Background: Dozens of randomized controlled trials (RCTs) and meta-analyses have demonstrated the efficacy of repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder (MDD) treatment, but there has not been a meta-analysis report which evaluates the efficacy and tolerability of rTMS used as an augmentative strategy for antidepressants in treatment-resistant depression (TRD) treatment. We thus conducted this meta-analysis, aimed at clarifying whether rTMS enhances the efficacy of TRD.
Methods: We searched MEDLINE and Cochrane Central Register of Controlled Trials for RCTs for studying the efficacy of rTMS versus (vs) sham condition when combined with antidepressants in TRD treatment, and screened the references of the previous meta-analysis about the rTMS for MDD treatment. Response rates and NNT were chose as the primary outcomes, and remission rates, change from baseline of HAMD scores, dropouts were used as secondary outcomes. For dichotomous data, an intention-to-treat analysis principle was applied; for continuous data, we calculated the standard mean difference between groups with a random-effect model. Sensitivity analysis was done to explore the source of heterogeneity and the factors which potentially impact the efficacy.
Results: Seven RCTs were finally included in the meta-analysis. The total sample size was 279, with 171 in the rTMS group and 108 in the sham group. The pooled response and remission rate for the rTMS and sham group was 46.6% and 22.1%, respectively; the pooled odds ratio (OR) was 5.12 [95% confidence interval (CI) 2.11-12.45, z = 3.60, p = 0.0003, and the associated number needed to treat (NNT) was 3.4. rTMS group achieved a significant reduction of HAMD score than the sham group, the pooled SMD of change from baseline was 0.86 [95% confidence interval (CI) 0.57-1.15, z = 5.75, p < 0.00001]. Because of the small number of included RCTs, the preplanned sensitivity and subgroup analyses were finally abandoned. The dropouts in both groups were relatively low, indicating the high acceptability of rTMS.
Conclusions: For TRD patients, augmentative rTMS after the failure of medications significantly increases the effect of antidepressants, and rTMS was a safe strategy with relatively low adverse events and low dropout rate, suggesting that augmentative rTMS is an effective intervention for TRD.