Medical research by Dr. Eric Finzi & Dr. Norman E. Rosenthal on Botox as a treatment for Depression.
While Botox is commonly used for cosmetic purposes, doctors say the reasoning behind the treatment for depression may not be what you expect.
“We don’t believe it has anything to do with looks,” says researcher Dr. Eric Finzi of Chevy Chase Cosmetic Center.
Rather, he says it’s because facial expressions are part of the circuit of the brain related to mood.
George Washington University in Washington, DC, is currently recruiting volunteers for a new study testing Botox to help symptoms of social anxiety.
To see if you qualify for the free study, go to
Social anxiety disorder (SAD), also known as social phobia, is a psychiatric condition affecting 12% of adults, approximately 20 million Americans, according to the National Comorbidity Survey Replication (NCS-R) (1) and noted by the National Institutes of Mental Health. SAD typically begins in the teenage years. The anxiety disorder is characterized by a high level of fear in social situations causing emotional distress and isolation, affecting work, community and romantic relationships. The George Washington University is currently recruiting volunteers for a new study testing the ability of botulinum toxin A, commonly known as Botox, to help symptoms of social anxiety. To see if one qualifies for this free study taking place at GWU in Washington, DC, go to www.GWUanxiety.com.
This pioneering research is being led by Eric Finzi, MD, PhD, the first to publish a study using Botox to treat depression (2), and Daniel Lieberman, MD, Professor of Psychiatry and Behavioral Sciences at The George Washington University School of Medicine & Health Sciences. This study is testing whether Botox injected into the frown muscles (the muscles that pull the eyebrows together to produce a worried look) will help with social anxiety as it does with depression.
“The same part of the brain involved in depression, the amygdala, is also involved in SAD (3,4),” explains Dr. Eric Finzi. “It is my hope this common and debilitating disorder, social anxiety, will be helped by Botox treatment,” he adds.
Dr. Lieberman notes, “Although Botox is used primarily for cosmetic purposes, its effect on anxiety and depression have nothing to do with changes in appearance. It seems that paralyzing the frown muscles actually quiets down a part of the brain that amplifies negative emotions (5).” Social anxiety is a debilitating illness that often goes untreated. It is common for some sufferers to self-medicate with alcohol or other drugs to reduce fears at social events. If undiagnosed or untreated, social anxiety can lead to alcoholism, eating disorders or other kinds of substance abuse.
One of the more effective ways to treat social anxiety is with cognitive behavioral therapy (CBT). However, it is time consuming and it can be difficult to find a therapist with the proper training. Physicians often prescribe antidepressants, but more than half fail to respond adequately (6). In addition, antidepressant’s side effects may cause other unwanted health issues for users. Botox has a very favorable side effect profile, and has been in use for more than twenty years.
In 2014, Eric Finzi, MD, PhD and psychiatrist Norman E. Rosenthal, MD, Clinical Professor of Psychiatry at Georgetown Medical School, published the largest randomized, double-blind, placebo controlled trial on the effect of Botox on depression (7). They found that more than half of subjects suffering from moderate to severe depression showed a substantial improvement (greater than or equal to a 50% reduction in depressive symptoms) as measured by the MADRS, a standard depression scale. The study showed that Botox may help relieve depression both by itself as well when it is added to boost other treatments. There have been two other randomized controlled trials showing the effectiveness of Botox to treat depression, with similar results (8). Clinical trials are currently underway to get FDA approval for this novel treatment.
Persons interested in more information and to see if they qualify as a volunteer for this experimental treatment of social anxiety, can go to www.GWUanxiey.com. For more information about Botox to treat depression, go to BotoxForDepression.com.
MEDIA INQUIRIES CONTACT: Michelle Delino or by email:
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Resources:
1. Kessler, Ronald C., et al. “Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication.” Archives of general psychiatry 62.6 (2005): 593-602.
