IMPORTANCE: Transcranial direct current stimulation (tDCS) trials for major depressive disorder (MDD) have shown positive but mixed results. OBJECTIVE: To assess the combined safety and efficacy of tDCS vs a common pharmacological treatment (sertraline hydrochloride, 50 mg/d). DESIGN: Double-blind, controlled trial. Participants were randomized using a 2 × 2 factorial design to sertraline/placebo and active/sham tDCS. SETTING: Outpatient, single-center academic setting in São Paulo, Brazil. PARTICIPANTS: One hundred twenty antidepressant-free patients with moderate to severe, nonpsychotic, unipolar MDD. INTERVENTIONS: Six-week treatment of 2-mA anodal left/cathodal right prefrontal tDCS (twelve 30-minute sessions: 10 consecutive sessions once daily from Monday to Friday plus 2 extra sessions every other week) and sertraline hydrochloride (50 mg/d). MAIN OUTCOME MEASURES In this intention-to-treat analysis, the primary outcome measure was the change in Montgomery-Asberg depression rating scale score at 6 weeks (end point). We considered a difference of at least 3 points to be clinically relevant. The analysis plan was previously published. Safety was measured with an adverse effects questionnaire, the young mania rating scale, and cognitive assessment. Secondary measures were rates of clinical response and remission and scores on other scales. RESULTS: At the main end point, there was a significant difference in Montgomery-Asberg depression rating scale scores when comparing the combined treatment group (sertraline/active tDCS) vs sertraline only (mean difference, 8.5 points; 95% CI, 2.96 to 14.03; P = .002), tDCS only (mean difference, 5.9 points; 95% CI, 0.36 to 11.43; P = .03), and placebo/shamtDCS (mean difference, 11.5 points; 95% CI, 6.03 to 17.10; P < .001). Analysis of tDCS only vs sertraline only presented comparable efficacies (mean difference, 2.6 points; 95% CI, -2.90 to 8.13; P = .35). Use of tDCS only (but not sertraline only) was superior to placebo/shamtDCS. Common adverse effects did not differ between interventions, except for skin redness on the scalp in active tDCS (P = .03). There were 7 episodes of treatment-emergent mania or hypomania, 5 occurring in the combined treatment group. CONCLUSIONS AND RELEVANCE: In MDD, the combination of tDCS and sertraline increases the efficacy of each treatment. The efficacy and safety of tDCS and sertraline did not differ. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01033084.
RCT Entities:
IMPORTANCE: Transcranial direct current stimulation (tDCS) trials for major depressive disorder (MDD) have shown positive but mixed results. OBJECTIVE: To assess the combined safety and efficacy of tDCS vs a common pharmacological treatment (sertraline hydrochloride, 50 mg/d). DESIGN: Double-blind, controlled trial. Participants were randomized using a 2 × 2 factorial design to sertraline/placebo and active/sham tDCS. SETTING:Outpatient, single-center academic setting in São Paulo, Brazil. PARTICIPANTS: One hundred twenty antidepressant-free patients with moderate to severe, nonpsychotic, unipolar MDD. INTERVENTIONS: Six-week treatment of 2-mA anodal left/cathodal right prefrontal tDCS (twelve 30-minute sessions: 10 consecutive sessions once daily from Monday to Friday plus 2 extra sessions every other week) and sertraline hydrochloride (50 mg/d). MAIN OUTCOME MEASURES In this intention-to-treat analysis, the primary outcome measure was the change in Montgomery-Asberg depression rating scale score at 6 weeks (end point). We considered a difference of at least 3 points to be clinically relevant. The analysis plan was previously published. Safety was measured with an adverse effects questionnaire, the young mania rating scale, and cognitive assessment. Secondary measures were rates of clinical response and remission and scores on other scales. RESULTS: At the main end point, there was a significant difference in Montgomery-Asberg depression rating scale scores when comparing the combined treatment group (sertraline/active tDCS) vs sertraline only (mean difference, 8.5 points; 95% CI, 2.96 to 14.03; P = .002), tDCS only (mean difference, 5.9 points; 95% CI, 0.36 to 11.43; P = .03), and placebo/sham tDCS (mean difference, 11.5 points; 95% CI, 6.03 to 17.10; P < .001). Analysis of tDCS only vs sertraline only presented comparable efficacies (mean difference, 2.6 points; 95% CI, -2.90 to 8.13; P = .35). Use of tDCS only (but not sertraline only) was superior to placebo/sham tDCS. Common adverse effects did not differ between interventions, except for skin redness on the scalp in active tDCS (P = .03). There were 7 episodes of treatment-emergent mania or hypomania, 5 occurring in the combined treatment group. CONCLUSIONS AND RELEVANCE: In MDD, the combination of tDCS and sertraline increases the efficacy of each treatment. The efficacy and safety of tDCS and sertraline did not differ. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01033084.
Authors: M Bauer; T Banaschewski; A Heinz; I Kamp-Becker; A Meyer-Lindenberg; F Padberg; M A Rapp; R Rupprecht; F Schneider; T G Schulze; H-U Wittchen Journal: Nervenarzt Date: 2016-09 Impact factor: 1.214
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