Yohimbine Enhancement of Exposure Therapy for Social Anxiety Disorder: A Randomized Controlled Trial
Abstract
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.
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There is experimental evidence that pharmacological interoceptive exposure therapy can reduce anxiety disorder symptom severity either as monotherapy or as an augmentative approach.
“There is also experimental evidence that pharmacological interoceptive exposure therapy can reduce anxiety disorder symptom severity either as monotherapy (7,121–123) or as an augmentative approach (124).”
From Interoception and Mental Health: A Roadmap. (2018) · cites this paper as [124]
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“The National Comorbidity Survey Replication reported the lifetime prevalence of SAD at 12.1%, higher than any other anxiety disorder except specific phobia (Kessler et al., 2005).”
MethodInfluentialSelf-citationL-DOPA improves extinction memory retrieval after successful fear extinction
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Hypoventilation Therapy Alleviates Panic by Repeated Induction of Dyspnea
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“Similar results were found for socially anxious patients receiving yohimbine-enhanced exposure therapy (38).”
ResultSelf-citationHow stress hormones shape memories of fear and anxiety in humans
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“Contrary to our hypothesis, participants in the YOH condition did not report greater improvement after treatment relative to the placebo condition, which is in contrast to the fi ndings of previous research (e.g. Powers et al., 2009; Smits et al., 2014, Tuerk et al., 2018).”
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Self-citationDose Timing of D -Cycloserine to Augment Exposure Therapy for Social Anxiety Disorder
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“…assigned to aerobic exercise would experience greater symptom reduction compared to those assigned to rest and, following recent findings (Smits et al., 2013, 2014; Telch et al., 2014), that fear level at the end of the VRET session would moderate the relationship between exercise and…”
BackgroundInfluentialSelf-citationNeuroenhancement of Exposure Therapy in Anxiety Disorders
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“Several studies have suggested that administering such neuroenhancers prior to successful exposures might enhance treatment outcome [6,7].”
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“Yohimbine may also have anxiolytic effect, especially when combined with cognitive behavioral therapy [28].”
BackgroundMemory creation and modification: Enhancing the treatment of psychological disorders.
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“This effect has also been replicated for other putative memory enhancers including yohimbine (Smits et al., 2014) and methylene blue (Telch et al., 2014).”
Self-citationExtinction: Behavioral Mechanisms and Their Implications ☆
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New Developments in Cognitive-Behavioral Therapy for Social Anxiety Disorder
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“Yohimbine improvement of exposure therapy efficacy has been tested in two studies that enrolled patients with claustrophobic fears and social anxiety disorder [115, 117].”
BackgroundAlpha-2 Adrenoreceptor Antagonist Yohimbine Potentiates Consolidation of Conditioned Fear
Sperl, M. F. J., Panitz, C., Skoluda, N., Nater, U. M., Pizzagalli, D. A., Hermann, C., & Mueller, E. M. (2022) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyac038 · Cited by 17 · see citing works
“Studies in humans suggest that yohimbine facilitates exposure therapy in PTSD (Tuerk et al., 2018), social anxiety disorder (Smits et al., 2014), and claustrophobia (Powers et al., 2009).”
Neuromelanin-sensitive MRI for mechanistic research and biomarker development in psychiatry
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Bidirectional emotional regulation through prefrontal innervation of the locus coeruleus
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Starting from something: augmenting exposure therapy and methods of inquiry
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Self-citationA transdiagnostic meta-analysis of acute augmentations to psychological therapy
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Looking Beyond Fear and Extinction Learning: Considering Novel Treatment Targets for Anxiety
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Interoception and Mental Health
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Cognitive-Behavioral Therapy Enhancement Strategies
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Post-extinction L-DOPA administration to reduce the return of fear in humansPreprint
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Mechanisms of Action in the Treatment of Social Anxiety Disorder
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Self-citationExercise and Fear and Safety Learning
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Empirical status of mechanisms of change.
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Self-citationA Comparison between Psychosocial and Pharmacological Treatments
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Behavioral interventions to eliminate fear responses
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An Overview of Yohimbine in Sports Medicine
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The anxiogenic drug yohimbine is a reinforcer in male and female rats
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- Authors
- Smits, J. A. J., Rosenfield, D., Davis, M. L., Julian, K., Handelsman, P. R., Otto, M. W., Tuerk, P., Shiekh, M., Rosenfield, B., Hofmann, S. G., & Powers, M. B.
- Affiliations
- The University of Texas at Austin (US)
- Southern Methodist University (US)
- Boston University (US)
- Medical University of South Carolina (US)
- Corresponding author
- Smits, Jasper A.J.
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 75
- Issue
- 11
- Pages
- 840-846
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2166378848
- Cited by
- 86
- References
- 48
- Citations by year
- 2025: 4 · 2024: 6 · 2023: 6 · 2022: 5 · 2021: 2 · 2020: 5 · 2019: 4 · 2018: 10 · 2017: 12 · 2016: 8 · 2015: 12 · 2014: 12
- FWCI
- 14.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- yohimbine, social anxiety disorder, exposure therapy, augmentation therapy, extinction learning, treatment response
- MeSH terms
- Adult, Anxiety Disorders, Combined Modality Therapy, Extinction, Psychological, Fear, Female, Humans, Implosive Therapy, Male, Yohimbine, Treatment Outcome
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