High-definition Transcranial Direct Current Stimulation (HD-tDCS) as Augmentation Therapy in Late-life Depression (LLD) With Suboptimal Response to Treatment - Double-blinded Randomized Sham-controlled Trial
Trial Snapshot
- Phase
- Not Applicable
- Sponsor
- The University of Hong Kong
- Enrollment
- 58
- Locations
- 1
- Primary Endpoint
- Change in the Depressive symptoms
Study Overview
Brief Summary
To determine the efficacy of a 2-week daily programme (10 sessions) of HD-tDCS to augment antidepressant therapy in subjects with late-life depression who had residual depressive symptoms despite adequate dosage and duration of antidepressant therapy.
Detailed Description
Background:
Hong Kong is facing a significant challenge in ageing population. A significant proportion of older adults suffered from depression. As the local population is ageing rapidly, the burden of late-life depression (LLD) will continue to increase. LLD is associated with a poorer long term prognosis, a more chronic course and a higher relapse rate comparing with adult-onset depression. Treatment response towards medication is unsatisfactory. Over 50% of patients with LLD do not achieve symptomatic remission. With the growing ageing population in Hong Kong, LLD becomes a pressing problem. The mainstream treatment of LLD is antidepressant and electroconvulsive therapy (ECT). Despite these methods being shown to be effective, there are limitations in each of these treatments. A new treatment option or augmentation therapy would be needed to improve the treatment response in LLD. Transcranial direct current stimulation (tDCS) is a non-invasive neurostimulation method. It applies a weak, direct electric current over the scalp region. It is a very safe intervention tool. It exerts the treatment effect probably through the change in the activity of neurons and modulation in synaptic release probability uptake and sensitivity. It enhances the long-term plasticity (LTP) and changes the rate of neurotransmitter release. High-definition tDCS (HD-tDCS) allows for more accuracy and focus on targeting the specific brain region. Recent evidence suggested that tDCS and serotonin enhance each other's function. Controversial outcomes were reported in previous randomised controlled trials (RCT) focusing on adult patients with depression. There is no RCT done among patients with LLD. An open-label pilot study was conducted by our team in 2018 which showed a significant improvement in depressive symptoms and mild improvement in cognitive domains after 2 weeks of HD-tDCS intervention.
Objectives:
This study is a double-blinded randomized sham-controlled trial to test the effectiveness of HD-tDCS as augmentation therapy for antidepressants in patients with LLD. The investigators hypothesized that active HD-tDCS is significantly more effective than sham control in reducing depressive symptoms.
Design:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Care Provider)
Eligibility Criteria
- Ages
- 60 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •60 years of age or above
- •Right-handedness, as determined by the Edinburgh Handedness Inventory (to homogenise neuroanatomical targeting)
- •Chinese ethnicity
- •Fulfil the criteria of Major Depressive Disorder (single or recurrent episode) and in partial remission, defined by the 5th Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)
- •Presence of mild to severe level of depressive symptoms measured and defined by HAM-D-17 score ≥8 and ≤ 52[22]
- •Suboptimal treatment response with at least one adequate antidepressant trial defined as full or best tolerated doses at least 6 weeks
- •Stable dosage of antidepressants or other treatments for depression in recent 4 weeks
- •Valid informed written consent
Exclusion Criteria
- •A DSM-5 diagnosis other than Depressive Disorders (e.g., bipolar and related disorders, schizophrenia spectrum and other psychotic disorders).
- •A Hong Kong Chinese version of the Montreal Cognitive Assessment (HK-MoCA) score below the second percentile according to the subject's age and education level (to exclude subjects with existing dementia)
- •Alcohol or substance dependence
- •Active suicidal ideation or a suicide attempt within the past month
- •Concomitant unstable medical condition or major neurological conditions
- •Significant communication impairment
Arms & Interventions
active HD-tDCS
The participants will be instructed to relax during the first 5 minutes of the session while the equipment is set up. A mild stimulation (with a level of only 2 milliamps stimulation) will be delivered for 20 minutes, with the current gradually increased and decreased over 30 seconds. The patients will be instructed to relax and remain motionless during the intervention. The administrator will closely monitor the impedance throughout each session and record any side effects experienced by the participants. The participants will be allowed 5 minutes of rest after the intervention and will be actively asked about any discomfort. Each session will last around 30 minutes, with a total of 10 sessions (two consecutive weeks of treatment for 5 days per week).
Intervention: High-definition Transcranial Direct Current Stimulation (Device)
sham-HD-tDCS
The procedure for sham stimulation will be identical, except that the current will be gradually ramped down to zero after the first 30 s, thus giving the same initial sensation of HD-tDCS. The stimulator will be programmed to switch the current on and off, so no intervention by the operator will be required. The computer will be placed behind the subjects' heads so they cannot see the readout.
Intervention: High-definition Transcranial Direct Current Stimulation (Device)
Outcomes
Primary Outcomes
Change in the Depressive symptoms
Time Frame: Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.
the clinical response rate and the remission rate as measured with the HAM-D-17. A clinical response will be defined as a reduction of 50% or more in the HAM-D-17 score. A HAM-D-17 score of 7 or less will be used as an indicator of remission. Scores range from 0 to 52, with higher scores indicating more severe depression.
Secondary Outcomes
- Change in the Working Memory(Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.)
- Change in Adverse effects and risk indicators(Assessed immediately after each (in total 10) individual treatment session.)
- Change in the Global Cognition(Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.)
- Change in the Executive Functioning(Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.)
- Change in the Verbal Fluency(Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.)
- Change in the Attention(Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.)
- Change in the Anxiety symptoms(Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.)
- Change in Daily functioning(Assessed at baseline, immediately after the intervention, and 4 and 12 weeks after the intervention.)
Investigators
Dr. Cheng Pak Wing, Calvin
Clinical Assistant Professor
The University of Hong Kong