Botox, a medication derived from a bacterial toxin, is commonly injected to ease wrinkles, migraines, muscle spasms, excessive sweating and incontinence. Forehead injection of the medication is also currently being tested in clinical trials for its ability to treat depression.

Researchers have mined database to see what nearly 40,000 people reported happened to them after treatment with Botox for a variety of reasons.

In the study, published in Scientific Reports, the team discovered that people who received Botox injections -- at six different sites, not just in the forehead -- reported depression significantly less often than patients undergoing different treatments for the same conditions.

"For years, clinicians have observed that Botox injected for cosmetic reasons seems to ease depression for their patients," said the senior author. "It's been thought that easing severe frown lines in forehead region disrupts a feedback loop that reinforces negative emotions. But we've found here that the mechanism may be more complex, because it doesn't really matter where the Botox is injected."

The FAERS database contains more than 13 million voluntary reports of adverse effects people experienced while taking a medication. The team have found they can also use the database to look at absence of a health complaint when a person takes a medication, if compared to a control group. In this case, they searched for the absence of depression.

The team focused on nearly 40,000 FAERS reports of people experiencing adverse events after Botox treatment. The reports cover Botox treatment for eight different reasons and injection sites, including forehead, neck, limbs and bladder. Then the team applied a mathematical algorithm to look for statistically significant differences between Botox users and patients who received different treatments for the same conditions.

Here's what they found: Depression was reported 40 to 88 percent less often by Botox-treated patients for six of the eight conditions and injection sites.

"This finding is exciting because it supports a new treatment to affect mood and fight depression, one of the common and dangerous mental illnesses -- and it's based on a very large body of statistical data, rather than limited-scale observations," the author said.

To be clear, the data used in this study was not collected for the purpose of exploring the association between Botox use and depression exclusively. In addition, the FAERS data represents only the subset of Botox users who experienced negative side effects. While the team excluded reports in which a person was also taking antidepressants, the use of other prescription and over-the-counter medications could have been underreported in some cases.

The clinical trial underway are directly testing Botox treatment for people with depression, a gold standard approach for gathering insights on the relationship between a medication and a health condition. Since that trial is only testing forehead injection of Botox, the author says additional clinical trials may be necessary to work out the best site and dose to administer the medication specifically for the treatment of depression.

Likewise, more research is needed to determine the mechanism by which Botox acts as an antidepressant, the author says. The team hypothesize a few possibilities worth investigating: Botox could be transported to the regions of the central nervous systems involved in mood and emotions. Or, since Botox is commonly used to treat chronic conditions that may contribute to depression, its success in relieving the underlying problem may indirectly also relieve depression.

The World Health Organization estimates that more than 264 million worldwide experience depression. Depression is frequently treated with psychotherapy, selective serotonin reuptake inhibitors, dopamine-norepinephrine reuptake inhibitors and/or serotonin-norepinephrine reuptake inhibitors. Yet these approaches are ineffective for nearly one-third of patients. That's why clinicians and researchers are exploring other therapeutic options, including electroconvulsive therapy, transcranial magnetic stimulation, ketamine infusions and, more recently, Botox forehead injections.

https://www.nature.com/articles/s41598-020-69773-7

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fpostmarketing-safety&filter=22