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)

Conclusions

This study showed that augmentative rTMS was significantly superior to sham condition in TRD treatment, and the two groups did not differ significantly in dropout rates or side effects, indicating the advantage of rTMS in the efficacy and acceptability for clinical treatment of TRD. As the number of included RCTs was relatively low and the heterogeneity of RCTs in subgroup analysis is higher than expected by chance, we did not explore the potential confounding factors which may influence the effect of rTMS. Future studies should have more rigid design, such as reporting the method of allocation concealment and blinding in details, carrying out longer non-interventive follow-up to make clear of long-term efficacy of rTMS, and improving the design of sham condition to alleviate placebo effect further. Additionally, combination with neuroimaging technique for identifying the best stimulation location is expected.

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Acknowledgements
This study was supported by the National Natural Science Foundation of China (81171286 & 91232714 to Lingjiang Li, 81101004 to Yan Zhang, 81301155 to Li Zhang), National Basic Research Program of China (+2013CB835100 and 2009CB918303 to Lingjiang Li). The authors would like to offer sincere gratitude to all the people who participated in the study.

Table 1. Main characteristics of included RCTs
Study	Sample size (n)		Diagnosis	TRD definition	Medication regimen	rTMS parameters				Outcome assessment	Follow-up?	Adverse effects
Study	rTMS	sham	Diagnosis	TRD definition	Medication regimen	Frequency, Hz	Intensity (%MT)	Sessions	Total pulses	Outcome assessment	Follow-up?	Adverse effects
Garcia-Toro et al. [36]	17	18	DSM-IV MDD	Failed 2 or more ADs, 6 weeks minimum	continue current treatment	20	90	10	12000	HAMD-21	2w of an open trial	Scalp discomfort and slight headaches
Rossini et al. [38]	18	17	DSM-IV MDD & ≥ 26 in HAMD-21	Failed 2 or more ADs, 6 weeks minimum	continue current treatment	15	100	10	6000	HAMD-21	3w of follow up	Mild headache; discomfort at the site of stimulation
Rossini et al. [38]	19					15	80		6000
Garcia-Toro et al. [37]	10	10	DSM-IV MDD	Failed 2 or more ADs, 1 month minimum	continue current treatment	20,1	110	10	12000	HAMD-21	2w of follow up	Scalp discomfort and headaches
Garcia-Toro et al. [37]	10					20,1	110		12000
Bretlau et al. [27]	22	23	DSM-IV MDD	Failed 2 or more ADs, 6 weeks minimum	Escitalopram from 10 mg/d to 20 mg/d	8	90	15	19200	HAMD-17	9w of follow up	Reduced sleep length and greater concentration difficulties (sham group)
Martinot et al. [39]	16	14	DSM-IV-R MDD& ≥18 in MADRS & ≥16 in HAMD	Failed 2 or more ADs, 4 weeks minimum	minimal and stable dosage of previous treatment	10	90	10	16000	HAMD-21	N	Not mentioned
Martinot et al. [39]	18					10	90		16000
Bakim et al. [30]	12	12	DSM-IV MDD & ≥18 in MADRS & ≥20 in HAMD	Failed 2 or more ADs, 6 weeks minimum	continue current treatment	20	80	30	24000	HAMD-17	N	Mild headache and mild discomfort
Bakim et al. [30]	11					20	100		24000
Chen et al. [35]	10	11	DSM-IV MDD & ≥ 18 in HAMD-17	Failed 2 or more ADs, 6 weeks minimum	continue current treatment, stable dose	20	90	10	8000	HAMD-17	9w of follow up	Not mentioned(1 dropouts for unspecific somatic complaints, sham group)