Olanzapine-associated neuroleptic malignant syndrome

Abstract

Neuroleptic malignant syndrome (NMS) is an uncommon but serious idiosyncratic reaction associated with antipsychotic medication. The purpose of this study was to reveal and analyze the clinical characteristics of the reported cases of NMS in patients given the novel antipsychotic olanzapine. A MEDLINE search related to olanzapine-induced NMS cases reported in the international literature was conducted. All cases were critically reviewed and examined against three different sets of NMS diagnostic criteria (DSM-IV, Addonizio, Levenson). The authors identified 17 cases of possible NMS associated with olanzapine. Ten of the reported NMS cases were definitely NMS meeting all three sets of criteria and three cases were probable NMS meeting two sets of criteria. Most of the patients exhibited a full-blown NMS. There were four definite NMS cases associated with olanzapine monotherapy. Three of them had concurrent serious physical illnesses and one had a previous NMS episode. Olanzapine can cause NMS, mainly in susceptible or predisposed patients.

Introduction

Olanzapine is a thienobenzodiazepine class atypical antipsychotic drug, similar to clozapine both in structure and in effects on neurotransmitters (Stephenson and Pilowsky, 1999). It was approved for use in 1996. Prospective clinical trials have shown that olanzapine has a lower propensity to induce extrapyramidal symptoms than conventional antipsychotics Tran et al., 1997, Martin et al., 1997. This is thought to be a function of the greater affinity of olanzapine for the serotonin 5-hydroxytryptamine_2A (5-HT_2A) receptors than the dopamine D₂ receptors (Stephenson and Pilowsky, 1999).

Neuroleptic malignant syndrome (NMS) is a rare but serious and potentially fatal reaction associated with antipsychotic medication. The diagnosis is maintained on the basis of the classical findings, i.e., extrapyramidal symptoms, fever, altered consciousness and autonomic dysfunction Caroff, 1980, Levenson, 1985, Shalev and Munitz, 1986.

The introduction of the atypical antipsychotics raised expectations that these drugs would not cause NMS. However, this was not the case. Several NMS cases associated with clozapine and risperidone have been reported Sachdev et al., 1995, Hasan and Buckley, 1998, Karagianis et al., 1999. Recently, there have been reports of NMS in association with both quetiapine and olanzapine Kohen and Bristow, 1999, Caroff et al., 2000.

The aims of this study were: (a) to critically examine the recently reported NMS cases induced by olanzapine, (b) to retrospectively analyze all olanzapine-induced NMS cases against three different well-established sets of NMS criteria.