Clozapine and Neuroleptic Malignant Syndrome: Case Report and Risk Analysis of Monotherapy vs. Combination Therapy

Traditionally, patients who are considered treatment-resistant, or who present with more severe symptoms, are often considered for clozapine therapy. The combination of clozapine with another SGA, or on FGA, is also commonly utilized for such severe cases, and may be considered standard-of-care given the prevalence of these strategies. The following case report involves a chronically symptomatic schizophrenic who developed NMS on a combination of long acting injectable aripiprazole and clozapine. A review of the literature regarding clozapine associated NMS in combination with other agents vs. monotherapy indicates that, at least based on case reports, it is possible that combination clozapine-aripiprazole therapy may convey a higher risk of NMS than either agent as monotherapy.