Postmarketing safety surveillance data reveals antidepressant effects of botulinum toxin across various indications and injection sites

Abstract

The World Health Organization estimates the number of people suffering from depression to be over 264 million. Current monoamine transmission modulating therapeutics, even with proper adherence and acceptable tolerability, are not effective for nearly one third of the patients, leading clinicians to explore other therapeutic options such as electroconvulsive therapy, transcranial magnetic stimulation, ketamine infusions, and, more recently, glabellar botulinum toxin, BoNT, injections. The scale and mechanism of antidepressant action of BoNT is unclear and maybe hypothetically attributed to the disruption of proprioceptive facial feedback reinforcing negative emotions. Here we verify the antidepressant effect of botulinum toxin by analysis of over 40 thousand BoNT treatment reports out of thirteen million postmarketing safety reports in the FDA Adverse Event Reporting System, FAERS. The results of the analysis indicate that patients who received BoNT injections to treat hyperhidrosis, facial wrinkles, migraine prophylaxis, spasticity, and spasms, had a significantly lower number of depression reports when compared to patients undergoing different treatments for the same conditions. These findings suggest that the antidepressant effect of BoNT is significant, and, surprisingly, is observed for a broad range of injection sites.

Figure 1

Analysis flow chart, and inclusion/exclusion terms for cohort selection, used in adverse event rate comparison between botulinum toxin and control cohorts.

Figure 2

Study cohorts by indication and injection site. Christos Georghiou/shutterstock.com, decade3d—anatomy online/shutterstock.com.

Figure 3

Frequencies and reporting odds ratios (RORs) of depression events. (a) Frequencies of depression events for patients administered botulinum toxin for cosmetic use (BoNT N = 20,684, control N = 1,214), migraine (BoNT N = 4,180, control N = 56,675), spasms and spasticity, excluding facial muscles (BoNT N = 2,335, control N = 45,824), torticollis (BoNT N = 1,360, control N = 6,765), blepharospasm (BoNT N = 487, control N = 153), hyperhidrosis (BoNT N = 601, control N = 712), sialorrhea (BoNT N = 157, control N = 1,174), neurological and urinary bladder disorders (BoNT N = 915, control N = 30,827). (b) Reporting odds ratios were calculated comparing frequencies of depression reports in patients administered botulinum toxin for each indication and respective control sub-cohorts. Ranges represent 95% confidence intervals (95% CI) (see “Methods”). BoNT botulinum toxin, AE adverse event, ROR reporting odds ratios.