Antipsychotic Rechallenge After Neuroleptic Malignant Syndrome with Catatonic Features

Abstract

Neuroleptic malignant syndrome (NMS) is a life-threatening condition that can occur in patients who require long-term antipsychotic therapy, and who therefore must be rechallenged with antipsychotics after their NMS episode. Current guidelines are based on limited data and recommend that rechallenge be undertaken by titrating from low doses of low-potency antipsychotics, after a period of two weeks following resolution of symptoms. We present the case of a patient with an NMS course complicated by residual catatonia course and a literature review with analysis to determine whether time to rechallenge, potency of rechallenge drug, and dose of rechallenge drug are independent predictors of NMS recurrence in patients. One hundred thirteen instances of neuroleptic rechallenge in non-catatonic NMS cases and 29 cases of rechallenge in NMS with catatonic features were identified through broad Medline and PsycInfo database searches and were analyzed by a single reviewer for rechallenge data. Fifty-five cases involved female patients, and 87 male patients; patients ranged in age from 12 to 86, with a mean of 37. There was no statistically significant relationship found between rate of NMS recurrence and time elapsed before rechallenge, either for all cases or by subgroup. Although the recurrence rate for patients rechallenged with highest-potency antipsychotics was found to be higher than those rechallenged with lowest-potency drugs,the relationship was not significant. The maximum antipsychotic dose reached during rechallenge was significantly lower among patients with recurrence of NMS than those who did not recur, likely due to recurrences early in dose titration. There was no statistically significant relationship between starting dose and recurrence. Based on our analysis, time between resolution of symptoms and rechallenge may have no bearing on risk of recurrence, in contrast to current recommendations. Dose of rechallenge drug is also unlikely to be an independent predictor of recurrence. Several studies, including ours, have shown a statistically insignificant but consistent positive relationship between potency of rechallenge drug and risk of recurrence.