Brain STimulation for ANxiety and Depression in Youth

Mental health disorders are a leading cause of disability, and approximately 14% of adolescents are diagnosed globally. Within Canada, the prevalence of mental health disorders is increasing, with youth aged 15-24 years being greatly impacted. Broadly, mental health disorders include anxiety, post-traumatic stress disorders, depression, schizophrenia, disruptive behaviour, and neurodevelopmental disorders such as autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). Mental health disorders are associated with clinically significant disrupted behaviour, emotional regulation, and thinking, and can limit one's ability to participate in activities of daily living and drastically impact quality of life. Moreover, a variety of negative outcomes can be associated with these mental health disorders, including health and development-related concerns regarding educational achievement, substance abuse, violence, reproductive and sexual health. In Canada, suicide was the fourth leading cause of death in children (age 1-14; after cancer, accidental injuries and congenital malformations) and the second leading cause of death in youth (age 15-19; after accidental injury) in 2023 according to Stats Can. https://www150.statcan.gc.ca/.

The literature suggests the peak age of mental health disorder onset within the general global population is 14.5 years; a recent meta-analysis of 192 epidemiological studies also reported approximately 83% of individuals with neurodevelopmental disorders experienced onset by the age of 18 years. Further, approximately 52% of individuals with anxiety or fear-related disorders, 48% with feeding or eating disorders or problems, 45% with obsessive-compulsive or related disorders, 28% with stress disorders, and 12% with mood disorders experienced onset by the age of 18 years. The high prevalence of mental health disorders within the child and youth population, and the limited options and availability of therapy choices is contributing to the need to explore additional treatment opportunities.

Interventions for mental health disorders commonly include psycho-social and pharmacological approaches, though these therapies are largely modelled after adult populations, with some indication that medications are not as effective in children and adolescents. Pharmacotherapy may be accompanied by side-effects, and adverse experiences with psychotropic medications at a young age reportedly contribute to poor long-term adherence to other psychiatric therapies. Many families and patients have strong preference for nonpharmaceutical treatments, which can limit options. Another proposed intervention strategy for mental health disorders involves non-invasive brain stimulation, including transcranial magnetic stimulation (TMS). TMS elicits changes in neural population activation with the use of repetitive TMS (rTMS) or theta-burst stimulation. TMS has been used for the treatment of anxiety and depression in adults, and both TMS and TBS have been well-tolerated in children, with only mild transient side effects noted. TMS may be an effective adjunct or sole treatment for mental health disorders in youth; for example, when combined with antidepressants, rTMS increased the treatment effect in 8-24-year-olds with depression, and therefore the clinical application of TMS for mental health disorders in youth requires further investigation. In the United States, rTMS has been approved for the treatment of depression in adolescents starting at the age of 15, and there are encouraging results in implementation studies in other jurisdictions. To ensure adolescents in Canada have access to this therapy, clinical care pathways (such as appropriate referral criteria, outcome measures, and resource requirements) must be better understood.

There are indications that TMS is effective and safe in many populations that are at high risk of depression. For example, TMS has shown to be safe and effective for treatment of depression during pregnancy. In contrast, the use of antidepressants during pregnancy is associated with a risk (though low) of adverse effects for both mother and fetus. Furthermore, treatment of anxiety and depression in complex populations with co-occurring conditions, such as in patients with neurodevelopmental disorders, has limited research in general and in neurostimulations specifically. Despite the recent approval in the United States, evidence for neurostimulation in children and adolescents is lagging behind that of adults. Given the burden of disease in this population, improvement in research, particularly implementation and clinical integration, is both a clinical and ethical imperative.

Inclusion criteria

• aged between 6 and 18 years old
• diagnosis of anxiety or depression made by a qualified medical professional
• active anxiety and/or depression symptoms

Exclusion criteria

• status epilepticus in past 12-months
• presence of any disease, medical condition, or physical condition that, in the opinion of the study investigator may compromise, interfere, limit, affect, or reduce the participant's ability to complete the study
• hospitalization for suicide attempt within the past 3 months (unless participant is under the daily supervision of a physician, such as in a mental health day treatment program)
• TMS-related contraindications, including implanted medical devices (e.g., pacemaker)
• if actively taking prescription medication, no changes in medication for at least 3 months prior to entry into the study, with no anticipation of change in the frequency or dose over the duration of the study, unless changes to medication are required for participant safety
• unable to understand instructions in English