Transcranial direct current stimulation (tDCS) is a safe and effective add-on therapy for type I or II bipolar depression, researchers found.
In an intention-to-treat analysis of 52 patients in the randomized, double-blind, Bipolar Depression Electrical Treatment Trial (BETTER), active tDCS had significantly greater antidepressive effects than a sham procedure (differential effect size of −1.68 with a number needed to treat of 5.8, P=0.01), André Russowsky Brunoni, MD, PhD, of the University of São Paulo in Brazil, and colleagues reported online in JAMA Psychiatry.
“We were excited to show evidence that tDCS can be clinically effective for this population,” Brunoni told MedPage Today, adding that in their study, the rate of treatment-emergent affective switches (TEAS) was similar between groups. “Nonetheless,” he said, “I would recommend extra caution when applying tDCS for bipolar depressed patients who frequently present manic switches.”
The study of tDCS was devised as an add-on trial in patients with bipolar depression receiving a stable pharmacologic regimen in the sham-controlled BETTER trial, which was conducted from July 1, 2014, to March 30, 2016. A parallel design was used to randomly assign 59 patients to either sham or active tDCS.
All patients had type I or II bipolar disorder with a major depressive episode and were receiving a stable pharmacologic regimen with Hamilton Depression Rating Scale-17 (HDRS-17) scores scores higher than 17. There was also a high prevalence of comorbid anxiety disorders in the study population. A third of patients had experienced an acute depressive episode that was unresponsive to at least two treatment regimens.
Of the 59 patients, a total of 52 (26 active and 26 sham) received all 12 tDCS treatment sessions. This included 10 daily 30-minute sessions of active or sham tDCS on weekdays and then one session every 2 weeks until week 6.
Participants lay in comfortable reclining chairs while scalp electrodes delivered weak, direct currents into the dorsolateral prefrontal cortex (DLPFC) region of the brain — an area responsible for cognitive control and emotion regulation, which is hypoactive in depression. Patients were allowed to read or use their smartphones but not sleep. Talking with staff was minimal.
As for secondary outcomes, the researchers found 19 patients in the active group and eight patients in the sham group achieved sustained response, with significantly greater effects for the tDCS group (HR 2.86, 95% CI 1.25 to 6.61, P=0.01) and a number needed to treat of 2.69.
Similarly, 10 active-group patients and five sham-treated patients achieved sustained remission, though benefit wasn’t significantly greater for tDCS in further analyses.
Adverse events, including TEAS leading to manic or hypomanic episodes, were similar between active and sham tDCS. Patients receiving active treatment had more localized skin redness than those receiving sham (54% versus 19%, P=0.01) but these effects were short-lived, and didn’t result in any study discontinuations, or affect blinding.
Brunoni and colleagues concluded that their results suggest tDCS is an “effective and tolerable add-on treatment in this subsample of patients with type I or II bipolar disorder who were in a major depressive episode … Although preliminary, our results are promising and encourage further trials to examine the efficacy of tDCS in a large bipolar disorder sample.”
They noted that since tDCS effects are subtle, as they induce “small changes in the membrane potential, greater effects may be achieved when simultaneously combining tDCS with other treatments such as pharmacotherapy, other brain stimulation therapy, or psychotherapy. Therefore, different tDCS protocols, particularly combination therapies, could be explored in further studies.”
Recently, the research group published a large non-inferiority trial investigating tDCS efficacy in unipolar depression, and just completed a trial testing tDCS efficacy for schizophrenia. A trial looking at the efficacy of using tDCS in obsessive-compulsive disorder is underway, Brunoni said.
“Our next steps will be to better understand the mechanisms of action of tDCS,” he said, “using it in combination with neuroimaging techniques such as spectroscopy and resting state MRI.”