Glabellar Botulinum Toxin Injection Improves Depression Scores: A Systematic Review and Meta-analysis

PURPOSE: In 1872, Charles Darwin described a theory arguing for an interplay between a person’s facial expressions and his or her psychological mood. Subsequent research has investigated this idea, especially in relation to the “frowning muscles” of the glabellar region and their effects on symptoms of major depressive disorder (MDD). With the development of OnabotulinumtoxinA (BoNT) and the ability to chemodenervate the facial muscles, this association has been tested in multiple studies measuring changes in validated depression scores among patients treated with glabellar BoNT injections. Here, we performed a systematic review of the psychiatric literature to provide plastic surgeons a clear and comprehensive summary of the evidence supporting a role for glabellar BoNT injections in the treatment of MDD.

METHODS: A systematic review and meta-analysis of the relevant literature was performed in accordance with PRISMA guidelines. PubMed, the Cochrane Library databases, EMBASE, and Scopus were searched in August 2020 using the keywords [“botox” OR “botulinum”] AND [“mood” OR “depression”] for articles published between 1980 and 2020. Only prospective cohort studies and randomized controlled trials on the use of glabellar BoNT injections for the primary purpose of treating depression were considered. Meta-analysis was performed to aggregate changes in depression scores in association with the injection of BoNT specifically in the glabellar region.

RESULTS: After review of 499 potentially relevant articles, nine were selected based on predetermined inclusion criteria. All nine studies included in the systematic review reported an improvement in mean depression scores from baseline to the primary endpoint. All five randomized controlled trials reported an improvement in mean depression scores relative to placebo at 6 weeks post-treatment, with a weighted average change of −8.39 points (P < 0.0001). The aggregate standardized mean difference from baseline to the primary endpoint across all nine prospective studies was −1.61 standard deviations (P < 0.0001).

CONCLUSIONS: This systematic review indicates that glabellar BoNT injection may be an effective adjunct in the treatment of MDD. There are multiple theories for the exact mechanism by which BoNT interacts with mood, including facial feedback and direct biochemical effects. Given the frequency with which plastic surgeons administer BoNT, they should be aware of the evidence for a potential antidepressant effect of this safe, rapidly-acting medication.