The Fine Lines: Why Some Experts Think Botox Can Help Mental Health

In 2006, a dermatologist named Eric Finzi and a psychologist named Erika Wasserman published a study in which ten patients with major depression received botulinum toxin (colloquially known as Botox) in their forehead frown lines. Two months after the injection, nine of the 10 patients, the researchers wrote, “were no longer depressed.” The tenth “had an improvement in mood.”

Botulinum toxin is a drug derived from bacteria present in places like forests and lakes and the intestinal tracts of mammals and fish. Doctors use it to temporarily paralyze muscles, which helps with reducing skin wrinkles as well as treating conditions like eyelid spasms and migraines. The drug often comes under the brand names Botox, Dysport, Xeomin, or Jeuveau—although the first has become the go-to term for it, like Band-Aid for bandages or Kleenex for tissues. For the purposes of this story, “Botox” refers to the drug in general. 

Worldwide, over 264 million people suffer from depression, which the World Health Organization characterized as persistent sadness and a lack of interest or pleasure in rewarding or enjoyable activities. There are psychological and pharmacological treatments for the condition, but some studies have shown that these aren’t effective for nearly one-third of patients. This has inspired the search for alternative treatments, including psilocybin, ketamine, and Botox.

Alternative and available treatments can be particularly important for certain locales. Botox and other cosmetic procedures are on the rise in Asia, for example, while discussions around mental health continue to be stigmatized in the Philippines and other countries. Using Botox to treat depression could make getting help easier for many. If it works. 

“I simply did not believe that a cosmetic treatment could have such profound antidepressant results. As such, I got into this research to refute the original findings,” psychiatrist Michelle Magid, who has written extensively about the antidepressant effects of Botox, told VICE. “I was completely surprised when my study findings mirrored the original findings.”

Since the 2006 study, several randomized, double-blind, and placebo-controlled studies by Magid and other researchers seem to confirm the antidepressant effects of the drug. This has led Magid and her colleagues to claim that Botox is a ready-to-use tool for managing depression. But these studies have been critiqued for their small sample sizes (ranging from 28 to 74 patients) and their inability to control placebo in the experiments (partly because the subjects could observe the obvious muscle-relaxing effects of Botox injections). 

Another reason the drug hasn’t quite taken off as a means to treat depression is that experts aren’t sure how it works. 

Botox is perhaps best known for its cosmetic applications. That makes one theory pretty obvious: Looking good makes people feel better. Magid explained that while this might be true in general, it’s not the leading theory as to why Botox helps with depression. She cited a 2009 study that compared the moods of people who received Botox in the forehead with the moods of people who received glycolic peels, laser treatments, fillers, Botox in other areas, and other cosmetic treatments. The study showed that the Botox patients had less irritability, anxiety, and depression than those who received the other cosmetic treatments. Another study Magid conducted with her colleagues in 2016 showed that Botox patients with a more robust response to the drug (i.e. fewer wrinkles after the treatment), did not necessarily have the biggest improvement in mood.

Instead, the leading theory is what experts call the “facial feedback hypothesis,” which states that the movements and expressions of one’s face can influence one’s emotions. Basically, smiling can make you happier and frowning can make you sadder.

“The leading idea is that Botox reduces depression because it reduces frowning,” said Jeff Larsen, a social psychologist. “But our research tells us that [the] effects of emotional expressions on emotional experiences like sadness are very weak.”

In 2019, Larsen and his colleagues, Nicholas Coles and Heather Lench, published a study reviewing around 50 years of data, including the results of nearly 300 experiments testing the facial feedback theory. It showed that the effects of facial movements on felt emotions were “significant but small.”

Another theory for how Botox in the forehead works as an antidepressant is that it calms the amygdala, which is the part of the brain that is activated in trauma, fear, and depression, and is responsible for processing fearful or threatening stimuli. MRI studies have shown decreased amygdala activity after Botox injections in the forehead. The researchers wrote that this could theoretically lead to improvements in mood and reactions to negative stimuli. 

“I suppose one theoretical risk is that our fear response would be reduced and we too may not invoke the appropriate flight or fight response to dangerous situations,” said Magid, who added that the risk is not something to be too worried about. “The decreased amygdala activity that we see after Botox injections is similar to the decreased activity that we see after antidepressant treatment. I think we're calming a hypervigilant amygdala, which is probably a good thing.”

Botox may also influence the way people, with or without depression, process other people’s emotions. When people see another face, they unconsciously mimic the expression on that face. This helps them identify and, to an extent, feel the emotion that the other person is experiencing. A small study published this year found that because the drug paralyzes certain muscles when injected into areas of the face, it also prevents patients from unconsciously mimicking, and therefore identifying and understanding, other people’s facial expressions. 

