Abstract
BackgroundOsteoarthritis (OA) of the knee is a common cause of chronic pain. Analgesics that are currently available have limited efficacy and may be poorly tolerated. Tricyclic antidepressants are used as analgesics for other chronic conditions, but they have not been evaluated as analgesics in OA.AimTo investigate the analgesic efficacy of nortriptyline in people with knee OA.Design and settingA two-arm, parallel-group, 1:1, double-blind, randomised, placebo-controlled trial in Christchurch, New Zealand.MethodParticipants were recruited from orthopaedic outpatient clinics, primary care, and through public advertising. Adults with knee OA and a pain score of ≥20 points on the 50-point Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain subscale were randomised to receive either nortriptyline or identical placebo for 14 weeks. The primary outcome was knee pain at 14 weeks measured using the WOMAC pain subscale. Secondary outcomes included: function; stiffness; non-steroidal anti-inflammatory drug, opioid, and/or paracetamol use; each participant’s global assessment; and adverse effects at 14 weeks.ResultsOf the 205 randomised participants, 201 (98.0%) completed follow-up at 14 weeks. The baseline-adjusted mean WOMAC pain subscale score at week 14 was 6.2 points lower (95% confidence interval = −0.26 to 12.6, P = 0.06) in the nortriptyline arm versus the placebo arm. Differences in secondary outcomes generally favoured the nortriptyline arm, but were small and unlikely to be clinically relevant. However, the following were all more commonly reported by participants taking nortriptyline than those taking a placebo: dry mouth (86.9% versus 51.0%, respectively, P<0.001), constipation (58.6% versus 30.4%, respectively, P<0.001), and sweating (31.3% versus 20.6%, respectively, P = 0.033).ConclusionThis study suggests nortriptyline does not significantly reduce pain in people with knee OA. The adverse effect profile was as expected.
Highlights
IntroductionOsteoarthritis (OA) is the commonest joint disease and is a major cause of pain and disability, reduced quality of life, and large healthcare costs. [1,2,3,4] The burden of disease is predicted to rise. [5, 6]OA management is focused on advice, exercise, weight loss (if obese), analgesia and maintenance of function. [7] The analgesics currently recommended for OA are not ideal: paracetamol is minimally effective [8] and has been linked with increased risk of mortality, cardiovascular disease, gastrointestinal bleeding and renal adverse events. [9] Oral non-steroidal anti-inflammatory drugs (NSAIDs) are effective in reducing pain, [10] but are associated with renal, gastrointestinal and cardiovascular toxicity. [11] Opioids may be used despite poor evidence of efficacy, significant side effect burden, and risk of dependency. [12,13,14] Patients may be offered intra-articular corticosteroid injections, but their analgesic efficacy and safety are uncertain. [15] Knee OA may be treated with joint replacement, but access to this intervention is limited by resource constraints in many countries, [16] and by patient co-morbidity
General practice Osteoarthritis, Knee Analgesia Antidepressive Agents, Tricyclic Randomized Controlled Trial [Publication Type]. How this fits in Patients with knee OA frequently require analgesics, but the analgesics commonly used are not ideal being either insufficiently effective or having serious side effects
We hypothesised that tricyclic antidepressants (TCAs), which are used as analgesics in other chronically painful conditions, may be helpful for patients with OA
Summary
Osteoarthritis (OA) is the commonest joint disease and is a major cause of pain and disability, reduced quality of life, and large healthcare costs. [1,2,3,4] The burden of disease is predicted to rise. [5, 6]OA management is focused on advice, exercise, weight loss (if obese), analgesia and maintenance of function. [7] The analgesics currently recommended for OA are not ideal: paracetamol is minimally effective [8] and has been linked with increased risk of mortality, cardiovascular disease, gastrointestinal bleeding and renal adverse events. [9] Oral non-steroidal anti-inflammatory drugs (NSAIDs) are effective in reducing pain, [10] but are associated with renal, gastrointestinal and cardiovascular toxicity. [11] Opioids may be used despite poor evidence of efficacy, significant side effect burden, and risk of dependency. [12,13,14] Patients may be offered intra-articular corticosteroid injections, but their analgesic efficacy and safety are uncertain. [15] Knee OA may be treated with joint replacement, but access to this intervention is limited by resource constraints in many countries, [16] and by patient co-morbidity. [7] The analgesics currently recommended for OA are not ideal: paracetamol is minimally effective [8] and has been linked with increased risk of mortality, cardiovascular disease, gastrointestinal bleeding and renal adverse events. Aim To investigate the analgesic efficacy of nortriptyline in people with knee OA. 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. Stiffness, non-steroidal antiinflammatory drug, opioid and/or paracetamol use, participant global assessment, and adverse effects at 14 weeks.
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