Depression affects over 120 million people globally, making it one of the leading causes of disability in the world. A recent search of MEDLINE, EMBASE, Cochrane, and Scopus through May 5, 2014, for studies evaluating the efficacy of botulinum toxin A in depression showed it can produce significant improvement in depressive symptoms and is a safe adjunctive treatment for patients receiving pharmacotherapy for depression. Only randomised controlled trials were included in the meta-analysis. A pooled mean difference in primary depression score, and pooled odds ratio for response and remission rate with 95% confidence interval (CI) were estimated using the random-effects model.
In 1872, Charles Darwin recognised these features as a specific expression of sadness and attributed them to the activity of so-called ‘grief muscles’ in the frown area. Negative emotions, such as anger, fear, and sadness are prevalent in depression and are associated with hyperactivity of the corrugator and procerus muscles in the glabellar region of the face. Darwin formulated a new theory called the ‘facial feedback hypothesis’, which implied a mutual interaction between emotions and facial muscle activity. Although there are various effective treatments, therapeutic response remains unsatisfactory, and depression can develop as a chronic condition in a considerable proportion of patients.
More recently, Larsen showed experimental evidence that voluntary contraction of facial muscles can channel emotions, which are conversely expressed by activation of these muscles. Heckmann published data suggesting that treatment of the glabellar (frown) region with botulinum toxin produces a change in facial expression from angry, sad, and fearful to happy and this can impact on emotional experience.
Many therapists, including Sommer (2003) have shown that patients who have been treated in the frown area reported an increase in emotional wellbeing and reduced levels of fear and sadness beyond what would be expected from the cosmetic benefit alone. Hennenlotter (2009) went one stage further and showed that botulinum toxin treatment to the frown area stopped the activation of limbic brain regions normally seen during voluntary contraction of the corrugator and procerus muscles.
This indicated that feedback from the facial musculature in this region in some way modulated the processing of emotions. Many other researchers have continued down this road with Havas (2010) noting that the processing time for sentences with negative affective connotation was prolonged in women after botulinum toxin treatment of the frown area. Neal and Chartrand (2011) speculated that the treatment interfered with the ability to decode the facial expression of other people. This is where things were until recently with many authors suggesting that this capacity to counteract negative emotions could be put to some clinical use during the treatment of depression. There were some papers, including one with ten female patients in the Journal of Derm. Surgery by Finzi and Wasserman (2006) that postulated that botulinum toxin in the frown area 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 utilised. I noted by letter at the time that patients’ self-report of depressive symptoms by administration of the Beck Depression Inventory (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 to ensure that patients’ psychiatric symptoms are accurately classified, a thorough psychiatric interview must be conducted. More recently, two centres, 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, they conducted a randomised controlled trial of botulinum toxin injection to the frown region as an adjunctive treatment of major depression. The study was carried out independently of any commercial entity. Participants in the study were recruited from local psychiatric outpatient units and psychiatrists in private practice. To avoid attracting candidates who were primarily motivated by receiving this treatment for cosmetic reasons, botulinum toxin treatment, was not explicitly mentioned. At each study visit participants were assessed using the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS), the Beck Depression Inventory (BDI) self-rating questionnaire and the Clinical Global Impressions Scale (CGI).
The study concluded for the first time that a single botulinum treatment of the glabellar region could reduce the symptoms of major depression. This effect developed within a few weeks and persisted until the end of the sixteen-week follow-up period. The effect sizes in the study were large and the response and remission rates were high. There is now enough evidence to suggest 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.
As a final note, 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 being treated for PTSD may be now treated with botulinum toxin. Even to the uninitiated, it would appear to have turned the full circle.
