Effect of single-dose imipramine on chronic low-back and experimental pain. A randomized controlled trial.

Schliessbach, Jürg; Siegenthaler, Andreas; Bütikofer, Lukas; Limacher, Andreas; Juni, Peter; Vuilleumier, Pascal H; Stamer, Ulrike; Arendt-Nielsen, Lars; Curatolo, Michele (2018). Effect of single-dose imipramine on chronic low-back and experimental pain. A randomized controlled trial. PLoS ONE, 13(5), e0195776. Public Library of Science 10.1371/journal.pone.0195776

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Antidepressants are frequently prescribed as co-analgesics in chronic pain. While their efficacy is well documented for neuropathic pain, the evidence is less clear in musculoskeletal pain conditions. The present study therefore evaluated the effect of the tricyclic antidepressant imipramine on chronic low-back pain in a randomized, double-blinded placebo-controlled design. To explore the mechanisms of action and the influence of drug metabolism, multimodal quantitative sensory tests (QST) and genotyping for cytochrome P450 2D6 (CYP2D6) were additionally performed. A single oral dose of imipramine 75 mg was compared to active placebo (tolterodine 1 mg) in 50 patients (32 females) with chronic non-specific low-back pain. Intensity of low-back pain was assessed on a 0-10 numeric rating scale at baseline and every 30 minutes after drug intake. Multimodal QST were performed at baseline and in hourly intervals for 2 hours. Pharmacogenetic influences of cytochrome P450 were addressed by CYP2D6 genotyping. No significant analgesic effect was detected neither on low-back pain nor on any of the sensory tests in the overall analyses. However, evidence for an interaction of the imipramine effect and CYP2D6 genotype was found for electrical and for pressure pain detection thresholds. Intermediate but not extensive metabolizers had a 1.20 times greater electrical pain threshold (95%-CI 1.10 to 1.31) and a 1.10 times greater pressure pain threshold (95%-CI 1.01 to 1.21) 60 minutes after imipramine than after placebo (p<0.001 and p = 0.034, respectively). The present study failed to demonstrate an immediate analgesic effect of imipramine on low-back pain. Anti-nociceptive effects as assessed by quantitative sensory tests may depend on CYP2D6 genotype, indicating that metabolizer status should be accounted for when future studies with tricyclic antidepressants are undertaken.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic and Policlinic for Anaesthesiology and Pain Therapy
04 Faculty of Medicine > Pre-clinic Human Medicine > CTU Bern
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine (ISPM)

UniBE Contributor:

Schliessbach, Jürg, Siegenthaler, Andreas, Bütikofer, Lukas (B), Limacher, Andreas, Vuilleumier, Pascal Henri, Stamer, Ulrike


600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services




Public Library of Science




Tanya Karrer

Date Deposited:

17 May 2018 09:36

Last Modified:

29 Mar 2023 23:36

Publisher DOI:


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