International randomized-controlled trial of transcranial Direct Current Stimulation in depression

Loo, Colleen; Husain, Mustafa M.; McDonald, William M.; Aaronson, Scott T.; O’Reardon, John P.; Alonzo, Angelo; Weickert, Cynthia Shannon; Martin, Donel; McClintock, Shawn M.; Mohan, Adith; Lisanby, Sarah H.

doi:10.1016/j.brs.2017.10.011

Cited by 174 publications

(137 citation statements)

References 28 publications

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“…As evidence has shown that the highest cortical current density in tDCS might not be induced directly under the target electrode, the spatial focality of conventional tDCS thus remains questionable. This implies that the treatment efficacy of tDCS could be adversely affected, which might also explain the discrepancy in previous findings …”

Section: Introductionmentioning

confidence: 64%

“…This lends support for tDCS's treatment potential for those with LLD as a monotherapy or augmentation with antidepressants. However, it should be noted that controversial findings observed no antidepressant differences between active and sham tDCS for depression …”

Section: Introductionmentioning

confidence: 93%

“…A 4 × 1 ring set‐up would be the most typical design, whereby a central anodal electrode is surrounded by four return cathodal electrodes. The density of the cortical field and spatial focality can be adjusted by altering the diameter of the ring set‐up . Other strengths of HD‐tDCS over tDCS include longer lasting treatment effects due to a more precise cortical field and better tolerability .…”

Section: Introductionmentioning

confidence: 99%

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High‐definition transcranial direct current stimulation—An open‐label pilot intervention in alleviating depressive symptoms and cognitive deficits in late‐life depression

et al. 2019

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The efficacy of high‐definition transcranial direct current stimulation (HD‐tDCS) in late‐life depression (LLD) remains unknown due to limited research on its therapeutic effects on the hallmarks of LLD—the depressive and cognitive symptoms. The present open‐label pilot study aimed to examine the effectiveness of HD‐tDCS as an augmentation therapy with antidepressants in improving the depressive and cognitive symptoms for LLD. Significant improvements were hypothesized in the depressive, cognitive, and daily functioning outcomes over time. A total of 15 subjects with LLD (13 females, mean age = 73.27 ± 6.25) received five consecutive daily sessions of 20‐minute active HD‐tDCS interventions weekly for 2 weeks, with a 2 mA anodal stimulation over F3 and cathodal stimulation over FC1, AF3, F7, and FC5. Depressive symptoms and cognitive and daily functioning were assessed across five assessment timepoints. The results revealed that the HD‐tDCS was effective in reducing the depressive severity and the remission rates, with a sustained effect at both the 1‐month and 3‐month follow‐up. Pre‐post improvements were seen in the overall cognitive functioning and in verbal fluency, but not in executive functioning. Our pilot study provides a preliminary result of HD‐tDCS in LLD, which was a safe and effective treatment in alleviating depressive symptoms, with mild cognitive improvements observed. Further larger scale randomized controlled trials are needed to confirm this result.

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Section: Introductionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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High‐definition transcranial direct current stimulation—An open‐label pilot intervention in alleviating depressive symptoms and cognitive deficits in late‐life depression

et al. 2019

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“…Given the relatively short time span of the three testing time points (baseline, follow‐up at 4 weeks, follow‐up at 8 weeks), it is possible that improved neurocognitive outcome scores could have been related to practice effects (Beglinger et al, 2005). Notwithstanding, the observed effects were independent of the significant mood improvements that occurred in both the unipolar and bipolar samples (Loo et al, 2018). Of the participants enrolled in the study, only 36 were diagnosed with bipolar disorder, which may have minimized statistical power to detect changes in neurocognitive functions.…”

Section: Discussionmentioning

confidence: 86%

“…With regard to specific domains of function related to depression, tDCS may be useful in treating psychomotor retardation and dysphoria symptoms (Alonzo, Chan, Martin, Michell, & Loo, 2013; D'Urso et al, 2017), and has been shown to restore impaired neuroplasticity in patients with depression (Player et al, 2013; Player et al, 2014). We recently reported the antidepressant results of our international, randomized controlled clinical trial in which patients with major depressive disorder or bipolar disorder were randomized to active or “sham” tDCS (Loo et al, 2018). The study found significant improvements in mood in both active and sham conditions across the 4‐week treatment period, though there were no differences between groups.…”

