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

Abstract

Randomized controlled trials (RCTs) have shown an antidepressant effect of glabellar botulinum toxin (BoNT) injections. In the FDA Adverse Event Reporting System (FAERS) database, BoNT injection is associated with reduced incidence rates of depression across various non-psychiatric indications, which confirms the previous findings independently of specific expectations to an antidepressant effect of BoNT. The rationale of using BoNT to treat depression is to interrupt proprioceptive body feedback that may reinforce negative emotions. Negative emotions also occur in other mental disorders, suggesting a transdiagnostic therapeutic potential of BoNT in psychiatry. Here we report an analysis of the FAERS database, in which we found that, compared to alternative treatments, BoNT injections were associated with lower incidence of anxiety symptoms and related disorders. Among seven indications/injection sites, we found this protective effect of BoNT in cosmetic use/facial muscles, migraine/facial and head muscles, spasms and spasticity/upper and lower limbs, torticollis and neck pain/neck muscles, and sialorrhea/parotid and submandibular glands (reporting odds ratios 0.79-0.27). These findings are encouraging for possible future RCTs on the use of BoNT as a treatment for anxiety and related disorders.

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 (ROR) of anxiety and related adverse events (AE). (a) Relative frequencies of anxiety events for patients administered botulinum toxin (BoNT) for various indications. (b) Reporting odds ratios with 95% confidence intervals (CI) as calculated by comparing frequencies of anxiety reports in patients administered botulinum toxin for each indication and respective control sub-cohorts.