Objective  To systematically review the efficacy and safety of repetitive transcranial magnetic stimulation (rTMS) combined with agomelatine in the treatment of depression.

Methods  PubMed, Embase, Cochrane Library, Web of Science, CNKI, VIP, WanFang Data, SinoMed and Yiigle databases were electronically searched to collect randomized controlled trials (RCTs) of comparison between rTMS combined with agomelatine (combined group) and agomelatine or combined pseudostimulation (control group) in the treatment of depression from inception to May 10, 2024. Meta-analysis was performed by using RevMan 5.4 software, GRADE grading system for evaluating the level of evidence for observational indicators, and TSA 0.9.5.1Beta software for trial sequential analysis.

Results  A total of 15 RCTs involving 1 196 patients were included. Meta-analysis showed that compared with control group, combination group had a higher effective rate (RR=1.24, 95%CI 1.15 to 1.34, P<0.001), lower depression scale score (SMD=-2.95, 95% CI-3.71 to -2.19, P<0.001), anxiety scale score (SMD=-2.21, 95%CI -3.29 to -1.14, P<0.001), PSQI score (MD=-1.69, 95%CI -2.79 to -0.59, P=0.003). There was no statistical difference between the two groups in terms of NE level, 5-HT level and incidence of adverse reactions (P>0.05). GRADE quality grading of the evidence showed moderate-quality evidence for the effectiveness rate and incidence of adverse reactions, with the depression scale score and the NE level of the evidence being low-quality, and the level of evidence for the anxiety scale score, the PSQI score, and the 5-HT content was very low. The trial sequential analysis results showed that in terms of effective rate, the analysis results of combination group superior to control group were reliable, and the conclusion could exclude false positives.

Conclusion  The rTMS combined with agomelatine in the treatment of depression has advantages in improving effective rate, depression scale score, anxiety scale score and PSQI score compared with agomelatine alone or combined pseudostimulation, incidence of adverse reactions were equivalent to those of agomelatine aloneor or combined pseudostimulation.

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