Breakthrough - β0ToxinA® for Depression?

Episodes of major depression last from six to nine months. The crisis can occur once as a result of a significant psychological trauma, or may develop slowly as a consequence of numerous personal disappointments and problems, respond to
treatment, and never occur again within the patient's lifetime (single episode depression), or it can be recurrent. Some studies have indicated that the more depressive episodes a person experiences, the less time elapses between them. In
about 20% of cases this disorder has a chronic course.

Symptoms vary, yet the major depression diagnosis is made on the basis of a combination of at least five of the following categories lasting for two weeks or longer:

• Persistent depressed, sad, anxious, or empty mood

• Feeling worthless, helpless, or experiencing excessive or inappropriate guilt and self-hatred

• Hopelessness about the future, excessive pessimistic feelings

• Loss of interest and pleasure in usual activities, inactivity and withdrawal

• Decreased energy and chronic fatigue

• Loss of memory, difficulty making decisions or concentrating

• Irritability, restlessness or agitation

• Sleep disturbances, either difficulty sleeping, or sleeping too much

• Loss of appetite and interest in food, or overeating, with weight gain

• Recurring thoughts of death, or suicidal thoughts or actions

The exact cause of depression is unknown although it seems to be due to chemical imbalances in the brain and many researchers are questioning whether genetics or stress plays the major role. Stress appears to be a prominent cause in triggering the first 1-2 episodes of this disorder, but not in subsequent episodes where genetics and temperament seem to play the most important role. Those with a parent or sibling who has had major depression may be 1.5 to 3 times more likely to develop the condition than those who do not. Some people appear to develop "endogenous depression" without any identified psychological causes.

Medical conditions often causing depression are: endocrine disorders (such as hypothyroidism, hyperparathyroidism, Cushing's disease, diabetes mellitus), neurological disorders (multiple sclerosis, Parkinson's Disease, migraine, various
forms of epilepsy, encephalitis, brain tumours), medications (antihypertensive agents such as calcium channel blockers, beta blockers, analgesics, and some antimigraine medications).

About 20-25% of people suffering from cancer, stroke, diabetes, and myocardial infarction are likely to develop major depressive disorder sometime during the presence of their medical illness. It has moreover been shown that other mental
health conditions often co-exist with this pathology. Some of these are alcohol/drug abuse, anxiety and panic, obsessive-compulsive behaviour, eating disorders, and borderline personality.

A recent World Health Organization report predicts that depression will be the leading cause of disability and premature death in the industrial world by the year 2020.

Nowadays, without treatment, 10 to 15% of people suffering from severe major depressive disorder commit suicide. Over age 55, there is a fourfold increase in death rate.

Depression can be treated in a variety of ways as response is very subjective. About two-thirds of treated patients recover completely. The other one-third may recover only partially or not at all. Medications include tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin re-uptake inhibitors (SSRIs), and some newer, or second-generation, antidepressant drugs. Lithium and thyroid supplements may be needed to enhance the effectiveness of antidepressants. Electroconvulsive therapy (ECT) may improve the mood of severely depressed or suicidal people who do not respond to other treatments. Research is now being conducted on transcranial magnetic stimulation (TMS). Some studies have shown
that antidepressant drug therapy combined with psychotherapy (in particular cognitive therapy) appears to have better results than either therapy alone. Also, herbal or natural treatments, dietary supplements, and other alternative treatments have been used with varying results, just like interventions to restore a normal sleep cycle, and light therapy.

In the future a new treatment with botulinum toxin may be available according to an article that appeared in May's issue of Dermatologic Surgery, the official journal of the American Society for Dermatologic Surgery (ASDS). In it Dr. Eric Finzi, MD, PhD, a dermatologist in Chevy Chase, Md. reported the results of a small-scale pilot trial conducted on ten volunteer female patients, aged 36 to 63, who were recruited from his dermatology practice, and were evaluated by a clinical psychologist (his co-author, Erika Wasserman).

All the women met the standards (DSM-IV criteria) for ongoing major depression (for an average of 3,5 years, with one patient suffering for 17 years with no improvement from conventional treatments), and were evaluated with the Beck Depression Inventory II (BDI-II) before receiving botulinum toxin A treatment. Seven of the ten patients had tried one or more antidepressants, and four had been treated with psychotherapy. Dr Finzi required that there be no change in treatments for three months before the toxin injections. None had used botulinum toxin prior to entering the study. Five injections were given into the glabellar frown lines. Two months later, all patients were re-evaluated clinically and through self-reported surveys. Nine out of ten recovered from their depressive symptoms (nearly twice the success rate claimed for antidepressants) and one  who turned out to have bipolar disorder  showed an improvement in mood.

