Yohimbine Enhancement of Exposure Therapy for Social Anxiety Disorder: A Randomized Controlled Trial

Department of Psychology and Institute for Mental Health Research (JAJS, MLD, MBP), The University of Texas at Austin, Austin. Electronic address: .
Biological psychiatry (Impact Factor: 10.26). 10/2013; 75(11). DOI: 10.1016/j.biopsych.2013.10.008
Source: PubMed


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.
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.
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.
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.

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Available from: Stefan G Hofmann, Oct 14, 2014
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    • "Here yohimbine (vs. placebo) significantly improved the outcome of exposure therapy when combined with in vivo exposure for claustrophobia (Powers et al., 2009) and social anxiety disorder (Smits et al., 2014). Yet, in a virtual reality exposure therapy for specific phobia (fear of flying) yohimbine had no effect (Meyerbroeker et al., 2012). "
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    • "Our findings are incongruent with the putative mechanism of action of DCS augmentation (i.e., enhancement of extinction learning consolidation), and evidence from preclinical and prior clinical research that demonstrated that the degree of extinction learning during extinction training/exposure therapy moderated the efficacy of DCS enhancement for several anxiety disorders (Bolkan & Lattal, 2014; Bouton et al., 2008; Smits, Rosenfield, Otto, Marques, et al., 2013a; Smits, Rosenfield, Otto, Powers, et al., 2013b; Weber et al., 2007), including PTSD (Rothbaum et al., 2014). Interestingly, two additional studies have since documented that the efficacy of other cognitive enhancers of exposure therapy (e.g., yohimbine, methylene blue) also depends on the level of extinction learning as indexed by low end fear (Smits et al., 2014; Telch et al., 2014). "
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    • "A number of so-called cognitive enhancers have been uncovered, including yohimbine that increases central noradrenergic transmission (Tam et al. 2001). Following an initial report of several years ago where yohimbine facilitated extinction in mice (Cain, Blouin, & Barad, 2004), recent studies have shown moderate to mixed effects of yohimbine as adjunct to extinction learning (Holmes & Quirk, 2010; Smits et al., 2014). An important limitation of this novel strategy is that it does not eradicate the original fear memory: The conditioned fear response returned when the animals were tested outside of the extinction context (Morris & Bouton, 2007). "
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