Botulinum Neurotoxin Therapy for Depression: Therapeutic Mechanisms and Future Perspective

Abstract

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.

Botulinum Neurotoxins in Central Nervous System: An Overview from Animal Models to Human Therapy

“…The effect of BoNT/A was associated with an enhancement of 5-HT level and the expression of brain derived neurotrophic factor in hippocampus, hypothalamus, prefrontal cortex, and amygdala, together with the transiently increased levels of p-ERK and CREB. These preclinical studies, together with some indirect clinical evidence [114,115], suggest BoNT/A as alternative treatment for depression. However, the direct injection of BoNTs to the brain is a procedure that poses ethical and practical difficulties to translate therapeutical benefit from animal model to human.…”

Postmarketing safety surveillance data reveals protective effects of botulinum toxin injections against incident anxiety

“…However, the cumulating evidence of the efficacy of BoNT in such indications is not per se evidence of the accuracy of this rationale. Our previous study, which showed an antidepressant effect of BoNT across a broad range of indications and injection sites, opened up a broad spectrum of possible explanations for this effect 8 , 40 . Some of theses explanations are compatible with the facial feedback hypothesis while others challenge it.…”

Botulinum Toxin in Facial Aesthetics Affects the Emotion Process: A Meta-analysis of Randomized Controlled Trials

“…The evaluation of well-being promoted by BT-A application goes beyond the aesthetic benefits. The potential therapeutic in the emotional states shown in several clinical studies toward the new use of BT-A, mainly in patients who do not respond to antidepressant medications [ 29 , 30 ]. It is important to consider that different symptoms and depression grades can contribute to heterogeneity of the improvement of depression statements, and it is not clear if the severity of the mood state requires higher BT-A dosages (units/muscle).…”