivan”, Jankomir 11, Zagreb, Croatia

Sažetak

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 sideeffect.
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.

Ključne riječi

malignant neuroleptic syndrome (MNS); CYP2D6 polymorphism; TaqI A DRD2 polymorphism; antipsychotic drugs

Hrčak ID:

48646

URI

https://hrcak.srce.hr/48646

Datum izdavanja:

10.2.2010.

Posjeta: 1.065 *