Clinicians have long noticed that patients receiving botulinum toxin A to eliminate wrinkles from their brows often reported an improvement in mood. Until now, though, the assumption was that they were just feeling better about their appearance, which increased their self-confidence. Yet this study suggests that something else may be at work as Finzi found that even patients who were not seeking cosmetic improvement showed a dramatic decrease in depression symptoms.

In 1872 Charles Darwin maintained that you are the emotions you express on your face. "Smooth the brow, brighten the eye ..." the pioneering psychologist William James wrote in 1890, describing a self-help technique for overcoming depression, "and your heart must be frigid indeed if it does not gradually thaw." And countless song lyrics and age-old literary wisdom have expressed the same concept, that modern psychology has finally proven: the mere act of smiling, even forcedly, makes people feel better as it promotes the release of mood-elevating endorphins in the brain, so the opposite could also be true. It is the facial feedback hypothesis according to which a positive expression provides feedback, physiological and perceptual, that affects the experience of emotion (and indeed both Alcoholics Anonymous and cognitive therapy for depression encourage patients to fake wellbeing in their behaviour).

Frown muscle activity, on the other hand, has been found to be a predictor of depression treatment outcome, according to a 1981 study in the British Journal of Psychiatry.

Illogical as it may seem, since frowning is an expression of an underlying emotional state, and therefore an effect and not a cause, to a surprising degree, the facial muscles control emotions, as well as the other way around. That is why patients with Mobius syndrome, a partial facial paralysis, seem not to experience emotions with the same intensity as normal people. Dr. Finzi told the Washington Post "Maybe the frown is not just an end result of the depression; maybe you need to frown in order to be depressed." He hypothesizes that there may be a direct feedback between the facial frown muscles and the depression centre of the brain. The facial muscles may feed information to the emotion centres of the brain, which in turn respond with chemicals that produce happy or sad feelings. The loop is complete when those feelings are sent back to the brain, reinforcing expressions on the face. "I thought if I could interrupt this cycle and prevent the frown, maybe a depressed patient would get better," said Finzi. It is one theory that some researchers have held, though as yet there is no proof of such a neurological underpinning. Scientists have proven, however, that facial expressions can alter heart rate, skin temperature and blood volume.

As was to be expected, the revolutionary study arouse a lot of controversy and met with skepticism by clinical psychologists such as ASDS president-elect Alastair Carruthers, and University of Michigan professor of psychiatry Michelle Riba, immediate past president of the American Psychiatric Association, who maintain its results are just anecdotal as there are many flaws in how it was performed. Namely: the group of people studied was very small and the follow-up period very brief, there was no clear information as to what severity of depression the patients were experiencing, and depression assessments were based on reports by the patients themselves. Moreover, it lacked random sampling (the group did not represent a cross-section of the population), control group (every study participant received botulinum toxin and none received a placebo), and double blind (both patients and the researcher knew they were receiving treatment  and this is especially important in research on depression, where individuals taking placebo often improve dramatically).

Finzi, who has applied for a patent to protect the treatment for depression, acknowledges that the study was limited by fact that he had no outside funding and agrees that the effects of the toxin on depression must be investigated further in much larger and more thorough studies and research before any conclusions about a link can be established. Yet, as the first pioneer trial to evaluate the effect of botulinum toxin on major depression, it deserves close attention by the scientific community and may lead to a new important β0ToxinA® application. We will certainly hear more about it in the years to come.


  • Adler, Jerry and Springen, Karen, Health, Can You Really Botox the Blues Away? Newsweek May 29, 2006.
  • Brink, Susan, A lift for faces -- and moods? Times May 22, 2006.
  • Finzi, Eric; Wasserman, Erika, Treatment of Depression with Botulinum Toxin A: A Case Series. Dermatologic Surgery, Volume 32, Number 5, May 2006, pp. 645- 650(6).
  • Hagan, Pat, Can Botox even cure Depression? Daily Mail, May 23 2006.
  • Morrant JCA, Depression And Some Newer Antidepressants. BC Medical Journal 1997; 39(12):636-640.
  • Nordqvist, Christian, Botox Into Frown Lines Can Help Patients With Major Depression Medical News Today 21 May 2006.
  • Vedantam, Shankar, Botox Appears to Ease Depression Symptoms, Sunday, May 21, 2006; Page A09.
  • Young, Samuel M. Jr., Proteolysis of SNARE proteins alters facilitation and depression in a specific way, PNAS February 15, 2005 vol. 102 no. 7 2614-2619.

To learn more about this condition, you can visit the website of the Depression and Bipolar Support Alliance
See also:

We hope you enjoyed this article.
And, while wishing you good and relaxing holidays,
we inform you that the next issue of our newsletter will appear in September.



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