Neuroleptic Malignant Syndrome (NMS) Literature Review: Treatments and Outcomes

Out on PubMed in Acta Psychiatrica Scandinavica is this literature review from investigators in Germany, with Sascha Sartorius as senior author:The Neuroleptic Malignant Syndrome - A systematic case series analysis focusing on therapy regimes and outcome.

Kuhlwilm L, Schönfeldt-Lecuona C, Gahr M, Connemann BJ, Keller F, Sartorius A.Acta Psychiatr Scand. 2020 Jul 13. doi: 10.1111/acps.13215. Online ahead of print.PMID: 32659853 

The abstract is here:

Introduction: Neuroleptic Malignant Syndrome (NMS) is a rare, potentially life-threatening antipsychotic-associated disorder that requires an efficient and timely therapy. The aim of the study was to compare the effectiveness of different NMS therapies and to analyze its outcome depending on NMS severity.

Method: Systematic search for NMS cases in biomedical databases. The focus of the analysis was on therapy with dantrolene, bromocriptine and electroconvulsive therapy (ECT) when each was compared with symptomatic therapy. Primary outcomes were the survival rate and the duration of treatment.

Result: 405 case reports were included. Overall, no statistically significant differences regarding mortality rate or duration of treatment were found between dantrolene, bromocriptine or ECT compared to supportive care. A subgroup analysis regarding NMS severity showed that the mortality under specific NMS pharmacotherapy (dantrolene, bromocriptine) and under ECT was significantly lower than under purely symptomatic therapy in severe NMS (p = 0.018). The difference was not significant in mild and moderate cases.

Discussion: An overall superiority of the specific NMS therapy (dantrolene, bromocriptine and ECT) was not found in this study. When regarding severity classification, specific therapies were superior but only in severe cases, and ECT showed the lowest mortality rate. In previous case-series, an effect on survival or the duration of the disease could only be observed in part for specific therapies, but the evidence available is inconsistent. The results of this study support our hypothesis that NMS treatment with dantrolene, bromocriptine and ECT is advantageous over purely symptomatic therapy in severe NMS cases.

Keywords: Antipsychotics; Neuroleptic Malignant Syndrome; Therapy; Treatment.

And from the text:

This review article clearly demonstrates that the optimal treatment of NMS is not yet ensured.

The optimal treatment should be driven by the clinical severity of the syndrome. For the first

time, available NMS cases from the literature were analyzed regarding their severity level as

defined by Woodbury & Woodbury (22). We showed that the influence on mortality of the

various therapies differs depending on the severity of NMS. For severe cases, specific NMS

therapy (with dantrolene, bromocriptine or ECT) is superior to purely symptomatic therapy.

Within the ECT treatment groups, mortality rate was lowest, which could be an argument to

upgrade  ECT  from  a  second  line  therapy  to  a  first  line  therapy  for  severe  cases.  Further

studies on the pathophysiology and causal treatment of NMS are necessary.

 This is an impressive piece of work to have amassed over 400 reports of NMS from the literature. The stratification by severity is novel and very useful. Highlighting the need for specific  therapies, particularly ECT, in severe NMS is a timely reminder for practitioners about the seriousness of this syndrome, which has an overall mortality of 8.4%. The authors also discuss the relationship of NMS to the diagnostic entity malignant catatonia.