Volume 30, Issue 174, August 2026

Botulinum toxin as an innovative treatment for depression and anxiety disorders: a review of clinical evidence and mechanisms of action

Weronika Kubiak^1♦, Aleksandra Wyciślok¹, Amelia Sobanek¹, Erwin Górski¹, Jakub Deptuch¹, Filip Szewczyk¹, Zuzanna Szczerba², Justyna Koziarska³

¹Institute of Dentistry of the Central Clinical Hospital of the Medical University of Łódź, Pomorska 251, 92-213 Łódź, Poland
²Navia Clinic, Dowborczyków 34, 90-019 Łódź, Poland
³Independent Public Healthcare Institution in Tarczyn, Warszawska 42, 05-555 Tarczyn, Poland

^♦Corresponding author
Weronika Kubiak, Institute of Dentistry of the Central Clinical Hospital of the Medical University of Łódź, Pomorska 251, 92-213 Łódź, Poland

ABSTRACT

MDD is currently the leading cause of disability worldwide, affecting approximately 5% of the general population. A great clinical problem is that nearly one-third of patients do not improve despite standard pharmacotherapy and psychotherapy, which we call treatment-resistant depression. This circumstance requires the search for new, unconventional therapeutic approaches, such as BoNTA. This study intends to investigate the mechanisms of action of BoNT-A and to evaluate its value and success in the treatment of depression and other affective disorders. This paper reviews current clinical evidence and scientific research on the use of BoNT-A in psychiatry and neurology. The analysis includes both clinical studies involving humans and animal model studies explaining the neurobiological basis of the toxin’s effects. The present paper searched the literature on electronic databases, including PubMed, using the keywords: “BoNT-A”; “MDD”; “Anxiety disorders”; “NMDA receptors”. The effects of BoNT-A are wide and not limited only to muscle relaxation. The most important mechanism is the Facial Feedback Hypothesis - a paralysis of the “sadness muscles” that interrupts the transmission of negative proprioceptive signals to the amygdala and improves mood. At the molecular level, the toxin modulates NMDA receptors, increases BDNF expression, and affects monoaminergic systems. Clinical evidence confirms a significant reduction in depressive and anxiety symptoms. BoNT-A may help treat affective disorders. It may affect brain areas involved in emotions. Current studies show promising results, but more research is needed to understand how it works and whether it is effective in the long term.

Keywords: BoNT-A, MDD, Anxiety disorders, Facial Feedback Hypothesis, NMDA receptors

Medical Science, 2026, 30, e177ms3910

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DOI: https://doi.org/10.54905/disssi.v30i174.e177ms3910

Published: 30 August 2026