Abstract
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.
Highlights
Tricyclic antidepressants (TCAs) are frequently used in chronic pain therapy
We report the results of a randomized, double-blinded and placebo-controlled sub-study which investigated the effect of a single oral dose of the TCA imipramine on both low-back and experimental pain in humans
Exclusion criteria were pain intensity at rest 9)
Summary
Tricyclic antidepressants (TCAs) are frequently used in chronic pain therapy. Albeit most effective in neuropathic pain [1,2], they are as well prescribed in many other painful conditions, including fibromyalgia, headaches or chronic low-back pain. There are several reasons for using TCAs in chronic low-back pain: they favorably influence concomitant mood disorders, may improve sleep quality and exert an analgesic effect. Some clinical studies have reported beneficial effects of TCAs in chronic low-back pain [4,6], assessed by outcomes such as pain intensity or functional improvement after trial periods of several weeks. These findings, might as well be related to the effects of TCAs on sleep quality or mood, and do not provide sufficient mechanistic information about the action of these drugs. With regard to acute pain, there is currently hardly any evidence for the use of antidepressants [12]
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