Review
Transcranial direct current stimulation (tDCS) in the treatment of depression: Systematic review and meta-analysis of efficacy and tolerability

https://doi.org/10.1016/j.neubiorev.2015.07.012Get rights and content

Highlights

  • We identified 10 RCTs (N = 393) of tDCS as treatment for MDE.

  • tDCS was superior to sham tDCS (k = 11, g = 0.30, 95% CI = [0.04, 0.57], p = 0.027).

  • N = 346 to detect (80% power) this effect (N = 49/N = 12693 for bounds of CI).

  • Current data do not support the use of tDCS in treatment resistant depression.

  • Larger studies over longer periods of treatment are needed.

Abstract

Background

Transcranial direct current stimulation (tDCS) is a potential alternative treatment option for major depressive episodes (MDE).

Objectives

We address the efficacy and safety of tDCS in MDE.

Methods

The outcome measures were Hedges’ g for continuous depression ratings, and categorical response and remission rates.

Results

A random effects model indicated that tDCS was superior to sham tDCS (k = 11, N = 393, g = 0.30, 95% CI = [0.04, 0.57], p = 0.027). Adjunctive antidepressant medication and cognitive control training negatively impacted on the treatment effect. The pooled log odds ratios (LOR) for response and remission were positive, but statistically non-significant (response: k = 9, LOR = 0.36, 95% CI[−0.16, 0.88], p = 0.176, remission: k = 9, LOR = 0.25, 95% CI [−0.42, 0.91], p = 0.468). We estimated that for a study to detect the pooled continuous effect (g = 0.30) at 80% power (alpha = 0.05), a total N of at least 346 would be required (with the total N required to detect the upper and lower bound being 49 and 12,693, respectively).

Conclusions

tDCS may be efficacious for treatment of MDE. The data do not support the use of tDCS in treatment-resistant depression, or as an add-on augmentation treatment. Larger studies over longer treatment periods are needed.

Section snippets

Background

Depressive disorders are prevalent, recurrent, often run a chronic course, and are associated with significant worldwide morbidity and mortality (Kessler et al., 2003, Prince et al., 2007). Treatment with antidepressant medication is often suboptimal in terms of efficacy, safety and tolerability (Rush et al., 2006, Anderson et al., 2008). Psychological interventions are associated with significant rates of suboptimal effectiveness, even when combined with antidepressant medication (NICE, 2009).

Method

A literature search and meta analysis were conducted following the recommendations of the Cochrane collaboration (Chandler et al., 2011) and the PRISMA guidelines (Liberati et al., 2009). Two authors (DM and NH) performed the systematic review and data extraction. All discrepancies were resolved by consensus.

Randomised controlled trials (RCTs)

We identified ten randomised controlled trials of tDCS in depression using PRISMA methodology (Fig. 1a), and quality-assessed each trial using the Cochrane Collaboration's tool for assessing risk of bias in randomised trials (Higgins et al., 2011)—this yielded an acceptable profile of Risk of Bias across the RCTs included in the meta-analysis (Fig. 1b). Due to the diversity of study designs, we made the following decisions about the analysis of individual studies: (1) Boggio et al. (2008)

Current meta-analysis: Continuous treatment effects

Across all studies the combined treatment effect was significant and consistent with a small effect size (k = 11, g = 0.30, 95% CI = [0.04, 0.57], p = 0.027)(see Fig. 2a). The ‘probability of superiority’ metric (Loo et al., 2010) indicated a 62% chance that a randomly sampled individual receiving active tDCS would have a greater reduction in depressive symptoms than a randomly sampled individual receiving sham tDCS 95% CI [52% 72%]. A ‘leave one out’ analysis revealed that removing Boggio et al. (2008)

Current meta-analysis: Categorical treatment effects (response and remission rates)

