Efficacy and safety of tramadol in the treatment of opioid withdrawal: A meta-analysis of randomized controlled trials

Background: Pharmacotherapeutic options for the treatment of opioid withdrawal are limited by abuse potential, adverse effects, and lack of availability of existing drugs. The results from previous clinical trials on tramadol are contradictory and non-conclusive; hence the present meta-analysis was conducted to evaluate the efficacy and safety of tramadol in the treatment of opioid withdrawal. Methods: Reviewers extracted data from eight relevant clinical trials after a literature search on MEDLINE/ PubMed, Cochrane databases, and clinical trial registries. Quality assessment was done using the risk-of-bias assessment tool, and the random-effects model was used to estimate effect size in frequentist and Bayesian approaches. Subgroup analysis, meta-regression, and sensitivity analysis were done as applicable. PRISMA guidelines were followed in reporting findings. Results: Tramadol significantly reduced opioid withdrawal scale score (SMD: -0.44; 95%CI: -0.76 to -0.13; PI: -1.54 to 0.71; p = 0.006) when all comparators were considered together in the frequentist approach but the reduction was non-significant in Bayesian approach. However, the subgroup analysis revealed no significant difference between tramadol and comparators like placebo (SMD: -1.12; 95%CI: -2.69 to 0.45) buprenorphine (SMD: -0.21; 95%CI: -0.43 to 0.01), clonidine (SMD: -0.26; 95%CI: -0.55 to 0.02) and methadone (SMD: -0.84; 95%CI: -1.78 to 0.10). Meta-regression showed non-significant associations between the SMD in opioid withdrawal score with the duration and dose of tramadol therapy. There were no significant differences in treatment retention at the end of studies between tramadol and comparators. Safety data in the individual studies were inadequate to analyze. Conclusion: Authors conclude that the efficacy of tramadol in reducing opioid withdrawal symptoms is not significantly different from comparators with low certainty of evidence against placebo, moderate against methadone, whereas with high certainty of evidence against buprenorphine and clonidine.