Double-blind, randomized pilot clinical trial targeting alpha oscillations with transcranial alternating current stimulation (tACS) for the treatment of major depressive disorder (MDD).

Major depressive disorder (MDD) is one of the most common psychiatric disorders, but pharmacological treatments are ineffective in a substantial fraction of patients and are accompanied by unwanted side effects. Here we evaluated the feasibility and efficacy of transcranial alternating current stimulation (tACS) at 10 Hz, which we hypothesized would improve clinical symptoms by renormalizing alpha oscillations in the left dorsolateral prefrontal cortex (dlPFC). To this end, 32 participants with MDD were randomized to 1 of 3 arms and received daily 40 min sessions of either 10 Hz-tACS, 40 Hz-tACS, or active sham stimulation for 5 consecutive days. Symptom improvement was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) as the primary outcome. High-density electroencephalograms (hdEEGs) were recorded to measure changes in alpha oscillations as the secondary outcome. For the primary outcome, we did not observe a significant interaction between treatment condition (10 Hz-tACS, 40 Hz-tACS, sham) and session (baseline to 4 weeks after completion of treatment); however, exploratory analyses show that 2 weeks after completion of the intervention, the 10 Hz-tACS group had more responders (MADRS and HDRS) compared with 40 Hz-tACS and sham groups (n = 30, p = 0.026). Concurrently, we found a significant reduction in alpha power over the left frontal regions in EEG after completion of the intervention for the group that received per-protocol 10 Hz-tACS (n = 26, p < 0.05). Our data suggest that targeting oscillations with tACS has potential as a therapeutic intervention for treatment of MDD.

Randomized trial of transcranial alternating current stimulation for treatment of auditory hallucinations in schizophrenia.

BACKGROUND: Approximately 30% of patients with schizophrenia experience auditory hallucinations that are refractory to antipsychotic medications. Here, we evaluated the feasibility and efficacy of transcranial alternating current stimulation (tACS) that we hypothesized would improve auditory hallucination symptoms by enhancing synchronization between the frontal and temporo-parietal areas of the left hemisphere. METHOD: 22 participants were randomized to one of three arms and received twice daily, 20 min sessions of sham, 10 Hz 2 mA peak-to-peak tACS, or 2 mA tDCS over the course of 5 consecutive days. Symptom improvement was assessed using the Auditory Hallucination Rating Scale (AHRS) as the primary outcome measure. The Positive and Negative Syndrome Scale (PANSS) and the Brief Assessment of Cognition in Schizophrenia (BACS) were secondary outcomes. RESULTS: Primary and secondary behavioral outcomes were not significantly different between the three arms. However, effect size analyses show that tACS had the greatest effect based on the auditory hallucinations scale for the week of stimulation (1.31 for tACS; 1.06 and 0.17, for sham and tDCS, respectively). Effect size analysis for the secondary outcomes revealed heterogeneous results across measures and stimulation conditions. CONCLUSIONS: To our knowledge, this is the first clinical trial of tACS for the treatment of symptoms of a psychiatric condition. Further studies with larger sample sizes are needed to better understand the effect of tACS on auditory hallucinations.