Yohimbine enhancement of exposure therapy for social anxiety disorder: a randomized controlled trial

Biol Psychiatry. 2014 Jun 1;75(11):840-6. doi: 10.1016/j.biopsych.2013.10.008. Epub 2013 Oct 16.


Background: Preclinical and clinical trials suggest that yohimbine may augment extinction learning without significant side effects. However, previous clinical trials have only examined adults with specific phobias. Yohimbine has not yet been investigated in the augmentation of exposure therapy for other anxiety disorders.

Methods: Adults (n = 40) with a DSM-IV diagnosis of social anxiety disorder were randomized to placebo or yohimbine HCl (10.8 mg) 1 hour before each of four exposure sessions. Outcome measures were collected at baseline, each treatment session, posttreatment, and 1-month follow-up.

Results: Yohimbine was well tolerated. Yohimbine augmentation, relative to placebo augmentation, resulted in faster improvement and better outcomes on self-report measures of social anxiety disorder severity (Liebowitz Social Anxiety Scale, d = .53) and depressed mood severity (Beck Depression Inventory, d = .37) but not on the clinician-rated measures (Clinical Global Impressions-Severity Scale, d = .09; Clinical Global Impressions-Improvement Scale, d = .25). Between-group differences on the Liebowitz Social Anxiety Scale were moderated by the level of fear reported at the end of an exposure exercise (end fear), such that the advantage of yohimbine over placebo was only evident among patients who reported low end fear.

Conclusions: The results provide moderate support for yohimbine as a therapeutic augmentation strategy for exposure therapy in social anxiety disorder, one that may be especially effective when coupled with successful exposure experiences. Beneficial effects for yohimbine were readily evident for self-report measures but not for clinician-rated outcomes of social anxiety severity and improvement.

Trial registration: ClinicalTrials.gov NCT00958880.

Keywords: Cognitive behavioral therapy; cognitive enhancer; exposure therapy; social anxiety disorder; social phobia; yohimbine.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anxiety Disorders / drug therapy*
  • Anxiety Disorders / therapy
  • Combined Modality Therapy
  • Extinction, Psychological
  • Fear
  • Female
  • Humans
  • Implosive Therapy*
  • Male
  • Treatment Outcome
  • Yohimbine / therapeutic use*


  • Yohimbine

Associated data

  • ClinicalTrials.gov/NCT00958880