Introduction: Botulinum toxin A (Botox) injection into the glabellar region is currently being studied as a treatment for major depressive disorder (MDD). Authors of this article explored efficacy data of this novel approach in a pooled analysis.

Methods: A literature search revealed 3 randomized studies on this topic. Individual patient data and clinical end points shared by these 3 trials were pooled and analyzed as one study (n=134).

Results: In the pooled sample, the Botox group (n=59) and the placebo group (n=75) did not differ in the baseline variables. Efficacy outcomes revealed Botox superiority over placebo: Improvement in the Hamilton Depression Rating Scale or Montgomery-Asberg Depression Rating Scale 6 weeks after baseline was 45.7% for Botox vs. 14.6% for placebo (p<0.0001), corresponding to a BOTOX response rate of 54.2% (vs. 10.7%) and Botox remission rate of 30.5% (vs. 6.7%).

Discussion: Equaling the status of a meta-analysis, this study increases evidence that a single treatment of Botox into the glabellar region can reduce symptoms of MDD (major depressive disorder). Further studies are needed to better understand how Botox exerts its mood-lifting effect.
Affecting more than 350 million individuals worldwide, depression is one of the greatest medical challenges of our time. There are several effective psychotherapeutic, pharmacological, and somatic options for the treatment of depression, but still a considerable proportion of patients do not attain remission. Thus, there is a need to develop further methods of treatment.

The injection of botulinum toxin A (Botox) into the glabellar frown muscles of the forehead is an emerging novel approach in the treatment of depression: after an auspicious first case series, we recently conducted 3 independent randomized, controlled trials and consistently showed that a single glabellar treatment with BOTOX reduces symptoms of depression.

The treatment of glabellar frown lines for cosmetic reasons is an approved indication for BOTOX and is the most frequent intervention in aesthetic medicine. Several studies have shown that this particular cosmetic treatment may exert psychological effects, which may contribute to its popularity. In one study, BOTOX in the forehead was compared to other cosmetic treatments; BOTOX in other regions besides the forehead, Restylane, glycolic peels, and laser treatments. Those who received BOTOX in the forehead reported feeling less depressed, irritable, and anxious, as compared to the control group, despite both groups feeling “equally attractive” after the intervention. This indicates that BOTOX in the forehead has positive mood effects above and beyond the euphoria that one gets from improved appearance.

The mood-lifting effect of such a Botox treatment may be explained by the facial feedback hypothesis, which dates back to Charles Darwin. In theory, contraction of facial muscles sends a message to the emotional centers of the brain. Smiling can reinforce and maintain feelings of well-being, whereas frowning can lead to the opposite. Therefore it is assumed that the paralysis of the injected frown muscles interrupts a proprioceptive feedback loop from the face to the emotional brain, therefore reducing the ability to feel negative emotions. In depression, there is a relative over-activity of frown muscles, which has been confirmed electrophysiologically, and whose elimination by Botox treatment could potentially soften the correspondent experience of fear, anger, and sadness.

M. Magid  et al.

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