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Neurotoxins: Expanding Uses of Neuromodulators in Medicine—Major Depressive Disorder

Magid, Michelle MD; Keeling, Brett H. MD; Reichenberg, Jason S. MD

Plastic and Reconstructive Surgery: November 2015 - Volume 136 - Issue 5S - p 111S–119S
doi: 10.1097/PRS.0000000000001733
Neurotoxins: Original Articles

Background: Botulinum toxin A (BTA) is one of the most diversely used medications of the 21st century and is now being researched as a treatment for major depressive disorder (MDD).

Methods: The authors performed a literature search of PubMed, Web of Science, and the Cochrane Register of Controlled Trials. The primary investigators of the studies were contacted for additional unpublished data.

Results: The authors identified 5 studies that met the criteria of using BTA in the treatment of MDD. All studies showed significant reduction in depressive symptoms with BTA injected into the glabellar muscles. In a pooled analysis, botulinum toxin (n = 59) vs placebo (n = 75) had a –47% vs –16% reduction in self-rated depression scores (P < 0.0001) and a –46% vs –15% reduction in expert-rated depression scores (P < 0.0001), respectively. Adverse reactions were mild (temporary headaches and local irritation immediately after injection) and did not differ between active group (13.6%) and placebo group (9.3%) (P = 0.44).

Conclusions: Botulinum toxin injections in the glabellar frown muscles have been associated with a significant improvement in depressive symptoms. Given the prevalence of MDD, the promising results of preliminary trials, and the excellent tolerability of this treatment intervention, larger studies are warranted.

Supplemental Digital Content is available in the text.

Austin, Tex.

From the Department of Psychiatry, University of Texas Medical Branch; Department of Psychiatry, Texas A&M Health Science Center; and Department of Dermatology, University of Texas, Dell Medical School.

Received for publication March 7, 2015; accepted May 26, 2015.

Pooled analysis data discussed in this article was presented at the World Congress of Psychiatry, September 14–18, 2014, Madrid, Spain.

Disclosure: Dr. Magid received a young investigator grant from the Brain and Behavior Research Foundation to fund her original study on the treatment of depression using botulinum toxin A. In November 2012, that is, after conclusion and as a result of the original study, she became a consultant with Allergan. Dr. Keeling and Dr. Reichenberg declare no other conflict of interest. Dr. Reichenberg’s spouse (Dr. Magid) is a consultant for Allergan.

Supplemental digital content is available for this article. A direct URL citation appears in the text; simply type the URL address into any Web browser to access this content. A clickable link to the material is provided in the HTML text of this article on the Journal’s Web site (

Michelle Magid, MD, Austin Psychcare, P.A., 1600 West 38th Street, Suite 404, Austin, TX 78731,

©2015American Society of Plastic Surgeons