Abstract: Nineteen studies randomising a total of 2863 women were included in this review. There were three main comparison groups: 15 studies compared non-opioid drugs with placebo or no treatment (2133 women); three studies compared non-opioid drugs with opioids (563 women); and three studies compared one type of non-opioid drug with a different type or dose of non-opioid drug (590 women). Some of the studies included three or more groups and so have been put in more than one comparison. Overall, there was little difference between groups for most of the comparisons. Any differences observed for outcomes were mainly limited to one or two studies. Non-opioid drugs (sedatives) were found to offer better pain relief (mean difference (MD) -22.00; 95% confidence interval (CI) -35.86 to -8.14, one trial, 50 women), better satisfaction with pain relief (sedatives and antihistamines) (risk ratio (RR) 1.59; 95% CI 1.15 to 2.21, two trials, 204 women; RR 1.80; 95% CI 1.16 to 2.79, one trial, 223 women) and better satisfaction with the childbirth experience (RR 2.16; 95% CI 1.34 to 3.47, one trial, 40 women) when compared with placebo or no treatment. However, women having non-opioid drugs (NSAIDs or antihistamines) were less likely to be satisfied with pain relief compared with women having opioids (RR 0.50; 95% CI 0.27 to 0.94, one trial, 76 women; RR 0.73; 95% CI 0.54 to 0.98, one trial, 223 women). Women receiving the antihistamine hydroxyzine were more likely to express satisfaction with pain relief compared with the antihistamine promethazine (RR 1.21; 95% CI 1.02 to 1.43, one trial, 289 women). Women receiving sedatives were more likely to express satisfaction with pain relief compared with antihistamines (RR 1.52; 95% CI 1.06 to 2.17, one study, 157 women). The majority of studies were conducted over 30 years ago. The studies were at unclear risk of bias for most of the quality domains. Opioids appear to be superior to non-opioids in satisfaction with pain relief, while non-opioids appear to be superior to placebo for pain relief and satisfaction with the childbirth experience. There were little data and no evidence of a significant difference for any of the comparisons of non-opioids for safety outcomes. Overall, the findings of this review demonstrated insufficient evidence to support a role for non-opioid drugs on their own to manage pain during labour.

Plain-language summary: There was little evidence on the effectiveness and safety of most non-opioid drugs. However, evidence from single trials or at most two trials, suggests that some non-opioid drugs may work in providing pain relief. Non-opioid drugs were found to offer better pain relief (sedatives: one trial, 50 women), better satisfaction with pain relief (sedatives and antihistamines: two trials, 204 women; one trial, 223 women respectively) and better satisfaction with the childbirth experience (sedatives: one trial, 40 women) when compared with placebo. Women taking non-opioid drugs (NSAIDs or antihistamines) were less likely to be satisfied with pain relief when compared with women receiving opioids (one trial, 76 women; one trial 223 women). Women having the antihistamine hydroxyzine were more satisfied with their pain relief than those taking the antihistamine promethazine (one trial, 289 women) and women having sedatives were more satisfied with their pain relief than those having antihistamines. There were little data and no evidence of a significant difference for any of the comparisons of non-opioids for safety outcomes. The majority of studies were conducted over 30 years ago and the quality of all studies was questionable. No study used paracetamol.