Background/Purpose: Osteoarthritis (OA) is the most common joint disease and is a major cause of pain and disability There is currently no cure for OA and management is focused on relief of pain and maintenance of function Tricyclic antidepressants (TCAs) have long been used in other chronic pain conditions, but their analgesic effect in OA has not previously been evaluated. To investigate the analgesic effectiveness of nortriptyline in people with OA of the knee.

Methods: We undertook 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. 205 adults with knee OA as defined by the American College of Rheumatology clinical criteria for the classification of idiopathic OA of the knee, 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 (n=103) or placebo (n=102) in addition to their usual analgesia for 14 weeks. Treatment was divided into a dose-adjustment phase (weeks 0 to 7) and a steady-dose phase (weeks 8 to 14).  Participants were instructed to commence taking one capsule (25mg of nortriptyline or placebo) daily for two weeks at which time they were contacted by a research nurse by telephone who advised participants to increase (or decrease) their dose by one capsule per day according to the participant’s level of knee pain and adverse effects.  Further dose adjustments occurred at four, six and eight weeks, up to a maximum dose of four capsules daily (100 mg nortriptyline daily in the treatment group).  Primary outcome was knee pain at 14 weeks measured using the WOMAC pain sub-scale.  Secondary outcomes included function, stiffness, non-steroidal anti-inflammatory (NSAID), opioid and/or paracetamol use, participant global assessment, and adverse effects at 14 weeks.

Results: The baseline adjusted mean WOMAC pain subscale score at week 14 was 6.15 points lower (95% CI -0.26 to 12.6, p = 0.060) 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.  For example the number needed to treat to achieve one responder was 10 (95% CI = 4.2 to Inf, p = 0.14).  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 provides a clinically insignificant reduction in pain in people with knee OA.  Adverse effect profile was as expected.
Trial registration: Australian New Zealand Clinical Trials Registry: ACTRN12614000683639.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/nortriptyline-in-knee-arthritis-nortika-a-randomised-controlled-double-blind-trial-of-nortriptyline-for-pain-in-knee-osteoarthritis/