Does Blocking Facial Feedback Via Botulinum Toxin Injections Decrease Depression? A Critical Review and Meta-Analysis

Abstract

Researchers have proposed that blocking facial feedback via glabellar-region botulinum toxin injections (GBTX) can reduce depression. Random-effects meta-analyses of studies that administered GBTX to individuals with depression indicate that, 6 weeks postintervention, GBTX groups were significantly less depressed compared to placebo groups ( d = 0.83) and pretreatment levels ( d = 1.57). However, we noted the following concerns: (a) effect sizes were extraordinarily large, (b) authors failed to provide information to compute 51% of relevant effect sizes, (c) 96% of effect sizes came from studies conducted by investigators with conflicts of interest, (d) there is some evidence of publication bias, and (e) studies used ineffective blinding procedures. These considerations suggest that confidence in GBTX as a treatment for depression is premature.

Efficacy of onabotulinumtoxinA in the treatment of unipolar major depression: Systematic review, meta-analysis and meta-regression analyses of double-blind randomised controlled trials

“…Our work expands on two previous meta-analyses by Coles et al (2019) and Parsaik et al (2016). Parsaik et al included the three small RCTs available at the time and reported that the mean difference in depression scores between onabotulinumtoxinA and placebo was as large as -9.80 points difference of rating scales (95% CI -12.90 to -6.69).…”

“…Therefore, it is possible that patients who continued in the study were also those who benefitted from the intervention the most. As Coles et al (2019) noted, the effect size of onabotulinum-toxinA in comparison to placebo is large. Our work suggests an effect size of 1.09 is much larger than the effect size of 'facial feedback effects' in the 0.17-0.42 range and of antidepressants versus placebo trials equivalent to approximately 0.30 (Cipriani et al, 2018).…”

“…A further complication is the notion that the reduction in the motor activity of the corrugator and procerus muscles ( Carruthers and Carruthers, 1992 ) is the putative underlying mechanism responsible for the antidepressant action of onabotulinumtoxinA according to the ‘facial feedback hypothesis’. This hypothesis suggests that the toxin blocks negative facial expressions which feedback into a biased cognitive appraisal towards self and others responsible for low mood, resulting in mood improvement beyond the duration of action of the toxin ( Coles et al, 2019 ). It is important to highlight that this mechanism was not tested formally in the included studies, and it is therefore difficult to conclude how this intervention works.…”

“…The putative mechanism of action postulates that facial expressions, including frowning, produce sensory feedback, which can negatively influence emotions. When injected for such an indication in individuals with major depression, onabotulinumtoxinA is believed to modify ongoing emotional responses by providing a positive cue which reduces ‘facial negative feedback’, resulting in measurable beneficial clinical response without any major side effects ( Ascher et al, 2004 ; Coles et al, 2019 ). This work appraises the evidence from randomised controlled trials (RCTs) for the use of onabotulinumtoxinA in major depression.…”

“…This work appraises the evidence from randomised controlled trials (RCTs) for the use of onabotulinumtoxinA in major depression. Previous work has indicated that onabotulinumtoxinA is efficacious in treating major depression ( Coles et al, 2019 ; Parsaik et al, 2016 ). The aim of this meta-analysis was to review systematically all of the available data, primarily extracted from randomised, double-blind, placebo-controlled trials, on the use of onabotulinumtoxinA for the treatment of major depression.…”