Botulinum Toxin: An Unconventional Tool for the Treatment of Depression?
Abstract
Background/Objectives: Major depressive disorder (MDD) represents a leading cause of global disability, with approximately one-third of patients exhibiting treatment resistance (TRD) despite adequate pharmacological interventions. This treatment gap underscores the urgent need for novel therapeutic strategies. Recently, a series of data suggests that botulinum neurotoxin of type A (BoNT-A), traditionally used for neuromuscular and cosmetic indications, could constitute a potential antidepressant tool. This narrative review critically examines the current preclinical and clinical findings of BoNT-A in MDD. Methods: A comprehensive search of PubMed, Scopus, and Web of Science was conducted up to June 2025, including randomized controlled trials, observational studies, animal models, and mechanistic investigations. Search terms included "Botulinum Toxin," "BoNT type A", "Depression", "Major Depressive Disorder", "Facial Feedback", and "Neurobiology". Results: Some randomized and observational studies would indicate that glabellar BoNT-A injections might lead to significant reductions in depressive symptoms in patients with MDD and TRD. Proposed mechanisms include both peripheral modulation of emotional expression and brain effects, such as reduced amygdala hyperactivity, increased BDNF expression, and enhanced monoaminergic transmission. Preclinical studies confirm that BoNT-A modulates limbic and brainstem circuits, possibly implicated in affective regulation. The few…
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