Olanzapine-induced neuroleptic malignant syndrome after 10 years of treatment

To the Editor

Neuroleptic malignant syndrome (NMS) is a dangerous, life-threatening condition that can be caused by antipsychotic drugs (Ananth et al., 2004; Yasugi et al., 2010). Food and Drug Administration (FDA) reports from 1999–2012 indicate that the frequency of NMS decreases when treatment with olanzapine is continued for a longer period (eHealthMe, 2013).

According to an eHealthMe report compiled from the FDA reports, 11,204 patients taking olanzapine had suffered adverse effects, of which 417 patients had NMS during the first 6 months of treatment (eHealthMe, 2013). However, so far nobody has recorded a patient who has had NMS in the initial stages of typical neuroleptic treatment and another episode of NMS after 10 years of olanzapine treatment. To our knowledge, this report is the first to record the occurrence of NMS, 10 years after the implementation of olanzapine.

A 63-year-old patient with a 20-year history of paranoid schizophrenia was admitted to the psychiatry ward due to non-compliance of antipsychotic treatment. The patient had previously had NMS 10 years ago during treatment with a typical neuroleptic. At the time of admission, the patient was commenced on olanzapine at a dose of 10 mg/day and the dose of the drug was titrated up to 15 mg/day on treatment day 7. On day 10, the signs and symptoms of NMS appeared. Muscular rigidity, hyperpyrexia (42°C), loss of consciousness, tachycardia, diaphoresis, and an increase in blood pressure were observed. Laboratory results showed leukocytosis (22,000/mm³), an increase in creatine phosphokinase (CPK) levels (962 U/l on day 10 and 1000 U/l on day 12). Other symptoms of inflammation were excluded. NMS was recognized and olanzapine treatment was discontinued. The symptoms of NMS described by us in this report confirm findings from previous case reports (Trollor et al., 2009).

The patient subsequently received dantrolene 200 mg/day, bromergone 7.5 mg/day; lorazepam 6 mg/day, and relanium 100 mg/day and felt better. There was a reduction in fever (38°C), CPK (868 U/l and leukocytosis (15,000/mm³). During the following day of treatment, the patient became unconscious with general muscular rigidity and was intubated due to respiratory failure. Laboratory results showed an increased level of CPK (1100U/l) and leukocytosis (22,000/mm³). The patient received a course of electroconvulsive therapy (ECT) under anaesthesia. Despite treatment, the condition of the patient became critical. Acute renal failure developed and the patient died. Acute renal failure and hyperpyrexia were the most likely cause of death. Earlier findings confirm the hypothesis as it has been shown that acute renal failure coexisting with hyperpyrexia in NMS increases the risk of death by about 50% (Casamassima et al., 2010).

This report claims that even olanzapine treatment within the therapeutic range is burdened with the high risk of NMS, even after 10 years of treatment. Due to the risk of death caused by olanzapine after so many years of treatment, it is crucial to choose a sufficient but safe dose and to closely monitor for the signs and symptoms of the potentially fatal NMS.