2. Finzi, Eric, and Erika Wasserman. “Treatment of depression with botulinum toxin A: a case series.” Dermatologic Surgery 32.5 (2006): 645-650.
3. Labuschagne, Izelle, et al. “Oxytocin Attenuates Amygdala Reactivity to Fear in Generalized Social Anxiety Disorder.” Neuropsychopharmacology 35 (2010): 2403- 2413.
4. Victor, Teresa A., et al. “Relationship between amygdala responses to masked faces and mood state and treatment in major depressive disorder.” Archives of general psychiatry 67.11 (2010): 1128-1138.
5. Kim, M. Justin, et al. “Botulinum toxin-induced facial muscle paralysis affects amygdala responses to the perception of emotional expressions: preliminary findings from an ABA design.” (2014).
6. Trivedi, Madhukar H., et al. “Evaluation of outcomes with citalopram for depression using measurement-based care in STAR* D: implications for clinical practice.” American journal of Psychiatry 163.1 (2006): 28-40.
7. Finzi, Eric, and Norman E. Rosenthal. “Treatment of depression with onabotulinumtoxinA: a randomized, double-blind, placebo controlled trial.” Journal of psychiatric research 52 (2014): 1-6.
8. Magid, M., et al. “Treating depression with botulinum toxin: a pooled analysis of randomized controlled trials.” Pharmacopsychiatry 25.06 (2015): 205-210.
Treating Depression with Botulinum Toxin: A Pooled Analysis of Randomized Controlled Trials
Introduction: Botulinum toxin A (BTA) injection into the glabellar region is currently being studied as a treatment for major depressive disorder (MDD). Here we explore efficacy data of this novel approach in a pooled analysis.
Methods: A literature search revealed 3 RCTs on this topic. Individual patient data and clinical end points shared by these 3 trials were pooled and analyzed as one study (n=134) using multiple regression models with random effects.
Results: In the pooled sample, the BTA (n=59) and the placebo group (n=75) did not differ in the baseline variables. Efficacy outcomes revealed BTA superiority over placebo: Improvement in the Hamilton Depression Rating Scale or Montgomery-Asberg Depression Rating Scale 6 weeks after baseline was 45.7% for BTA vs. 14.6% for placebo (p<0.0001), corresponding to a BTA response rate of 54.2% (vs. 10.7%) and a BTA remission rate of 30.5% (vs. 6.7%).
Discussion: Equalling the status of a meta-analysis, this study increases evidence that a single treatment of BTA into the glabellar region can reduce symptoms of MDD. Further studies are needed to better understand how BTA exerts its mood-lifting effect. Read More…
Forbes.com’s Matthew Herper, a reporter on the Pharma and Healthcare beat, covered the recent annual meeting of the American Psychiatric Association in Toronto and wrote about the collective data findings on Botox to treat depression. Herper writes, “the analysis of the data published so far presented here at the American Psychiatric Association in Toronto seem to support the idea that Botox injections in the face can ease depressed mood.” Read more.
Dr. Eric Finzi will be a guest on NPR Boston’s The Colin McEnroe Radio Show today at approximately 1:06PM EST talking about the Botox for Depression research study findings published in the Journal of Psychiatric Research (May 2014). The study “Treatment of Depression with onabotulinumtoxinA: A Randomized Double-Blind, Placebo Controlled Trial” found that 52% of subjects suffering from moderate to severe depression showed a relief from depression after injection of botulinum toxin to the glabellar area between the eyes, compared with only 15% of those who received the saline placebo. A second phase to this study is in the works.
This year marks commemorates the 25th anniversary of the first approved uses of BOTOX® and to honor its heritage as a medical advancement. You can listen to the program LIVE at http://wnpr.org/programs/colin-mcenroe-show and click on “stream us live” link.
