Treatment of Depression with Botulinum Toxin

Can medical aesthetic treatments improve mental health?

Aims: Depressive disorders, as defined by the International Classification of Diseases (11th Revision), involve a depressive mood (feeling sad, irritable, or empty) along with other symptoms affecting a person’s ability to function. Botulinum toxin, used for conditions like migraines and muscle spasms, is being researched as a treatment for depression. The theory is based on facial feedback, where paralysing facial muscles could reduce the brain’s ability to process negative emotions, potentially improving mood. This review aims to explore how botulinum toxin might work in depression treatment and summarize the current research and future directions in this field.Methods: We searched PubMed. Inclusion criteria were paper should discuss depression and botulinum. We excluded papers before 2010 and papers which included botulinum toxin in patient comorbid migraine.Results: Magid et al. reviewed 2 case series, 3 randomized controlled trials (RCTs), and one meta-analysis on botulinum toxin for depression. 29\39 U was injected. They concluded that botulinum toxin was not yet an appropriate treatment.Kugar and Wollmer examined studies on botulinum toxin’s effects on depression, especially patients with chronic migraine. 29/39 U was injected. Some improvement but called for further research.Wollmer et al. (2019) analysed 4 RCTs and 3 case series, confirming the efficacy of botulinum toxin in treating depression. They found a lasting effect of about 3 months with a single treatment but recommended further research.Qian et al. (2020) conducted a systematic review of RCTs and concluded that botulinum toxin might offer a new treatment option for major depressive disorder. However, the effects on depression secondary to other conditions remain unclear.Danilo et al. (2021) analysed 5 RCTs, finding botulinum toxin more effective than a placebo in treating depression. They noted low risk of bias, with statistically significant results.Yang Li et al. (2021) reviewed 10 RCTs and confirmed that studies support botulinum toxin as a potential alternative treatment for depression.Wollmer et al. (2022) evaluated 5 studies and found botulinum toxin effective for patients although the exact mechanisms are still under study.Conclusion: While botulinum toxin has shown potential in treatment for depression, particularly for patients who didn’t respond to antidepressants or who experience side effects, the current evidence remains preliminary. Several studies indicate that botulinum toxin may offer symptomatic relief. However, the overall quality of the evidence is limited by small sample sizes, methodological inconsistencies, and the need for more trials.

ObjectivesEffective strategy for the treatment of depression is limited. This study was to evaluate the safety and efficacy of botulinum toxin A (BoNT/A) in the treatment of depression.MethodsSeventy‐six patients were assigned to the BoNT/A group (n = 52) and sertraline control group (n = 24). For the BoNT/A group, BoNT/A was injected into the frowning muscle, depressor muscle, occipital frontalis muscle, lateral canthus, and bilateral temporal region at 20 sites. Five units per site and a total of 100 units of BoNT/A were given. Patients in the sertraline control group were medicated with sertraline 50–200 mg (114.58 ± 52.08 mg) per day. Depression was assessed by the 17‐item Hamilton Depression Scale (HAMD‐17), 14‐item Hamilton Anxiety Scale (HAMA‐14), Self‐rating Depression Scale (SDS), and Self‐rating Anxiety Scale (SAS). All participants were followed up for 12 weeks.ResultsScores of HAMD, HAMA, SDS, and SAS decreased significantly in both BoNT/A and sertraline groups after treatment for 12 weeks. Overall, there were no differences in decreased magnitude between the two groups (p > .05). The HAMA, SDS, and SAS results showed that the onset time of BoNT/A was earlier than that of sertraline. Side effects rates were 15.38% for BoNT/A and 33.33% for sertraline.ConclusionThis study demonstrated significant antidepressant effects of BoNT/A. The efficacy of BoNT/A was comparable with established antidepressant sertraline. The onset time of BoNT/A was earlier than sertraline, and the proportion of side effects was less than sertraline. Therefore, BoNT/A could be a safe and effective option for the treatment of depression.

Botulinum toxin (BTX) plays an important role in the treatment and prophylaxis of migraine and is also used for the treatment of focal dystonia, spasm, hypersalivation, and hyperhydrosis. Recent clinical trials suggest that BTX treatment of muscles involved in the development of negative emotions may also have an antidepressant effect. This article gives a systematic review of the literature regarding BTX in the treatment of major depression. We screened the databases of Medline and Scopus using the search terms [("botulinum toxin" OR "botox") AND ("antidepressant" OR "depression" OR "depressed")]. The website www.clinicaltrials.gov was screened with the same search terms in order to detect current studies. As of April 2013, we identified 3 studies that evaluated the antidepressant effects of BTX in the treatment of major depression. An improvement in mood after treatment with BTX was seen in a case series of 10 depressed patients. In a randomised, placebo-controlled study of thirty patients assigned to a verum (BTX, n = 15) or placebo (saline, n = 15) group, treatment with BTX has also shown a positive effect on mood. Another prospective, open-label study evaluated the antidepressive effect of BTX in 25 subjects with major depression. On www.clinicaltrials.gov we identified 2 ongoing studies, which are currently investigating the antidepressant effect of BTX. Recently published studies have shown a reduction of depressive symptoms after treatment of the glabellar frown lines with BTX injections. Further clinical studies in larger patient samples are necessary to prove the efficacy and safety of BTX injections used for the treatment of depressive disorders.

A series of randomized controlled trials have shown the efficacy of glabellar botulinum toxin (BTX) injection as a treatment for depression in women. We wanted to extend these findings and assess how they may be translated to a real-world setting. For that purpose, 42 patients with severe, in most cases chronic and treatment-resistant depression received adjunctive treatment with BTX in private practice. Depression severity was rated before and 3 weeks after the treatment using the Hamilton Depression Rating Scale, the Montgomery Åsberg Depression Rating Scale, and the Beck Depression Inventory. Almost all of the patients improved clinically, with depression scores dropping by 27% on all 3 scales in the sample as a whole. These changes were highly significant (P<0.001, paired t test or Wilcoxon test) and the absolute prepost score differences were similar to those observed in previous randomized controlled trials. Importantly, treatment effects did not differ between male (n=23) and female (n=19) patients. These findings suggest that glabellar BTX injection may also be effective in the treatment of severe depression and in the treatment of depression in men, when treatment is carried out not just in clinical trials but in real-world settings.

Evaluation of: Wollmer MA, de Boer C, Kalak N et al. Facing depression with botulinum toxin: a randomized controlled trial. J. Psychiatr. Res. 46(5), 574–581 (2012).Depression has a number of significant symptoms such as depressed mood, lack of volition/energy, suicidal ideation, low concentration, sleep disturbance, anger, anxiety, psychomotor retardation, fear and sadness. In addition, various facial expressions such as frowning and sadness can also be easily recognized in depressed patients. In fact, major muscles involved in the development of such negative emotion have been reported in depressed patients, for instance, corrugators and procerus muscles in the glabellar regions of the face. Electromyography studies have also reported that depressed patients had overactivity of such grief muscles during different affective imagery paradigms. Furthermore, subjective emotion has also been found to be affected by differential facial expression via an image feedback system. Interestingly, anecdotal open-label studies have shown that botulinum toxin may have a role in treatment of depression and a recent randomized-placebo controlled study has also confirmed the effect of botulinum toxin in reduction of depressive symptoms for the first time. This article will discuss the putative role of botulinum toxin in a treatment of depression in the context of the clinical significance, limitations and future research directions.

Major depression is a common and serious disease that may be resistant to routine pharmacologic and psychotherapeutic treatment approaches. To evaluate the efficacy of botulinum toxin A treatment of glabellar frown lines in treating patients with major depression, using a small open pilot trial. Patients who met DSM-IV criteria for ongoing major depression in spite of pharmacologic or psychotherapeutic treatment were evaluated with the Beck Depression Inventory II (BDI-II) before receiving botulinum toxin A to their glabellar frown lines. Two months later, all patients were re-evaluated clinically and with the BDI-II. Ten depressed patients were treated with botulinum toxin A, and 9 of 10 patients were no longer depressed 2 months after treatment. The tenth patient had an improvement in mood. To our knowledge, these are the first reported cases of depression treated with botulinum toxin A.

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Injection of botulinum toxin (BoNT) into the glabellar region of the face is a novel therapeutic approach in the treatment of depression. This treatment method has several advantages, including few side effects and a long-lasting, depot-like effect. Here we review the clinical and experimental evidence for the antidepressant effect of BoNT injections as well as the theoretical background and possible mechanisms of action. Moreover, we provide practical instructions for the safe and effective application of BoNT in the treatment of depression. Finally, we describe the current status of the clinical development of BoNT as an antidepressant and give an outlook on its potential future role in the management of mental disorders.

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