Botulinum toxin may directly reduce depression by altering brain activity

Researchers and clinicians continue to explore how botulinum toxin, typically recognized by the brand name Botox, may help patients beyond its well-known cosmetic uses, including its potential role in easing symptoms of depression. To better understand this connection, Managed Healthcare Executive spoke with Mark Nestor, M.D., Ph.D., director of SCA Dermatology in Aventura, Florida.

Botulinum toxin works by blocking the release of acetylcholine, a key chemical that nerves use to signal muscles. When injected into a muscle, it stops nerve endings from sending contraction signals, which leads to temporary muscle paralysis, according to a research article published in the Indian Journal of Dermatology.

In this process, the toxin enters nerve cells, prevents acetylcholine-filled vesicles from fusing with the cell membrane and disrupts nerve signaling for several weeks. Its effects begin within a few days, peak in about a week and last two to three months. Due to the toxin reducing muscle and gland activity, it’s used to treat conditions such as dystonia, muscle spasms, overactive smooth muscle and excessive sweating.

When asked whether its effect on depression is biological or psychological, Nestor said the answer is more complex than many expect. He shared that the effect appears to be direct when certain facial muscles are treated, especially in the glabellar region between the eyebrows.

"It's a direct effect for certain areas, and that's really the key issue," Nestor said. "When you treat the glabella, there's feedback, and the functional MRI show(s) that the amygdala responds differently. You can't frown, you're not feeling as sad because the amygdala is firing differently."

He shared that frowning is closely linked to how the brain processes emotions, and when people frown less, the brain receives different signals. This effect has been shown in studies that had nothing to do with feeling more attractive or happy with one’s appearance, he added.

Not being able to frown may also have social benefits. People may appear more open or positive, which can make conversations easier and even help in work settings.

As research continues, Nestor’s insights, which were shared ahead of his discussion at the 2025 Fall Clinical Dermatology meeting in late October, show that botulinum toxin may be much more than a cosmetic treatment. Its potential to influence how people feel and respond emotionally could offer new options for patient care in the future.