The risk of relapse in major depressive disorder (MDD) is associated with high worldwide disease burden. Cognitive behavioral therapy (CBT) and its modifications might be effective in relapse prevention. The aim of this review was to evaluate the efficacy of these treatments for reducing relapse of MDD. Methods: The retrieval was performed in the databases of MEDLINE via Pubmed, EMBASE and PsycINFO via OVID, The Cochrane Library and four Chinese databases. Clinical trials registry platforms and

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... references of relevant articles were retrieved as well. Hazard ratio (HR) and corresponding 95% confidence interval (CI) were used to pool evidences. Results: A total of 16 eligible trials involving 1945 participants were included. In the first 12 months, CBT was more efficacious than control in reducing the risk of developing a new episode of depression for MDD patients in remission (HR:0.50, 95%CI:0.35-0.72, I 2 = 11%). Mindfulness-based cognitive therapy (MBCT) was more efficacious than control only among patients with 3 or more previous depressive episodes (HR:0.46, 95%CI:0.31-0.70, I 2 = 38%). Besides, compared with maintenance antidepressant medication (m-ADM), MBCT was a more effective intervention (HR:0.76, 95%CI:0.58-0.98, I 2 = 0%). These positive effects might be only maintained at two and nearly 6 years follow up for CBT. Conclusion: The use of CBT for MDD patients in remission might reduce risk of relapse. Besides, the effect of MBCT was moderated by number of prior episodes and MBCT might only be effective for MDD patients with 3 or more previous episodes. Further exploration for the influence of previous psychological intervention is required.