rTMS for Depression in Young Adults With Autism

The current clinical trial is focused on evaluating the efficacy of rTMS for treatment of depression in youth and young adults (hereafter called transition aged youth, TAY) with autism spectrum disorder (ASD). The motivation to undertake the current efficacy study is driven by: (1) the substantial impact of depression on TAY with ASD (based on prevalence and contribution to disability/impairment); (2) lack of evidence-based treatments for depression in autism (there are no current trials rigorously evaluating any treatment for depression, i.e., psychotherapeutic, pharmacotherapeutic, brain stimulation); (3) rTMS has demonstrated efficacy in non-autistic individuals to improve symptoms of depression and may be better tolerated in youth than medication treatment; (4) a prior pilot rTMS study focused on treatment of executive function deficits in autism indicated that high frequency rTMS delivered using a rigorous randomized control trial (RCT) protocol can be feasibly implemented in TAY with autism, is well tolerated (mild to moderate adverse effects and low drop out), and has the potential to improve symptoms of depression.

The investigators will use a randomized, double-blind, sham-controlled design of bilateral theta burst stimulation (BL-TBS) to dorsolateral prefrontal cortex (DLPFC) administered 5 days per week for 6 weeks (30 sessions). The investigators will recruit n=80, 16-35 year old participants with autism that do not have co-occurring intellectual disability (ID). In the current study, the target population will be individuals with autism, without ID who have co-occurring clinically significant depression. Pre/post treatment MRI will be used to study mechanisms of treatment response. The investigators will build on their previous pilot rTMS study in autism with two key innovations. First, the investigators will use theta burst stimulation (TBS) for depression as opposed to conventional rTMS. TBS is a newer form of rTMS shown to be non-inferior to conventional rTMS for depression with a similar safety profile. Tolerance of intermittent TBS (iTBS, delivered at 100% RMT to right DLPFC in ten 9-17 year-olds with ASD) has already been shown in autism in a prior open-label study. Importantly, TBS can be delivered in a fraction of the time needed for conventional rTMS. This shorter administration time may be critical for participant retention as sensory sensitivity is a major feature of autism. A shorter administration also has important practical implications for future clinical access. The investigators will use BL-TBS based on: preliminary data of improved antidepressant efficacy with a bilateral (over unilateral) TBS approach that combines left excitatory with right inhibitory DLPFC stimulation, as well as findings that bilateral (over unilateral) rTMS may improve suicidal ideation in MDD.

Eligibility Criteria:
Inclusion Criteria:

* Fluent in English
* ASD diagnosis confirmed by the clinician/clinical team, and IQ\> or =70
* Able to participate in the informed consent process, provide voluntary informed consent and provide a spontaneous narrative description of the key elements of the study
* Clinical stability: determined by a physician, no switch of psychotropic medications or increase in dosage in the last 30 days; no change in other therapeutic interventions in last 30 days
* BDI-II score ≥21 that is sustained over a lead-in period of two weeks
* Global Assessment of Function (GAF) scores (≤60) that is sustained over a lead-in period of two weeks AND/OR VABS-III below adequate functioning at baseline assessment.

Exclusion Criteria:

* A history of a DSM-5 substance use disorder (other than tobacco) within the past six months; or a positive baseline urine drug screen
* Significantly debilitating medical or neurologic illness, or acute or unstable medical illnesses as determined by study physician
* Metal implants or a pace-maker, claustrophobia that would preclude the MRI scan
* Actively suicidal (i.e., suicidal ideation with plan and intent) or high risk for suicide as assessed by a study psychiatrist
* History of seizures
* Taking benzodiazepines at a dose greater or equal to 2mg Lorazepam or any anticonvulsant medication
* Prior rTMS treatment
* Pregnancy