Transcranial Direct Current Stimulation (tDCS) for Treatment Resistant Depression (TRD): A Systematic Review

Introduction

Treatment-resistant depression (TRD) refers to a condition where an individual with major depressive disorder (MDD) experiences little or no symptom relief despite 2 or more treatment attempts that are considered adequate trials. Novel nonpharmacologic approaches such as noninvasive brain stimulation (NIBS) have been increasingly utilized as treatments for TRD. NIBS involves stimulating specific areas of the brain to induce neuronal changes and eventually modulate neural circuits via plasticity, which are thought to regulate mood or other neuropsychiatric symptoms. Transcranial direct current stimulation (tDCS) is a form of NIBS which involves the use of electric currents. This approach has been increasingly explored either as a primary or adjunctive treatment in TRD. We conducted a systematic review to investigate the effectiveness of tDCS in treating depression and TRD.

Methods

Comprehensive web-based search of databases (Medline, Embase, Cochrane, APA PsycINFO, Web of Science, and Scopus) from 2012 to 2023 was conducted using the search keywords including tDCS, MDD, and treatment resistant depression. Here we report the primary outcomes from randomized controlled trials (RCT) and open-label studies.

Results

A total of 14 clinical trials comprised of 967 participants with mean age 49.8 years (range 18 and older) were reviewed. The most common method of stimulation is anode placed over F3 and cathode placed over F4 in accordance with the International 10-20 Electroencephalogram System standard. Active tDCS sessions comprised of ramp-up phase (15-30 seconds) followed by 30 minutes of 2 mA intensity and ramp-down phase (15-30 seconds). Earlier studies also employed shorter duration of 20 minutes and lower current of 1 mA. Treatment frequency varies from twice daily to 3 times per week and duration varies from 5 days to 20 days. Four of the 14 trials (29%) reported tDCS to be not efficacious. Only 1 of 4 studies included older adults with a mean age of 61.8. This study showed tDCS was not superior to sham in treating TRD. Ten of 14 (71%) studies showed various positive responses related to tDCS alone or in combination with other therapeutic treatments. For example, a recent study with a larger sample size (n = 245) showed non-inferiority compared to either selective serotonin reuptake inhibitor or cognitive behavior therapy (effect size: -0.78 to -1.37 based on number of weeks after tDCS treatment). However, only 1 of the 10 studies focused on patients with late life depression (mean age = 74.8). This study showed tDCS increased inhibitory processing and cognitive flexibility, which were measured by Stroop test and Trail Making Test - part B. The most common site of stimulation is using the anode over the left dorsolateral prefrontal cortex. The main adverse effects of tDCS are redness of the skin, itching, headache, paresthesia (burning and tingling) at the stimulation site. Incidence of the side effects does not seem to be associated with repeated sessions of tDCS.

Conclusions

There is favorable evidence suggesting that tDCS is clinically effective in treating TRD as measured by response, symptom improvement, and disease remission in comparison to sham treatment. Additionally, tDCS has shown to enhance cognition and has the potential to augment psychotherapy. Further studies are needed to determine treatment benefit in currently psychiatrically hospitalized TRD patients. Moreover, the evidence for tDCS in elderly depressed patients is very limited, warranting further investigation.