BehindTheMedspeak: Can Botox Cure Depression?

That's the preliminary finding of a most provocative study published this month in the journal Dermatologic Surgery.

Here's the abstract.

Treatment of Depression with Botulinum Toxin A: A Case Series

Background: Major depression is a common and serious disease that may be resistant to routine pharmacologic and psychotherapeutic treatment approaches.

Objective: To evaluate the efficacy of botulinum toxin A treatment of glabellar frown lines in treating patients with major depression, using a small open pilot trial.

Methods: Patients who met DSM-IV criteria for ongoing major depression in spite of pharmacologic or psychotherapeutic treatment were evaluated with the Beck Depression Inventory II (BDI-II) before receiving botulinum toxin A to their glabellar frown lines. Two months later, all patients were re-evaluated clinically and with the BDI-II.

Results: Ten depressed patients were treated with botulinum toxin A, and 9 of 10 patients were no longer depressed 2 months after treatment. The tenth patient had an improvement in mood.

Conclusion: To our knowledge, these are the first reported cases of depression treated with botulinum toxin A.

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Shankar Vedantam wrote about the work in a story that appeared in the May 21 Washington Post.

It follows.

Botox Appears to Ease Depression Symptoms

Kathleen Delano had suffered from depression for years.

Having tried psychotherapy and a number of antidepressant drugs in vain, she resigned herself to a life of suffering.

Then she tried Botox, the drug that became a rage a few years ago for smoothing out facial wrinkles.

In 2004, her physician injected five shots of the toxin into the muscles between Delano's eyebrows so that the Glenn Dale woman could no longer wrinkle her brow.

Eight weeks later, according to a unusual study published this month, her depression had lifted.

"I didn't wake up the next morning and say, 'Hallelujah, I am well, I am healed,'" she said in an interview, but she noticed changes.

"I found myself able to do the things I hadn't been doing. I feel I broke out of the shackles of depression to be in the mood to go out, to reconnect with people."

The pilot study of 10 patients is the first to provide empirical support for what a number of clinicians say they have noticed anecdotally: People who get their furrowed brows eliminated with Botox (botulinum toxin A) often report an improvement in mood.

Until now, the assumption was that they were just feeling better about their appearance.

But the new study by local dermatologist Eric Finzi suggests that something else may be at work.

Finzi found that even patients such as Delano, who were not seeking cosmetic improvement, showed a dramatic decrease in depression symptoms.

"Maybe the frown is not just an end result of the depression; maybe you need to frown in order to be depressed," Finzi said in an interview.

"I don't think it has anything to do with making you look better. These patients were not coming to me for Botox; they were coming because I was offering a new treatment for depression."

Some patients in Finzi's study were receiving other treatments for depression; Finzi required that there be no change in those treatments for three months before he injected the Botox.

Finzi agreed that the effects of Botox on depression must be investigated in a much larger study before any conclusions about a link can be established, but a growing body of work suggests that changing expressions can influence mood.

People asked to smile while watching a cartoon, for instance, report it is funnier than people who are not asked to smile.

Alastair Carruthers, president-elect of the American Society for Dermatologic Surgery, agreed that Finzi's study provides new insight into a phenomenon clinicians have noticed.

"Anyone who has injected much Botox into the frown area has had people come in and say they can't believe how they feel better as a result," said Carruthers, clinical professor in dermatology at the University of British Columbia in Vancouver, in an interview.

"We've not really been able to put our fingers on why.... We have been doing research based on appearance, but it may be due to some mood-altering effect of Botox that we don't understand."

Finzi's study was published this month in the society's journal, Dermatologic Surgery.

Of the 10 depressed patients in the Washington area whom Finzi studied, nine recovered from their depressive symptoms, and one -- who turned out to have bipolar disorder, or manic depression -- showed an improvement in mood.

Delano, a marketing director, said that by the time she got involved in the study, she had turned down so many invitations for social gatherings that people had stopped asking her.

She went to see Finzi for a transient skin problem, which is when she heard he was recruiting patients for a novel treatment study of depression.

He gave her two rounds of Botox injections.

"After a couple of days, the muscles in your forehead, you can't constrict them," she said.

"You don't have that anxiety look. You can't furrow your brow... [but] for me there was not a dramatic cosmetic difference."

But where once she would hide out at home in the evenings and on weekends, Delano said, she found herself enthusiastically cheering her 8-year-old son at sports games.

Her relationship with her boyfriend also improved, she said.

Finzi, who practices dermatology in Greenbelt and Chevy Chase, said his hunch was that Delano's facial muscles provided feedback to her brain.

"My theory on why this works is there is a feedback between the muscles of facial expression and the brain," said Finzi, who has applied for a patent on using Botox for depression.

"With yoga, you focus on your breathing, and it has an effect on your mind. My hypothesis is the facial muscles... have an effect on depression."

The theory is similar to one proposed by Robert Zajonc, a psychologist at Stanford University, who thinks facial muscles may alter the temperature of blood flowing in the brain.

Relaxation techniques such as yoga and tai chi may help cool the brain and result in a more positive mood, Zajonc said.

Whatever the mechanism, moods can clearly be influenced by expressions, not just the other way around, said Paul Ekman, emeritus professor of psychology at the University of California at San Francisco, who has spent decades exploring the connection between emotions and expressions.

"If you make a facial expression voluntarily, you can change the autonomic and central nervous system to generate that emotion," he said.

But Ekman said the relationship between emotions and expressions is probably too complex to explain Finzi's finding.

It is unlikely, he said, that simply altering one's expressions can relieve depression.

More plausible, Ekman said, is that changing expressions can help heighten or decrease emotional states.

Or it is possible that by frowning less, patients in Finzi's study seemed less forbidding to others, which helped to strengthen their social connections.

In turn, that may have helped ease the depression, Ekman said.

Even depressed people who do not believe they frown all the time could seem forbidding to others, Ekman said: People rarely see themselves as others see them.

And although misery may love company, the reverse is not true.

"We don't like to talk to people who are frowning all the time or who are looking in anguish," Ekman said.

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Gives a whole new meaning to "put on a happy face," what?

It's been shown conclusively using functional MRI that psychotherapy changes brain metabolism in real time: when people feel better, different areas light up from when they're down.

Makes perfect sense to me that if feelings can change your expression, changing your expression is equally capable of changing your feelings.

That's why bookofjoe is good for you:

anything that makes you laugh — even if it's my own ineptitude and foolishness displayed here again and again, ad infinitum — can't help but pump up your brain for the better.

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Addendum: Wednesday morning, May 24, 8:31 a.m.

After sleeping on this subject it occurred to me this morning, as I was grinding my coffee beans (just the anticipation of this daily pleasure is enough, it would appear, to kickstart my peabrain motor), that perhaps the "Botox Effect," if you will, stems not from a change in facial expression with retrograde feedback to the brain but, rather, from the Botox itself.

In other words, you could inject the Botox into any muscle in the body — your arm, your butt, wherever — and the anti-depression "side effects" would kick in.

That changes everything.

The fact that Botox might not cross the blood-brain barrier — I suspect it doesn't — wouldn't matter if mediators released by the drug do find their way into the brain.

Just a thought.