itbs in refractory pediatric depression

Conditions: Depression

Summary: this work will mark the first step in understanding the neural targets for rtms in youth with difficult to treat depressive symptoms, creating benchmarks for optimizing the safety and efficacy of rtms for pediatric populations through precision targeting, and encourage funding applications for larger sham- controlled randomized clinical studies.

problem statement: depression is a global health problem with limited novel and targeted solutions. currently available interventions (medication and psychotherapy) have failed to provide adequate clinical improvement in 40% of adolescents with depression and only produce remission in 30% of youth. there is a clear need to develop better targeted interventions for this growing population of youth. specific aims aim 1: to examine the efficacy of a targeting strategy to optimize repetitive transcranial magnetic stimulation (rtms) delivered to the left dorsolateral prefrontal cortex (dlpfc) to reduce depressive symptoms in adolescents between 12-17 years of age. hypothesis 1: six weeks of open-label daily intermittent theta-burst stimulation (itbs) sessions delivered to the left dlpfc will be effective at reducing depressive symptoms between baseline and 10- week follow-up. hypothesis 2: itbs over left dlpfc will decrease functional connectivity between left dlpfc and subcallosal cingulate cortex (scc) and will reduce depression-related hyperconnectivity between nodes of the default mode network (dmn). hypothesis 3: higher anti-correlation between left dlpfc and scc and lower cingulate glutamate concentrations will predict better clinical outcome following itbs. aim 2: to determine the tolerability of itbs in adolescents between 12-17 years of age. hypothesis 1: itbs will be well tolerated without any more than minimal side effects. hypothesis 2: itbs will result in sufficient cortical excitability, as measured by 64-channel-eeg pre, during, and post itbs, to induce an antidepressant effect but not induce seizures or other adverse events.

Eligibility criteria:
inclusion criteria: * 10 participants ages 12-21 years of age * with at least moderate to severe depressive symptoms confirmed by the children's depression rating scale-revised (cdrs-r\>40) or hamilton rating scale for depression (hrsd-17 ≥ 18) * able to commit to protocol schedule and provide informed consent by a legal guardian and assent by a youth participant * have had at least one prior antidepressant treatment failure with adequate dose and duration exclusion criteria: * prior neurological diagnosis (neurodevelopmental disorders, strokes/traumatic brain injuries, brain tumor, epilepsy) * contraindications for tms or mri e.g. have any implanted metal * unstable medical conditions * acute suicide risk, defined as an attempt in past 6 months that required medical treatment, or history of ≥2 suicide attempts in the past 12 months, or has a clear cut plan for suicide * pregnancy, suspected pregnancy or not on birth control if sexually active; 6) inability to locate and quantify a motor threshold * any factor that the pi determines to be reason for exclusion.

Keywords: depression transcranial magnetic stimulation adolescent treatment refractory