Non-invasive Brain Stimulation and Cognitive Processing in Depression
Condition: Unipolar Major Depressive Disorder
MeSH terms: Depressive Disorder; Depressive Disorder, Major
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Transcranial direct current stimulation (tDCS); Cognitive Behavioural Therapy
Intervention type(s): Device; Behavioral
Intervention description(s): Patients - tDCS arm: 1 mA current delivered for 20 minutes once a week for 8 weeks, immediately prior to CBT.
Patients - Sham arm: brief current change at the beginning (0 min) and end of each stimulation session (20 min) in order to mimic the effect of an actual stimulation, but no current delivered in between.; 8 sessions of one hour (once weekly) immediately after tDCS or sham stimulation
Other intervention name(s): NeuroConn DC-STIMULATOR PLUS, number 0061.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment