In the first open-label trial of botulinum toxin a (bt) for depression, 8 of 10 subjects went into remission within 2 months after a single treatment of the corrugator (frown) muscles with BT.1 Subsequently, results from 3 randomized controlled trials (RCTs) showed that a single injection of BT into the corrugator muscles had significant antidepressant effects (Figure 1).2-4 In the largest RCT, BT appeared to be equally effective as either monotherapy or augmentation therapy.3
We present here the evidence for using BT as a treatment for depression, discuss possible mechanisms for this effect, and address some questions about this novel treatment.
At first glance the use of BT to treat depression may seem surprising; however, a line of thinking dating back to the 1800s might have predicted it. While it is commonly recognized that our emotions influence our facial expressions, the reverse is less obvious. Yet both Charles Darwin and William James proposed this to be so.
Darwin observed that strong contraction of the brow muscles, forming an omega sign between the eyebrows, is an indicator of melancholy—the sign disappeared when a person felt better. James famously stated that he was sad because he cried; not that he cried because he was sad. Both men hypothesized that facial expressions of sorrow or grief sent signals to the emotional part of the brain, inducing or exacerbating feelings of distress.
Facial feedback hypothesis
Over time numerous studies confirmed what became known as the “facial feedback hypothesis.” Researchers systematically investigated the effects on emotions when, either consciously or unconsciously, muscles of facial expression were activated. The voluntary contraction of facial muscles into a smile or frown induced feelings of happiness or sadness, respectively. Frowning, regardless of why, causes people to rate unpleasant photographs more negatively, cartoons less funny, and stories less appealing. Conversely, smiling makes everything more appealing. Facial expressions appear to aid the brain in assigning a valence to emotions and are thus important for decision-making.
The effects of facial expressions on emotions extend to bodily functions outside of our normal conscious control. Ekman and colleagues5 showed that re-creation of facial movements associated with expressions such as happiness, sadness, anger, and fear change autonomic nervous system responses. Heart rate, blood pressure, and sweating are all altered by contracting facial muscles, and this effect is stronger than recalling a strong emotional memory. In summary, converging lines of evidence suggest that contraction of facial muscles affects mood; smiling promotes happy mood while frowning promotes gloomy mood.
Evidence for botulinum toxin treatment of depression
So far, there have been 2 open-label studies and 3 RCTs of the effects on depression after BT injection into corrugator muscles (Table).
Open-label studies. In the first test of the facial feedback hypothesis, as applied to depression, 10 people who had been depressed for a year or more received a single treatment with BT.1 Scores on the Beck Depression Inventory (BDI) decreased by 73% (P < .005). In a second case series of 25 depressed individuals, scores on the BDI decreased by 54% 12 weeks after 1 BT treatment (14.9 point drop on BDI; P < .001).6
Dr. Finzi is Clinical Assistant Professor of Psychiatry, George Washington University, Washington, DC; Dr. Rosenthal is Clinical Professor of Psychiatry, Georgetown Medical School, Washington, DC.
Dr. Finzi reports that he is a named inventor on 2 patents to treat depression with botulinum toxin; he has been a consultant to Allergan; and he is a co-inventor on a patent to treat social anxiety disorder with botulinum toxin. Dr. Rosenthal reports that he has applied for patents to use botulinum toxin to treat social anxiety disorder, PTSD, and seasonal affective disorder; the first of these 3 patent applications has been granted.
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