When people decide to have botulinum toxin injections to smooth out the fine lines and wrinkles on their face, they may expect to look better rested, more relaxed, and maybe even a bit more youthful. They may be surprised to discover that they also end up feeling calmer—and not just because of the changes they see in the mirror. Research has examined the effects of botulinum toxin A injections on depressed mood and anxiety and found that they can lead to substantial improvements in these symptoms.
Botulinum toxin is a poisonous biological substance produced by the bacterium Clostridium botulinum that’s naturally found on plants and in soil and water. When used as a therapeutic injectable neurotoxin, it temporarily paralyzes muscles, thus reducing or eliminating unwanted wrinkles or frown lines. (Commonly used brands that are approved by the Food and Drug Administration include Botox, Dysport, Xeomin, and Jeuveau.) But many people don’t realize that botulinum toxin injections are also used to treat non-cosmetic conditions such as chronic migraines, hyperhidrosis (excessive sweating), cervical dystonia (a painful condition involving involuntary contractions of neck muscles), and an overactive bladder, among others.
Now physicians and scientists are exploring the toxin’s impact on mood disorders. Experts say that although botulinum toxin injections aren’t approved for the treatment of depression or anxiety, preliminary research is promising though more clinical trials need to be done to support their use for these conditions.
“Depression is a significant illness and one-third of patients with depression don’t respond to antidepressants,” says Michelle Magid, an associate professor of psychiatry at the Dell Medical School at the University of Texas at Austin. “When that happens, we need to think outside the box. All of us are looking for extra tools for our treatment toolbox.”
In a study in the June 2023 issue of the journal Toxins, researchers found that 53 percent of the men and women seeking treatment for depression who received botulinum toxin A injections into the frown muscles between their eyebrows (the glabellar muscles) experienced a significant improvement in their symptoms.
An earlier study in Brain and Behavior found that people with depression who received botulinum toxin A injections into various frown-related muscles experienced a reduction in their depression comparable to those who took sertraline (a selective serotonin reuptake inhibitor antidepressant) after 12 weeks; however, the mood improvements kicked in earlier with the injections, and there were fewer side effects than with the antidepressant.
With results like these, the assumption is that “getting cosmetic procedures makes you look better, which can make you feel better,” Magid says. “But there’s more going on.”
Facial expressions and emotions
There are actually several theories about what’s happening below the surface. One is related to the so-called “facial feedback hypothesis”—the idea “that the relationship between internal emotional states and facial expressions is a bidirectional one,” explains Norman Rosenthal, a clinical professor of psychiatry at Georgetown University who has investigated the effects of botulinum toxin injections on depression and social anxiety. “If you’re sad it will be reflected on your face. But if your face takes on a sad or distressed expression, it will reflect back to your brain and trigger the actual feeling.”
So, if the muscles involved in expressing anger or sadness are inhibited from frowning or creating an unhappy facial expression, your brain won’t receive the signal that you’re feeling that way. In other words, both muscle memory and cognitive memory are involved in emotional experiences: Your facial muscles remember a particular state of mind and your mind relies on your muscles to help trigger feelings.
When botulinum toxin injections “break the connection between your muscle memory and your psychological state, you may achieve therapeutic effect” if you’re prone to depression or anxiety, says Ruben Abagyan, a physical and computational chemist and professor in the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California, San Diego.
In a review of three randomized controlled trials, involving a total of 134 people, Magid and her colleagues found that a single treatment with botulinum toxin A in the glabellar region of the forehead reduced symptoms of major depressive disorder. That led to improved mood, better sleep, and more energy and hopefulness in 54 percent of the subjects, including remission of depression in 31 percent of the participants.
Surprisingly deep effects
Further evidence of effects on the brain comes from a Scientific Reports study in which researchers used botulinum toxin injections to induce temporary paralysis in the frown muscles and used functional magnetic resonance imaging (fMRI) to measure the participants’ brain activity while they viewed pictures of happy and angry faces. The researchers found that by inhibiting contraction of the glabellar muscles, thus preventing frowning, the injections altered how the participants’ amygdala responded to the emotional faces.