The following information is published on Allergan, the makers of Botox’s website:
While BOTOX® Cosmetic (onabotulinumtoxinA) has become a household name, BOTOX® was the first botulinum toxin type A treatment to be approved by the U.S. Food and Drug Administration as an orphan drug for two rare, eye muscle disorders. This journey, which started in 1989, began with the approval of BOTOX® to treat strabismus (a misalignment of the eyes, commonly known as crossed eyes) and blepharospasm (uncontrolled blinking of the eyelid). Strabismus affects nearly four in every 100 adults,1 and blepharospasm affects an estimated 20,000 to 50,000 people in the United States, with 2,000 new cases diagnosed annually.2 Since that time, BOTOX® therapeutic has been approved for other significant medical conditions including Cervical Dystonia, Severe Underarm Sweating when topical agents don’t work sufficiently, Upper Limb Spasticity, Chronic Migraine, Overactive Bladder when an anticholinergic doesn’t work or the side effects are intolerable, and urinary incontinence due to overactive bladder caused by a neurologic condition when an anticholinergic doesn’t work or the side effects are intolerable.
“BOTOX® is an innovative product whose potential to treat medical conditions across a variety of therapeutic categories continues to expand even today,” said David E.I. Pyott, Chairman of the Board and Chief Executive Officer, Allergan. “The more we research the medical value of this treatment, the more we learn about this biologic and the areas of clinical unmet need where it may provide some benefit. Since BOTOX® was first approved 25 years ago, the list of indications it treats has grown exponentially – not just in the United States, but globally. Today, physicians in 88 countries treat 27 different conditions with BOTOX® and the possibilities continue to grow with Allergan’s research.”3
The video, which outlines the 25-year history of development for BOTOX® therapeutic, features first-hand accounts from patients who chronicle their journey from diagnosis to treatment, as well as physicians who share their personal experiences in advancing the development of this brand, showcasing its therapeutic roots.
For each person that views the video, Allergan will support four patient advocacy organizations that are partnering with the company to help raise awareness, educate and support people living with any of the medical conditions currently being treated with BOTOX®. Support will be given to:
“The history of BOTOX® therapeutic is really a remarkable story of how a substance from nature has been successfully harnessed for medical benefit,” said Scott Whitcup, M.D., Allergan’s Executive Vice President, Research and Development and Chief Scientific Officer, “It’s also a human interest story that starts with the scientists and the physicians who observed the impact of BOTOX® in treating certain medical conditions, tracked that impact and did something about it. Without this pioneering spirit, we would not have been able to pursue the clinical development and FDA approval of many of the therapeutic indications we now have for BOTOX®.”
To learn more about BOTOX® and to view the 25th anniversary video please visitwww.BOTOX.com.
About BOTOX®(onabotulinumtoxinA)BOTOX® is a prescription-only medical product that contains tiny amounts of a highly purified botulinum toxin protein refined from the bacterium, Clostridium botulinum. When injected at doses approved by the U.S. Food and Drug Administration (FDA) into a specific muscle or gland, BOTOX® neurotoxin is expected to produce a safe, as well as effective result, usually lasting up to approximately three to ten months, depending on the approved indication and on the individual patient.
BOTOX®was first approved in 1989 by the U.S. Food and Drug Administration (FDA) for the treatment of two eye muscle disorders, making it the first botulinum toxin type A product to be approved in the world. Since then, BOTOX®has been recognized by regulatory authorities as an effective treatment for 27 different indications in approximately 88 countries, benefiting patients worldwide.
Today, BOTOX®neurotoxin is approved to treat a total of eight medical conditions in the United States, including:
Michele Magid, MD, University of Texas Southwestern
Guest Blogger and Botox and depression researcher, Michele Magid, MD, (University of Texas, Southwestern) shares her insight on the phenomenon Psychiatrists around the globe are pondering in this blog post, “Do We Frown Because We’re Depressed, Or Are We Depressed Because We Frown?
