Title of the Study: Effect of Adjunctive High-Definition Transcranial Direct Current Stimulation in Treatment of Depression- A Double Blinded Randomized Sham-Controlled Study

    BACKGROUND

Major depressive disorder (MDD) is a persistent, incapacitating illness. Major depression is thought to affect 4.4 to 20% of the overall population. Behind anxiety disorders, depression is the second most prevalent mental disorder in terms of lifetime prevalence. Between 5 and 17% of people will experience a major depressive episode in their lifetime. The National Mental Health Survey found that 5.3% of Indians experience depression at some point in their lifetime. The social cost of the disease is enormous.  Depression is associated with a 19.7 percent suicide risk  and a 1.6 percent risk of all-cause mortality. In addition, despite obtaining proper psychological and pharmaceutical therapy, over 30% of patients still have refractory depression, necessitating the use of alternative therapies. These possibilities include electroconvulsive therapy (ECT) and Non Invasive Brain Stimulation [NIBS] methods like deep- transcranial magnetic stimulation (TMS) and repetitive-TMS, which the  Food and Drug Administration [FDA] has now approved for the treatment of MDD in cases of refractory depression. Transcranial Direct Current Stimulation [tDCS] has produced favourable findings in numerous meta-analyses and is safer than the other 2 procedures.

Justification of study

Studies have shown promising effect of tDCS in patients with depression who respond partially to antidepressants . By providing current in a focused manner, HD-tDCS appears to be better than traditional tDCS. Also studies have shown increased neuroplasticity and longer lasting after effects with HD-tDCS as compared to tDCS. Currently there are only a few studies that have assessed utility of HD-tDCS in depression. And thus need for further studies.

 Transcranial Direct Current Stimulation

Transcranial direct current stimulation (tDCS) is a neurostimulation technique that offers beneficial qualities for therapeutic usage, such as safety, tolerability, ease of use, lack of major adverse effects, and capacity to be employed remotely.

  tDCS in depression

Neuroimaging research has revealed interhemispheric asymmetry between the dorsolateral prefrontal (DLPFC) cortices in depression. The left DLPFC is hypofunc­tional, whereas the right DLPFC is hyper-functional. The most often utilized protocol among the many ones is up to 10 sessions of anodal stimulation over the left DLPFC and cathodal inhibition over the right DLPFC with a current intensity of 2mA for 20 minutes. There is evidence that active tDCS is more effective than sham tDCS in treating depressed symptoms that won’t go away. By causing changes in neural activity and by modifying synaptic release probability absorption and sensitivity, it delivers its therapeutic impact. tDCS changes the rate of neurotransmitter release and strengthens long-term plasticity. To obtain a desired result, it must have effects up to an hour after stimulation.  tDCS was demonstrated to modify DLPFC activity, which may modify the hypoactive state of the DLPFC in individuals with depression. A meta-analysis, revealed that active tDCS significantly reduced depression compared to sham, as well as response and remission. Active tDCS is useful in treating depression, according to both qualitative and quantitative research. Recent research also noticed contentious results. The efficacy of tDCS and the antidepressant escitalopram is compared in a recent double-blind, placebo-controlled research. Escitalopram was shown to be superior to tDCS despite there being no difference in the rates of response or remission . In a different sizable worldwide RCT of adult patients with depression, neither active nor sham stimulation reduced depressed symptoms in those with unipolar or bipolar depression.  The contradictory findings call for additional high-quality RCTs to evaluate the effectiveness of tDCS.

  HD-tDCS

Traditional tDCS’s spatial crudity is one of its key flaws. The peak cortical current density might not be exactly beneath the target electrode , which would likely change the effects of tDCS and explain the discrepancies in the findings of previous tDCS investigations. To solve this issue, high definition tDCS (HD-tDCS) was created. Usually, there are more than two small electrodes used when doing HD-tDCS. The‘4 × 1 ring set-up’ which includes a center anode electrode surrounding by four return cathode electrodes, is the montage that is utilized the most frequently. The diameter of the ring of electrodes can be changed to alter the density of the cortical field and spatial focality. The increased impacts of neuroplasticity may also be demonstrated by longer-lasting after-effects, as in a prior research with HD-tDCS , in addition to improving the spatial focality of stimulation. At the same time, it was discovered that the tolerability was comparable to that of conventional tDCS. A recent open-labeled pilot study on (HD-tDCS) as an augmentation therapy in late-life depression (LLD) with suboptimal response to treatment revealed that the HD-tDCS was effective in lowering the depressive severity and the remission rates, as well as improving cognitive functions.

      RESEARCH QUESTION

Is adjunctive active HD-tDCS on dorsolateral prefrontal cortex better than sham HD-tDCS in reducing the severity of symptoms in patients of depression?

 Aim: To assess the effect of adjunctive HD-tDCS on dorsolateral prefrontal cortex in reducing the severity of symptoms in patients of depression.

Primary objective

To compare the effect of adjunctive active HD-tDCS on dorsolateral prefrontal cortex with sham HD-tDCS in reducing the severity of symptoms and improving remission rate in patients of depression

Secondary objective

To evaluate the impact of HD-tDCS on patients’ global cognition, anxiety symptoms, and daily functioning.

    METHODOLOGY

 Patients with diagnosis of depression in department of psychiatry will be screened for the participation in the study Written informed consent will be taken. Eligibility for enrolment in the study will be done based on inclusion and exclusion criteria. Subsequently, randomization will be done. The patients who are eligible for the study will be randomized into two groups (active HD-tDCS and Sham HD-tDCS) by block randomization in blocks of 4.

Active HD-tDCS group: Will receive 10 sessions (1 per day) over 2 weeks; 2mA current and for 20  minutes in each session that is spaced over at least 24 hours.

Sham HD-tDCS group: Will receive 10 sessions (1 per day) over 2 weeks; 0.2mA current and for 20 minutes in each session that is spaced over at least 24 hours.

The severity of the symptoms and subsequent improvement will be assessed with the help of scales like Hamilton Depression Rating Scale(HAMD), Hamilton Anxiety Raing Scale(HAM-A), Montreal Cognitive Assessment (MoCA), Global Assessment of Functioning (GAF)

ASSESSMENT TIME POINTS FOR OUTCOME VARIABLES:

1.     Baseline: Just before the delivery of first session (Day 0)

2.     After completion of 10 sessions of HD-tDCS.

3.     Follow-up: After 4 weeks from the day of last session