Repetitive Transcranial Magnetic Stimulation as an Augmentative Strategy for Treatment-resistant Depression

A Meta-analysis of Randomized, Double-blind and Sham-Controlled Study

Bangshan Liu; Yan Zhang; Li Zhang; Lingjiang Li


BMC Psychiatry. 2014;14(342) 

In This Article


To our knowledge, this is the first meta-analysis exploring the efficacy of augmentative rTMS for TRD. We included 7 RCTs and our results demonstrated that rTMS is significantly superior to sham condition in TRD treatment, the pooled OR was 5.12 (95% CI 2.11–12.45, z = 3.60, p = 0.0003), and the associated NNT was 3.4, indicating a relatively high efficacy of rTMS in TRD treatment. Moreover, our results showed that patients receiving rTMS treatment achieved significantly greater decrease in HAMD scores than those who receiving sham condition (SMD = 0.97, 95% CI 0.64–1.31, z = 6.00, p < 0.00001). Additionally, our results manifested that the baseline depression severity and dropout rates of the two groups did not differ significantly.

Although more than 10 meta-analyses about the efficacy of rTMS on depression had been published, there was only one meta-analysis[19] focused on the treatment-resistant patients. Nevertheless, the study by Lam et al. found a relatively high heterogeneity between the included RCTs, and this may be due to their enrollment of studies which used rTMS either as monotherapy or augmentation to antidepressants. Our results overcome the weakness by limiting the included studies only to the RCTs using rTMS as an augmentative strategy. For other meta-analyses, most of them had chosen change from baseline of HAMD scores or end-point HAMD scores as the primary outcome assessment, this may facilitate reserving the information of each individual study, but the outcomes of these studies are usually complicated and not easy for doctors and patients to understand. In this study, we provided an easily understood result by choosing response rate and NNT as the primary outcomes.

Despite the advantages aforementioned, our study has some limitations. Firstly, the strict inclusion criteria in this study may help to reduce heterogeneity and enhance the reliability of our results, but it may also limit our results only suitable for the condition of augmentative rTMS for TRD patients, thus we cannot know the efficacy of rTMS used as monotherapy for TRD patients or used as augmentative strategy for non-resistant MDD patients from the results of our study. However, that is not we intentioned to know and previous meta-analyses[14,19,24] had told us the answers to the above questions. Secondly, the quality of included RCTs is relatively low. Like other relevant meta-analyses,[14,19] most included RCTs in this study did not report the method of allocation concealment and implementation and maintenance of blinding, which may lower the scoring of study quality. Thirdly, as mentioned in other meta-analyses and RCTs, the sham condition used in most studies cannot fully eliminate the placebo effect,[10] because some patients receiving rTMS treatment can perceive the vibration of electromagnetic coil while the patients in the sham group cannot experience the effect. Moreover, the "5-cm" location method is often criticized for its inaccuracy,[42,43] and it is unknown where is the exact stimulated location. Fourth, the follow-up duration of included studies was relatively low, and most studies designed open rTMS treatment in the follow up period. These factors make it impossible to estimate the median- or long-term naturalistic efficacy of rTMS. Fifth, as the number of included RCTs was relatively low, the predetermined subgroup analyses were finally not successfully conducted for the high heterogeneity. Therefore, it is unclear whether the intensity, frequency and total pulses of rTMS and drug strategy had contributed to the accuracy of the present results, and it should be settled by future studies.