Smiling makes us feel better! In a TED talk, researcher Ron Gutman discussed the facts that people with bigger smiles tended to live longer lives, have happier marriages, and appear more competent to others.1 In addition, smiling can reduce stress levels by decreasing cortisol, and improve mood by increasing endorphins.1 Gutman’s talk received criticism as it was unclear whether the link between smiling and success was correlative or causative.2
According to evolutionary theorist Charles Darwin and philosopher/psychologist William James, the relationship is causative—we are happy because we smile, we are sorry because we cry, and we are angry because we clench our teeth, not the other way around.3,4 In other words, changes in facial expression create and enhance emotion and are not merely a consequence of that emotion.
If facial expression can influence emotional experience, then what would happen if depressed patients were no longer able to frown?
Three recent studies5–7 (with sample sizes of 30 to 85) set out to answer this question. Male and female participants with major depressive disorder were injected with botulinum toxin A (BTA) into the forehead region, causing a reduced ability to frown (ie, paralysis of the corrugator and procerus muscles, which control expressions of fear, anxiety, and anguish). In all 3 double-blind, placebo-controlled trials, BTA was associated with a statistically significant reduction in depressive symptoms compared with placebo. More interestingly, in our 24-week trial,7 the antidepressant effects of BTA continued even after the cosmetic effects had worn off.
Today Show interviews Dr. Eric Finzi 7/11/14
If botulinum toxin in the frown muscles improves symptoms of depression, why?
Some may argue that looking aesthetically better leads to feeling better, but our study7 excluded those with concern about their frown lines. Others argue that the more pleasant and less depressed we look, the more inviting we are to others, leading to improved social interactions and, subsequently, improved mood. These arguments, however, do not explain why mood continues to improve even when the BTA is no longer cosmetically active.
A final argument is that BTA in the forehead alters peripheral feedback to the brain. A recent study8 showed that people who were given BTA in the frown muscles had reduced activity in the left amygdala on functional magnetic resonance imaging (fMRI) when mimicking angry facial expressions. In theory, paralysis of the forehead muscles reduces sensory information from the trigeminal tract to the brainstem, which then alters activity between the brainstem and left amygdala. These findings are important as hyperactivity in the left amygdala has been linked to anxiety, depression, posttraumatic stress disorder, and heightened fear responses.9 In one study,10 20 depressed patients exhibited exaggerated left amygdala activity when shown pictures of emotional faces, especially fearful faces. After antidepressant treatment, left amygdala hyperactivity returned to normal.
Is botulinum toxin a viable treatment option for major depressive disorder?
Regardless of whether one subscribes to a more behavioral or biological mechanism of action, further trials are warranted to determine if BTA is indeed a viable therapeutic option for depression and if specific patient populations are more likely to respond (eg, a recent study11 showed that higher agitation scores are predictive of response). If larger trials can replicate the findings of the 3 small trials, BTA may become a novel treatment in the management of major depressive disorder.
Financial disclosure: Dr Magid received grant/research support from the Brain and Behavior Institute, Young Investigator Award, to fund this study. After completion and as a result of the study, Dr. Magid became a consultant for Allergan.
References
1. Gutman R. The hidden power of smiling. TED Talks. March 2011.http://www.ted.com/talks/ron_gutman_the_hidden_power_of_smiling.
2. Grohol J. Ron Gutman: smiling while confusing correlation with causation.http://psychcentral.com/blog/archives/2012/08/19/ron-gutman-smiling-while-confusing-correlation-with-causation/.
