Neuroleptic Malignant Syndrome and Low-Dose Olanzapine

Mr. A, an 86-year-old man with an 8-month history of dementia with paranoia, was successfully treated for several months with olanzapine, 5 mg/day, until signs of parkinsonism led to a dose decrease to 2.5 mg/day. Two months later, when the daytime temperature was 96°F, he came to the hospital with uncontrollable shaking, confusion, a temperature of 105.6°F, and significant cogwheel rigidity. Paramedics believed his apartment’s temperature had exceeded 110°F. His admission and 2-hour blood pressures were notable for fluctuation: 110/72 mm Hg and 162/62 mm Hg, respectively. The results of laboratory tests included an aspartate aminotransferase level of 72 U/liter (normal=10–47), a creatinine kinase level of 1184 U/liter (normal=45–230), and a mildly elevated cardiac isoenzyme level of 39 U/liter (normal=0–6), with a relative index of 3.3 (normal=0–2.5). Mr. A was diagnosed with myocardial infarction, and olanzapine was suspended, given presumptive neuroleptic malignant syndrome.

By hospital day 5, Mr. A’s tremors had resolved, his cogwheel rigidity had minimized, his alertness had improved, his temperature had returned to normal, his creatinine kinase level had decreased to 245 U/liter, and his aspartate aminotransferase level had returned to normal. That night, he was rechallenged with one dose of olanzapine, 2.5 mg. The next morning, he was shaking vigorously, his temperature was 100.6°F, and he was notably more rigid. Olanzapine was discontinued, and his temperature again returned to normal, his tremor disappeared, and his cogwheel rigidity decreased substantially. His creatinine kinase level returned to normal, and he was treated with quetiapine, 25 mg/day, for several days with no signs of neuroleptic malignant syndrome.