Data for response rates were available from 9 of the 11 effects (Fig. 3a). The pooled LOR for response was positive, but did not reach significance (k = 9, LOR = 0.36, 95% CI[−0.16, 0.88], p = 0.176), Heterogeneity between studies did not exceed that expected by chance (Q (8) = 6.18, p = 0.627) and the I2 statistic indicated that only 0.86% of the heterogeneity could not be explained by sampling error. Cumulative meta-analysis revealed that the meta-analytic combination of effects yielded an increase of

Current meta-analysis: Safety and tolerability

Dropout rates were available from nine studies (Table 5) and were analysed in a random effects model using the log odds ratio as an effect size measure (effect sizes greater than 0 indicate a greater likelihood of dropout in the active relative to the sham tDCS group). The analysis revealed no significant differences in drop out rates (k = 9 LOR = 0.05, 95% CI = [−1.0, 1.10], p = 0.928).

Discussion

We carried out a meta analysis of 10 RCTs comparing active tDCS to sham tDCS, including 393 participants with major depressive episodes in the context of unipolar or bipolar disorders. tDCS was used as mono therapy or as adjunctive treatment for depression in conjunction with medication and/or cognitive control training (CCT). Analysis of continuous outcomes—depression rating scale scores, demonstrates clear superiority of active tDCS over sham tDCS in the treatment of MDE. The combined

Limitations

The main limitation of this meta analysis is the low number of participants in most included trials. As demonstrated by our precision and power calculations, all but one of these trials (Brunoni, 2013) are probably underpowered. This is likely to explain the lack of separation between active and sham tDCS in terms of categorical response and remission outcomes; as well as limiting the number of moderators reaching statistical significance. There is a lack of evidence regarding longer-term

Conclusions

Based on current evidence, the following conclusions may be drawn: First, tDCS may represent an effective treatment option for patients presenting with major depressive episodes. Second, tDCS offers a generally acceptable tolerability profile, which may make it a useful alternative to antidepressant medication in patients who do not wish to take medication and for those who cannot tolerate antidepressant medication. Third, the current body of evidence does not support the use of tDCS in

Conflict of interest disclosures

None declared.

Funding sources

None declared.

References (49)

  • M.A. Nitsche et al.

    Treatment of depression with transcranial direct current stimulation (tDCS): a review

    Exp. Neurol.

    (2009)
  • U. Palm et al.

    Skin lesions after treatment with transcranial direct current stimulation (tDCS)

    Brain Stimul.

    (2008)
  • M. Prince et al.

    No health without mental health

    Lancet

    (2007)
  • A. Priori et al.

    Repetitive transcranial magnetic stimulation or transcranial direct current stimulation?

    Brain Stimul.

    (2009)
  • J. Ruohonen et al.

    tDCS possibly stimulates glial cells

    Clin. Neurophysiol.

    (2012)
  • R.A. Segrave et al.

    Concurrent cognitive control training augments the antidepressant efficacy of tDCS: a pilot study

    Brain Stimul.

    (2014)
  • A. Vercammen et al.

    Transcranial direct current stimulation influences probabilistic association learning in schizophrenia

    Schizophr. Res.

    (2011)
  • I. Anderson et al.

    Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2000 British Association for Psychopharmacology guidelines

    J. Psychopharmacol.

    (2008)
  • D.M. Blumberger et al.

    A randomized double-blind sham-controlled study of transcranial direct current stimulation for treatment-resistant major depression

    Front Psychiatry

    (2012)
  • 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

    Int. J. Neuropsychopharmacol.

    (2008)
  • A.R. Brunoni et al.

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

    Int. J. Neuropsychopharmacol.

    (2011)
  • A.R. Brunoni

    The sertraline vs electrical current therapy for treating depression clinical study

    JAMA Psychiatry

    (2013)
  • J. Chandler et al.

    Methodological Standards for the Conduct of New Cochrane Intervention Reviews Version 2.1

    (2011)
  • G. Cumming

    Understanding the New Statistics

    (2012)
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