TMS in the Treatment of the Sequelae of Closed Brain Injury
Condition: Depression; Closed Head Injury
MeSH terms: Brain Injuries; Craniocerebral Trauma; Head Injuries, Closed; Wounds and Injuries; Depression
Study type: Interventional

Summary: 
      Depression is very common in people who have experienced a traumatic brain injury. Few
      treatments have been found to be effective in treating depression in this situation. We
      intend to investigate the effectiveness of a form of brain stimulation, transcranial magnetic
      stimulation, which has been found to be effective in treating depression in people who have
      not undergone a brain injury. By evaluating new methods of treating depression in this
      population, we hope to increase the options available for treating people in this difficult
      situation. Furthermore, problems with aspects of thinking are also commonly present post
      brain injury, as in some individuals with depression. Various brain stimulation techniques,
      including transcranial magnetic stimulation (TMS) have been shown to have a positive effect
      on cognition. We also intend to investigate whether a therapeutic effect on cognitive
      deficits is present following TMS, in addition to any effects on depression. New treatment
      protocols will be developed, and understanding of the pathology and treatment of post
      traumatic brain injury depression will be enhanced.
    

Detailed description: 
      It is plausible to propose that the same treatment paradigm may result in an improvement in
      mood and cognition with the possibility that these changes will be self reinforcing resulting
      in enhanced quality of life and reduced service demands.

      The proposal for the use of rTMS in the treatment of post TBI depression is also supported by
      aetiological models. In particular, rTMS would seem to have considerable potential to improve
      pathophysiological changes relevant to the treatment of post TBI depression and cognitive
      dysfunction. Early models of the mechanism of action of rTMS treatment in depression were
      based on the observation that rTMS is able to produce localised changes in cortical activity
      [7]. The standard treatment paradigm generally has been found to produce an increase in local
      prefrontal cortical excitability. However, more recently there has been an increased
      understanding that rTMS modulates distal brain regions as well and potentially the strength
      of connections between brain regions. It has been proposed that its therapeutic effects in
      non TBI-related depression occur through modulation of dorsal frontal - subcortical limbic
      connectivity and potentially the actual integrity and strength of connections between these
      regions. If this is the case, altering cortical - cortical or cortical - subcortical
      connectivity may lead to therapeutic benefits in post TBI depression due to likely
      involvement of white matter changes in the development of TBI related mood disorder.

      Aims/Objectives/Hypothesis/es Primary Aim: To assess the effectiveness of rTMS in treating
      depression post traumatic brain injury.

      Secondary Aim: To gain preliminary data as to the possible effectiveness of rTMS in treating
      cognitive deficits post traumatic brain injury.

      Hypothesis 1: Active bilateral sequential rTMS will lead to an improvement in the symptoms of
      post TBI depression, as measured by MADRS scores, when compared to sham treatment Hypothesis
      2: Active bilateral sequential rTMS will lead to an improvement in cognitive executive
      functioning in individuals post TBI, when compared to sham treatment Hypothesis 3: Active
      bilateral sequential rTMS will lead to an improvement in life satisfaction and level of
      functioning in individuals post TBI, when compared to sham treatment.

      Methodology Experimental Design and Randomisation Procedures The study has been designed to
      allow the reporting of results in a manner consistent with the international CONSORT
      guidelines. The study will involve a 4-week (20 session) randomized double-blind clinical
      trial with 2 treatment arms conducted at the Alfred Psychiatry Research Centre in Melbourne.
      Randomization will occur via the generation of a computer number sequence. Subjects will be
      randomized immediately prior to the commencement of the first treatment session, after the
      measurement of bilateral resting motor thresholds with standard means.

      The main study phase (phase 1) will involve the 4 week randomized controlled trial conducted
      under strict double-blind conditions. Fidelity of the blinding process will be assessed at
      the end of this period with patients and raters. Phase 2 will involve the provision of open
      label treatment to patients who received sham treatment and wish to receive 'active' rTMS.

      Responders to active treatment from phase 1 or 2 (defined as a 50% reduction in MADRS scores
      persisting for 1 week following the end of acute treatment) will enter phase 3, a 6 month
      maintenance phase. During this time, a single rTMS treatment session will be provided every
      week for 2 months and then every 2 weeks for 4 months. Acute treatment for up to 4 weeks will
      be reinstated if there is a persistent (2 week) increase in MADRS score of >25%.
    

Intervention name(s): rTMS; Sham rTMS
Intervention type(s): Device; Device
Intervention description(s): Bilateral rTMS; sham rTMS
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Depression; TBI; TMS; Major Depression resulting from a mild to moderate closed head injury