In total, we included 91 studies and 4652 participants in the review. We added 42 studies with 2839 participants for this update. Altogether, we included 51 different treatments for
pruritus in four different patient groups. The overall risk of bias profile was heterogeneous and ranged from high to low risk. The main reason for giving a high risk of bias rating was a small sample size (fewer than 50 participants per treatment arm). Seventy-nine of 91 studies (87%) had fewer than 50 participants per treatment arm. Eight (9%) studies had low risk of bias in the specified key domains; the remaining studies had an unclear risk of bias (70 studies, 77%) or a high risk of bias (13 studies, 14%). Using GRADE criteria, we judged that the certainty of evidence for the primary outcome (i.e.
pruritus) was high for kappa-
opioid agonists compared to placebo and moderate for
GABA-analogues compared to placebo. Certainty of evidence was low for
naltrexone,
fish-oil/
omega-3 fatty acids, topical
capsaicin,
ondansetron and
zinc sulphate compared to placebo and
gabapentin compared to
pregabalin, and very low for
cromolyn sodium,
paroxetine,
montelukast,
flumecinol, and
rifampicin compared to placebo. We downgraded the certainty of the evidence mainly due to serious study limitations regarding risk of bias, imprecision, and inconsistency. For participants suffering from uraemic
pruritus (UP; also known as
chronic kidney disease (CKD)-associated
pruritus (CKD-aP)), treatment with
GABA-analogues compared to placebo likely resulted in a large reduction of
pruritus (visual analogue scale (VAS) 0 to 10 cm): mean difference (MD) -5.10, 95% confidence interval (CI) -5.56 to -4.55; five RCTs, N = 297, certainty of evidence: moderate. Treatment with
kappa-opioid receptor agonists (
difelikefalin,
nalbuphine,
nalfurafine) compared to placebo reduced
pruritus slightly (VAS 0 to 10 cm, MD -0.96, 95% CI -1.22 to -0.71; six RCTs, N = 1292, certainty of evidence: high); thus, this treatment was less effective than
GABA-analogues. Treatment with
montelukast compared to placebo may result in a reduction of
pruritus, but the evidence is very uncertain (two studies, 87 participants): SMD -1.40, 95% CI -1.87 to -0.92; certainty of evidence: very low. Treatment with
fish-oil/
omega-3 fatty acids compared to placebo may result in a large reduction of
pruritus (four studies, 160 observations): SMD -1.60, 95% CI -1.97 to -1.22; certainty of evidence: low. Treatment with
cromolyn sodium compared to placebo may result in a reduction of
pruritus, but the evidence is very uncertain (VAS 0 to 10 cm, MD -3.27, 95% CI -5.91 to -0.63; two RCTs, N = 100, certainty of evidence: very low). Treatment with topical
capsaicin compared with placebo may result in a large reduction of
pruritus (two studies; 112 participants): SMD -1.06, 95% CI -1.55 to -0.57; certainty of evidence: low.
Ondansetron,
zinc sulphate and several other treatments may not reduce
pruritus in participants suffering from UP. In participants with cholestatic
pruritus (CP), treatment with
rifampicin compared to placebo may reduce
pruritus, but the evidence is very uncertain (VAS: 0 to 100, MD -42.00, 95% CI -87.31 to 3.31; two RCTs, N = 42, certainty of evidence: very low). Treatment with
flumecinol compared to placebo may reduce
pruritus, but the evidence is very uncertain (RR > 1 favours treatment group; RR 2.32, 95% CI 0.54 to 10.1; two RCTs, N = 69, certainty of evidence: very low). Treatment with the
opioid antagonist naltrexone compared to placebo may reduce
pruritus (VAS: 0 to 10 cm, MD -2.42, 95% CI -3.90 to -0.94; two RCTs, N = 52, certainty of evidence: low). However, effects in participants with UP were inconclusive (percentage of difference -12.30%, 95% CI -25.82% to 1.22%, one RCT, N = 32). In
palliative care participants with
pruritus of a different nature, the treatment with the
drug paroxetine (one study), a
selective serotonin reuptake inhibitor, compared to placebo may reduce
pruritus slightly by 0.78 (numerical analogue scale from 0 to 10 points; 95% CI -1.19 to -0.37; one RCT, N = 48, certainty of evidence: low). Most adverse events were mild or moderate. Two interventions showed multiple major adverse events (
naltrexone and
nalfurafine).
AUTHORS CONCLUSIONS: