From Bench to Bedside: Understanding the Science behind the Pharmacologic Management of MDMA- and other Sympathomimetic-Mediated Hyperthermia

Objective: To evaluate the scientific rationale and efficacy of pharmacologic and nonpharmacologic treatments for sympathomimetic-induced hyperthermia and related sequelae. Data Sources: Literature was accessed through MEDLINE (1940-September 2010) using the terms MDMA [3,4-methylenedioxymethamphetamine], methamphetamine, toxicity, and hyperthermia. In addition, reference citations from identified publications were reviewed. Study Selection and Data Extraction: All articles written in English identified from data sources were evaluated. Data Synthesis: The treatment of sympathomimetic-induced hyperthermia is a challenging problem for health-care professionals. The lack of clinical trials further complicates the development of evidence-based treatment algorithms. Preclinical studies have mostly been with the sympathomimetic MDMA and have demonstrated a reversal of MDMA-induced hyperthermia with a mixed serotonin 5-HT 1A agonist/5-HT 2A antagonist or mixed α 1 - and β 1,2,3 -adrenergic receptor antagonists.

Conclusions: Because of the nature by which patients are exposed to these agents, therapeutic interventions for sympathomimetic-mediated hyperthermia still lack evidence from clinical trials with human subjects. Pharmacologic treatments that should be avoided are antipyretics and the ryanodine receptor antagonist dantrolene. Promising future therapies may involve mixed 5-HT 1A agonist/5-HT 2A antagonists such as the atypical antipsychotic olanzapine, or mixed α 1 - and β 1,2,3 -adrenergic receptor antagonists such as carvedilol, as current preclinical research suggests.