3. Darwin, C. The Expression of the Emotions in Man and Animals. London, England: John Murray; 1872.
4. James, William. The Principles of Psychology. New York, NY: Henry Holt & Co; 1890.
5. Wollmer MA, de Boer C, Kalak N, et al. Facing depression with botulinum toxin: a randomized controlled trial. J Psychiatr Res. 2012;46(5):574–581. PubMed
6. Finzi E, Rosenthal NE. Treatment of depression with onabotulinumtoxin A: a randomized, double-blind, placebo controlled trial [published online ahead of print December 16, 2013]. J Psychiatr Res. Abstract
7. Magid M, Reichenberg JS, Poth PE, et al. Treatment of major depressive disorder using botulinum toxin A: a 24-week randomized, double-blind, placebo-controlled study. J Clin Psychiatry [published online ahead of print May 13, 2014]. Abstract
8. Hennenlotter A, Dresel C, Castrop F, et al. The link between facial feedback and neural activity within central circuitries of emotion—new insights from botulinum toxin-induced denervation of frown muscles. Cereb Cortex. 2009;19(3):537–542. PubMed
9. Shin LM, Liberzon I. The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology. 2010;35(1):169–191. PubMed
10. Sheline YI, Barch DM, Donnelly JM, et al. Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biol Psychiatry. 2001;50(9):651–658. PubMed
11. Wollmer MA, Kalak N, Jung S, et al. Agitation predicts response of depression to botulinum toxin treatment in a randomized controlled trial. Front Psychiatry. 2014;5:36. PubMed
The authors of three independent double-blind, randomized, placebo controlled clinical trials will present “Botulinum Toxin, An Emerging Therapeutic for Depression” and their respective research study findings to mental health professionals at the XVI World Congress of Psychiatry (WCP2014) meeting in Madrid, Spain, on September 18th from 12:45-13:30 in Room 11 at the Madrid Congress and Convention Center.
The WCP2014, organized by the World Psychiatric Association will take place September 14-18 in Madrid, and will focus on access, quality and humane care. Over ten thousand psychiatrists from all over the world are expected to be in attendance.
According to the World Health Organization, over 350 million people of all ages suffer from depression globally. As of 2012 in the United States, an estimated 16 million adults aged 18 or older had at least one major depressive episode in the past year. Unfortunately, most people never seek treatment. Left undiagnosed and untreated, depression can worsen, cause untold suffering, and may even result in suicide.
Oral antidepressants are designed to boost mood and relieve depression. However, one third of patients do not respond to oral medications. In addition, for some sufferers, side effects such as fatigue, nausea, insomnia, sedation and lack of sexual drive may be poorly tolerated. By contrast, botulinum toxin has few side effects in the doses used to treat depression.
Botulinum toxin is FDA approved to treat a wide variety of health issues including urinary incontinence, migraine headaches, cerebral palsy, excessive sweating, and cervical dystonia, among others.
In the largest study to date on the effect of botulinum toxin on depression, researchers Eric Finzi, MD, PhD, and Norman E. Rosenthal, MD, found that 52% of subjects suffering from moderate to severe depression showed relief from depression after injection of botulinum toxin to the glabellar area between the eyes, compared with only 15% of those who received the saline placebo. The study, “Treatment of depression with onabotulinumtoxinA: A randomized, double-blind, placebo controlled trial” was published in Journal of Psychiatric Research, Volume 52 (May 2014). These findings help to confirm a novel concept for mental health – using facial expressions to influence thoughts and feelings.
Dr. Eric Finzi, a dermasurgeon and artist in the Washington, DC, metropolitan area, made global headlines in 2006 when his pilot study was the first to report the inhibition of facial frowning with Botox injection could help depressed patients. In The Face of Emotion, How Botox Affects Our Mood and Relationships, published by Palgrave Macmillan in 2013, Finzi explains his groundbreaking research and study findings in narrative form, weaving personal stories and rich historical accounts to showcase how his theory came to light. Finzi’s thinking, which dates back to Charles Darwin and William James’s facial feedback theory, marshals together evidence from psychology, neuroscience, art, evolutionary biology, family and patients, to show that facial expressions are a central driving force of our emotions, and that there is an unlikely ally available to tame them: Botox.
Finzi explains, “Botulinum toxin’s inhibition of frowning gives us a novel tool to influence mood. We believe that the brain monitors the state of contraction of facial muscles, and this feedback to the brain is powerful. We look forward to presenting the results from the three clinical trials to the world psychiatric community.”
