Nortriptyline for pain in knee osteoarthritis in general practice: a double blind randomised controlled trial

Abstract

Background: Osteoarthritis (OA) of the knee is a common cause of chronic pain. The currently available analgesics have limited efficacy and may be poorly tolerated. Aim: To investigate the analgesic efficacy of nortriptyline in people with knee OA. Design and setting: A two-arm parallel-group 1:1 double blind randomised placebo-controlled trial. Participants were recruited from orthopaedic outpatient clinics, primary care, and by public advertising. Method: Adults with knee OA and with pain rated as >20 points on the 50 point Western Ontario and McMaster University (WOMAC) pain sub-scale were randomised to receive either nortriptyline or identical placebo for 14 weeks. Primary outcome was knee pain at 14 weeks measured using the WOMAC pain sub-scale. Secondary outcomes included function, stiffness, non-steroidal anti-inflammatory drug, opioid and/or paracetamol use, participant global assessment, and adverse effects at 14 weeks. Results: Of the 205 randomised participants, 201 (98%) completed follow-up at 14 weeks. The baseline-adjusted mean WOMAC pain subscale score at week 14 was 6.15 points lower (95% CI -0.26 to 12.6, p = 0.06) in the nortriptyline vs. the placebo arm. Differences in secondary outcomes generally favoured the nortriptyline arm, but were small and unlikely to be clinically relevant. Dry mouth (87% vs. 51%, p < 0.001), constipation (69% vs. 30%, p < 0.001), and sweating (31% vs. 21%, p = 0.033) were all more commonly reported by participants taking nortriptyline. Conclusion: This study suggests nortriptyline does not significantly reduce pain in people with knee OA. Adverse effect profile was as expected.