@article{1b94a95cbfc6492eadc7d6c176077dc0,
title = "Efficacy of onabotulinumtoxinA in the treatment of unipolar major depression: Systematic review, meta-analysis and meta-regression analyses of double-blind randomised controlled trials",
abstract = "Background: OnabotulinumtoxinA is a novel therapeutic intervention whose mechanism of action is believed to modify the negative facial feedback, thus abating symptoms of depression. This putative new antidepressant agent offers minimal systemic side effects and negligible risk of pharmacological interactions. We set out to examine the evidence for the use of onabotulinumtoxinA in major depression. Methods: A systematic search of the literature identified double-blind randomised controlled trials (RCTs) investigating the use of onabotulinumtoxinA in the treatment of major depression versus placebo. Data, reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA), was combined in meta-analyses (PROSPERO registration ID: CRD42020183538). Results: The search identified five RCTs (four double-blind) comparing onabotulinumtoxinA to placebo. OnabotulinumtoxinA was more effective than placebo when administered within the 20–40 IU dose range in double-blind RCTs. The analysis was free of publication bias and significantly heterogeneous. Meta-regression analyses indicated that onabotulinumtoxinA was more efficacious in women and in higher doses in female patients and less effective with polypharmacy, especially when an increasing number of antidepressants were prescribed. The effectiveness of onabotulinumtoxinA was higher in more recently published double-blind RCTs. Conclusion: The meta-analysis supports the efficacy of the intervention with the results being highly heterogeneous across studies. In view of the heterogeneity of the findings and the significant moderators of benefit (sex, year of study completion and the interaction between sex and dose), more research is required to better understand the role of onabotulinumtoxinA in the treatment of depression.",
keywords = "OnabotulinumtoxinA, double-blind randomised controlled trial, major depression, meta-analysis",
author = "Danilo Arnone and Hassan Galadari and Rodgers, {Carl J.} and Linda {\"O}stlundh and Aziz, {Karim Abdel} and Emmanuel Stip and Young, {Allan H.}",
note = "Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This report represents independent research funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King{\textquoteright}s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. Funding Information: The authors declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: D.A. received travel grants from Jansen-Cilag and Servier and sponsorship from Lundbeck. E.S. received lecturing fees from Jansen Canada and from Lundbeck, Canada and UAEU. A.H.Y. reports paid lectures and advisory boards for the following companies with drugs used in affective and related disorders: AstraZeneca (AZ), Eli Lilly, Lundbeck, Sunovion, Servier, LivaNova, Janssen, Allegan, Bionomics, Sumitomo Dainippon Pharma, COMPASS, consultancies to Johnson & Johnson and Livanova, received honoraria for attending advisory boards and presenting talks at meetings organised by LivaNova. Principal Investigator in the Restore-Life VNS registry study funded by LivaNova, principal Investigator on ESKETINTRD3004: “An Open-label, Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression”, on “The Effects of Psilocybin on Cognitive Function in Healthy Participants”, on “The Safety and Efficacy of Psilocybin in Participants with Treatment-Resistant Depression (P-TRD)”. Grant funding (past and present): NIMH (USA); CIHR (Canada); NARSAD (USA); Stanley Medical Research Institute (USA); MRC (UK); Wellcome Trust (UK); Royal College of Physicians (Edin); BMA (UK); UBC-VGH Foundation (Canada); WEDC (Canada); CCS Depression Research Fund (Canada); MSFHR (Canada); NIHR (UK). Janssen (UK). Lead Investigator for Embolden Study (AZ), BCI Neuroplasticity study and Aripiprazole Mania Study. Investigator initiated studies from AZ, Eli Lilly, Lundbeck, Wyeth, Janssen. No shareholdings in pharmaceutical companies. The other authors report no conflict of interest. Publisher Copyright: {\textcopyright} The Author(s) 2021.",
year = "2021",
month = aug,
doi = "10.1177/0269881121991827",
language = "English",
volume = "35",
pages = "910--918",
journal = "Journal of Psychopharmacology",
issn = "0269-8811",
publisher = "SAGE Publications Ltd",
number = "8",
}