NBC News Today Show correspondent Tom Costello interviews Dr. Eric Finzi and two Botox to treat depression research study participants about the unbelievable treatment for depression.
Today Show interviews Dr. Eric Finzi 7/11/14
VIEW VIDEO: Today Show July 11, 2014 featuring Botox to treat depression study
Writer Taffy Brodesser-Akner tries Botox to treat her depression and shares her story with readers of Pacific Standard magazine in the July 2014 issue.
READ:
Satirist Stephen Colbert recently joked about the Botox for Depression study findings in this Comedy Central The Colbert Report entitled Cheating Death: Depression Edition. Study co-author, Dr. Norman Rosenthal, explains the science behind the research findings in this video.
Dr. Norman Rosenthal’s written BLOG on the subject:
I have always gravitated to research approaches that are off the beaten track, such as the study of SAD and light therapy that I spearheaded at the National Institute of Mental Health (NIMH) over 30 years ago. At that time, seasonal affective disorder (SAD) had not yet been identified: we went on to name it and describe its typical symptoms. Light therapy, as it’s used for SAD, was unknown. My colleagues thought I had lost it. Yet now we recognize that millions of people the world over suffer from SAD and countless people have benefited from light therapy.
It was this same out-of-the-box instinct for a winner that went on alert when my colleague, Dr. Eric Finzi, a local dermatologist approached me with a novel idea for treating depression. Some years before, after leaving the NIMH, I had opened up a private clinical research organization in the hope of doing innovative and creative studies. Although that was possible to some extent (for example, I was able to study the effects of Transcendental Meditation on bipolar disorder and post-traumatic stress disorder), the reality of the work revolved mostly around testing new drugs. So, I was always on the lookout for something really different and exciting.
Dr. Finzi had read the work of Charles Darwin and the famous psychologist William James, both of whom had suggested that cues from the body, including the face, had a powerful effect on human emotions. Darwin called the frown muscles between the eyebrows “the grief muscles,” and suggested that they were not just a reflection of sorrow, but also fueled it. An extensive subsequent literature supported this “facial feedback hypothesis,” and numerous experiments showed that facial expressions affect the way we feel.
Finzi has described this history in a highly readable book, The Face of Emotion. Now Finzi had an idea as to how these insights could be used to treat depression – by means of botulinum toxin (Botox), which is known to paralyze muscles. How would it be, he wondered, if we paralyzed the frown muscles between the eyebrows in a double-blind study with saline as a control? An encouraging pilot study suggested it might work. But this would now need to be tested in a controlled study. Would I be interested in conducting such a study in my research organization? Well, I loved the idea! And that was the beginning of an enjoyable collaboration.
Another reason why Finzi’s idea appealed to me so much is that over a decade before he approached me, I had written a book about the science of emotion, called The Emotional Revolution. In it I wrote:
Among the sensory nerves that influence our mood are those that pass directly through the skull and into the brain. These are known as the cranial nerves. Exposure to light stimulates one pair of these nerves, the optic nerves. Another pair, the olfactory nerves, transmits sensations of smell to the brain. The fragrance of lemons lifts the mood of depressed patients with SAD.
It was highly plausible to me that frowning might send signals to the brain via different cranial nerves – the facial and trigeminal nerves. But in this case, it seemed, the signals aggravated a person’s mood rather than relieving it. So it made all the sense in the world to me that blocking these signals might reverse depression.
So Finzi and I embarked on a controlled study of Botox for depression in collaboration with a great team of psychiatrists and administrators at my research organization. We entered 74 depressed people into a double blind, placebo controlled study and when we finally analyzed the data, the results were clear and strong. Botox beat placebo, significantly reducing depression levels, regardless of whether patients were already on antidepressants (to which they had not responded) or were untreated.
As a psychiatrist who has treated many people with depression, I am truly excited at this new treatment option. Although there are many available treatments for this very painful affliction, they are often only partially effective and have troublesome side-effects. I am delighted that we now have a new treatment option which can be used safely