Is transcranial direct current stimulation, alone or in combination with antidepressant medications or psychotherapies, effective in treating major depressive disorder? A systematic review and meta-analysis

Abstract

Background: Transcranial direct current stimulation (tDCS) has shown mixed results for depression treatment. The efficacies of tDCS combination therapies have not been investigated deliberately. This review aims to evaluate the clinical efficacy of tDCS as a monotherapy and in combination with medication, psychotherapy, and ECT for treating adult patients with major depressive disorder (MDD) and identified the factors influencing treatment outcome measures (i.e. depression score, dropout, response, and remission rates).

Methods: The systematic review was performed in PubMed/Medline, EMBASE, PsycINFO, Web of Sciences, and OpenGrey. Two authors performed independent literature screening and data extraction. The primary outcomes were the standardized mean difference (SMD) for continuous depression scores after treatment and odds ratio (OR) dropout rate; secondary outcomes included ORs for response and remission rates. Random effects models with 95% confidence intervals were employed in all outcomes. The overall effect of tDCS was investigated by meta-analysis. Sources of heterogeneity were explored via subgroup analyses, meta-regression, sensitivity analyses, and assessment of publication bias.

Results: Twelve randomised, sham-controlled trials (active group: N = 251, sham group: N = 204) were included. Overall, the integrated depression score of the active group after treatment was significantly lower than that of the sham group (g = - 0.442, p = 0.017), and further analysis showed that only tDCS + medication achieved a significant lower score (g = - 0.855, p < 0.001). Moreover, this combination achieved a significantly higher response rate than sham intervention (OR = 2.7, p = 0.006), while the response rate remained unchanged for the other three therapies. Dropout and remission rates were similar in the active and sham groups for each therapy and also for the overall intervention. The meta-regression results showed that current intensity is the only predictor for the response rate. None of publication bias was identified.

Conclusion: The effect size of tDCS treatment was obviously larger in depression score compared with sham stimulation. The tDCS combined selective serotonin re-uptake inhibitors is the optimized therapy that is effective on depression score and response rate. tDCS monotherapy and combined psychotherapy have no significant effects. The most important parameter for optimization in future trials is treatment strategy.

Keywords: Antidepressant; Combination therapy; Major depressive disorder; Meta-analysis; Systematic review; Transcranial direct current stimulation; Treatment strategy.

Fig. 1

PRISMA study selection flowchart. The sum of excluded studies for each reason is not equal to the total number because some articles have more than one exclusion reason

Fig. 2

Forest plots of primary outcomes: a depression score, b dropout rate. mono = tDCS alone; +medicine = tDCS + medication; + psycho = tDCS + psychotherapy; +ECT = tDCS + ECT. SMD, standardised mean difference; OR, odds ratio; CI, confidence interval. ^aStimulation duration, 30 min. ^bStimulation duration, 20 min. “Excluded” in brackets means the events in both active and sham groups are zero, and thus, the study was excluded from further analysis

Fig. 3

Forest plots of secondary outcomes: a response rate, b remission rate. mono = tDCS alone; +medicine = tDCS + medication; +psycho = tDCS + psychotherapy; +ECT = tDCS + ECT. SMD, standardised mean difference; OR, odds ratio; CI, confidence interval. ^aStimulation duration is 30 minutes. ^bStimulation duration is 20 min. “Excluded” in brackets means the events in both active and sham groups are zero, and thus, the study was excluded from further analysis