TEST for Major Depression
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: National Institute of Mental Health (NIMH)
No Placebo Group
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this trial?Background:
People with TRD are often helped by electroconvulsive therapy (ECT). But ECT can affect memory and thinking. Researchers want to study a treatment called TEST that uses less electricity.
Objective:
To study the safety and feasibility of TEST and assess its antidepressant effects.
Eligibility:
Adults aged 25-64 with major depression that has not been relieved by current treatments.
Design:
Participants will be admitted to the NIH Clinical Center for 5-18 weeks over 2-3 treatment phases. Their medications may be adjusted.
Participants will be interviewed about their depression, side effects, and other treatments they are receiving. They will complete questionnaires. They will give blood and urine samples. Their brain waves and heart rhythm will be recorded. They will take tests of memory, attention, mental functioning, and thinking.
Participants will have magnetic resonance imaging (MRI) scans of the head and brain. They will lie on a table that slides in and out of the scanner. Pictures of brain chemicals will also be taken. They may complete tasks during the MRI.
Participants will receive TEST and/or sham treatments. They may receive optional ECT. An intravenous catheter will be placed in an arm vein to receive general anesthesia. Two electrodes will be placed on the front of their head. An electric current will be passed from the ECT machine through the electrodes. For sham treatments, they will not receive the electric current. Their breathing, heart rate, brain function, blood pressure, and body movements will be measured.
Participants will have 7 follow-up visits over 6 months. Visits can be done via telehealth.
Participation will last for up to 42 weeks.
How is Transcranial Electric Stimulation Therapy (TEST) different from other treatments for major depression?
Transcranial Electric Stimulation Therapy (TEST), also known as transcranial direct current stimulation (tDCS), is unique because it is a non-invasive brain stimulation technique that modulates brain activity using a low electrical current. Unlike traditional antidepressant medications, it does not involve drugs and can be administered at home under supervision, offering a potential alternative for those who do not respond well to medications.
1351011What data supports the effectiveness of the treatment Transcranial Electric Stimulation Therapy (TEST) for major depression?
Research shows that transcranial direct current stimulation (tDCS), a part of TEST, is a promising non-drug therapy for major depression, with studies indicating it can be effective for acute episodes and potentially beneficial when combined with other treatments.
2341011Is transcranial electric stimulation therapy (TEST) safe for humans?
Transcranial electric stimulation, including tDCS and tACS, is generally considered safe for humans, with no serious adverse events reported in over 18,000 sessions. Mild side effects like headaches and skin sensations are possible, but serious issues are rare.
678912Will I have to stop taking my current medications?
Participants must stay on the same daily dose of their psychiatric medications for at least 6 weeks before starting the trial and throughout the study, unless the investigator advises otherwise. If you need to reduce your medication dosage, it must be done at least 4 weeks before the trial begins.
Eligibility Criteria
Adults aged 25-64 with major depression not improved by standard treatments, including medication or rTMS. They must be stable on current psychiatric medications for at least 4 weeks before and during the trial, agree to use effective contraception if applicable, and not have a history of substance abuse in the past year or certain medical conditions that could interfere with the study.Inclusion Criteria
I agree to not change my psychiatric medication dose during the study.
I am between 25 and 64 years old.
My depression score is severe according to the MADRS.
My mania symptoms are mild, based on a specific test score.
I have not changed or added any psychiatric medications for at least 6 weeks.
Exclusion Criteria
I have had brain surgery, metal implants in my head, devices not compatible with MRI, or significant head trauma.
I understand the study and can pass the consent form test.
I have had seizures, but only those caused by electroconvulsive therapy.
Participant Groups
The TEST procedure is being studied as an alternative to ECT for treatment-resistant depression. It involves less electricity than traditional ECT and aims to reduce side effects like memory loss. Participants will undergo MRI scans, interviews, questionnaires, blood tests, and brain function assessments over several phases lasting up to 42 weeks.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Transcranial Electric Stimulation Therapy (TEST)Experimental Treatment3 Interventions
TEST involves bifrontal electrical brain stimulation at a dose below the seizure threshold, applied in the same manner as standard electroconvulsive therapy (ECT), with scalp electrodes, under anesthesia, using a standard ECT device (modified or unmodified) that can deliver a range of doses below seizure threshold.
