There is a good amount of evidence from RCTs on the efficacy of paracetamol in people with osteoarthritis but trial data is mainly for people with osteoarthritis of the hip or knee. Paracetamol reduces pain in the short term compared with placebo, but appears to be less effective than oral standard or coxib nonsteroidal anti-inflammatory drugs (NSAIDs), especially in people with moderate-to-severe pain. Paracetamol can be used alone or in conjunction with other analgesics, although there is a limited quantity and quality of data on the efficacy of paracetamol used in combination with other analgesic drugs. Paracetamol is less likely than NSAIDs to cause gastrointestinal (GI) adverse events.

• The National Institute for Health and Clinical Excellence (NICE) looked at studies on the efficacy and safety of paracetamol (compared with oral standard or coxib NSAIDs) for symptomatic relief from pain in adults with osteoarthritis. One Cochrane review and six additional studies were appraised. Five of these additional studies are not discussed further as there were high numbers of drop-outs in four of them, and one additional study [Fries and Bruce, 2003] just confirmed that the rates of serious GI adverse events increase with higher doses of paracetamol or ibuprofen, that the most serious problems occur in people at higher risk, and that little risk of serious GI toxicity has been found in over-the-counter use.
• A Cochrane review (15 RCTs, n = 5986) assessed the efficacy and safety of paracetamol compared with placebo as well as both standard and coxib NSAIDs (celecoxib, diclofenac, ibuprofen, naproxen, and rofecoxib) for treating osteoarthritis (mainly of the hip or knee) [Towheed et al, 2006]. Literature searches were conducted up to July 2005.
• Paracetamol compared with placebo: seven RCTs were found.
• Paracetamol was superior to placebo in five of the seven RCTs. A pooled analysis of pain reduction (when resting, moving, sleeping, and overall) in the five trials was statistically significant, standardized mean difference (SMD) –0.13 (95% CI –0.22 to –0.04) but the clinical significance was inconclusive.
• Assessment of pain, physical function, and stiffness using WOMAC scales found similar results for paracetamol and placebo.
• When measuring pain on a visual analogue scale (0–100), pain relief with paracetamol decreased by 4 points more than placebo.
• The NNT to improve pain ranged from 4–16.
• Paracetamol compared with NSAIDs (both standard and coxibs): ten RCTs were found.
• Paracetamol was less effective overall than NSAIDs in terms of: pain reduction; WOMAC pain, stiffness, function, and total scales; global assessments (both patient and investigator); and functional status.
• NSAIDs were found to be significantly more effective than paracetamol for:
• Pain at rest: three RCTs (n = 573): SMD –0.20 (95% CI –0.36 to –0.03) for ibuprofen 2400 mg, diclofenac, diclofenac plus misoprostol, celecoxib, naproxen. Four RCTs (n = 594): SMD –0.19 (95% CI –0.35 to –0.03) for ibuprofen 1200 mg, diclofenac plus misoprostol, rofecoxib 25 mg, naproxen.
• Overall pain: eight RCTs (n = 2538): SMD –0.25 (95% CI –0.33 to –0.17) for ibuprofen 2400 mg, diclofenac, diclofenac plus misoprostol, celecoxib, naproxen. Seven RCTs (n = 1812): SMD –0.31 (95% CI –0.40 to –0.21) for ibuprofen 1200 mg, diclofenac plus misoprostol, rofecoxib 25 mg, naproxen.
• The review found no significant differences between NSAIDs and paracetamol for pain on motion and Lequesne pain index, but NSAIDs were more effective than paracetamol in terms of: WOMAC pain, stiffness, function, and total scales; global assessments (both patient and investigator); and functional status.
• People taking ibuprofen or naproxen (i.e. standard NSAIDs) compared with paracetamol were more likely to experience a GI adverse event, RR 1.47 (95% CI 1.08 to 2.00).
• No significant difference was found overall between the safety of paracetamol and NSAIDs, although the median trial duration was only 6 weeks.
• An RCT (n = 581) published subsequently of adults with mild-to-moderate osteoarthritis pain of the hip or knee randomized to receive paracetamol or naproxen, compared results in terms of safety or efficacy, over 6 or 12 months [Temple et al, 2006]:
• WOMAC pain — no significant difference in treatment effect at 6 months between paracetamol and naproxen.
• WOMAC stiffness — both groups of people taking paracetamol or naproxen had a similar outcome at 6 months.
• WOMAC function — both groups of people taking paracetamol or naproxen had a similar outcome at 6 months.
• Number of people with one or more adverse events — no significant difference in treatment effect at 6 months between paracetamol and naproxen.
• Number of people with a serious adverse event — no significant difference at 6 months between paracetamol and naproxen.
• Number of GI adverse events (constipation and peripheral oedema) — significantly less constipation and peripheral oedema at 6 months in people taking paracetamol compared with naproxen.
• Number of withdrawals due to adverse events — no significant difference at 6 months between paracetamol and naproxen.
• For information on the effect of paracetamol compared with opioid analgesics, see Opioid analgesics.

[National Collaborating Centre for Chronic Conditions, 2008]