Olanzapine-Induced Neuroleptic Malignant Syndrome With Mental Retardation

Mr. A was a 21-year-old black man with mild to moderate mental retardation believed to be related to the meningitis he suffered as a child. He had been treated for several years with low-dose haloperidol for behavioral difficulties and, as a result, suffered from abnormal dystonic and dyskinetic movements. On two previous occasions, he met the criteria for probable neuroleptic malignant syndrome, with creatinine kinase level elevations to 12,000 U/liter on one occasion and 1,000 to 2,000 on the other.

Mr. A’s medication regimen consisted of clonazepam, 1 mg/day, benztropine mesylate, 1 mg/day, and lorazepam as needed because a trial of tetrabenazine had failed. He was then started on a regimen of olanzapine. The dose was gradually increased to 12.5 mg over a 12-day period, in which some decrease in agitation and improved behavior were noted. On day 13, Mr. A became extremely agitated and had an increase in abnormal movements as well as mild rigidity. Olanzapine was immediately discontinued. His rectal temperature rose to 40.6°C and was measured on another occasion as 40.2°C. His creatinine kinase level rose to 6030 U/liter (normal range=20–195), and his WBC count rose to 17.4×10⁹/liter (normal range=4–11). Tachycardia (124 bpm) and hypertension (systolic pressure=150 mm Hg, diastolic pressure=100 mm Hg) were also recorded. These met the criteria for neuroleptic malignant syndrome (2).

We treated Mr. A with oral liquid diazepam to help control his extreme agitation, which appeared to be the predominant symptom, along with his dystonic and dyskinetic movements. We also administered dantrolene, 50 mg/day. His creatinine kinase level values had decreased to 393 U/liter by day 6 and had returned to near normal (208 U/liter) by day 8. Any attempt to decrease his dose of dantrolene resulted in an increase in his creatinine kinase level, his WBC count, and temperature. Mr. A had risk factors of extreme psychomotor agitation (5) and mental retardation (6). Our choice of treatment with oral liquid diazepam was indicated because of Mr. A’s extreme agitation (7).