Adjunctive Transcranial Direct Current Stimulation for Cognition in Major Depression
Condition: Depression
MeSH terms: Depression; Depressive Disorder
Study type: Interventional
Phase: Phase 4

Summary: 
      People who have depression often have symptoms besides sad mood. Cognitive symptoms, such as
      poor memory, concentration, and decision making, are associated with disability in many
      spheres of life, and these symptoms often persist even when antidepressant treatment improves
      other symptoms (mood, energy, sleep, anxiety). Antidepressants alone fail to produce full
      remission for many patients, so it is important to study adjunctive treatments which can be
      added onto medication treatment and help restore cognitive function. The method of
      transcranial direct current stimulation (tDCS) has been shown by others to improve working
      memory and cognitive functions, and also to help with other symptoms of depression. tDCS
      involves passing a small, constant current between saline-moistened pads placed on the scalp.
      In this proposed study, 20 individuals with major depression who have cognitive difficulties
      despite taking antidepressants will participate. Over the course of a two-week period, each
      person will receive 5 sessions of either active tDCS or inactive treatments, in addition to
      their medication. Each session lasts for 20 minutes, and will be administered on alternating
      days (M-W-F). Assessments of depressive symptoms, cognitive function, and brain activity will
      be made prior to any sessions, after the first one, and after the fifth (final) session;
      brain function will be assessed by measuring the brain's electrical activity ("brain waves").
    

Detailed description: 
      Transcranial direct current stimulation (tDCS), also sometimes termed "DC polarization" or
      "brain polarization," is a non-invasive procedure that has been used successfully as a
      therapeutic intervention in a number of patient populations. tDCS involves the passing of
      very weak currents through an area of interest of the brain, by placing electrodes on the
      scalp at the appropriate locations. DC polarization has been shown to alter the amplitude of
      evoked potentials in the visual cortex (Antal et al., 2004), and cortical processing in the
      parietal lobe also can be modulated by tDCS (Rogalewski et al., 2004). From a more
      physiologically-relevant perspective, tDCS of the motor cortex has been shown to improve
      motor function in patients following stroke (Hummel and Cohen, 2005; Hummel et al., 2006;
      Boggio et al., 2006b) when applied to the prefrontal cortex. tDCS has been shown to improve
      working memory in healthy individuals (Fregni et al., 2005b), and in individuals with major
      depressive episode. In MDD it has more recently been shown to improve depression rating
      self-report scores (Fregni et al., 2006a) and cognitive performance (Fregni et al., 2006b).
      Performance on a executive function task (go/no-go) was also shown to be enhanced with tDCS
      in adults with MDD (Boggio et al., 2006a). tDCS has been evaluated in subjects with
      Parkinson's disease and found to have therapeutics benefit (compared with inactive treatment)
      on the Unified Parkinson's Disease Rating Scale and neuropsychological measures (reaction
      time, pegboard task) as well as motor evoked potentials (Fregni et al., 2006c).

      Several recent studies have affirmed the safety of tDCS. Iyer and colleagues (2005) showed
      that, in a sample of 103 subjects, no one asked for the tDCS procedure to be stopped due to
      discomfort. Gandiga and colleagues (2006) compared sham to active tDCS and showed no
      differences in self-report ratings of discomfort. Nitsche and colleagues (2004) performed
      structural MRI scans on healthy individuals who underwent 1 hour exposures to tDCS; they
      found no evidence of structural change in the brain or alterations in blood-brain barrier
      permeability.

      With regard to persistent challenges in the management of MDD, individuals with depression
      have shown cognitive deficits, particularly in working memory and other frontal lobe
      functions (Dunkin et al., 2000; Sweeney et al., 2000 Jaeger et al., 2006; Rose and Ebmeier
      2006; Rose et al., 2006) and declarative memory (e.g., Beaden et al., 2006). By improving
      cognitive function in subjects with cognitive complaints that persist despite
      pharmacotherapy, it may be possible to improve the completeness of recovery from depression
      and reduce any functional disability (Jaeger et al., 2006).

      There are no published reports yet of the effects of tDCS on brain function in subjects with
      MDD. Cordance is a quantitative electroencephalography (QEEG) measure which allows for
      non-invasive measurement of regional brain function (Leuchter et al., 1994a, 1994b, 1999;
      Cook et al., 1998). It is sensitive to changes in brain function in subjects who are
      responding to treatment for MDD (Cook and Leuchter 2001; Cook et al., 2002, 2005; Leuchter et
      al., 2002) and is being evaluated for use a a biomarker which predicts treatment outcome in
      MDD (NIMH Project R01MH069217, Cook PI). It is well suited to evaluating brain function in
      subjects with MDD during a clinical trial experiment.

      Our hypotheses are

        1. Subjects who are randomized to receive active tDCS treatments will show greater
           improvement in cognitive task performance than subjects who receive inactive treatments.

        2. Subjects who are randomized to receive active tDCS treatments will show greater
           improvement in depression symptom severity scores than subjects who receive inactive
           treatments.

        3. Subjects who are randomized to receive active tDCS treatments will show greater changes
           in prefrontal brain function, as assessed with quantitative EEG cordance, than subjects
           who receive inactive treatments.
    

Intervention name(s): Transcranial direct stimulation
Intervention type(s): Device
Intervention description(s): sessions of 20 minutes each
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Diagnostic