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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, six weeks post-intervention, GBTX groups were significantly less depressed compared to placebo groups (*d* = 0.83) and pre-treatment levels (*d* = 1.57). However, we noted the following concerns: (1) effect sizes were extraordinarily large, (2) authors failed to provide information to compute 51% of relevant effect sizes, (3) 96% of effect sizes came from studies conducted by investigators with conflicts of interest, (4) there is some evidence of publication bias, and (5) studies used ineffective blinding procedures. These considerations suggest that confidence in GBTX as a treatment for depression is premature.
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