Clinical and pharmacologic risk factors for neuroleptic malignant syndrome: a case–control study

Background: Pharmacologic and clinical risk factors for neuroleptic malignant syndrome have been suggested. High neuroleptic dose, rapid dosage increase, and parenteral administration were identified as risk factors in a case–control study; however, there are limited data regarding potential clinical risk factors. Methods: To examine potential clinical risk factors, we conducted a case–control study, comparing 12 cases to 24 controls, all treated with neuroleptics at our center. In addition to examining previously postulated pharmacologic risk factors, we also assessed for presence of psychomotor agitation, confusion, disorganization, and catatonia. Results: Significant differences were found between cases and controls for psychomotor agitation, confusion, disorganization, catatonia, mean and maximum neuroleptic dose, parenteral neuroleptic injections, neuroleptic dose increase within 5 days of the episode, magnitude of neuroleptic dose increase from initial dose, and extrapyramidal signs. Conclusions: This study demonstrated that psychopathological features such as psychomotor agitation, confusion, disorganized behavior, and catatonia may be risk factors for the neuroleptic malignant syndrome, in addition to pharmacologic risk factors and extrapyramidal signs, including akathisia. In clinical practice, careful monitoring for prodromal signs of neuroleptic malignant syndrome is required during neuroleptic treatment of patients with psychomotor agitation, confusion, and/or disorganization, while in the presence of catatonia these drugs should be avoided.