Pathophysiological Understanding and Treatment of PTSD: an rTMS Approach
Condition: Stress Disorders, Post-Traumatic; Brain Injuries; Transcranial Magnetic Stimulation; Magnetic Resonance Spectroscopy; Biomarkers; Depression, Anxiety
MeSH terms: Brain Injuries; Stress Disorders, Post-Traumatic
Study type: Interventional

Summary: 
      In Canada, the prevalence of PTSD is approximately 12%, similar to Canadian military
      personnel. Current treatments for PTSD are limited in efficacy and durability - indicating a
      dire need for novel interventions in this population. Transcranial magnetic stimulation (TMS)
      has a high degree of safety and has been studied as an intervention for many mental health
      and neurological conditions; even showing initial promise for PTSD. We propose to study this
      further in a randomized sham controlled trial of TMS for PTSD.
    

Detailed description: 
      In Canada, the prevalence of PTSD is approximately 12%, similar to Canadian military
      personnel. However, a 2002 study of members of Canadian Armed Forces found there was a
      striking positive correlation between the number of missions taken by the regular/reserve
      force and increase risk of developing PTSD, suggesting a dire need for further treatment
      options. Transcranial magnetic stimulation (TMS), a neuromodulation technique applied to the
      brain, has been studied as a treatment that has the potential to improve symptoms in a
      variety of neurological/mental health conditions. TMS is a safe and non-invasive technique
      that applies an electrical current to the brain to induce neuronal depolarization, changing
      regional brain function with the goal of improving neurological/psychiatric symptoms.
      Although multiple studies using TMS have suggested it as an efficacious treatment option for
      PTSD, clear knowledge gaps exist that prevent it from becoming evidence-based clinical care.

      A recent meta-analysis on TMS and PTSD found that no study has examined the difference
      between genders, and recommended that further studies with larger sample sizes, equal male
      and female participants, and more stringent study designs were required. Our study is novel
      and seeks to bridge the gap from research to clinical care by completing a study
      investigating repetitive TMS (rTMS) treatment for PTSD that recruits a large sample size,
      uses a randomized controlled clinical trial with a sham lead-in, and follows a stringent TMS
      protocol with equal sex participants.

      Not all individuals with PTSD respond to TMS treatment, and no study to date has explored
      what biomarkers may predict TMS responders in the PTSD population. Previous studies propose
      glutamate, BDNF and glutamatergic changes on MR spectroscopy may be altered in other mental
      health illnesses, which suggests they may be useful biomarkers of TMS response in PTSD.
      Therefore, this study will be the first of its kind to develop predictive biomarkers of
      response by sampling serum BDNF, glutamate, and glutamatergic changes in MR spectroscopy pre-
      and post rTMS treatment, in patients with PTSD that respond to TMS compared to those that do
      not.

      Recent studies have shown single-pulse TMS is beneficial for some individuals with chronic
      PTSD, and emerging evidence suggests there are specific phenotypes within PTSD that may
      require different TMS protocols. A recent study by Etkin et al. explored whether there were
      multiple phenotypes within chronic PTSD that would explain treatment responses. They found
      individuals with PTSD that scored significantly lower on verbal memory tasks (LVMS) (list
      repetition) had significantly impaired functional connectivity in the brain's ventral
      attention network (VAN) compared to patients with PTSD that had normal scores (NVMS). This
      suggests there may be a subgroup of patients with PTSD that would respond better to TMS in
      the right dorsal medial prefrontal cortex (DMPFC) (corresponding to the VAN) than to the
      right dorsal lateral prefrontal cortex (DLPFC).
    

Intervention name(s): Repetitive Transcranial Magnetic Stimulation to Right Dorsolateral Prefrontal Cortex; Sham Repetitive Transcranial Magnetic Stimulation; Repetitive Transcranial Magnetic Stimulation to Right Dorsomedial Prefrontal Cortex
Intervention type(s): Device; Device; Device
Intervention description(s): Transcranial magnetic stimulation (TMS) works by delivering a magnetic pulse to a focal brain region. TMS has a high degree of safety and has been studied as an intervention for many mental health and neurological conditions. Repetitive TMS (rTMS) delivers pulses at a set time interval in order to modulate neural activity in that region.; The sham TMS coil will make a similar sound to the real rTMS coil, but will not deliver a magnetic pulse. This is a no-treatment device.; Transcranial magnetic stimulation (TMS) works by delivering a magnetic pulse to a focal brain region. TMS has a high degree of safety and has been studied as an intervention for many mental health and neurological conditions. Repetitive TMS (rTMS) delivers pulses at a set time interval in order to modulate neural activity in that region.
Other intervention name(s): rTMS to DLPFC; rTMS to DMPFC
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Group 1: Treatment of the right dorsolateral prefrontal cortex Group 2: Treatment of the right dorsomedial prefrontal cortex
Masking: Double (Participant, Investigator)
Primary purpose: Treatment