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

Abstract

ObjectiveWe performed a meta-analysis of randomized, double-blind, controlled trials (RCTs) to systematically investigate the therapeutic effects and tolerability of transcranial alternating current stimulation (tACS) for the treatment of patients with major depressive disorder (MDD).MethodsElectronic search of PubMed, PsycINFO, EMBASE, Chinese National Knowledge Infrastructure, Wanfang database, and the Cochrane Library up to 1 April 2022. Double-blind RCTs examining the efficacy and safety of tACS for patients with MDD were included. The primary outcome was the improvement of depressive symptoms following a course of tACS treatment. Data were analyzed using Review Manager Version 5.3 (Cochrane IMS, Oxford, UK). Study quality was assessed using the Cochrane risk of bias and Jadad scale. Publication bias was assessed using a funnel plot and the Egger test.ResultsWe identified 883 articles, of which 4 RCTs with 5 active treatment arms covering 224 participants with MDD on active tACS (n = 117) and sham tACS (n = 107) were eligible for inclusion. Meta-analysis of depressive symptoms at post-tACS found an advantage of active tACS over sham tACS (n = 212, standard mean difference (SMD) = −1.14, 95% confidence interval (CI): −2.23, −0.06; I2 = 90%, P = 0.04). The significant superiority of active tACS over sham tACS in improving depressive symptoms remained in a sensitivity analysis. Active tACS was significantly superior to sham tACS regarding depressive symptoms at the 4 week follow-up (SMD = −1.07, 95% CI: −2.05, −0.08; I2 = 88%, P = 0.03) and study-defined remission [risk ratio (RR) = 2.07, 95% CI: 1.36, 3.14, I2 = 9%, P = 0.0006]. The discontinuation rate due to any reason was similar between the two groups (P > 0.05). All included studies were rated as high quality (Jadad score ≥ 3), with funnel plots of primary outcome not suggestive of publication bias.ConclusiontACS appeared to be modestly effective and safe for improving depressive symptoms in patients with MDD, although further studies are warranted.

Transcranial alternating current stimulation for schizophrenia: a systematic review of randomized controlled studies

“…The findings from this meta-analysis suggest that tACS could be a viable non-pharmacological intervention for individuals with schizophrenia. Beyond its effectiveness in improving total and negative psychopathology of schizophrenia, tACS has been explored as a treatment for major depression (MDD) ( 45 ), chronic insomnia ( 46 ), attention deficit hyperactivity disorder (ADHD) ( 47 ), and pain disorders ( 48 ). For instance, a recent meta-analysis has determined that tACS effectively alleviates depression symptoms in individuals with MDD ( 45 ) while ensuring safety.…”

“…Beyond its effectiveness in improving total and negative psychopathology of schizophrenia, tACS has been explored as a treatment for major depression (MDD) ( 45 ), chronic insomnia ( 46 ), attention deficit hyperactivity disorder (ADHD) ( 47 ), and pain disorders ( 48 ). For instance, a recent meta-analysis has determined that tACS effectively alleviates depression symptoms in individuals with MDD ( 45 ) while ensuring safety. Furthermore, a systematic review of RCTs ( n = 73) has demonstrated tACS as an effective and safe therapeutic approach for chronic insomnia ( 46 ).…”

“…Importantly, as compared with tDCS, tACS seemed to cause fewer adverse effects ( 58 ). Therefore, tACS has been also proven as a safe intervention for patients suffering from MDD ( 45 ), chronic insomnia ( 46 ), and healthy participants ( 59 ).…”

Efficacy and safety of intermittent theta burst stimulation versus high-frequency repetitive transcranial magnetic stimulation for patients with treatment-resistant depression: a systematic review

“…Noninvasive brain stimulation techniques, such as transcranial magnetic stimulation (TMS) ( 10 ), transcranial direct current stimulation (tDCS) ( 11 ), and transcranial alternating current stimulation (tACS) ( 12 ), provide a nonpharmacological alternative for MDD. High-frequency (≥ 5 Hz) repetitive transcranial magnetic stimulation (HF-rTMS) was approved by the Food and Drug Administration (FDA) as a noninvasive brain stimulation technique for TRD in 2008 ( 13 ).…”

Stanford neuromodulation therapy for treatment-resistant depression: a systematic review

“…Furthermore, a real-world study found a significant reduction of depressive symptoms in patients suffering from TRD after receiving esketamine nasal spray (5). Apart from antidepressant medication, strategies such as vagus nerve stimulation (6), electroconvulsive therapy (7,8), transcranial alternating current stimulation (9), and transcranial magnetic stimulation (TMS) [e.g., deep TMS (10), accelerated TMS (11), intermittent theta-burst stimulation (iTBS) (12), accelerated iTBS (13), bilateral TBS (14), and continuation TBS (15)], have been developed as a nonpharmacological alternative for the treatment of MDD.…”