A study in a 2022 issue of the journal Acta Neurologica Belgica examined the effects of botulinum toxin injections in people with hemifacial spasm, a neuromuscular disorder that involves frequent spasms of the muscles on one side of the face and is often accompanied by psychological distress. The researchers found that the injections dramatically improved the participants’ emotional states—particularly their depression, anxiety, and their ability to accurately perceive and respond to other people.
There’s even scientific evidence on MRI scans that injecting botulinum toxin into the forehead decreases activity in the amygdala, which is active during experiences of fear, depression, anger, and other negative emotions. This may be one reason why people with agitated depression—a “mixed state” form of depression that is characterized by irritability, anxiety, and unease, as well as sadness or low mood—“respond better to Botox than to medications,” Magid says. “When people have agitation with depression, it’s a very hard depression to treat.”
The mood changes associated with botulinum toxin injections don’t only occur when the injections are administered to the forehead and face. When Abagyan and his colleagues examined the postmarketing safety surveillance data for botulinum toxin injections for a variety of indications—cosmetic uses, migraine, muscle spasticity, neck pain, excessive sweating, and others—they found a lower incidence of anxiety and depression among those who had the injections than among those in the control groups. “It doesn’t matter where Botox is injected—the effects are the same,” Abagyan says. “This was unexpected.”
Potential upsides and downsides
Another unexpected result is that botulinum toxin injections may have a positive ripple effect on other people. Research described in the Journal of Cosmetic Dermatology suggests that when botulinum toxin injections soften someone’s frown lines or the “11’s” between their eyebrows, it can alter the way other people respond to them—namely, by reducing their negative emotions.
“Your expressions and moods have repercussions for those around you,” explains study lead author Mark Nestor, a dermatologist and director of the Center for Clinical Cosmetic Research in Aventura, Florida. This effect is linked to “the theory of embodied emotions—the idea that social interactions are related to emotional contagion,” he explains. “When you’re around people who are frowning, you end up feeling bad.” By contrast, when you’re with people who look relaxed and content, you may feel that way, too.
Naturally, some psychologists are skeptical about the efficacy of botulinum toxin injections for mood disorders. Nicholas Coles, a social psychologist and research scientist at Stanford University who has analyzed some of the published literature on this subject, says “the evidence seems too good to be true.” For one thing, he notes that placebo effects are not being controlled for in these studies because saline injections don’t have a noticeable effect on patients’ appearances and their ability to contract their facial muscles.
What’s more, “we need to keep in mind that sadness and other negative feelings are more of a symptom of depression rather than one of the root causes,” adds Jeff Larsen, a professor of psychology at the University of Tennessee who has collaborated with Coles on this research. “Even if Botox injections can help reduce the feelings of sadness in the short run, it’s not at all clear how they could target the cognitive distortions—catastrophizing, all-or-none thinking, and the like—that produce those feelings in the first place.” As a result, he adds, “we can expect any effects of Botox injections on negative feelings to be short-lived.”
Even so, the injections have already shown some advantages over other treatments for mood disorders, according to proponents of this approach. The injections have fewer side effects than antidepressants do (the main one is temporary injection site irritation), experts say. And they won’t interact with other medications—including antidepressants or anti-anxiety drugs.
Unfortunately, the mood-enhancing effects of botulinum toxin injections aren’t permanent, just as they aren’t for cosmetic purposes. They typically last three to four months, though some people may need injections less frequently as time goes by. These injections also aren’t inexpensive: Injections of 30 units of botulinum toxin can cost $400 to $500, Magid says. But some people believe the effects are worth the price tag.
Magid recalls a patient who had seasonal affective disorder and tried antidepressants to improve her symptoms, but they didn’t help. For her 40th birthday, she got botulinum toxin injections in her forehead for aesthetic reasons and she was surprised to discover she began feeling better emotionally. Since then, the woman has continued to have Botox injections twice a year, Magid says, and “she has been depression-free for six years.”
There also may be an enduring psychological boost that occurs from botulinum toxin injections. After all, “feeling better is a self-perpetuating state,” Rosenthal says. “It propels people to do positive things for themselves—they may become motivated to meditate, exercise, or become more social, for example.” The cumulative effects of making these changes can lead to a more upbeat state of mind that lasts.