Depression: A Cosmetic Cure?

"Fake it until you make it." This phrase, though often met with derision, constitutes some practical advice when dealing with a devastating problem like chronic depression.

There are, at the base of it, two major psychotherapeutic approaches to the treatment of depression. One way to explore relationships and history to find past trauma and metabolize it in order to get through it and better under stand current pain. Another approach is to focus on appropriate lifestyle and coping habits to reduce depression. The phrase "fake it until you make it" speaks to the second "cognitive behavioral" method.* One extreme (but interesting) version of behavioral therapy is called "solutions based" therapy. I learned about it in residency and dabbled a bit with the ideas in practice, but saw it popularized most recently in the scorching (but intolerably paced, plotted, and characterized) "50 Shades" trilogy. Solutions based therapy apparently helped the billionaire hero, but not enough so he could give up his sex dungeon. It takes a co-ed implausibly promoted to senior book editor to do that.

Two Door Cinema Club: Sleep Alone

In any event, solutions-based therapy begins with the "miracle question." Let's say in the middle of the night while you were asleep, a miracle happened and you were cured of depression. How do you know you were cured? What do you feel when you wake up in the morning that is different? How is your energy? What does your face look like when you first see yourself in the mirror? How would your loved ones know you are cured and what would they see? The idea is to focus on those "solutions." If being happy means having energy in the morning and looking at yourself in the mirror and seeing  bright smile, then maybe changing some habits so your sleep improves and grinning at yourself in the mirror can be part of the cure.

There is some neurobiological truth to the smile therapy. The mere act of smiling sends positive signals to the brain and can lift the spirit, while the act of scowling can make you feel immediately grumpier. It's subtle, but give it a try.

Believe it or not, there is some research to suggest that treatment with botox, paralyzing certain muscles to prevent deep scowling, can be an effective antidepressant treatment as well. And no, this treatment is not exactly "evolutionary psychiatry" but I do like to explore novel ways to look at the pathology and treatment of mental illness, and I would say the cosmetic cure qualifies. Even looking at smiling faces makes people happier. Do you think our ancient ancestors were more carefree than we are? More relaxed? More apt to smile? I wish I knew the answer to that question. It's not preserved in the fossil record.

Can butulinum toxin improve mood in depressed patients?

The largest and perhaps most famous trial of resistant depression patients was the STAR*D trial (and I did have the privilege of sitting in on some of the weekly research meetings at MGH while this trials were being conducted).  "Resistant" depression means depression that lingers despite antidepressant treatment. Only 30% of these patients find significant relief from the medication antidepressants that are available, of whatever variety. Nearly 50% of medicated patients discontinue antidepressants within 6 months, though most data suggests that treatment of 9-12 months after remission is most effective.

Other new technologies, such as inserted vagus nerve stimulation (VNS) devices and transcranial magnetic stimulation (TMS) have tried to fill the void in resistant depression treatment. They remain out of reach for most patients as insurance will generally not pay for them. The other treatment for severe resistant depression is electroshock therapy, which tends to be quite effective but has many side effects and can be very disruptive. In truth, the data for resistant depression for most modalities is poor. Not much we've discovered so far will work well, and drug companies don't want to spend millions on a trial that will likely result in failure. To find a new experimental method used in resistant patients is actually rather exciting.

(Lest we get too excited) the study I'm reviewing is merely a pilot trial.  30 people with resistant depression (average duration of 16 years) were randomly assigned to botox injection or saline placebo injection (and by the end 90% of people were able to tell whether or not they got the active agent, which pretty much negates the blinding). The single injection was made into the glabellar region (right at the top of the nose, where forehead scowling lines will center). To try to preserve a bit of experimental blinding at least for the raters for the follow ups, everyone wore a skullcap to cover the forehead. Scale ratings were done via the rather classic Hamilton D 17 item depression scale.  Inclusion into the trial involved full structured clinical interview with a diagnosis of major depressive disorder, which is gold standard. Response to treatment was tracked from week 2 to 16 weeks after the injection.

HAM-D scores improved a whopping 10.1 points in the treatment group in 6 weeks versus 1.7 in the control group. Nonresponse is characterized as a <25% reduction, partial response a 25-50% reduction, and >50% reduction in HAM-D score is considered "remission" and the holy grail of psychiatry in resistant depression treatment. In this trial, partial response in the treatment group was 86.7% vs. 26.7% of the placebo. That's a pretty big deal in resistant depression. Actual depression remission occured in 33.3% of active treatment vs. 13.3% of placebo which was not statistically significant given the small sample size. Let me put it thusly:

In this little study, a single botox injection was a bit better than the classic antidepressants and really blows the expensive and/or invasive TMS or VNS treatments out of the water. The only side effect reported was a mild short-term headache. Antidepressants tend to cause sexual dysfunction and/or weight gain or stomach upset or sweating or a number of other issues, and botox needs to be repeated only every 4 months or so, rather than daily pills.

There are a lot of limitations in this study. It was small. Mostly women. Mostly the melancholic subtype of resistant depression (which can actually be easier to treat). Most of the patients guessed correctly whether they were in the treatment group or not, so blinding was a huge issue. But the theory is that the more positive facial expressions after botox treatment deliver positive neurofeedback, improving mood, and causing the treatment effect.

But, as a psychiatrist, the most exciting procedure I tend to perform on patients is checking blood pressure. It might be nice to inject some botox now and again. I'm a terrible evolutionary psychiatrist, when it comes down to it.

*In actuality, most therapists in practice combine the two methods, and a manualized and studied version of that is called short-term dynamic psychotherapy, the textbook of which was written by one of my teachers in residency, Leigh McCullough, PhD. I was saddened to learn she died of ALS earlier this year.