Unipolar Major Depressive Disorder Clinical Trial
Official title:
Neural, Cognitive, and Clinical Effects of Prefrontal Cortex Stimulation to Enhance Psychotherapy in Depression: a Double-blind Randomized Controlled Trial
Depression is a serious mental health problem that affects millions. Depression is usually treated using drugs and/or psychotherapy, but neither approach is successful for everyone, and some people do not respond to either. Therefore it is crucial that we continue to seek new methods for treating depression, and develop enhancements to existing treatments. In recent years, trials have documented improvements in depressive symptoms using noninvasive brain stimulation techniques, such as transcranial direct current stimulation, or tDCS. Our aim in this research is to investigate the effects of brain stimulation combined with psychological therapy in depression, an area that remains largely unexplored. Specifically, stimulation of the dorsolateral prefrontal cortex (DLPFC), a brain region known to work inefficiently in depression, has been shown to result in an improvement of depressive symptoms, as well as in the patient's 'cognitive control' abilities. Because 'cognitive control' processes, such as concentrating and ignoring distracting thoughts, are engaged during psychological therapies for depression, we predict that DLPFC stimulation should improve how patients respond to psychological therapy. This study has considerable implications as it will potentially benefit a large number of patients for which current treatments are ineffective.
We propose to investigate the effect of applying transcranial direct current stimulation
(tDCS) over the left dorsolateral prefrontal cortex (LDLPFC) immediately prior to each of 8
sessions of cognitive behavioural therapy (CBT), a type of psychological therapy. In addition
we will investigate whether tDCS effects on CBT are due to changes in cognitive control using
both behavioural and neuroimaging measures.
We hypothesize that tDCS, thanks to its enduring effects, should improve the benefits of CBT,
through the enhancement of cognitive control in the patient.
Null hypothesis: mood and cognitive performance will be equivalent in depressed individuals
who undergo tDCS and those who undergo sham stimulation.
Experimental hypothesis: mood and cognitive performance will be improved in depressed
individuals who undergo tDCS relative to those who undergo sham stimulation.
Sixty patients suffering from depression will be recruited, and a double-blind,
sham-controlled, randomised design will be used. This design means that neither participants
nor researchers are aware of the conditions they have been assigned to, and has been chosen
to eliminate participant expectancy ("placebo") effects and researcher bias. To ensure that
30 participants are included in each group, we will use a balanced assignment algorithm at
entry into the study, which will maximise statistical power. Since the results of a study of
this type have never previously been reported (to our knowledge), clinical equipoise exists,
mandating the use of a sham stimulation arm. Patients with depression will be randomly
assigned to one of two groups: tDCS or sham stimulation. To ensure that 30 participants are
included in each group, we will use a balanced assignment algorithm at entry into the study.
The whole study will be spread over 16 weeks for each participant with the following time
course:
- start: baseline MRI brain scan while completing a cognitive control task; measures of
depressive symptoms
- weeks 1 to 8: one session per week of tDCS or sham stimulation (20 min, while completing
a cognitive control task) immediately followed by CBT (1 hour); measures of depressive
symptoms
- end of week 8: post-treatment MRI scan while completing a cognitive control task and
measures of depressive symptoms
- week 9 to 16: up to one session per week of CBT as usual (1 hour) without stimulation
- end of week 16, or end of CBT (whichever is sooner): measures of depressive symptoms
MRI scans will have two purposes, (1) localising the area of the DLPFC for stimulation, and
(2) comparing brain responses to a cognitive control task before and after treatment.
The tDCS will be delivered using neuroConn stimulators. A 1 milliamp (mA) current will be
delivered for 20 minutes through damp sponges soaked in saline solution and attached to the
head of the patient using a cap. One electrode will be placed on the forehead over the
LDLPFC, and the other on the left shoulder blade or left cheek to record baseline electrical
signal. In the sham condition, there will be a brief current change at the beginning and end
of each stimulation session, in order to mimic the effect of an actual stimulation, but no
current will be delivered in between.
CBT sessions will be delivered weekly, immediately after the tDCS or sham stimulation for the
first 8 weeks, and provided by qualified psychological therapists as part of standard
National Health Services (NHS) care.
Mood will be assessed before the start of the study (first MRI scan), each week for the 8
week stimulation phase, at the second MRI scan and after 16 weeks, using the Montgomery and
Asberg Depression Rating Scale (MADRS).
Patients will perform a task to assess their cognitive control abilities during the MRI
scans, as well as during each of the 8 stimulation sessions. During this task, visual stimuli
will be presented to the subject, who will have to make different responses to these stimuli
by pressing buttons on a response box.
;