Targeting Neuroadaptation in Tramadol Dependence: Systematic Review of Anticonvulsant Efficacy and Safety

Abstract

Background: Tramadol dependence is a growing public health concern, particularly in low- and middle-income countries. While opioid substitution therapies remain the mainstay of treatment, emerging evidence suggests anticonvulsants may have a role in mitigating withdrawal symptoms, cravings, and relapse.

Objective: To systematically review the literature on the potential benefits of anticonvulsants in the management of tramadol dependence.

Methods: Following PRISMA guidelines, we searched PubMed, Scopus, Web of Science, and African Journals Online (AJOL) from January 2000 to July 2025. Inclusion criteria were clinical trials, observational studies, and case reports assessing the effect of anticonvulsants such as carbamazepine, Gabapentin, Pregabalin in tramadol dependence management. Data extraction covered study design, sample size, intervention type, outcomes (withdrawal, relapse, adverse events). Risk of bias was assessed using the Cochrane ROB-2 tool.

Results: Eleven studies met inclusion criteria (5 Randomized Clinical Trials (RCTs), 3 observational studies, 3 case reports; total n=547 participants). Gabapentin (300– 1200 mg/day) reduced withdrawal severity and cravings in three RCTs. Carbamazepine showed modest benefit in reducing withdrawal-related seizures in two trials. Pregabalin demonstrated reductions in craving scores and improved sleep quality in one observational study. Case reports highlighted topiramate as a potential adjunct for relapse prevention. Adverse effects were generally mild (dizziness, sedation).

Conclusion: Anticonvulsants, particularly gabapentin and pregabalin, show promise in tramadol dependence management, but evidence remains limited by small sample sizes and heterogeneous methodologies. Larger, well-designed RCTs are warranted.