Magid said this may be beneficial for people with depression because they sometimes misread the facial expressions of others. A neutral face is perceived as angry or sad. A face that’s actually angry or sad can be overwhelming for people with depression, Magid said. In theory, Botox can help patients more accurately interpret other people’s facial cues. But this could also mean that happy or other positive facial cues can appear less happy or positive to people with Botox in their faces, making their own reactions less happy or positive. 

Ruben Abagyan, a professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California, San Diego, said that the antidepressant effects of Botox aren’t about frowns or forehead wrinkles, “since even injections into limbs have a comparable effect.”

In 2020, Abagyan published a study that he said proved that the beneficial effects of Botox don’t depend on the site of injection. The study analyzed over 40,000 Botox treatment reports, including those of patients who received Botox to treat hyperhidrosis, facial wrinkles, migraine prophylaxis, spasticity, and spasms. Those patients had a significantly lower number of depression reports compared to patients who had different treatments for the same conditions. 

“I believe that Botox is a good candidate to be studied further for its likely antidepressive effects. However, it needs to be evaluated within the context of other emerging therapies and our understanding of depression subtypes, combinations with existing treatments, a balance between beneficial and adverse effects of each type of treatment,” said Abagyan.

Magid has recommended Botox to some of her patients with depression, particularly to those who cannot tolerate other medications or those who require other treatment strategies. Besides Botox, she also recommends these patients non-medication options, like psychotherapy, lifestyle changes, and transcranial magnetic stimulation. 

“In patients who are good candidates, I usually go over the risks and benefits, and then I print out a picture of the Botox injection configuration, to give it to their dermatologist. I tell them that their dermatologist can call me with any questions,” said Magid.

For her, using Botox to treat depression is a low-risk procedure. The main risks, she said, are eyelid drooping, which is rare in experienced injectors; the cost, as each treatment costs about $400 to $500, and people may get three to four treatments a year; and that the treatment may not work. Other risks of Botox include swelling, bruising, or infections at the injection site, and headaches or flu-like symptoms. The drug may sometimes spread to other parts of the body, where it could cause muscle weakness, vision or breathing problems, or allergic reactions. Some experts fear that bad Botox reactions are severely under-reported and have called for tighter regulation around the substance. 

Magid said that treatments for any condition warrant scrutiny and larger clinical trials before they become widely accepted. Larsen has helped provide much of the scrutiny against Botox as a treatment for depression.

Also in 2019, Larsen and his colleagues published a meta-analysis of studies around the use of Botox to treat depression. A meta-analysis is basically a study of studies, and Larsen’s meta-analysis included the studies of Magid and other researchers. 

“Our meta-analysis tells us that the published literature overestimates Botox’s effectiveness—so much so that it’s not even clear whether Botox has any effect at all. We’re not saying it has no effect. We’re just saying that the evidence isn’t conclusive,” Larsen said.

For Larsen, the conclusion that Botox is an effective treatment for depression is simply premature. He said that the clinical trials that provide the most valid evaluations of a treatment’s effect on any condition are those with the largest number of patients. While the studies published on Botox as a treatment for depression may show marked improvements in their patients, Larsen said there needs to be more clinical trials with larger sample sizes to make any conclusions. Until those are available, he said experts must proceed with caution. 

Medicine, Larsen said, isn’t magic. There has to be a mechanism by which any treatment helps an ailment. It’s one thing that experts don’t know exactly how Botox works as a treatment for depression. But Botox may also only be a skin-deep solution. 

“Clinical depression is far, far more than just being really sad. Feelings of depression—the painful conscious experience of it—are the symptom, not the cause. It’s not at all clear to us how Botox could hit the underlying causes of depression,” said Larsen. “Even if the inability to frown makes someone less sad, how could it ease their feelings of inadequacy or tendency to interpret everything in the worst way possible, not to mention the neurochemical imbalances that are all wrapped up with those cognitive distortions?”

Larsen said that everyone wants more effective treatments for depression, and it would be great if something as simple as Botox could be helpful. People should not go looking for a “magic bullet” to treat the condition, and Botox may never replace psychotherapy and psychopharmacology, but more rigorous research that proves its effectiveness may merit adding it to the mix of tools people use to assuage suffering. 

Magid shared the sentiments. 

“As a scientist, I’m always going to push for more research,” she said. “I'm eager to see more studies done on 'Botox for depression' as a novel intervention.  We need more tools in our toolbox to combat the prevalent and deadly disease.”

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