Efficacy of combined nicotine replacement therapy (NRT) and bupropion compared to bupropion alone for smoking cessation: a systematic review and meta-analysis

Introduction Smoking is a major preventable cause of morbidity and premature death worldwide. Both bupropion and NRT help achieve smoking cessation. However, evidence on whether the combination of bupropion and NRT is more effective than bupropion alone remains uncertain. The aim of this study was to compare the efficacy and safety of bupropion combined with NRT with bupropion monotherapy. Methods The Cochrane Library, Embase, PubMed, and Web of Science were systematically searched for original articles published in English. Randomized controlled trials (RCTs) that compared bupropion plus NRT therapy with bupropion were included. Qualitative and quantitative analyses were conducted and the risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Results Nine RCTs involving 4005 participants (53.8% female) were included in this study. The mean age across studies ranged from 27 to 55 years. The risk of bias results showed that two RCTs were rated as high, one was low, and six were unclear. Pooled analysis indicated that bupropion combined with NRT significantly improved biochemically validated 7-day point prevalence abstinence at the end of treatment [risk ratio (RR) = 1.35, 95% confidence interval (CI): 1.22–1.50, I 2 = 21%]. At long-term follow-up (≥6 months), bupropion plus NRT showed a non-significant benefit over bupropion monotherapy (RR = 1.10, 95% CI: 0.90–1.34, I 2 = 52%). Adverse events were generally comparable between groups, except for a higher incidence of nausea in the combination therapy group (10.9% vs. 7.3%; RR = 1.42, 95% CI 1.04–1.94, I 2 = 0%). No significant subgroup differences were found based on the types of NRT (nicotine patch, gum, or lozenge) (χ 2 = 0.89, p = 0.64). Conclusion Combination therapy of bupropion and NRT was associated with superior short-term smoking cessation outcome compared with bupropion alone, with a comparable safety profile except for increased risk of nausea. However, the long-term benefit of combination therapy over bupropion monotherapy was attenuated and non-significant. Further high-quality RCTs with adequate long-term follow- up are needed to confirm these findings.