The purpose of this study is to gather information regarding the use of a new type of transcranial magnetic stimulation (TMS) called theta burst stimulation (TBS) for suicidal ideation in adolescents with Major Depressive Disorder (MDD). The investigators hope to learn if this TMS treatment improves suicidal ideation over 10 days and clinical outcomes over 1 year of follow-up.

The proposed study will examine sequential bilateral accelerated theta burst stimulation (aTBS). Three sessions are administered daily for 10 days (5 days per week). During each session continuous theta burst stimulation (cTBS) in which 1800 pulses are delivered continuously over 120 seconds to the right dorsolateral prefrontal cortex (RDPFC) is administered first, followed by iTBS in which 1800 pulses are delivered in 2 second bursts, repeated every 10 seconds for 570 seconds (1800 pulses) to the left dorsolateral prefrontal cortex (LDPFC). The theta burst stimulation (TBS) parameters were adopted from prior work, with 3-pulse 50 Hz bursts given every 200 ms (at 5 Hz) with an intensity of 80% of active motor threshold. The comparison group will receive 3 daily sessions of bilateral sham TBS treatment for 10 days. Subjects in both groups will take part in a daily psychotherapeutic treatment program.

The proposed study will examine sequential bilateral accelerated theta burst stimulation (aTBS). Three sessions are administered daily for 10 days (5 days per week). During each session continuous theta burst stimulation (cTBS) in which 1800 pulses are delivered continuously over 120 seconds to the right dorsolateral prefrontal cortex (RDPFC) is administered first, followed by iTBS in which 1800 pulses are delivered in 2 second bursts, repeated every 10 seconds for 570 seconds (1800 pulses) to the left dorsolateral prefrontal cortex (LDPFC). The theta burst stimulation (TBS) parameters were adopted from prior work, with 3-pulse 50 Hz bursts given every 200 ms (at 5 Hz) with an intensity of 80% of active motor threshold. The comparison group will receive 3 daily sessions of bilateral sham TBS treatment for 10 days. Subjects in both groups will take part in a daily psychotherapeutic treatment program.

The study will enroll outpatient and inpatient adolescents (aged 12-18 years) with Major Depressive Disorder (MDD) of at least moderate severity defined as a Children's Depression Rating Scale Revised (CDRS-R) Score of 40 or greater and suicidal ideation defined as a score of 3 or greater on item 13 (Suicidal Ideation) of the CDRS-R.

Inclusion Criteria:

• Inpatients or outpatients
• Voluntary clinical patient with the capacity to assent to treatment and a parent or legal guardian with the capacity to consent
• Female or male
• 12-18 years of age
• Diagnosed with MDD based on Diagnostic and Statistical Manual for Mental Disorders, 5th edition (DSM-5) criteria122 with the Mini-International Neuropsychiatric Interview for Children and Adolescents (MINI Kid) in subjects 12-17 years of age;118 The Mini-International Neuropsychiatric Interview will be used for subjects who are 18 years of age117
• In a current episode of MDD with duration of at least 4 weeks but less than 3 years
• Depressive symptom severity as demonstrated by CDRS-R total composite score of 40 or greater and a suicidal ideation score of 3 or more on item 13 of the CDRS-R109
• Demonstrating that depressive symptom severity as evaluated at the screening visit does not improve between screening and baseline by 25% or more
• Eligible for transcranial magnetic stimulation (TMS) based on safety criteria104
• On a medically acceptable form of birth control if female
• Taking an antidepressant medication if recommended by the referring clinician and agreed upon by parents and patients. Please note that patients are not required to take an antidepressant medication for study participation for practical, ethical, and human subject protection concerns. Medication status and prior treatment resistance will be carefully recorded with the Antidepressant Treatment History Form113 criteria for relevant statistical considerations.

Exclusion Criteria:

• Diagnosis of a psychotic disorder, bipolar disorder, anorexia nervosa, bulimia nervosa, substance use disorders within the past year (with the exception of caffeine and tobacco).
• Intelligent quotient less than 70 (if there is a clinical concern, subjects will be psychometrically assessed with the Slosson Intelligence Test, Revised).123
• Positive urine drug screen at baseline
• Seizure history
• Any family history of epilepsy
• History of any treatment with electroconvulsive therapy or TMS
• Use of any investigational drug within 4 weeks of baseline
• Prior brain surgery
• Risk for increased intracranial pressure such as a brain tumor
• Head trauma with loss of consciousness
• Any true positive findings on the TMS safety screening form
• Pregnancy or suspected pregnancy
• Conductive, ferromagnetic, or other magnetic-sensitive metals implanted in the head-within 30 cm of the treatment coil excluding the mouth that cannot be safely removed (examples include cochlear implants, vagus nerve stimulators, deep brain stimulators, implanted electrodes/stimulators, aneurysm clips or coils, stents, bullet fragments, jewelry and hair barrettes).
• Implanted medication pumps and cardiac pacemakers
• Any unstable medical condition
• Inability to adhere to the protocol

Data will be uploaded and NIMH databases and shared as per NIMH and NIH policy

The use of the MagVenture Cool-B70 A/P coils facilitates blinding of the operator and subjects receiving aTBS or sham treatments. The study team members completing clinical rating scales will also not be allowed in the treatment suite during TBS treatment sessions and will be blinded to treatment assignment. A pre-post treatment expectancy and experience form will ask subjects and parents to make a guess regarding treatment arm (active or sham). Blinded study team members will also be asked to guess treatment assignments for each subject.