Botulinum toxin for depression with Dr. Michelle Magid

Michelle Magid, MD, conducts a Masterclass lecture on botulinum toxin for depression from the Psychopharmacology Update in Cincinnati. The meeting was sponsored by Global Academy for Medical Education and Current Psychiatry.

Dr. Magid is associate professor University of Texas in Austin, and associate professor of Texas A&M University in College Station. She disclosed serving as a speaker for Ipsen, maker of Dysport (abobotulinumtoxinA, or ABO), and as a consultant for Allergan, maker of Botox (onabotulinumtoxinA).

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What we know about botulinum toxin

• Botulinum toxin is the product of Clostridium botulinum. The neurotoxin inhibits the release of acetylcholine, resulting in flaccid muscle relaxation. Its clinical use started in 1989 to treat strabismus (crossed eyes) and blepharospasm, a dystonic reaction in the eyes. Currently, botulinum is a Food and Drug Administration–approved treatment of chronic migraine in adults.
• For use in depression, 30-40 units of botulinum toxin is injected into the glabellar region of the face (the forehead). A purported mechanism of action of botulism for depression includes the "facial feedback hypothesis," in which the activation of muscles of facial expression, consciously or unconsciously, influences emotions.
• Botulinum toxin for depression is an off-label treatment with four case series, five randomized, controlled studies, and a phase 2 trial by supported by Allergan.

New findings on use of botulinum toxin for depression

• Magid and colleagues completed a pooled analysis of three randomized, controlled trials totaling 134 patients. Fifty-nine people were included in the botulinum toxin intervention group with a Beck Depression Inventory (BDI) score of 29, and 75 individuals in the placebo group with BDI of 26. In each group, 64% of patients were continued on other medications for depression, and the groups had similar histories of long-standing depression.
• In the botulinum toxin group, 52% had a response to the intervention, with an at least 50% reduction in their baseline depression scores, compared with a limited response in the placebo group.
• In the pooled analysis, Dr. Magid's group analyzed whether the cosmetic effect of botulinum toxin could be a confounding factor. The investigators ruled out that effect by using a subanalysis to evaluate whether the decrease in wrinkles correlated with decrease in depression, and it did not.
• Allergan moved forward with a phase 2 proof-of-concept trial; the results were mixed. The endpoint was response rate in Montgomery-Åsberg Depression Rating Scale (MADRS) at week 6. With a 30-unit Botox dose, there was a statistically significant decrease in MADRS at week 9, but not at week 6. There was no statistically significant divergence in data between the placebo and intervention group with the 50-unit dose. Given the response rate at week 9, Allergan is proceeding with a phase 3 trial.
• The cost is about $400 per treatment, and the treatment is given three to four times a year, which makes the cost comparable to that of other psychopharmacologic treatments. Adverse events are mild and include headache and local site irritation. In the current studies, botulinum treatment has been used as both monotherapy and augmentation; however, there are not enough data to know whether one is more effective than the other.
• In conclusion, burgeoning psychopharmacology research on treatments such as botulinum toxin for depression and novel medications, such as esketamine and brexanolone, broaden our understanding of the etiology of depression. This research is generating novel modes of treatment that will help more patients with refractory illness.

References

Magid M et al. Treating depression with botulinum toxin: A pooled analysis of randomized controlled trials. Psychopharmacology. 2015 Sep;48(6):205-10.

Magid M et al. Treatment of major depressive disorder using botulinum toxin: A 24-week randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2014 Aug;75(8):837-44.

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