Antipsychotic dose escalation as a trigger for Neuroleptic Malignant Syndrome (NMS): literature review and case series report

Background: “Neuroleptic malignant syndrome” (NMS) is a potentially fatal idiosyncratic reaction to any medication which affects the central dopaminergic system. Between 0.5% and 1% of patients exposed to antipsychotics develop the condition. Mortality rates may be as high as 55% and many risk factors have been reported. Although rapid escalation of antipsychotic dose is thought to be an important risk factor, to date it has not been the focus of a published case series or scientifically defined. <p/>Aims: To identify cases of NMS and review risk factors for its development with a particular focus on rapid dose escalation in the 30 days prior to onset. <p/>Methodology: A review of the literature on rapid dose escalation was undertaken and a pragmatic definition of “rapid dose escalation” was made. NMS cases were defined using DSM-IV criteria and systematically identified within a secondary care mental health service. A ratio of titration rate was calculated for each NMS patient and “rapid escalators” and “non rapid escalators” were compared. <p/>Results: 13 cases of NMS were identified. A progressive mean dose increase 15 days prior to the confirmed episode of NMS was observed (241.7mg/day during days 1-15 to 346.9mg/day during days 16-30) and the mean ratio of dose escalation for NMS patients was 1.4. Rapid dose escalation was seen in 5/13 cases and non rapid escalators had markedly higher daily cumulative antipsychotic dose compared to rapid escalators. <p/>Conclusions: Rapid dose escalation occurred in less than half of this case series (n=5, 38.5%), although there is currently no consensus on the precise definition of rapid dose escalation. Cumulative antipsychotic dose – alongside other known risk factors - may also be important in the development of NMS

A retrospective analysis of cases with neuroleptic malignant syndrome and an evaluation of risk factors for mortality

Tatli, Ozgur/0000-0003-0263-7630WOS: 000424190600005PubMed: 29464217Objective: Neuroleptic malignant syndrome (NMS) is a neurological emergency rarely encountered in clinical practice but with a high mortality rate. Cases associated with atypical antipsychotic use or termination of dopamine agonists have been seen in recent years. The purpose of this study was to assess the presence of risk factors for mortality by investigating all clinical and laboratory characteristics of cases with NMS. Material and methods: This descriptive, cross-sectional study retrospectively investigated all clinical and laboratory characteristics by scanning the ICD-10 codes of patients presenting to the XXXX Faculty of Medicine Emergency Department and diagnosed with NMS between 2006 and 2016. Patients were divided into surviving and non-surviving groups, and the data elicited were subjected to statistical comparisons. Results: The mean age of the 18 patients diagnosed with NMS was 46.9 +/- 4.8 years, and 50% were women. In addition to antipsychotics among the drugs leading to NMS, the syndrome also developed as a result of levodopa withdrawal in three patients and metoclopramide use in one patient. Statistically significant differences were determined between the surviving and non-surviving patients in terms of blood pressure, blood urea nitrogen (BUN), creatine kinase (CK) and mean platelet volume (MPV) values (p <= 0.05). Conclusion: In this study the most common agent that cause NMS was atypical antipsychotics. Also advanced age, increased blood pressure and serum CK, BUN and MPV values were identified as potential risk factors for mortality in NMS. Copyright (C) 2017 The Emergency Medicine Association of Turkey. Production and hosting by Elsevier B.V. on behalf of the Owner. This is an open access article under the CC BY-NC-ND license