Rates of depression in the adolescent population are rising. Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) is an accelerated intermittent theta burst stimulation (aiTBS) protocol, a form of transcranial magnetic stimulation (TMS), that has received FDA clearance for treatment-resistant depression (TRD) in adults. One drawback of SAINT is that ten treatments are given in a day with a 50-minute intersession interval virtually occupying the participant’s entire day. Additionally, SAINT is understudied in teens and the treatment-naive population. We are conducting an open-label trial using established SAINT technology in which one cohort receives a truncated treatment protocol with the aim of improving clinical convenience. In this novel protocol, the number of treatments given in a day will be decreased from ten to five. Justification for this decrease in dose is supported by the SAINT clinical trials which found that highly treatment-resistant participants reached depression remission after an average of 26 sessions.
We propose investigating this truncated SAINT protocol in a population of treatment-naive teens aged 15-18 in their first major depressive episode. This is an auspicious population for this treatment modality for several reasons. First, the prevalence of teen depression is increasing. Second, rTMS has consistently demonstrated higher efficacy in patients with lower treatment-resistance including treatment-naive patients. Third, the successful application of rTMS in this population may prevent the initiation of pharmacotherapies, which have several shortcomings in this population including lower depression remission rates than adults, increases in suicidal ideation, long-term side effects, and discontinuation challenges. This study introduces a novel variation on SAINT and demonstrates its use in a population that would benefit substantially. Of note, there will also be a third cohort of participants aged 15-18 in their first major depressive episode
60 participants will be enrolled to receive either the traditional SAINT treatment (20), the truncated SAINT protocol (20), or pharmacotherapy only. Parents of study participants along with participants themselves will undergo pre-treatment and post-treatment interviews with the aim of measuring expectations, treatment preferences (neuromodulation as compared to pharmacotherapy or psychotherapy), and treatment convenience. The larger vision of this study is to provide pilot data for the safety, efficacy, and preference for rTMS in treatment-naive first depressive episode patients so that larger multisite randomized-controlled trials can further study this population and ultimately achieve FDA cleared first-line treatment status for rTMS.
The goal of this project is to demonstrate safety, efficacy, acceptability and treatment preference for a novel variation on the SAINT protocol in first depressive episode treatment-naive adolescents. We hypothesize that participants randomized to the truncated treatment protocol, which provides half the number of treatment sessions than the classic SAINT protocol, will have similar rates of treatment response and remission of symptoms of depression, but will also have a better treatment experience, as measured by acceptability and preference. We hypothesize both groups receiving rTMS will have better treatment response and remission rates as compared to the pharmacotherapy only cohort.
This funding will be used to cover resting-state functional connectivity magnetic resonance images (rsfc-MRI), and the creation precision rTMS targets using this data. This is one of the fundamental features of SAINT: personalized precision neuronavigated targeting. Funding will also be used to hire in-house faculty at UT Austin to build a secure REDcap page for study data. Lastly, funding will be used to support various researchers on this project, specifically, child psychologists who will be administering the study measures.
The Principal Investigator of this trial is Sean J. O'Sullivan, MD, PhD. Dr. O'Sullivan is a psychiatry resident at Dell Medical School at University of Texas at Austin. He has significant protected research time to complete this study over the next two years, and a track record working on SAINT trials with the founder of SAINT, Nolan Williams, MD. Dr. Williams will be advising this trial and his company, Magnus Medical, will be providing the neuronavigated targets. Dr. O'Sullivan's mentor for this project is Charles Nemeroff, MD, PhD, one of the most published psychiatrist in the world and the chair of psychiatry at Dell Medical School. J. Michele LaGrone, MD is a board certified Child and Adolescent psychiatrist who will serve as the study physician.
This study will be completed unless a severe adverse event occurs during the trial. This could include a suicide by a study participant or a seizure from a study participant. It is important to note that this study requires IRB approval at University of Texas at Austin and several safety measures are in place to mitigate the risk of a severe adverse event. However, treatment-naive adolescents with established major depressive disorder will be withheld the standard of care, pharmacotherapy and psychotherapy, in lieu of rTMS which does put them at a theoretical risk of suicide. Additionally, even though the FDA has deem rTMS very low-risk, a small risk of seizure (1 in 60,000 rTMS sessions which is lower than pharmacotherapy) remains. Additionally, adolescents have a higher-risk of seizure and rTMS is not FDA approved for this population.
More likely, this project may 'fail' if rTMS is not shown to be a more preferred or acceptable treatment than pharmacotherapy. Or, if the rTMS cohorts fails to demonstrate significant efficacy in relieving the symptoms of depression in this patient population. The most likely cause of this would be participant recruitment. Participants could have challenges in their life, such as socioeconomic, parental-related, or school-related causes of their depression. Such participants are unlikely to respond to rTMS.
It may also be challenging to hit recruitment goals for this project. However, we will be recruiting from a large child clinic (Texas Child Study Center) and believe that our recruitment targets will be hit based on the history of new patients at this clinic.
This project may also 'fail' if the truncated protocol is not scored higher than the classic protocol based on preference and acceptability measures, but also measure of depression symptoms.
We will be applying to several sources of funding including internal grants, state funding grants, and from psychiatry foundations such as the American Foundation for Suicide Prevention (Early Career Researcher Innovation Grant).