Efficacy and Biological Targets of Response to rTMS Therapy in Youth Depression
Condition: Depressive Symptoms
MeSH terms: Depression
Study type: Interventional

Summary: 
      Youth depression is a debilitating disorder that exacts enormous social, economic and
      personal cost. Unfortunately, treatments which are conventionally used to treat adult
      depression have often modest to no efficacy in youth and have side effects. Thus, there is a
      tremendous imperative to develop new treatments for youth depression. Investigators propose
      to examine the efficacy of a short form of repetitive transcranial magnetic stimulation
      (rTMS) for youth depression and examine its biological targets. This will be the first study
      examining the efficacy of a short rTMS protocol in youth diagnosed with depression who fail
      responding to or are intolerable to antidepressants. If the results are positive,
      investigators will have identified a novel treatment that may be both more efficacious,
      better tolerated and more acceptable treatment for youth depression. Finally, identifying the
      biological mechanisms leading to treatment efficacy will lead to more personalized treatments
      for youth depression and will be groundbreaking vis à vis understanding the mechanisms
      involved in this illness.
    

Detailed description: 
      The highest rates of depression are reported in youth 16-24 years of age and youth depression
      is a significant source of burden to the individual, their families, and to society.
      Unfortunately, current treatments (e.g., selective serotonin reuptake inhibitors), which are
      conventionally used to treat depression often have modest and sometimes no efficacy in youth.
      Also, accumulating evidence suggests that these medications may increase suicidal thoughts in
      adolescents and young adults below the age of 24. In addition to pharmacological treatments,
      cognitive behavioral therapy (CBT) has been used alone or in combination with medications for
      treating depression in this age group. Although randomized controlled trials and practice
      guidelines support the use of CBT alone and CBT with an antidepressant medication for
      adolescent depression, a large minority of adolescents do not respond to either treatment
      approaches.Thus, there is a tremendous imperative to develop new treatments for youth
      depression.

      Investigators propose to examine the efficacy of repetitive transcranial magnetic stimulation
      (rTMS) for youth depression. There are several reasons for pursuing this treatment: 1) rTMS
      applied to the dorsolateral prefrontal cortex (DLPFC), a cortical region implicated in
      pathophysiology of depression, is a safe and FDA approved treatment for adults with
      medication-resistant depression; 2) Young age is suggested to be a good predictor of response
      to rTMS treatment; 3) rTMS trials in adolescence and youth with medication resistant
      depression provide evidence that rTMS is a safe efficacious and well tolerated treatment for
      adolescents that does not increase suicidal thoughts. Additionally, recently rTMS parameter
      developments such as theta burst stimulation (i.e., TBS) provide compelling evidence for
      efficacy in less of the time it takes to administer conventional rTMS, thus lowering the
      overall costs and increasing the number of patients that can be treated.

      It is imperative that research investigate treatment related biological mechanisms, such that
      increases in understanding can lead to enhanced efficacy. Investigators will utilize a novel
      and powerful in vivo brain mapping technique of TMS combined with electroencephalography
      (TMS-EEG) that permits non-invasive assessment of inhibitory, connectivity and plasticity
      mechanisms from the DLPFC. The pathophysiology of depression has been linked to impairment in
      neural plasticity and connectivity and neural and behavioral inhibition - mechanisms that can
      be measured through TMS-EEG and maybe changed by TBS treatment. Therefore, investigating the
      association between TBS-related changes in plasticity, connectivity and inhibition may be key
      to understanding both the treatment mechanisms involved in youth depression and predictors of
      treatment response in this disorder.

      Therefore the specific aims in this study are twofold:

        1. To examine the efficacy of TBS applied to the DLPFC for youth depression, and

        2. To identify biological targets and predictors of response to TBS applied to the DLPFC
           for youth depression.
    

Intervention name(s): rTMS
Intervention type(s): Device
Intervention description(s): Participants will receive 10 active TBS rTMS sessions once daily on weekdays for 2 weeks.
Other intervention name(s): TBS
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: rTMS; Depression; Youth; TBS; Brain Stimulation; Electrophysiology; Imaging