Group II: Sham TESTPlacebo Group1 Intervention
Anesthesia alone
Transcranial Electric Stimulation Therapy (TEST) is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Transcranial Direct Current Stimulation (tDCS) for:
- Major Depressive Disorder
- Chronic Pain
- Stroke Rehabilitation
🇪🇺 Approved in European Union as Transcranial Direct Current Stimulation (tDCS) for:
- Major Depressive Disorder
- Chronic Pain
- Stroke Rehabilitation
- Schizophrenia
🇨🇦 Approved in Canada as Transcranial Direct Current Stimulation (tDCS) for:
- Major Depressive Disorder
- Chronic Pain
- Stroke Rehabilitation
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
National Institutes of Health Clinical CenterBethesda, MD
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Who is running the clinical trial?
National Institute of Mental Health (NIMH)Lead Sponsor
References
Transcranial direct current stimulation as a therapeutic tool for the treatment of major depression: insights from past and recent clinical studies. [2009]Transcranial direct current stimulation (tDCS) is a noninvasive method of brain stimulation that has been increasingly tested for the treatment of neuropsychiatric disorders. It has useful characteristics, such as low cost, ease of use, reliable sham methodology, and relatively powerful effects on cortical excitability. Because of its potential to modulate cortical excitability noninvasively, tDCS has been tested for the treatment of depression for several decades. Therefore, we reviewed evidence on the use of tDCS for major depression examining evidence from past and recent tDCS studies. We also briefly compared tDCS with other techniques of neuromodulation, namely deep brain stimulation, vagal nerve stimulation, and transcranial magnetic stimulation; and suggest future directions for the use of tDCS in major depression.
Transcranial direct current stimulation in treatment resistant depression: a randomized double-blind, placebo-controlled study. [2022]Anodal transcranial direct current stimulation (tDCS) of the prefrontal cortex has been proposed as therapeutic intervention in major depression. According to clinical needs, this study addresses the question whether tDCS is effective in treatment resistant major depressive episodes.
Interactions between transcranial direct current stimulation (tDCS) and pharmacological interventions in the Major Depressive Episode: findings from a naturalistic study. [2020]Transcranial direct current stimulation (tDCS) is a non-invasive, neuromodulatory technique with an emerging role for treating major depression.
The sertraline versus electrical current therapy for treating depression clinical study (select-TDCS): results of the crossover and follow-up phases. [2014]Transcranial direct current stimulation (tDCS) is a promising nonpharmacological therapy for major depression. In the Sertraline versus Electrical Current Therapy for Treating Depression Clinical Trial (SELECT-TDCS) trial, phase-I (Brunoni et al., JAMA Psychiatry, 2013) we found that tDCS is effective for the acute episode. Here, we describe tDCS effects during phases II (crossover) and III (follow-up) of this trial (NCTs: 01149889 and 01149213).
The Escitalopram versus Electric Current Therapy for Treating Depression Clinical Study (ELECT-TDCS): rationale and study design of a non-inferiority, triple-arm, placebo-controlled clinical trial. [2015]Major depressive disorder (MDD) is a common psychiatric condition, mostly treated with antidepressant drugs, which are limited due to refractoriness and adverse effects. We describe the study rationale and design of ELECT-TDCS (Escitalopram versus Electric Current Therapy for Treating Depression Clinical Study), which is investigating a non-pharmacological treatment known as transcranial direct current stimulation (tDCS).
Tolerability of Repeated Application of Transcranial Electrical Stimulation with Limited Outputs to Healthy Subjects. [2018]The safety and tolerability of limited output transcranial electrical stimulation (tES) in clinical populations support a non-significant risk designation. The tolerability of long-term use in a healthy population had remained untested.
Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. [2023]Low intensity transcranial electrical stimulation (TES) in humans, encompassing transcranial direct current (tDCS), transcutaneous spinal Direct Current Stimulation (tsDCS), transcranial alternating current (tACS), and transcranial random noise (tRNS) stimulation or their combinations, appears to be safe. No serious adverse events (SAEs) have been reported so far in over 18,000 sessions administered to healthy subjects, neurological and psychiatric patients, as summarized here. Moderate adverse events (AEs), as defined by the necessity to intervene, are rare, and include skin burns with tDCS due to suboptimal electrode-skin contact. Very rarely mania or hypomania was induced in patients with depression (11 documented cases), yet a causal relationship is difficult to prove because of the low incidence rate and limited numbers of subjects in controlled trials. Mild AEs (MAEs) include headache and fatigue following stimulation as well as prickling and burning sensations occurring during tDCS at peak-to-baseline intensities of 1-2mA and during tACS at higher peak-to-peak intensities above 2mA. The prevalence of published AEs is different in studies specifically assessing AEs vs. those not assessing them, being higher in the former. AEs are frequently reported by individuals receiving placebo stimulation. The profile of AEs in terms of frequency, magnitude and type is comparable in healthy and clinical populations, and this is also the case for more vulnerable populations, such as children, elderly persons, or pregnant women. Combined interventions (e.g., co-application of drugs, electrophysiological measurements, neuroimaging) were not associated with further safety issues. Safety is established for low-intensity 'conventional' TES defined as <4mA, up to 60min duration per day. Animal studies and modeling evidence indicate that brain injury could occur at predicted current densities in the brain of 6.3-13A/m2 that are over an order of magnitude above those produced by tDCS in humans. Using AC stimulation fewer AEs were reported compared to DC. In specific paradigms with amplitudes of up to 10mA, frequencies in the kHz range appear to be safe. In this paper we provide structured interviews and recommend their use in future controlled studies, in particular when trying to extend the parameters applied. We also discuss recent regulatory issues, reporting practices and ethical issues. These recommendations achieved consensus in a meeting, which took place in Göttingen, Germany, on September 6-7, 2016 and were refined thereafter by email correspondence.
Protocol on transcranial alternating current stimulation for the treatment of major depressive disorder: a randomized controlled trial. [2023]Transcranial alternating current stimulation (tACS) offers a new approach for adult patients with major depressive disorder (MDD). The study is to evaluate the efficacy and safety of tACS treating MDD.
A double-blind, randomized, sham-controlled study of cranial electrotherapy stimulation as an add-on treatment for tic disorders in children and adolescents. [2021]The aim of this study was to determine the efficacy and safety of cranial electrotherapy stimulation (CES) as an add-on treatment for TD.
Is transcranial direct current stimulation, alone or in combination with antidepressant medications or psychotherapies, effective in treating major depressive disorder? A systematic review and meta-analysis. [2022]Transcranial direct current stimulation (tDCS) has shown mixed results for depression treatment. The efficacies of tDCS combination therapies have not been investigated deliberately. This review aims to evaluate the clinical efficacy of tDCS as a monotherapy and in combination with medication, psychotherapy, and ECT for treating adult patients with major depressive disorder (MDD) and identified the factors influencing treatment outcome measures (i.e. depression score, dropout, response, and remission rates).
A Clinical Case Series of Acute and Maintenance Home Administered Transcranial Direct Current Stimulation in Treatment-Resistant Depression. [2023]Transcranial direct current stimulation (tDCS) is a noninvasive neurostimulation technique being translated clinically for the treatment of depression. There is limited research documenting the longer-term effectiveness and safety of tDCS treatment. This case series is the first report of remotely supervised, home-administered tDCS (HA-tDCS) for depression in a clinical setting.
Blinding efficacy and adverse events following repeated transcranial alternating current, direct current, and random noise stimulation. [2022]As transcranial electrical stimulation (tES) protocols advance, assumptions underlying the technique need to be retested to ensure they still hold. Whilst the safety of stimulation has been demonstrated mainly for a small number of sessions, and small sample size, adverse events (AEs) following multiple sessions remain largely untested. Similarly, whilst blinding procedures are typically assumed to be effective, the effect of multiple stimulation sessions on the efficacy of blinding procedures also remains under question. This is especially relevant in multisite projects where small unintentional variations in protocol could lead to inter-site difference. We report AE and blinding data from 1,019 participants who received up to 11 semi-consecutive sessions of active or sham transcranial alternating current stimulation (tACS), direct current stimulation (tDCS), and random noise stimulation (tRNS), at 4 sites in the UK and US. We found that AEs were often best predicted by factors other than tES, such as testing site or session number. Results from the blinding analysis suggested that blinding was less effective for tDCS and tACS than tRNS. The occurrence of AEs did not appear to be linked to tES despite the use of smaller electrodes or repeated delivery. However, blinding efficacy was impacted in tES conditions with higher cutaneous sensation, highlighting a need for alternative stimulation blinding protocols. This may be increasingly necessary in studies wishing to deliver stimulation with higher intensities.