To Enhance Cognition in Late Life Depression Using Transcranial Direct Current Stimulation

Sponsor

Centre for Addiction and Mental Health (Other)

Overall Status

Completed

CT.gov ID

NCT02212366

Collaborator

Ontario Ministry of Health and Long Term Care (Other)

Enrollment

Location

Arms

42.1

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Late Life Depression (LLD) is a serious health problem which not only causes depressed mood but also results in impairments in memory and attention. These impairments are likely to be resistant to treatment, which increases the chances of developing dementia even after successful treatment of mood.This study is a randomized controlled trial of transcranial Direct Current Stimulation (tDCS) in people with LLD to enhance their cognition after successful treatment of mood with established medications. tDCS is non invasive, relatively inexpensive and portable, and has been found to be safe.This study also serves as a pilot study to assess the effects of tDCS on cognition and neurophysiologic markers of cognition among patients with LLD. Primary study hypothesis is that participants Participants randomized to tDCS will perform better on a working memory task 2 weeks and 3 months following the tDCS course.

Condition or Disease	Intervention/Treatment	Phase
Cognition Depression	Device: Active TDCS Device: Sham TDCS	N/A

Detailed Description

tDCS is a non-invasive brain stimulation method that utilizes low intensity electrical current either to increase cortical excitability with an anodal electrode or to suppress cortical excitability with a cathodal electrode. tDCS produces its effects through long lasting changes in neuroplasticity: in animal studies, tDCS results in long-term potentiation and brain-derived neurotrophic factor secretion; in human studies, tDCS results in potentiation of neurophysiologic markers of neuroplasticity. Consistent with these preclinical findings, tDCS to the temporoparietal cortex or left DLPFC improves memory in patients with mild to moderate Alzheimer disease(AD). tDCS has also been tested among patients with depression - including by our group - but mainly as a treatment for depressive symptoms. In one recent large study one session of bilateral anodal tDCS was shown to enhance working memory among midlife participants with major depression prior to receiving any treatment. However, it is still not known (1) whether tDCS improves cognition beyond the partial improvement that is associated with resolution of depressive symptoms; or (2) whether it has a more fundamental and long lasting effect on cognition.

This trial will assess the acute and long-term effects of a 2-week course of daily (5 days/week) bilateral anodal tDCS of the DLPFC on cognition, and in particular working memory among 36 patients with LLD. We will recruit and randomize participants who have already been treated for LLD prior to consenting to the study and who still meet criteria for remission while on antidepressant medications.

This trial will also be used as a platform to explore the effect of tDCS on neurophysiologic measures of plasticity during working memory performance. Working memory is supported by re-entrant circuits, some are local within the DLPFC and others are long-range connecting the DLPFC to more posterior cortices. These networks result in high and low frequency neuronal oscillations that can be captured by electroencephalography (EEG). Using novel neurophysiologic analyses, our group and others have demonstrated that the modulation of high-frequency (particularly gamma) oscillations by low-frequency (particularly theta) oscillations - "theta-gamma coupling" - is a neurophysiologic marker of working memory. Thus, we will explore the effect of tDCS on theta-gamma coupling.

Study Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Enhancing Cognition in Patients With Late-Life Depression: A Randomized Controlled Trial of Transcranial Direct Current Stimulation

Study Start Date :

May 1, 2014

Actual Primary Completion Date :

Nov 1, 2017

Actual Study Completion Date :

Nov 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active TDCS 2-week course of daily (5 days/week) active bilateral anodal TDCS, duration 30 minute each session. Current 2 mA.	Device: Active TDCS Active Stimulation
Sham Comparator: Sham TDCS 2-week course of daily (5 days/week) Sham bilateral tDCS. Duration 30 minute each session.	Device: Sham TDCS Sham Stimulation

Arm

Intervention/Treatment

Experimental: Active TDCS

2-week course of daily (5 days/week) active bilateral anodal TDCS, duration 30 minute each session. Current 2 mA.

Device: Active TDCS

Active Stimulation

Sham Comparator: Sham TDCS

2-week course of daily (5 days/week) Sham bilateral tDCS. Duration 30 minute each session.

Device: Sham TDCS

Sham Stimulation

Outcome Measures

Primary Outcome Measures

To compare performance on working memory task (N-Back) and neuropsychological battery between active and sham TDCS groups [Two weeks following the TDCS course]

Secondary Outcome Measures

To compare performance on working memory task (N-Back) and neuropsychological battery between active and sham TDCS groups [Three months following the TDCS course]

Other Outcome Measures

To compare theta-gamma coupling as measured by electroencephalography between active and sham TDCS groups. [Two weeks following the TDCS]
To compare theta-gamma coupling as measured by electroencephalography between active and sham TDCS groups. [3 months following the TDCS]

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Women and men of any races or ethnicity
Age 60 and above
Major depressive disorder, single or recurrent per SCID DSM-IV criteria AND remission from that episode as defined by DSM IV-TR criteria for remission.
Montgomery-Asberg Depression Rating Scale (MADRS) score less than 10.
Ability to speak English fluently enough to complete all research assessments.
Corrected visual ability to read newspaper headlines; hearing capacity to respond to a raised conversational voice
Willingness and ability to provide consent

Exclusion Criteria:

DSM IV TR criteria for any dementia
DSM IV TR criteria for life-time bipolar disorder, schizophrenia, schizoaffective disorder, or other psychotic disorders
DSM IV TR criteria for any substance abuse or dependence within the past 6 months
Presence of psychotic features or any other symptoms that would make the participant unable to participate in the study.
Any medical contra-indications to tDCS.
Electroconvulsive therapy in the last 6 months.