Treatment of glabellar frown lines (the vertical lines between the eyebrows) with “wrinkle relaxers” is one of the most common procedures in aesthetic medicine today. With the increase in clinical use, and exciting new research, it is becoming apparent that fewer wrinkles might actually improve your mood and positively influence mental health outcomes for depression.
Important: this information is for educational purposes only and not intended as medical direction. Always seek personalised, medical advice from your healthcare professional on matters relating to mental health management.
When the muscle complex between the brows contracts, it forms vertical lines – a frown. We understand this expression as an indication of negative emotions like anger, fear and or sadness.
Recent clinical trials and preclinical research projects have shown that injection of neurotoxin to reduce or prevent this muscle contraction offers a rapid, effective, and relatively safe therapy for improving some of the symptoms of depression and may even lead to remission in some cases.
The Research
The first study in 2006 was a small case series of only 10 patients with depression, who each had their frown-lines injected with wrinkle-relaxer. Two months later nine out of 10 of case patients were in remission from their depression, and the remaining patient had significant improvement in their symptoms.
Since then, several randomised, controlled trials and a meta-analysis (where the results of lots of high-quality trials are pooled together and the overall data is then analysed) have shown that 50 -60% of patients with depression treated with wrinkle-relaxer injections to their frown lines experience a significant or total improvement in their symptoms.
A recent, small study in a group of depression patients compared two groups, one with anti-wrinkle injections to the frown lines, the other with treated with a standard dose of a commonly prescribed antidepressant medication. They measured the effects of both treatment strategies at 12 weeks and found significant antidepressant effects in the neurotoxin group that were comparable with the effects of the established antidepressant (sertraline) group.
Interestingly, symptom improvement occurred earlier in the neurotoxin group and with fewer side effects, than with the antidepressant group. The investigators concluded that wrinkle relaxers “could be a safe and effective option for the treatment of depression”.
How does it work?
Further research is required, however, there are a few hypotheses to explore:
- The Facial Feedback Hypothesis
Facial activity affects emotional responses. Interestingly, this idea was first proposed by Charles Darwin 1872 and long since confirmed.
Today we understand that the brain sends a signal to the frown muscles to contract and once they have done that, a separate signal goes back via a different pathway to the brain to say the job has been done. This reinforces the emotion that triggered the frown: sadness/anger/fear/anxiety.
This is also known as a proprioceptive feedback loop from the facial musculature to the emotional brain.
So, the theory goes that if we stop the first signal from the brain before it makes the muscle contact (which is how the neurotoxin in your wrinkle-relaxers work), then the feedback loop is broken, and with it, a negative emotional response.
- The Social Feedback Hypothesis
If we frown less (because the muscle action is reduced), we are immediately more amenable to other humans. The idea here is that this may improve the tone and quality of social interaction, creating a virtuous cycle of positive mood, social connection, and feedback.
Quite simply: if you are perceived as happy rather than angry or sad, the people around you will subconsciously respond positively, which then makes you feel good, and so on. The accumulative flow on is improved self-esteem and sense of self-worth. A kind of “fake it until you make it” situation. In the words of novelist Stanley Gordon West, “smile and the world smiles with you.” 🙂
- BNDP
This is where we get a bit science heavy.
Brain-derived neurotrophic factor is a polypeptide occurring naturally in the brain, it plays a functional role in all sorts of complicated stuff like neuronal differentiation and survival, neurogenesis, synaptic plasticity, connectivity, maintenance of morphology, learning and memory.
We know that in depression the levels of this peptide are reduced in various parts of the brain. Several commonly prescribed antidepressants, such as serotonin-selective reuptake inhibitors (SSRIs), work to increase the amount of BDNF in the hippocampus and the prefrontal cortex.
Interestingly, recent laboratory studies have shown that injecting wrinkle-relaxers into facial muscles can also improve regulation of BDNF levels in the hippocampus. This theory suggests that this up-regulation of BDNF levels may be a new mechanism behind the therapeutic effects of neurotoxins in the management of depressive symptoms.
How this occurs is not yet clear, but the research is promising.
- Monoamine Theory
Another one for the science-enthusiasts.
This theory relates to the known link between emotional disorders and reduced brain levels of two important neurotransmitters: 5-hydroxytryptamine (5-HT) or norepinephrine/noradrenaline (NE).
Antidepressants can increase the levels of these compounds by inhibiting their re-uptake into nerve terminals. Some of the antidepressants based on monoamine theory include tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOI), and SSRIs.
Recent studies on chronic, stressed mice have indicated that facial injection of wrinkle-relaxers significantly increases the 5-HT level in the hippocampus, hypothalamus, and prefrontal cortex.
It seems that these neurotoxins can improve up-regulation of monoamines levels (e.g., 5-HT and NE) in the brain. Further studies are needed to identify the precise alteration of the neurotransmitters and the mechanism of action to explain how this works.
The Future
New research suggests neurotoxin therapy may also be effective in the treatment of other mental disorders characterised by excessive negative emotions, such as borderline personality disorder, anxiety, and bipolar disorder. This is preliminary data only, so we are a long way from being able to apply it in treatment of these disorders.
However, given recent evidence of the effectiveness of neurotoxin in the treatment of depression may pave the way for greater use in the field of psychiatry in the future.
As for those of us in the aesthetic field, we’ll just carry-on improving frown lines and sharing the positive effects on appearance, facial messaging, mood, and social interactions! ☺
Mental Health Resources
Three million Australians are living with anxiety or depression. If you haven’t been feeling like yourself and think you might be depressed, please speak with your GP.
Beyond Blue provides information and support to help everyone in Australia achieve their best possible mental health, whatever their age and wherever they live. Visit the website to access their wealth of resources.
Dr. Sarah Boxley – Medical Director, SkinBox
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Darwinism.Darwin C Ind Med Gaz. 1872 Feb 1; 7(2):47.
Antidepressant-Like Action of Single Facial Injection of Botulinum Neurotoxin A is Associated with Augmented 5-HT Levels and BDNF/ERK/CREB Pathways in Mouse Brain. Li Y et al Neurosci Bull. 2019 Aug; 35(4):661-672.
The safety and efficacy of botulinum toxin A on the treatment of depression. Zhang Q, et al. Brain Behav. 2021 Sep;11(9):e2333