Section: Introductionmentioning

confidence: 99%

Neurocognitive effects of transcranial direct current stimulation (tDCS) in unipolar and bipolar depression: Findings from an international randomized controlled trial

et al. 2020

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Objective Transcranial direct current stimulation (tDCS) has been found to have antidepressant effects and may have beneficial neurocognitive effects. However, prior research has produced an unclear understanding of the neurocognitive effects of repeated exposure to tDCS. The study's aim was to determine the neurocognitive effects following tDCS treatment in participants with unipolar or bipolar depression. Method The study was a triple‐masked, randomized, controlled clinical trial across six international academic medical centers. Participants were randomized to high dose (2.5 mA for 30 min) or low dose (0.034 mA, for 30 min) tDCS for 20 sessions over 4 weeks, followed by an optional 4 weeks of open‐label high dose treatment. The tDCS anode was centered over the left dorsolateral prefrontal cortex at F3 (10/20 EEG system) and the cathode over F8. Participants completed clinical and neurocognitive assessments before and after tDCS. Genotype (BDNF Val66Met and catechol‐o‐methyltransferase [COMT] Val158Met polymorphisms) were explored as potential moderators of neurocognitive effects. Results The study randomized 130 participants. Across the participants, tDCS treatment (high and low dose) resulted in improvements in verbal learning and recall, selective attention, information processing speed, and working memory, which were independent of mood effects. Similar improvements were observed in the subsample of participants with bipolar disorder. There was no observed significant effect of tDCS dose. However, BDNF Val66Met and COMT Val158Met polymorphisms interacted with tDCS dose and affected verbal memory and verbal fluency outcomes, respectively. Conclusions These findings suggest that tDCS could have positive neurocognitive effects in unipolar and bipolar depression. Thus, tDCS stimulation parameters may interact with interindividual differences in BDNF and COMT polymorphisms to affect neurocognitive outcomes, which warrants further investigation.

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Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation Across Mental Disorders

Sabé,

Hyde,

Cramer

et al. 2024

JAMA Netw Open

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ImportanceNoninvasive brain stimulation (NIBS) interventions have been shown to be efficacious in several mental disorders, but the optimal dose stimulation parameters for each disorder are unknown.ObjectiveTo define NIBS dose stimulation parameters associated with the greatest efficacy in symptom improvement across mental disorders.Data SourcesStudies were drawn from an updated (to April 30, 2023) previous systematic review based on a search of PubMed, OVID, and Web of Knowledge.Study SelectionRandomized clinical trials were selected that tested transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) for any mental disorder in adults aged 18 years or older.Data Extraction and SynthesisTwo authors independently extracted the data. A 1-stage dose-response meta-analysis using a random-effects model was performed. Sensitivity analyses were conducted to test robustness of the findings. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.Main Outcomes and MeasuresThe main outcome was the near-maximal effective doses of total pulses received for TMS and total current dose in coulombs for tDCS.ResultsA total of 110 studies with 4820 participants (2659 men [61.4%]; mean [SD] age, 42.3 [8.8] years) were included. The following significant dose-response associations emerged with bell-shaped curves: (1) in schizophrenia, high-frequency (HF) TMS on the left dorsolateral prefrontal cortex (LDLPFC) for negative symptoms (χ2 = 9.35; df = 2; P = .009) and TMS on the left temporoparietal junction for resistant hallucinations (χ2 = 36.52; df = 2; P &lt; .001); (2) in depression, HF-DLPFC TMS (χ2 = 14.49; df = 2; P &lt; .001); (3) in treatment-resistant depression, LDLPFC tDCS (χ2 = 14.56; df = 2; P &lt; .001); and (4) in substance use disorder, LDLPFC tDCS (χ2 = 33.63; df = 2; P &lt; .001). The following significant dose-response associations emerged with plateaued or ascending curves: (1) in depression, low-frequency (LF) TMS on the right DLPFC (RDLPFC) with ascending curve (χ2 = 25.67; df = 2; P = .001); (2) for treatment-resistant depression, LF TMS on the bilateral DLPFC with ascending curve (χ2 = 5.86; df = 2; P = .004); (3) in obsessive-compulsive disorder, LF-RDLPFC TMS with ascending curve (χ2 = 20.65; df = 2; P &lt; .001) and LF TMS on the orbitofrontal cortex with a plateaued curve (χ2 = 15.19; df = 2; P &lt; .001); and (4) in posttraumatic stress disorder, LF-RDLPFC TMS with ascending curve (χ2 = 54.15; df = 2; P &lt; .001). Sensitivity analyses confirmed the main findings.Conclusions and RelevanceThe study findings suggest that NIBS yields specific outcomes based on dose parameters across various mental disorders and brain regions. Clinicians should consider these dose parameters when prescribing NIBS. Additional research is needed to prospectively validate the findings in randomized, sham-controlled trials and explore how other parameters contribute to the observed dose-response association.

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International randomized-controlled trial of transcranial Direct Current Stimulation in depression

Cited by 174 publications

References 28 publications

High‐definition transcranial direct current stimulation—An open‐label pilot intervention in alleviating depressive symptoms and cognitive deficits in late‐life depression

High‐definition transcranial direct current stimulation—An open‐label pilot intervention in alleviating depressive symptoms and cognitive deficits in late‐life depression

Neurocognitive effects of transcranial direct current stimulation (tDCS) in unipolar and bipolar depression: Findings from an international randomized controlled trial

Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation Across Mental Disorders

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