Conference Coverage

Botox shots may help lift major depression

View on the News

Two theories explain antidepressant effects

After reviewing much of the published literature on botulinum toxin (also known as onabotulinumtoxinA and Botox), I found the issue of whether the toxin is an effective treatment for depression to be both provoking and promising.

Double-blind placebo-controlled studies of major depressive disorder by Dr. Wollmer and colleagues (J. Psychiatric Res. 2012;46:574-81) and Dr. Finzi and Dr. Rosenthal (J. Psychiatric Res. 2014;52:1-6) found encouragingly positive results. After injections into five glabellar area sites at a single visit, significant improvement was noted, at least until the studies’ endpoints at 6 weeks. According to another study by Dr. Wollmer and colleagues, the presence of agitation (item 9 on the HAM-D) was what distinguished responders from nonresponders in their study.

At least two theories have been presented as to why botulinum toxin may have antidepressant effects. The facial feedback hypothesis postulates that facial expressions feed back to the brain and influence emotions. Trigeminal neuromodulation is hypothesized to improve depression through glutaminergic mechanisms. In view of the obvious alteration in facial expression after drug injection (the loss of what Charles Darwin referred to as omega melancholicum, or the omega sign), concern must be expressed that the studies were not truly double blind despite the best efforts of the investigators.

According to, which lists more than 500 studies of botulinum toxin, the drug is under investigation for a wide variety of medical conditions, including chronic migraine (already Food and Drug Administration approved), alopecia areata, cervical dystonia, ankle osteoarthritis, posterior hip cheek enlargement, keratoconus, psoriasis, vaginismus, restless legs syndrome, tennis elbow, vulvodynia, bruxism, hyperactive esophagus, and depression. The poster presentation at the recent APA annual meeting by Dr. Krüger and Dr. Wollmer is an indication that there will be much to follow that will be of interest to psychiatry.

Dr. James W. Jefferson is a clinical professor of psychiatry at the University of Wisconsin–Madison. He also serves as director of Healthcare Technology Systems, a company that develops clinical interactive voice response systems, also in Madison. Dr. Jefferson is double boarded in psychiatry and internal medicine.



NEW YORK – Botox injections contribute to a strong and sustained alleviation of depression in psychiatric patients, Dr. Tillmann H.C. Krüger and Dr. M. Axel Wollmer reported in a poster presentation at the annual meeting of the American Psychiatric Association.

The finding supports the concept that the facial musculature not only expresses but also regulates mood states, as explained by the facial feedback hypothesis.

In a randomized, double-blind placebo-controlled trial, Dr. Krüger of the Hannover (Germany) Medical School and Dr. Wollmer of Semmelweiss University in Hamburg, Germany, assigned 30 patients with major depression to receive adjuvant treatment in the form of botulinum toxin A (n = 15) or saline injections to the glabellar region of the face.

All patients had previously registered an insufficient response to standard treatments for depression at the time of study enrollment.

The primary endpoint was a change in the 17-item Hamilton Rating Scale for Depression (HAM-D).

After 6 weeks, the investigators found that the HAM-D scores for the Botox patients had dropped by an average of 47.1%, compared with 9.2% for placebo patients (P = .002).

Moreover, the investigators found that the agitation item on the HAM-D was the most accurate predictor of Botox response, with a precision of 78%.

Finally, improvements were also noted on the Beck Depression Inventory and the Clinical Global Impression scale; female patients had a somewhat greater response rate than males.

According to the investigators, their finding – originally reported in the Journal of Psychiatric Research (2012;46:574-81) – subsequently has been confirmed in two additional studies this year.

In the first, 74 subjects were randomized to facial injections of onabotulinumtoxinA or placebo; by 6 weeks, decreases of 50% or greater on the Montgomery-Asberg Depression Rating Scale were seen in 52% and 15% of treatment and placebo groups, respectively (J. Psychiatr. Res. 2014;52:1-6).

The second study, also a randomized controlled trial, is still in press. Those findings, along with the others, will be the topic of a forthcoming meta-analysis on the topic of Botox for depression. Dr. Michelle Magid, a psychiatrist at the University of Texas Southwestern–Austin, and Dr. Jason Reichenberg, a dermatologist at the university, reported preliminary findings from that study earlier this year at the annual meeting of the American Academy of Dermatology.

Future research also will address the efficacy of the treatment in other affective and personality disorders, Dr. Krüger and Dr. Wollmer added.

Dr. Krüger and Dr. Wollmer disclosed funding from the Gottfried und Julia Bangerter- Rhyner-Stiftung foundation in Germany, for their current study. Dr. Magid and Dr. Reichenberg are married, and Dr. Magid is a consultant for Allergan.

Recommended Reading

N-acetylcysteine may calm hair-pulling, skin-picking disorders
MDedge Psychiatry
Novel program cuts antipsychotics in metabolic patients
MDedge Psychiatry
Automated screening system might detect suicidality after trauma
MDedge Psychiatry
General screening for suicide not recommended yet
MDedge Psychiatry
Role of depression in first-episode psychosis clarified
MDedge Psychiatry
Suicidal acts rise with longer duration of high-risk mood disorder states
MDedge Psychiatry
Drugs approved in 2013
MDedge Psychiatry
CBT effective for social anxiety disorder even with comorbidities
MDedge Psychiatry
Lithium for bipolar disorder: A re-emerging treatment for mood instability
MDedge Psychiatry
Using CBT effectively for treating depression and anxiety
MDedge Psychiatry