The efficacy and safety of paracetamol for pain relief: an overview of systematic reviews

Abstract

Objective To evaluate the efficacy and safety of paracetamol as an analgesic medication in a range of painful conditions. Study design Systematic review of systematic reviews of the analgesic effects of paracetamol in randomised, placebo‐controlled trials. Conduct of systematic reviews was assessed with AMSTAR‐2; confidence in effect estimates (quality of evidence) was assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Data sources MEDLINE, EMBASE, PsycINFO, Cochrane Database of Systematic Reviews; systematic reviews published 1 January 2010 – 30 April 2020. Data synthesis We extracted pain and adverse events outcomes from 36 systematic reviews that assessed the efficacy of paracetamol in 44 painful conditions. Continuous pain outcomes were expressed as mean differences (MDs; standardised 0–10‐point scale); dichotomous outcomes were expressed as risk ratios (RRs). There is high quality evidence that paracetamol provides modest pain relief for people with knee or hip osteoarthritis (MD, –0.3 points; 95% CI, –0.6 to –0.1 points) and after craniotomy (MD, –0.8 points; 95% CI, –1.4 to –0.2 points); there is moderate quality evidence for its efficacy in tension‐type headache (pain‐free at 2 hours: RR, 1.3; 95% CI, 1.1–1.4) and perineal pain soon after childbirth (patients experiencing 50% pain relief: RR, 2.4; 95% CI, 1.5–3.8). There is high quality evidence that paracetamol is not effective for relieving acute low back pain (MD, 0.2 points; 95% CI, –0.1 to 0.4 points). Evidence regarding efficacy in other conditions was of low or very low quality. Frequency of adverse events was generally similar for people receiving placebo or paracetamol, except that transient elevation of blood liver enzyme levels was more frequent during repeated administration of paracetamol to patients with spinal pain (RR, 3.8; 95% CI, 1.9–7.4). Conclusions For most conditions, evidence regarding the effectiveness of paracetamol is insufficient for drawing firm conclusions. Evidence for its efficacy in four conditions was moderate to strong, and there is strong evidence that paracetamol is not effective for reducing acute low back pain. Investigations that evaluate more typical dosing regimens are required. PROSPERO registration CRD42015029282 (prospective).

Paracetamol: A Review of Guideline Recommendations

“…The numbers of studies, systemic reviews, and meta-analyses on paracetamol is high and growing. However, large, authoritative clinical trials are costly, and it is unclear whether they will be done [ 145 , 146 ].…”

“…Recently, Abdel Shaheed analyzed data from 36 publications and reported that paracetamol produced modest pain relief in hip and knee osteoarthritis, tension headache, and post-craniotomy pain and that it was ineffective in other conditions [ 145 ]; the authors concluded with the need for large, high-quality trials to reduce uncertainty about the efficacy of paracetamol in common pain conditions. In the last few months, new published studies report the safe use of paracetamol in patients with chronic kidney disease [ 147 ], the significant efficacy of paracetamol for post-arthroplasty pain [ 148 ], the lesser efficacy of paracetamol than ibuprofen for post-laminectomy pain [ 149 ], the opioid-sparing effects of paracetamol in the Emergency Department [ 150 ], the recommendations against paracetamol in lumbar spinal stenosis with neurogenic claudication [ 151 ], and the recommendations in favor of paracetamol for postcesarean pain [ 152 ] and for migraine [ 153 , 154 ].…”

Pharmacological management of chronic non-cancer pain in frail older people

“…Its efficacy in other painful conditions is uncertain. 20 In view of an increased risk of hepatotoxicity in older adults, sometimes at therapeutic doses, 21,22 and emerging evidence of a relative lack of efficacy of paracetamol, the benefits of long-term use need to be re-evaluated. Co-administration of paracetamol with other analgesics is common, however there is a lack of data on the efficacy of combination therapy in chronic non-cancer pain.…”

Getting the “balance” right in clinical trials

“…Differential use of co-interventions might lead to underestimation or overestimation of treatment effects 21112. Many placebo controlled trials of pain interventions, for example, report small or non-existent benefits 13. But these studies often allow pain relieving co-interventions while failing to record the type, frequency, or duration of co-interventions used in each study arm.…”