Olanzapine-associated neuroleptic malignant syndrome in a patient receiving concomitant rivastigmine therapy

Pharmacotherapy. 2008 Mar;28(3):403-5. doi: 10.1592/phco.28.3.403.


Neuroleptic malignant syndrome (NMS) is an idiosyncratic and uncommon but serious adverse effect that has been reported with both typical and atypical antipsychotic agents. We describe a 58-year-old man with Down syndrome and dementia who was receiving low-dose olanzapine and rivastigmine therapy; he developed NMS 4 months after starting olanzapine. The patient presented with altered mental status, rigidity, fever, diaphoresis, and tremor, and his creatine kinase level was elevated. Olanzapine was discontinued, and the patient fully recovered; antipsychotic therapy was not restarted. Based on the Naranjo adverse drug reaction probability scale, olanzapine was the probable cause of the patient's NMS. In addition, use of rivastigmine in combination with olanzapine may have placed the patient at greater risk for NMS, possibly due to an acetylcholine-dopamine imbalance. Clinicians should be aware of the potential for NMS even with low doses of antipsychotics, particularly in patients who have a limited ability to communicate. Concomitant administration of cholinesterase inhibitors such as rivastigmine may represent an unrecognized risk factor for NMS development.

Publication types

  • Case Reports

MeSH terms

  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use
  • Benzodiazepines / adverse effects*
  • Benzodiazepines / therapeutic use
  • Cholinesterase Inhibitors / adverse effects*
  • Cholinesterase Inhibitors / therapeutic use
  • Dementia / complications
  • Dementia / drug therapy
  • Down Syndrome / complications
  • Humans
  • Male
  • Middle Aged
  • Neuroleptic Malignant Syndrome / etiology*
  • Olanzapine
  • Phenylcarbamates / adverse effects*
  • Phenylcarbamates / therapeutic use
  • Rivastigmine


  • Antipsychotic Agents
  • Cholinesterase Inhibitors
  • Phenylcarbamates
  • Benzodiazepines
  • Olanzapine
  • Rivastigmine