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Amitriptyline’s anticholinergic adverse drug reactions–A systematic multiple-indication review and meta-analysis

Author

Listed:
  • Maria-Sophie Brueckle
  • Elizabeth T Thomas
  • Svenja Elisabeth Seide
  • Maximilian Pilz
  • Ana I Gonzalez-Gonzalez
  • Truc Sophia Dinh
  • Ferdinand M Gerlach
  • Sebastian Harder
  • Paul P Glasziou
  • Christiane Muth

Abstract

Background: Half the US population uses drugs with anticholinergic properties. Their potential harms may outweigh their benefits. Amitriptyline is among the most frequently prescribed anticholinergic medicinal products, is used for multiple indications, and rated as strongly anticholinergic. Our objective was to explore and quantify (anticholinergic) adverse drug reactions (ADRs) in patients taking amitriptyline vs. placebo in randomized controlled trials (RCTs) involving adults and healthy individuals. Methods: We searched electronic databases from their inception until 09/2022, and clinical trial registries from their inception until 09/2022. We also performed manual reference searches. Two independent reviewers selected RCTs with ≥100 participants of ≥18 years, that compared amitriptyline (taken orally) versus placebo for all indications. No language restrictions were applied. One reviewer extracted study data, ADRs, and assessed study quality, which two others verified. The primary outcome was frequency of anticholinergic ADRs as a binary outcome (absolute number of patients with/without anticholinergic ADRs) in amitriptyline vs. placebo groups. Results: Twenty-three RCTs (mean dosage 5mg to 300mg amitriptyline/day) and 4217 patients (mean age 40.3 years) were included. The most frequently reported anticholinergic ADRs were dry mouth, drowsiness, somnolence, sedation, fatigue, constitutional, and unspecific anticholinergic ADRs. Random-effects meta-analyses showed anticholinergic ADRs had a higher odd’s ratio for amitriptyline versus placebo (OR = 7.41; [95% CI, 4.54 to 12.12]). Non-anticholinergic ADRs were as frequent for amitriptyline as placebo. Meta-regression analysis showed anticholinergic ADRs were not dose-dependent. Discussion: The large OR in our analysis shows that ADRs indicative of anticholinergic activities can be attributed to amitriptyline. The low average age of participants in our study may limit the generalizability of the frequency of anticholinergic ADRs in older patients. A lack of dose-dependency may reflect limited reporting of the daily dosage when the ADRs occurred. The exclusion of small studies (

Suggested Citation

  • Maria-Sophie Brueckle & Elizabeth T Thomas & Svenja Elisabeth Seide & Maximilian Pilz & Ana I Gonzalez-Gonzalez & Truc Sophia Dinh & Ferdinand M Gerlach & Sebastian Harder & Paul P Glasziou & Christia, 2023. "Amitriptyline’s anticholinergic adverse drug reactions–A systematic multiple-indication review and meta-analysis," PLOS ONE, Public Library of Science, vol. 18(4), pages 1-17, April.
    • Handle: RePEc:plo:pone00:0284168
    DOI: 10.1371/journal.pone.0284168
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    References listed on IDEAS

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    2. Alessandro Liberati & Douglas G Altman & Jennifer Tetzlaff & Cynthia Mulrow & Peter C Gøtzsche & John P A Ioannidis & Mike Clarke & P J Devereaux & Jos Kleijnen & David Moher, 2009. "The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration," PLOS Medicine, Public Library of Science, vol. 6(7), pages 1-28, July.
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