Sequential Bilateral Accelerated Theta Burst Stimulation in Adolescents With Suicidal Ideation


About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

 Inclusion Criteria:

  • Inpatients or outpatients.
  • Voluntary clinical patient with the capacity to assent (or consent if 18) to treatment and a parent or legal  guardian with the capacity to consent (if younger than 18).
  • Biological female or male (nonbinary or other gender identities are not exclusionary).
  • 12-18 years of age.
  • Diagnosed with MDD based on Diagnostic and Statistical Manual for Mental Disorders, 5th edition (DSM-5) criteria with the Mini-International Neuropsychiatric Interview for Children and Adolescents (MINI Kid) in subjects 12-17 years of age; The Mini-International Neuropsychiatric Interview will be used for subjects who are 18 years of age.
  • 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 forty or greater and a suicidal ideation score of 3 or more on item 13 of the CDRS-R.
  • A minimum score of 1 (“wish to be dead”) on the C-SSRS severity of ideation subscale.
  • 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 criteria.
  • On a medically acceptable form of birth control during the 10 day acute treatment course if female and of child bearing potential.
  • 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 Form 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).
  • Lifetime diagnosis of a psychotic disorder confirmed by a research screening interview (including schizophrenia, major depressive disorder with psychotic features, and bipolar disorder with psychotic features).
  • Intelligent quotient less than 70 (if there is a clinical concern, subjects will be psychometrically assessed with the Slosson Intelligence Test, Revised).
  • Positive urine drug screen at baseline.
  • Patients with a history of epilepsy or unexplained seizures.
  • Any family history of epilepsy.
  • Patients medicated with drugs lowering the seizure threshold (examples: neuroleptic agents and tricyclic antidepressants).
  • 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.
  • Life-time history of head trauma with loss of consciousness for greater than 5 minutes duration.
  • Any true positive findings on the TMS safety screening form (TASS).
  • Pregnant or nursing patients.
  • 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).
  • Patients with any implanted stimulators or implants controlled by physiologic signals, including VNS, SCS, PNS, defibrillators and pacemakers.
  • Patients with neurological conditions that include a history of seizures, cerebrovascular disease, cerebral aneurysm, dementia, movement disorders, having a history of repetitive or severe head trauma, or with primary or secondary tumors in the CNS.
  • Patients with a history of increased intracranial pressure, history of severe headaches within the previous 1 year, or severe head trauma.
  • Implanted medication pumps and cardiac pacemakers.
  • Patients suffering from vascular, traumatic, tumoral, infectious, or metabolic lesions of the brain, even without a history of seizure, or without anticonvulsant medication.
  • Patients with an unstable medical illness (other than depression).
  • Inability to adhere to the protocol.

Eligibility last updated 1/20/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Paul Croarkin, D.O., M.S.

Open for enrollment

Contact information:

Can Ozger

(507) 422-2605

More information


  • Conventional treatments for youth depression, such as antidepressants, have modest efficacy, side effects, and ongoing controversies regarding safety. Repetitive transcranial magnetic stimulation (rTMS), specifically theta burst stimulation (TBS), applied to the dorsolateral prefrontal cortex (DLPFC) has demonstrated efficacy for the treatment of depression in adults. However, the feasibility and clinical response to TBS for youth depression has yet to be explored. Read More on PubMed
  • Repetitive transcranial magnetic stimulation (TMS) is now widely available for the clinical treatment of depression, but the associated financial and time burdens are problematic for patients. Accelerated TMS (aTMS) protocols address these burdens and attempt to increase the efficiency of standard TMS. This systematic review and meta-analysis aimed to examine accelerated TMS studies for depressive disorders in accordance with PRISMA guidelines. Inclusion criteria consisted of studies with full text publications available in English describing more than one session of TMS (repetitive or theta burst stimulation) per day. Studies describing accelerated TMS protocols for conditions other than depression or alternative neuromodulation methods, preclinical studies, and neurophysiology studies regarding transcranial stimulation were excluded. Eighteen articles describing eleven distinct studies (seven publications described overlapping samples) met eligibility criteria. A Hedges' g effect size and confidence intervals were calculated. The summary analysis of three suitable randomized control trials revealed a cumulative effect size of 0.39 (95% CI 0.005-0.779). A separate analysis including open-label trials and active arms of suitable RCTs revealed a g of 1.27 (95% CI 0.902-1.637). Overall, the meta-analysis suggested that aTMS improves depressive symptom severity. In general, study methodologies were acceptable, but future efforts could enhance sham techniques and blinding. Read More on PubMed
  • Suicide is a leading cause of death among youth. Prior research using transcranial magnetic stimulation (TMS) has implicated deficits in GABAergic cortical inhibition in adolescent suicidal behavior, yet no studies have assessed whether cortical inhibition varies over time in conjunction with changes in suicidal ideation (SI). This study examined dynamic changes in long-interval intracortical inhibition (LICI), a TMS measure of GABA-mediated inhibition, and their relationship with changes in SI in a small sample of adolescents undergoing pharmacologic treatment for depression. Read More on PubMed
  • This exploratory study sought to examine the effect of an acute course of high-frequency repetitive TMS on suicidal ideation in adolescents. Read More on PubMed
  • Although suicide is the second-leading cause of death in adolescents and young adults worldwide, little progress has been made in developing reliable biological markers of suicide risk and suicidal behavior. Converging evidence suggests that excitatory and inhibitory cortical processes mediated by the neurotransmitters glutamate and γ-aminobutyric acid (GABA) are dysregulated in suicidal individuals. This study utilized single- and paired-pulse transcranial magnetic stimulation (TMS) to assess excitatory and inhibitory cortical functioning in healthy control adolescents (n = 20), depressed adolescents without any history of suicidal behavior ("Depressed", n = 37), and depressed adolescents with lifetime history of suicidal behavior ("Depressed+SB", n = 17). In a fixed-effects general linear model analysis, with age, sex, and depression severity as covariates, no significant group main effects emerged for resting motor threshold, intracortical facilitation, short-interval intracortical inhibition, or cortical silent period. However, group main effects were significant for long-interval intracortical inhibition (LICI) at interstimulus intervals (ISIs) of 100 ms and 150 ms, but not 200 ms. Depressed+SB adolescents demonstrated impaired LICI compared to healthy control and Depressed adolescents, while healthy control and Depressed participants did not differ in LICI. Multiple linear robust regression revealed significant positive linear relationships between lifetime suicidal behavior severity and impairment in LICI at 100-ms and 150-ms ISIs. In a post hoc receiver operating characteristic analysis, LICI significantly discriminated Depressed from Depressed+SB youth in 100-ms and 150-ms paradigms. These findings suggest that GABA receptor-mediated inhibition is distinctly dysregulated in depressed adolescents with histories of suicidal behavior. Further research is warranted to establish the utility of cortical inhibition in the assessment of suicide risk and as a target for treatment interventions. Read More on PubMed