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Antipsychotics and Neuroleptic Malignant Syndrome (NMS)

Question. Are some antipsychotic drugs more prone to cause neuroleptic malignant syndrome (NMS) than others? Is olanzapine known to cause NMS as well? What else can you tell me about the possibilities that olanzapine will benefit schizophrenics? How is this drug better/worse than other choices? My husband was diagnosed with NMS last year while on Stelazine and since then has not taken any antipsychotic drugs. What would be the drug of choice if he is to try a new one?

Answer. Neuroleptic malignant syndrome is a severe disorder brought on by drugs used to treat psychosis. The older agents in this class are referred to as neuroleptics; newer atypical agents, such as clozapine (sold as Clozaril, Leponex, Fazaclo, Froidir; Denzapine, Zaponex in the UK; Klozapol in Poland, Clopine in Australia / New Zealand) and olanzapine (Zyprexa, Zyprexa Zydis, Zalasta, Zolafren, Olzapin, Rexapin), are properly termed antipsychotics. While the signs and symptoms vary greatly from patient to patient, neuroleptic malignant syndrome (NMS) is usually characterized by high fever, muscular rigidity, confusion or delirium and unstable blood pressure and pulse. To my knowledge, there is no convincing evidence that any of the available neuroleptics or antipsychotics are free of the NMS risk, nor evidence that one particular agent is especially safe. While it had been hoped that the atypical agents such as clozapine, olanzapine (and to some extent, risperidone) would produce fewer cases of neuroleptic malignant syndrome (NMS), I do not believe this has been demonstrated. Since NMS is relatively rare, it will probably take years before we have enough cases to compare agents in a reliable manner.

Antipsychotics_and_Neuroleptic_Malignant_Syndrome_(NMS)

There have been cases of neuroleptic malignant syndrome (NMS) reported with clozapine, which is chemically very similar to olanzapine; I have not yet seen NMS reported with olanzapine, but there is no reason to assume it could not occur. There is modest evidence that less potent agents (such as thioridazine) may be preferable to higher potency agents (such as haloperidol) when rechallenging a patient who has had neuroleptic malignant syndrome (NMS); in about two-thirds of cases, a patient who developed NMS on one agent can be successfully re-challenged on a lower potency agent. Potency is not the same as efficacy; it just refers to the dose needed for clinical effects. With respect to the advantages of olanzapine in schizophrenia, a good deal of data, involving over 3,000 patients, suggest that olanzapine may be superior to conventional neuroleptics.

Olanzapine has better effects on negative features of schizophrenia, such as apathy, social withdrawal; produces fewer neuromuscular side effects, such as tremor, muscle spasm; and may be safer in the long-run with respect to tardive dyskinesia, a slowly developing movement abnormality affecting the mouth, trunk, or extremities. Olanzapine may also be superior (e.g., to haloperidol) in treating depressive features of schizophrenia. But, it is still too early to say if it will produce lower rates of neuroleptic malignant syndrome (NMS).

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