Thursday, October 18, 2012

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.


  1. I've gained insight and some relief of my own generalized anxiety disorder and depression through cognitive-behavioral therapy and adopting a paleolithic lifestyle (honestly, exercising vigorously everyday and eating paleo has been THE most important factor in my mood change, CBT is a distant second), but the underlying causes of what I call my 'stalling' in life are still there. I may not be anxious all the time or feel horribly depressed about my past indiscretions, but I'm still apathetic and indecisive about my future, I can't get excited about a particular direction to take my career which is holding me back from jump-starting my life again.

    All that said, to rectify this last problem of making important major life choices and following-through on a life path, I've been reading as much positive psychology as I can. What I want to know is how much is 'Solution-Based' therapy affiliated with the newer positive psychology movement? I've never heard of it before, but the positive psychology focus is very similar, identifying what it would be like to live a good life and then changing mental habits to get you there. Seligman's learned optimism (contrasted with learned helplessness) was a majore eye-opener for me, and 'acting as if' or 'fake it till you make it' seems like a good way to become more optimistic. But, and here I get to my main point, how can you make this sustainable and resilient, because it may take long before your outward life starts to resemble your inner 'fake' attitude. Thanks!

  2. Fun paper! Will keep an eye out for Psyche Clinics/Botox Spas popping up in the near future! I wonder how insurance companies will take to Botox being classified as a "medical necessity".

    Have you seen the TED talk on smiling?

    1. Insurance is dealing with such issues without any hesitations - only FDA approved treatments are covered. I found it out because I thought botox may be helpful for my migraines and investigateg the possibility of the coverage.

  3. Could there be an evolutionary connection?

    One thing that strikes me (I didn't do any pubmed searches this time) is the possible relationship between the facial muscles off CNVII and the adjacent muscles handled by the vagus nerve. Could a botox treatment ostensibly aimed at facial muscles actually be spilling over to the nearby vagus? And thereby be a similar MOA to VNS? And one has to wonder, how much of the improvement via both methods comes from stimulating the brain (CNS) vs the gut (ENS)?

  4. There are some people who naturally have only horisontal wrinkles close to their hair line (like me)and no vertical wrinkles between brows. Could it be the marker for the low depression probability?

  5. I have personally tried acupressure which uses similar points like acupuncture and noticed a reduction in stress. Somewhat interesting also is that the acupressure points in between the eyes are believed to be related to visual acuity and my vision started to decline around the time my chronic depression started.

  6. Can we rule out a "hygiene hypothesis" type reaction to a bacterial toxin? What about antidepressant mycobacteria vaccae?
    Is this why botox is addictive?

  7. To control for this, inject it under skin elsewhere in the placebo group...somewhere that immobile skin won't be so flattering.

  8. I tried this about five years ago, just twice in six months I think. I liked the effects the first time, not so much the second. Exercise (heavy, endurance-style) made it wear off quicker than most, I heard. My fairly subtle but consistent depression seemed less but I became too suspicious of the toxins to do it thereafter.
    Then I found primal eating, the love of my life and now I get cross occasionally when our son (or husband) irritate me beyond endurance, but no more depression at all.

  9. I was hospitalized for psychosis and manic/depression the first time in 1981 when I was 19. I was hospitalized 6 more times and have lived in halfway houses, nursing homes and on the street, until 1988 when I'd been clean and sober for 5 years and went back to school at Purdue University to get my engineering degree. I experienced depression so bonecrushingly severe that I lost weight and sometimes couldn't sleep, experiencing nightmares. The one thing all of them had in common is the incessant and often unending ruminating in my mind, the non-stop thinking usually involving negative conceptions about the past or the future.

    In 1994, after being clean for over 11 years I was introduced to Tibetan Buddhism and, in particular, the practice of self-awareness and recovery mediated by self awareness-based intervention, born from meditation, that allows one to be aware of their own thoughts and risings of the mind in real-time. Though I'd seen numerous psychiatrists and been on a host of drugs, including haldol, trilifon, and thorazine (80's) to lithium (90's) [i know the former are not antidepressants], the severe bouts of depression hadn't gone away. In fact, one of the most severe was still to come in 1998.

    At this point, a turning began to happen. Through having more self-awareness of my own thoughts, formed conceptions and feelings, I began to wonder whether it was brain chemistry that was causing my depressions, ...or whether it was habituated patterns of thinking that caused brain chemistry to appear the way it did. It was clear that after being bludgeoned unendedly with one's own negative thoughts and thinking, and the thick dark feelings and conceptions of 'reality' it creates, that my body also took the toll in the form of the loss of appetite and weight, my ghoulish appearance, non-existant sexual energy and creative thinking.

    Using mediation based on selfawareness-based intervention, I was able to see the very negative thoughts and thinking that were making me feel 'bad'. In fact, I had a ground breaking moment in 1995 when on the way home from work, I was ruminating and replaying scenarios in my mind about the day, what I’d said to coworkers and my managers, self justifications and judgements, when suddenly I simply came back into the present moment and realized, with some shock, what I’d been doing in my mind, and particularly the dark, heavy depression-like atmosphere it had put me in. It was like being in a cramped, dark, stuffy room when suddenly the walls and ceiling disappeared and I found myself in the fresh, open air. I’ve never forgotten this moment because it was the first time I really noticed how negative thinking ravages the thinker, and I was so happy because it confirmed that I was on the right track, practicing meditation, beginning to have awareness around the actions of my mind.

    This experience confirmed for me both that awareness born from meditation is the root intervention and that it is the habituated negative thinking and ruminating that is the cause.

    I continue to practice meditation daily, but not as a tonic for my mind and the further development of self-awareness, but as part of a way I've found increasingly opens my mind and heart to the wisdom and compassion that is abundant, beyond conditions, within us.

    In the depth of depression, I agree that drugs are needed to help soften the rage of depressions deepest scourge upon our mind, but after the storm is done, we must become familiar with our own mind, notice it's habits and learn to cut through the dark life-blood of depression's hold on us through self-awareness of our own mind.

    I've been married for 13 years now and have held successful jobs at two large corporations, having left them and now doing therapeutic bodywork and talking to others about the usefulness of getting to know our own mind to reduce the stress in our own lives.

  10. Emily,

    I'm also beginning to give talks to graduate students in social work in addiction counseling at Loyola here in Chicago about the use of self-awareness, born from meditation, as a tool for self-mediation in noticing habituated negative thoughts, thinking and impulses in real-time, in the recovery from addiction, as well as depression -since they both have a common root in the mind. My first talk at Loyola University went over pretty well and I've been asked if I would come back at the start of classes in January to give adjunct talks about how using self-awareness allows us to do this, as well as the role that self-awareness can play in dissolving distance between therapist and client, and through a keen awareness of self and the causes of suffering, allow the therapist to enter an empathic communication with the client, directly making the client feel both heard and understood, connected.

  11. I just discovered your blog. Thank you for your insightful posts. I found this one particularly interesting.I work with the geriatric population (OT) and treat patients with all kinds of diagnoses. Many patients have depression as a secondary but I find that until you address it you cannot truly make gains. One of the first steps I take is to get them on a program to structure their day: their first goal is to get up and get dressed and groomed daily as if they were going out to meet someone at restaurant or office. If you can get them on board to do that their whole world turns around, same as botox but without the injections! :)The other approach from positive psychology that I find really helpful with my patients is keeping a "3 things that went well" journal.


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