TORONTO (FRONTLINE MEDICAL NEWS)A single injection of Botox in the forehead area may be an effective adjuvant treatment in patient with treatment-resistant depression, according to a meta-analysis presented at the annual meeting of the American Psychiatric Association.

“Botulinum toxin A injection in the glabellar region appears to induce a significant and sustained antidepressant effect when used as an adjunctive treatment for major depressive disorder,” said principal investigator Dr. Ajay K. Parsaik.

Dr. Parsaik, a resident in psychiatry at the University of Texas, Houston, conducted a meta-analysis of eligible randomized controlled trials comparing the efficacy of botulinum toxin A (onabotulinumtoxinA) with placebo in subjects with major depressive disorder. The results painted a consistent picture of efficacy: Treated patients had an average 9.8-point decrease on their primary depression scores compared to placebo, were 8 times more likely to respond to treatment (defined as a 50% or more reduction in primary depression score), and were about 4.5 times more likely to go into remission (a score ≤10 in one study and ≤7 in the other two). All findings were statistically significant in favor of botulinum toxin A.

However, the data remain limited: From 639 articles screened, the researchers found 3 RCTs and 2 more non-RCT studies. Two of the three RCTs were published in 2014 (the third in 2012), showing just how new this concept is. The RCTs data included 134 patients in total, more than 80% of whom were female. Mean age was 49 years. Follow-up varied from 6 weeks to 24 weeks, but results tended to be seen in about 2 weeks, Dr. Parsaik said.Not just for wrinkles anymore, botulinum toxin A (Botox) is used to treat muscle contractions and spasms, chronic migraine, hyperhidrosis, and urinary incontinence in adults with multiple sclerosis and spinal cord injury. But it’s actually Botox’s wrinkle-smoothing advantages that play a part in its use in major depression. The agent works by preventing the release of acetylcholine from nerve endings leading to muscle paralysis that continues until the nerve develops new endings to communicate with the muscles. Injected into the muscle above and between the eyebrows, Botox cosmetically improves the appearance of vertical frown lines between the eyebrows. It is this use that has appeared promising as an adjuvant therapy in the treatment of depression.

While the exact mechanism of Botox’s benefit in depression remains unclear, Dr. Parsaik said the facial feedback hypothesis remains a lead candidate: Facial movements can influence the emotional experience. Smiling makes you happy; frowning makes you sad.

Since the expression of negative emotions (fear, anger, sadness) involves contraction of corrugator muscles located on the medial end of the eyebrows, paralysis of these muscles blocks neuromuscular transmission and interrupts this facial feedback loop. Blinding is difficult to maintain in these studies, admitted Dr. Parsaik, and more study is certainly needed, including, he suggested, testing botulinum toxin A as a monotherapy in depressed patients.

Other possible mechanisms include that the treatment improved self-perception, which in turn, improved mood, or that happier facial expressions may facilitate better social interaction leading to better mood, he said. In response to this, a physician in the audience asked (tongue in cheek) whether it might be appropriate to buy patients tickets to comedy shows or offer penile and breast enlargements in an effort to increase happiness and self-perception.

Dr. Parsaik reported having no conflict of interest.