Botulin Injections May Relieve Major Depression

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BotulinoJust a single treatment with onabotulinumtoxinA (OBA), a botulinum toxin that is approved by the US Food and Drug Administration (FDA) for cosmetic purposes to treat frown lines, appears to ease depressive symptoms, new research suggests.
Results from the randomized, double-blind, placebo-controlled trial showed that OBA resulted in "significant and sustained" improvement in the depressive symptoms of patients with moderate to severe unipolar depression.
"This research is groundbreaking because it offers those who suffer from depression and their doctors an entirely new approach to treating the condition, one that doesn't conflict with any other treatments," study investigator Norman E. Rosenthal, MD, clinical professor of psychiatry, Georgetown Medical School, Washington, DC, said in a statement.
"The fact that this works on patients who were on 2 SSRIs [selective serotonin reuptake inhibitors] and on patients who were on no medication tells me that the mechanism of action is different from that of the SSRIs," he added.
However, he stressed that using OBA to treat depression is currently experimental and that OBA is not FDA approved for that purpose.The study was published in the May issue of the Journal of Psychiatric Research.

Facial Expressions and Mood Disorders
According to investigators, converging lines of evidence suggest there is a role for facial expressions in the pathophysiology and treatment of mood disorders.
For instance, they note, facial expression of negative emotions such as fear, sadness, and anger all involve contraction of the corrugator muscles, and multiple lines of evidence specifically implicate the corrugator muscles in depression.
OBA is a distinct subtype of botulinum toxin and was the first botulinum toxin subtype to be approved by the FDA for the treatment of frown lines. It is now one of several botulinum toxins that are commercially available, study author Eric Finzi, MD, PhD, from Chevy Chase Cosmetic Center in Maryland, said.
To determine the antidepressant effect of OBA, the investigators randomly assigned patients who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for major depressive disorder to receive 1 injection of either OBA (n = 33 patients) or saline (n = 41 patients) into the corrugator and procerus muscles, also known as the "frown muscles."
Both groups had similar demographic and clinical baseline characteristics. The mean age of the patients in the OBA group was 47.9 years (range, 37.6 - 58.2 years) and in the placebo group, 48.9 years (range, 39.6 - 58.2 years).
The majority of patients (91% in the OBA group and 80% in the placebo group) had recurrent depression, and 42% of the OBA patients and 41% of placebo patients were currently receiving antidepressants.
The primary outcome measure was the response rate, as defined by a decrease of 50% or more in the score on the Montgomery-Åsberg Depression Rating Scale (MADRS) at 6 weeks from the date of injection.
As shown on the MADRS scores, the response rates were 52% in the OBA group and 15% in the placebo group (P < .001).
Patients treated with OBA also had greater remission rates, as defined by a MADRS score of 10 or less, compared with patients in the placebo group (27% vs 7%; P < .03).
Finally, there was a 47.3% reduction in depressive symptoms, as assessed by the MADRS scores in the OBA group, compared with a 20.6% reduction in the placebo group.

Small but Interesting Study
Commenting on the study for Medscape Medical News, Peter D. Kramer, MD, clinical professor of psychiatry at Brown University Medical School, Providence, Rhode Island, who was not involved in the research, noted that the study's small size was a limitation.
He noted that the strongest finding was "that the patients who were already on antidepressants had a good remission rate."
"If the antidepressant effect of botulinum toxin is a real effect, then what is the mechanism? Is it that there is some feedback from your face to your brain, or is it that the rest of the world is somehow treating you differently?"
It may be that somehow the botulinum toxin is allowing the brain to be better able to make new connections or cells and thus allow patients to "move in a better direction," Dr. Kramer said.
"Another reason why I think this study is interesting is because I think Norm Rosenthal is an interesting writer. He was the big push behind seasonal affective disorder and reminding us that some people have worsening of depression in winter and that bright lights may be helpful, so he's very good at researching these nonmainstream treatments that turn out to be important. We don't know yet if botulinum toxin is one, but I think it's interesting, partly because it is research that comes from him," he said.

The study was funded by the Chevy Chase Cosmetic Center. Dr. Finzi reports that he has been awarded a patent for the treatment of depression with botulinum toxin, and that he is the sole owner of the Chevy Chase Cosmetic Center. Dr. Rosenthal and Dr. Kramer report no relevant financial relationships.

J Psychiatr Res. 2014;52:1-6. Abstract

Fran Lowry