Clin Psychopharmacol Neurosci.  2020 May;18(2):322-326. 10.9758/cpn.2020.18.2.322.

Risk of Neuroleptic Malignant Syndrome with Vesicular Monoamine Transporter Inhibitors

Affiliations
  • 1Department of Psychiatry, Corporal Michael J. Crescenz VA Medical Center and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

Abstract

Objective: Vesicular monoamine transporter-2 (VMAT2) inhibitors have been proven to be effective for the treatment of tardive dyskinesia and their use is likely to increase. The evidence base of published clinical reports was reviewed to evaluate the possible risk of neuroleptic malignant syndrome (NMS) with these drugs.
Methods
Pubmed, Embase, Web of Science and PsycINFO databases were queried for all years using terms for “neuroleptic malignant syndrome”, “hyperthermia” AND “vesicular monoamine transporter inhibitors”, “reserpine”, “tetrabenazine”, “valbenazine” or “deutetrabenazine”
Results
Thirteen clinical cases, ten of which involved tetrabenazine, were identified in which VMAT2 inhibitors were prescribed in patients with current or past NMS episodes. In most cases, the association was confounded by limited reporting of clinical data, variable temporal correlation with VMAT2 inhibitors, polypharmacy with antipsychotics, and uncertain differential diagnoses.
Conclusion
While rare cases of NMS meeting consensus criteria have been reported primarily with tetrabenazine, the risk with recently developed VMAT2 inhibitors may be even less. Evidence of causality of NMS with VMAT2 inhibitors is confounded by concomitant treatment with antipsychotics and diagnostic uncertainties in patients susceptible to basal ganglia dysfunction. Nevertheless, clinicians should remain vigilant for early signs of NMS in all patients treated with any drugs that affect brain dopamine activity.

Keyword

Neuroleptic malignant syndrome; Tardive dyskinesia; Antipsychotic agents; Tetrabenazine; Valbenazine; Deutetrabenazine; Huntington’s disease
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