In the Balance

Abstract

Objective: To report the development of neuroleptic malignant syndrome (NMS) after donepezil was added to maintenance haloperidol. Case Summary: An East Asian female in her mid-50s with a 25-year history of schizophrenia was prescribed fluvoxamine 150 mg daily, haloperidol decanoate 200 mg intramuscularly every 4 weeks, and benztropine 0.5 mg twice daily. Donepezil 5 mg daily was initiated for the treatment of possible dementia and 2 days later she appeared pale, displayed malaise, reported emesis, but was afebrile. The following day she was notably changed in behavior, withdrawn with a blunted affect. Decreased appetite, hyperthermia (temperatures 99.2-101°F), tachycardia, drooling, and slow, stiff movements with a creatine phosphokinase level of 1413 units/L (normal 26-192 units/L) were noted, and the patient was transferred to a medical hospital for treatment of suspected NMS. Symptoms improved with antipsychotic discontinuation, intravenous fluids, bromocriptine, and dantrolene. Five days after the adverse reaction the creatine phosphokinase significantly improved and she was noted to be more alert and responsive. Discussion: A literature search revealed 9 case reports of cholinesterase inhibitors causing NMS reactions either alone or, more commonly, when used in combination with antipsychotics. In this case, it was probable (Drug Interaction Probability Scale Score 6) the interaction between donepezil and haloperidol decanoate contributed to NMS. Conclusions: Use of cholinesterase inhibitors with antipsychotic medications may create an imbalance in acetylcholine and dopamine, which can precipitate the onset of NMS in susceptible individuals. These agents should be used cautiously in combination with careful monitoring for NMS.