ReviewTranscranial direct current stimulation (tDCS) in the treatment of depression: Systematic review and meta-analysis of efficacy and tolerability
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)
- et al.
Improving working memory: the effect of combining cognitive activity and anodal transcranial direct current stimulation to the left dorsolateral prefrontal cortex
Brain Stimul.
(2011) - et al.
Pilot study of feasibility of the effect of treatment with tDCS in patients suffering from treatment-resistant depression treated with escitalopram
Clin. Neurophysiol.
(2015) - et al.
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
J. Psychiatr. Res.
(2013) - et al.
Sertraline vs. electrical current therapy for treating depression clinical trial—SELECT TDCS: design, rationale and objectives
Contemp. Clin. Trials
(2011) - et al.
Transcranial direct current stimulation (tDCS) in unipolar vs. bipolar depressive disorder
Prog. Neuropsychopharmacol. Biol. Psychiatry
(2011) - et al.
Clinical research with transcranial direct current stimulation (tDCS): challenges and future directions
Brain Stimul.
(2012) - et al.
Transcranial direct current stimulation for the treatment of major depressive disorder: a summary of preclinical, clinical and translational findings
Prog. Neuropsychopharmacol. Biol. Psych.
(2012) - et al.
Cognitive control therapy and transcranial direct current stimulation for depression: a randomized, double-blinded, controlled trial
J. Affect. Disord.
(2014) - et al.
Background and rationale for the sequenced treatment alternatives to relieve depression (STAR*D) study
PSC
(2003) - et al.
Fronto-extracephalic transcranial direct current stimulation as a treatment for major depression: an open-label pilot study
J. Affect. Disord.
(2011)
Treatment of depression with transcranial direct current stimulation (tDCS): a review
Exp. Neurol.
Skin lesions after treatment with transcranial direct current stimulation (tDCS)
Brain Stimul.
No health without mental health
Lancet
Repetitive transcranial magnetic stimulation or transcranial direct current stimulation?
Brain Stimul.
tDCS possibly stimulates glial cells
Clin. Neurophysiol.
Concurrent cognitive control training augments the antidepressant efficacy of tDCS: a pilot study
Brain Stimul.
Transcranial direct current stimulation influences probabilistic association learning in schizophrenia
Schizophr. Res.
Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2000 British Association for Psychopharmacology guidelines
J. Psychopharmacol.
A randomized double-blind sham-controlled study of transcranial direct current stimulation for treatment-resistant major depression
Front Psychiatry
A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation for the treatment of major depression
Int. J. Neuropsychopharmacol.
A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation
Int. J. Neuropsychopharmacol.
The sertraline vs electrical current therapy for treating depression clinical study
JAMA Psychiatry
Methodological Standards for the Conduct of New Cochrane Intervention Reviews Version 2.1
Understanding the New Statistics
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