Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders

Pharmacol Ther. 2016 Mar;159:1-22. doi: 10.1016/j.pharmthera.2016.01.016. Epub 2016 Jan 28.


Dextromethorphan (DM) is a commonly used antitussive and is currently the only FDA-approved pharmaceutical treatment for pseudobulbar affect. Its safety profile and diverse pharmacologic actions in the central nervous system have stimulated new interest for repurposing it. Numerous preclinical investigations and many open-label or blinded clinical studies have demonstrated its beneficial effects across a variety of neurological and psychiatric disorders. However, the optimal dose and safety of chronic dosing are not fully known. This review summarizes the preclinical and clinical effects of DM and its putative mechanisms of action, focusing on depression, stroke, traumatic brain injury, seizure, pain, methotrexate neurotoxicity, Parkinson's disease and autism. Moreover, we offer suggestions for future research with DM to advance the treatment for these and other neurological and psychiatric disorders.

Keywords: Depression; Neurotoxicity; Pain; Seizure; Stroke; Traumatic brain injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antitussive Agents / pharmacokinetics
  • Antitussive Agents / pharmacology
  • Antitussive Agents / therapeutic use
  • Dextromethorphan* / pharmacokinetics
  • Dextromethorphan* / pharmacology
  • Dextromethorphan* / therapeutic use
  • Humans


  • Antitussive Agents
  • Dextromethorphan