clinical use during the treatment of depression. There were some papers; including preliminary data from an open case series with ten female patients in the Journal of Derm. Surgery by Finzi and Wasserman (2006) that postulated that botulinum toxin in the glabellar actually demonstrated a reduction in the symptoms of depression. However a footnote by editor Alastair Carruthers stated that the report must be considered anecdotal as there were no appropriate methods of control utilized. In addition, there were other methodological weaknesses including limited follow-up, lack of randomization, the absence of blind evaluation, and especially the small number of individuals included. It was considered by many that the method evaluating depression should have been more rigorous. I noted by letter at the time that patients’ self-report of depressive symptoms by administration of the BDI-II introduced a significant self-report bias. This is of more concern because of the potential for secondary cosmetic gain. While the BDI-II is an accepted method of evaluating an individual’s level of symptoms over time, self-report in isolation was not considered an acceptable method of diagnosing depression. It was concluded that in order to ensure that patients’ psychiatric symptoms are accurately classified; a thorough psychiatric interview must be conducted. More recently, two centers, the Psychiatric University Hospital of the University of Basel, Switzerland and the Medical School Hannover, Germany conducted a randomised, placebo-controlled, double-blind trial. The authors hypothesised that facial psychomotor features associated with depression are not just epiphenomena but integral components of the disorder and may be targeted in its therapy. To explore, if attenuation of these features may produce alleviation in the affective symptoms, they conducted a randomized controlled trial of botulinum toxin injection to the glabellar region as an adjunctive treatment of major depression. The study was investigator-initiated and was carried out independently of any commercial entity. Participants in the study were recruited from local psychiatric outpatient units and psychiatrists in private practice. In order to avoid attracting candidates who were primarily motivated by receiving this treatment for cosmetic reasons, botulinum toxin treatment,
botulinum toxin injection to the glabellar region may be an effective, safe, and sustainable intervention in the treatment of depression. The reason for this has not yet been fully evaluated but we must consider the concept that the facial musculature not only expresses, but also regulates, mood states. was not explicitly mentioned. Exclusion criteria included psychotic symptoms, suicidal tendency and clinical severity requiring immediate intervention. The same injection scheme was applied in the open case series (Finzl and Wasserman, 2006). At each study visit participants were assessed using the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS), the Beck Depression Inventory (BDI) selfrating questionnaire and the Clinical Global Impressions Scale (CGI). To conceal cosmetic changes from psychometric raters, participants wore an opaque surgical cap, which covered glabella and forehead during the examinations. The study concluded for the first time that a single botulinum treatment of the glabellar region with could reduce the symptoms of major depression. This effect developed within few weeks and persisted until the end of the sixteenweek follow-up period. The effect sizes in the study were large and the response and remission rates were high. It is still unknown how botulinum toxin actually reduces depression and it is postulated that several mechanisms may actually be involved: Because of the clinical data relating to botulinum toxin treatment on emotional perception, it is assumed that reduced proprioceptive feedback from the paralyzed facial muscles is a relevant mechanism of mood improvement. It is reasonable to assume an aesthetic benefit as the major cause of mood improvement, because the authors did not include patients who were cosmetically concerned about their frown lines. There is a small possibility of
either placebo effect or central pharmacological botulinum toxin effects including possible pharmacodynamics or pharmacokinetic interactions with the concomitant antidepressant therapy. In summary, there is growing evidence that botulinum toxin injection to the glabellar region may be an effective, safe, and sustainable intervention in the treatment of depression. The reason for this has not yet been fully evaluated but we must consider the concept that the facial musculature not only expresses, but also regulates, mood states. Because of the long treatment intervals it may also be an economic treatment option and the safety and tolerability record of botulinum toxin injections to the glabellar region is excellent. Further studies are required, including focus on muscles in lower sections of the face. It is possible that treatment of the depressor angularis oris and the mentalis muscles, for example, may also have mood-elevating effects and may enhance the clinical effect of the glabellar injection of botulinum toxin. Modulation of mood states with botulinum toxin may also be effective in the treatment of other clinical conditions involving negative emotions, like anxiety disorders. There also have been recent studies investigating the possibility of botulinum toxin for bipolar disorder and post-traumatic stress disorder. PTSD. There is a certain irony to the fact that soldiers returning from combat zones at risk of chemical warfare been treated for PTSD may be now treated with botulinum toxin. Even to the uninitiated, it would appear to have turned the full circle.
REFERENCES Facing depression with botulinum toxin: a randomized controlled trial. Journal of psychiatric research May 2012 Wollmer MA, de Boer C, Kalak N, Beck J, Götz T, Schmidt T, Hodzic M
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