Is tDCS a potential first line treatment for major depression?

Transcranial direct current stimulation (tDCS) is a novel treatment option for major depression which could be provided as a first-line treatment. tDCS is a non-invasive form of transcranial stimulation which changes cortical tissue excitability by applying a weak (0.5-2 mA) direct current via scalp electrodes. Anodal and cathodal stimulation leads to depolarisation and hyperpolarisation, respectively, and cumulative effects are observed with repeated sessions. The montage in depression most often involves anodal stimulation to the left dorsolateral prefrontal cortex. Rates of clinical response, remission, and improvements in depressive symptoms following a course of active tDCS are greater in comparison to a course of placebo sham-controlled tDCS. In particular, the largest treatment effects are evident in first episode and recurrent major depression, while minimal effects have been observed in treatment-resistant depression. The proposed mechanism is neuroplasticity at the cellular and molecular level. Alterations in neural responses have been found at the stimulation site as well as subcortically in prefrontal-amygdala connectivity. A possible mediating effect could be cognitive control in emotion dysregulation. Additional beneficial effects on cognitive impairments have been reported, which would address an important unmet need. The tDCS device is portable and can be used at home. Clinical trials are required to establish the efficacy, feasibility and acceptability of home-based tDCS treatment and mechanisms.

Adjunctive home-based transcranial direct current stimulation treatment for major depression with real-time remote supervision: An open-label, single-arm feasibility study with long term outcomes.

Current treatments for major depressive disorder (MDD) have limited effectiveness and acceptability. Transcranial direct current stimulation (tDCS) is a novel non-invasive brain stimulation method that has demonstrated treatment efficacy in MDD. tDCS requires daily sessions, however clinical trials have been conducted in research centers requiring repeated visits. As tDCS is portable and safe, it could be provided at home. We developed a home-based protocol with real-time supervision, and we examined the clinical outcomes, acceptability and feasibility. Participants were 26 MDD (19 women), mean age 40.9 ± 14.2 years, in current depressive episode of moderate to severe severity (mean 17-item Hamilton Rating Scale for Depression (HAMD) score 19.12 ± 2.12). tDCS was provided in a bilateral frontal montage, F3 anode, F4 cathode, 2 mA, each session 30 min, in a 6-week trial, for a total 21 sessions. Participants maintained their current treatment (antidepressant medication, psychotherapy, or were enrolled in online CBT). Two tDCS device brands were used, and a research team member was present in person or by real-time video call at each session. 92.3% MDD participants (n = 24) completed the 6-week treatment. Attrition rate was 7.7%. There was a significant improvement in depressive symptoms following treatment (mean HAMD 5.33 ± 2.33), which was maintained at 6 months (mean HAMD 5.43 ± 2.73). Acceptability was endorsed as "very acceptable" or "quite acceptable" by all participants. Due to the open-label feasibility design, efficacy findings are preliminary. In summary, home-based tDCS with real-time supervision was associated with significant clinical improvements and high acceptability which were maintained in the long term.

Brain-derived neurotrophic factor association with amygdala response in major depressive disorder.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) has an essential role in synaptic plasticity and neurogenesis. BDNF mediates amygdala-dependent learning for both aversive and appetitive emotional memories. The expression of BDNF in limbic regions is posited to contribute the development of depression, and amygdala responsivity is a potential marker of depressive state. METHODS: The present study examined the relationship between platelet BDNF levels and amygdala volume and function in major depressive disorder (MDD). Participants were 23 MDD (mean age 38.9 years) and 23 healthy controls (mean age 38.8 years). All participants were recruited from the community. MDD participants were in a current depressive episode of moderate severity and medication-free. Amygdala responses were acquired during a functional MRI task of implicit emotional processing with sad facial expressions. RESULTS: Significant correlation was observed between platelet BDNF levels and left amygdala responses, but no significant correlations were found with right amygdala responses or with amygdala volumes. LIMITATIONS: Interactions with neuroprotective as well as neurotoxic metabolites in the kyneurenine pathway were not examined. CONCLUSIONS: Relationship between BDNF levels and amygdala responsivity to emotionally salient stimuli in MDD could reflect the importance of BDNF in amygdala-dependent learning with clinical implications for potential pathways for treatment.