Compelling double-blind randomized studies in the Pubmed database suggest Botox significantly improves depression symptoms. Thirty participants were randomly assigned to receive either placebo or botulinum toxin A (BTA) injections in the forehead. Female participants received 29 units; male participants received 39 units. At week 12, the groups were crossed over.

Participants were evaluated at weeks zero, three, six, 12, 15, 18 and 24 for improvement in symptoms. Patients that received BTA at week zero (BTA-first group) and at week 12 (BTA-second group) had a statistically significant reduction in major depressive disorder (MDD) symptoms as compared to a placebo. Improvement in MDD continued over 24 weeks in the group that received BTA first even though the cosmetic effects of BTA wore off at 12 to 16 weeks.

The conclusion is a Botulinum toxin A injection in the glabellar region was associated with significant improvement in depressive symptoms and may be a safe and sustainable intervention in the treatment of MDD. One possible reason for the improvement is electromyography studies show that depressed people have hyper-reactive frown muscles and the injections counter this.

Today, Botox is FDA-approved for 11 therapeutic indications and most involve relief of pain including chronic migraines, overactive bladder, leakage of urine (incontinence) due to overactive bladder caused by a neurologic condition, cervical dystonia and spasticity. People think of Botox as a cosmetic intervention when in fact it is primarily used for non-cosmetic medical treatments.