Review
Clinical utility of transcranial direct current stimulation (tDCS) for treating major depression: A systematic review and meta-analysis of randomized, double-blind and sham-controlled trials

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Abstract

Objective

tDCS is a promising novel therapeutic intervention for major depression (MD). However, clinical trials to date have reported conflicting results concerning its efficacy, which likely resulted from low statistical power. Thus, we carried out a systematic review and meta-analysis on randomized, double-blind and controlled trials of tDCS in MD with a focus on clinically relevant outcomes, namely response and remission rates.

Method

We searched the literature for English language randomized, double-blind and sham-controlled trials (RCTs) on tDCS for treating MD from 1998 through July 2012 using MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials and SCOPUS. We also consulted the Web of Science's Citations Index Expanded for the selected RCTs up to July 2012. The main outcome measures were response and remission rates. We used a random-effects model and Odds Ratios (OR).

Results

Data were obtained from 6 RCTs that included a total of 200 subjects with MD. After an average of 10.8 ± 3.76 tDCS sessions, no significant difference was found between active and sham tDCS in terms of both response (23.3% [24/103] vs. 12.4% [12/97], respectively; OR = 1.97; 95% CI = 0.85–4.57; p = 0.11) and remission (12.2% [12/98] vs. 5.4% [5/92], respectively; OR = 2.13; 95% CI = 0.64–7.06; p = 0.22). Also, no differences between mean baseline depression scores and dropout rates in the active and sham tDCS groups were found. Furthermore, sensitivity analyses excluding RCTs that involved less than 10 treatment sessions or stimulus intensity of less than 2 mA did not alter the findings. However, tDCS used as monotherapy was associated with higher response rates when compared to sham tDCS (p = 0.043). Finally, the risk of publication bias in this meta-analysis was found to be low.

Conclusions

The clinical utility of tDCS as a treatment for MD remains unclear when clinically relevant outcomes such as response and remission rates are considered. Future studies should include larger and more representative samples, investigate how tDCS compares to other therapeutic neuromodulation techniques, as well as identify optimal stimulation parameters.

Section snippets

Search strategy

We identified articles for inclusion in this meta-analysis by:

  • Screening the bibliographies of the meta-analysis by Kalu et al. (2012) as well as of all included RCTs;

  • Searching MEDLINE, EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL) and SCOPUS from July 1, 1998 (when Priori et al. (1998) published their seminal paper on tDCS using contemporary stimulation parameters) until August 20, 2012;

  • Consulting the Web of Science's Citations Index Expanded for all included

Literature search

Of the 6 RCTs included in the previous meta-analysis on tDCS for MD, 5 were selected for the present investigation (Boggio et al., 2008; Fregni et al., 2006a; Loo et al., 2012, 2010; Palm et al., 2012). Also, we retrieved 37 references (after discarding duplicates) from MEDLINE, PsycINFO, EMBASE, CENTRAL and SCOPUS and 71 references (after discarding duplicates) from the Web of Science's Citations Index Expanded. Of these, 1 met our eligibility criteria (Blumberger et al., 2012). Please refer

Discussion

This is the first meta-analysis assessing the efficacy of tDCS for MD using clinically meaningful outcomes such as response and remission rates. Our results show that this neuromodulation technique is not more effective than sham tDCS. Indeed, following a mean of 10.8 ± 3.76 sessions, only 23.2% and 12.2% of depressed subjects receiving active tDCS were responders and remitters (versus 12.4% and 5.4% with sham tDCS), respectively. Furthermore, we did not find significant differences on dropout

Conclusion

The current meta-analysis, which included 200 depressed subjects, shows that the clinical utility of tDCS as treatment for MD remains unclear and that there is – at present – insufficient evidence to support the notion that tDCS is superior to placebo in achieving response and/or remission in subjects with MD. Future research should focus on the investigation of larger and more representative samples, on the potential differential efficacy of tDCS in subtypes of MD, and on how it compares to

Role of the funding source

We received no funding for this study.

Contributors

None.

Conflict of interest

Drs Berlim and Van den Eynde report no conflicts of interest. Dr Daskalakis received external funding through Neuronetics and Brainsway Inc, Aspect Medical and a travel allowance through Pfizer and Merck. Dr Daskalakis has also received speaker funding through Sepracor Inc and served on the advisory board for Hoffmann-La Roche Limited.

Acknowledgment

None.

References (48)

  • P.S. Boggio et al.

    A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation for the treatment of major depression

    International Journal of Neuropsychopharmacology

    (2008)
  • M. Borenstein et al.

    Introduction to meta-analysis

    (2009)
  • A.R. Brunoni et al.

    A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation

    International Journal of Neuropsychopharmacology

    (2011)
  • A.R. Brunoni et al.

    Clinical research with transcranial direct current stimulation (tDCS): challenges and future directions

    Brain Stimulation

    (2011)
  • H. Cooper et al.

    The handbook of research synthesis and meta-analysis

    (2009)
  • A.F. DaSilva et al.

    Electrode positioning and montage in transcranial direct current stimulation

    Journal of Visualized Experiments

    (2011)
  • A. Datta et al.

    Gyri-precise head model of transcranial DC stimulation: improved spatial focality using a ring electrode versus conventional rectangular pad

    Brain Stimulation

    (2009)
  • B. Dell'osso et al.

    Transcranial direct current stimulation for the outpatient treatment of poor-responder depressed patients

    European Psychiatry

    (2011)
  • C.A. Dockery et al.

    Enhancement of planning ability by transcranial direct current stimulation

    Journal of Neuroscience

    (2009)
  • S. Duval et al.

    Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis

    Biometrics

    (2000)
  • M. Egger et al.

    Bias in meta-analysis detected by a simple, graphical test

    British Medical Journal

    (1997)
  • D. Fergusson et al.

    Post-randomisation exclusions: the intention to treat principle and excluding patients from analysis

    British Medical Journal

    (2002)
  • R. Ferrucci et al.

    Comparative benefits of transcranial direct current stimulation (TDCS) treatment in patients with mild/moderate vs. severe depression

    Clinical Neuropsychiatry

    (2009)
  • F. Fregni et al.

    Transcranial direct current stimulation

    British Journal of Psychiatry

    (2005)
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