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

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.