Agitation Predicts Response of Depression to Botulinum Toxin Treatment in a Randomized Controlled Trial

Abstract

In a randomized, controlled trial (n = 30), we showed that botulinum toxin injection to the glabellar region produces a marked improvement in the symptoms of major depression. We hypothesized that the mood-lifting effect was mediated by facial feedback mechanisms. Here we assessed if agitation, which may be associated with increased dynamic psychomotor activity of the facial musculature, can predict response to the treatment. To test this hypothesis, we re-analyzed the data of the scales from our previous study on a single item basis and compared the baseline scores in the agitation item (item 9) of the Hamilton Depression Rating Scale (HAM-D) between responders (n = 9) and participants who did not attain response (n = 6) among the recipients of onabotulinumtoxinA (n = 15). Responders had significantly higher item 9 scores at baseline [1.56 + 0.88 vs. 0.33 + 0.52, t(13) = 3.04, d = 1.7, p = 0.01], while no other single item of the HAM-D or the Beck Depression Inventory was associated with treatment response. The agitation score had an overall precision of 78% in predicting response in a receiver operating characteristic (ROC) analysis (area under the curve, AUC = 0.87). These data provide a link between response to botulinum toxin treatment with a psychomotor manifestation of depression and thereby indirect support of the proposed facial feedback mechanism of action. Moreover, it suggests that patients with agitated depression may particularly benefit from botulinum toxin treatment.

Depression – An emerging indication for botulinum toxin treatment

“…Partial response (>25% reduction in HAM-D score; 87%) and response (>50% reduction in HAM-D score; 60%) rates were significantly higher in the BTA group than in the placebo group and 33% of the BTA treated patients attained remission. Those participants with higher levels of psychomotor agitation at the baseline (HAM-D item 9 > 2) had a particularly high probability to respond (100%, Wollmer et al, 2014).…”

Treating Depression with Botulinum Toxin: A Pooled Analysis of Randomized Controlled Trials

“…In this context, psychomotor endophenotypes of depression (e. g., agitated depression) may also be predictors of response and allow for a stratified or personalized application of BTA [32]. Future research should also address if BTA can be used in the treatment of bipolar depression or other affective disorders.…”

Effects of botulinum toxin type A facial injection on monoamines and their metabolites in sensory, limbic and motor brain regions in rats

“…Finzi and Wasserman were the first to report cases of depression treated with BTX-A [15]. The studies that followed [18,32,13,49,16,45,46,20,17,14,29,25] were also based on the facial feedback hypothesis and designed to evaluate antidepressant effects after injecting BTX-A into the corrugator and procerus muscles of the glabellar region. The hypothesis implies that the brain continuously assesses the extent of facial muscle contraction and muscle tension by proprioception.…”