Transcranial alternating current stimulation for treating depression: a randomized controlled trial

Abstract

Treatment of depression with antidepressants is partly effective. Transcranial alternating current stimulation can provide a non-pharmacological alternative for adult patients with major depressive disorder. However, no study has used the stimulation to treat first-episode and drug-naïve patients with major depressive disorder. We used a randomized, double-blind, sham-controlled design to examine the clinical efficacy and safety of the stimulation in treating first-episode drug-naïve patients in a Chinese Han population. From 4 June 2018 to 30 December 2019, 100 patients were recruited and randomly assigned to receive 20 daily 40-min, 77.5 Hz, 15 mA, one forehead and two mastoid sessions of active or sham stimulation (n = 50 for each group) in four consecutive weeks (Week 4), and were followed for additional 4-week efficacy/safety assessment without stimulation (Week 8). The primary outcome was a remission rate defined as the 17-item Hamilton Depression Rating Scale (HDRS-17) score ≤ 7 at Week 8. Secondary analyses were response rates (defined as a reduction of ≥ 50% in the HDRS-17), changes in depressive symptoms and severity from baseline to Week 4 and Week 8, and rates of adverse events. Data were analysed in an intention-to-treat sample. Forty-nine in the active and 46 in the sham completed the study. Twenty-seven of 50 (54%) in the active treatment group and 9 of 50 (18%) in the sham group achieved remission at the end of Week 8. The remission rate was significantly higher in the active group compared to that in the sham group with a risk ratio of 1.78 (95% confidence interval, 1.29, 2.47). Compared with the sham, the active group had a significantly higher remission rate at Week 4, response rates at Weeks 4 and 8, and a larger reduction in depressive symptoms from baseline to Weeks 4 and 8. Adverse events were similar between the groups. In conclusion, the stimulation on the frontal cortex and two mastoids significantly improved symptoms in first-episode drug-naïve patients with major depressive disorder and may be considered as a non-pharmacological intervention for them in an outpatient setting.

Transcranial alternating current stimulation and its effects on cognition and the treatment of psychiatric disorders: a systematic review and meta-analysis

“…From 6353 records, 12 research papers were included in this review. 3,10,13,[22][23][24][25][26][27][28][29][30] All studies were randomised-controlled trials. This process is detailed in the PRISMA flowchart in Figure 1.…”

“…Among individuals with depression, a total of 122 participants were included in the meta-analysis (Figure 3), with 62 in the intervention group and 60 in comparators from three studies. 10,25,30 An SMD of 1.14 (95% CI: 0.10, 2.18) (random effects) with notable heterogeneity (I2 = 72%) were found in the TACS compared to the control group. Of note, Alexander et al 10 randomised 32 patients with depression to receive 40-min sessions of either TACS at 10 Hz or 40 Hz or sham stimulation for five consecutive days.…”

Adjunctive transcranial alternating current stimulation for patients with major depressive disorder: A systematic review and meta-analysis

“…The current of 15 mA used in 3 out of 4 RCTs (75%, 3/4) ( 9 – 11 ) in this meta-analysis was higher than that used in previous reports ( 8 , 30 – 32 ). Therefore, it remains unclear whether a smaller current or lower frequency can have dramatic antidepressant efficacy ( 10 ). Importantly, both alpha-tACS ( 8 , 33 ) and gamma-tACS ( 6 , 34 ) can effectively ameliorate depressive symptoms of MDD, suggesting that there are some specific gamma or alpha frequencies or other unknown frequencies that can significantly improve the symptoms of MDD ( 10 ).…”

“…Although four recent randomized, double-blind, controlled trials (RCTs) ( 8 – 11 ) have examined the feasibility, efficacy and safety of tACS in treating adult patients with MDD, the findings have been inconsistent. Two RCTs consistently reported that tACS could significantly improve depressive symptoms in first-episode drug-naïve patients suffering from MDD ( 10 , 11 ). However, in Alexander et al’s ( 8 ) study, a negative finding was observed when comparing three different conditions (10 Hz-tACS, 40 Hz-tACS and sham tACS).…”

Neurostimulation as a treatment for mood disorders in patients: recent findings

“…Unlike tDCS, which uses direct current, tACS involves applying alternating currents on the scalp to stimulate the cortex and regulate its excitability. tACS appears to have a significant antidepressant effect when current is applied over the frontal region and both mastoid regions in an 8-week protocol [23]. The left dlPFC plays a key role in positive emotions and it is sometimes affected by disorders that lead to increased alpha oscillations in EEG.…”