Botulinum Neurotoxin Therapy for Depression: Therapeutic Mechanisms and Future Perspective

Depression is one of the most common mental disorders, which causes global burden. Antidepressants and psychotherapies are the mainstay of treatment for depression, which have limited efficacy. Thus, alternative approaches for preventing and treating depression are urgently required. Recent clinical trials and preclinical researches have clarified that peripheral facial injection of botulinum neurotoxin type A (BoNT/A) is a rapid, effective and relative safe therapy for improving some symptoms of depression. Despite its safety and efficacy, the underlying therapeutic mechanisms of BoNT/A for depression remains largely unclear. In the present review, we updated and summarized the clinical and preclinical evidence supporting BoNT/A therapy for the treatment of depression. We further discussed the potential mechanisms underlying therapeutic effects of BoNT/A on depression. Notably, we recently identified that the anti-depressant effects of BoNT/A associated with up-regulation of 5-HT levels and brain-derived neurotrophic factor (BDNF) expression in the hippocampus in a preclinical mouse model. In summary, these studies suggest that BoNT/A therapy is a potential effective and safe intervention for the management of depression. However, fundamental questions remain regarding the future prospects of BoNT/A therapy, including safety, efficacy, dose-response relationships, identification of potential predictors of response, and the precise mechanisms underlying BoNT/A therapy.