Cognitive control therapy and transcranial direct current stimulation for depression: A randomized, double-blinded, controlled trial

Abstract

Background: Based on findings that major depressive disorder (MDD) is associated to decreased dorsolateral prefrontal cortical (DLPFC) activity; interventions that increase DLPFC activity might theoretically present antidepressant effects. Two of them are cognitive control therapy (CCT), a neurobehavioral intervention that uses computer-based working memory exercises, and transcranial direct current stimulation (tDCS), which delivers weak, electric direct currents over the scalp. Methods:We investigated whether tDCS enhanced the effects of CCT in a double-blind trial, in which participants were randomized to sham tDCS and CCT (n=17) vs. active tDCS and CCT (n=20). CCT and tDCS were applied for 10 consecutive workdays. Clinicaltrials.gov identifier:NCT01434836.Results: Both CCT alone and combined with tDCS ameliorated depressive symptoms after the acute treatment period and at follow-up, with a response rate of approximately 25%. Older patients and those who presented better performance in the task throughout the trial (possibly indicating greater engagement and activation of the DLPFC) had greater depression improvement in the combined treatment group.Limitations: Our exploratory findings should be further confirmed in prospective controlled trials.Discussion: CCT and tDCS combined might be beneficial for older depressed patients, particularly for thosewho have cognitive resources to adequately learn and improve task performance over time.This combined therapy might be specifically relevant in this subgroup that is more prone to present cognitive decline and prefrontal cortical atrophy. KeywordsMajor depressive disorder; transcranial direct current stimulation; control cognitive therapy; noninvasive brain stimulation; randomized clinical trial; geriatric depression. 3

Transcranial electric stimulation and neurocognitive training in clinically depressed patients: A pilot study of the effects on rumination

“…Although the PASAT is known to induce frustration and negative self-referential thoughts (Siegle et al, 2007;2014), the individually adapted speed keeps the task tolerable for depressed participants.…”

“…As a result, working memory is trained in an emotional task context, which suggests that both the frontocingulate and limbic circuits are activated. Clinically depressed patients who received daily sessions (for two weeks) of this latter CCT showed a greater decrease in rumination than patients who had only received treatment as usual (Siegle et al, 2007;2014). Moreover, using functional magnetic resonance imaging (fMRI), patients demonstrated enhanced prefrontal activity during a digit sorting task and decreased amygdala activity during a personal relevance rating task after (as compared to before) the CCT (Siegle et al, 2007).…”

Strategies for replacing non-invasive brain stimulation sessions: recommendations for designing neurostimulation clinical trials

“…Three out of fifteen articles on tDCS reported the occurrence of missed neurostimulation visits [7,20]. defined participants who missed three or more consecutive neurostimulation visits out of 12 (25% of missed visits) as drop-outs [7].…”

“…Regarding the studies on tDCS in depression, missed neurostimulation visits were only replaced at the end of the treatment period in three trials [7,20,21]. In , only about 40% of the participants received the full intervention as designed, while about 60% had at least one session replaced at the end of the treatment period [7].…”

“…In the present review, we noticed that most RCTs did not report missed visits and less than 10% of the RCTs reviewed clearly stated how these missed visits were managed when they occurred. We proposed a plan to handle this issue by allowing up to 20% of appointments to be missed and replacing those visits at the end of the designated stimulations period as successfully done in several RCTs [20,21,27,48]. This method seems to have an appropriate balance between the rigor required in RCT and the flexibility needed for patients with depression or chronic pain, or other conditions inclined to missed treatment visits.…”