Suicidal ideation, suicide attempts, and deaths from suicide are critical global public health concerns. Suicide is a leading cause of mortality among adolescents and young adults (World Health Organization, 2021). Deaths related to suicide often coincide with the onset of an initial depressive episode (McGirr et al., 2008). Adolescence is a time of great risk and opportunity with dynamic neurodevelopmental changes and increased neuroplasticity. Targeted interventions during adolescence may reduce deaths by suicide and mitigate future suicide attempts (Herrman et al., 2022). Suicidal ideation and suicide attempts are pivotal risk factors for mortality related to suicide (Keyes and Platt, 2023). Among mental health disorders, depression exhibits the most robust association with morbidity and mortality related to suicidal thoughts and behaviors (Favril et al., 2022). However, it is essential to recognize that suicide may manifest independently of depression, necessitating focused research on suicide-specific interventions (Oliogu and Ruocco, 2024). A significant number of adolescents do not respond to standard evidence-based treatments for suicidal thoughts, behaviors, and depression (Cuijpers et al., 2013). Furthermore, antidepressant medications have a U.S. Food and Drug Administration (FDA) boxed warning for increased risk of suicidal thoughts and behaviors in youth (Fornaro et al., 2019). At present, TMS does not have a related boxed warning. In addition to this possible lower risk, the inherent regular clinical visits and evaluations with TMS interventions may facilitate the monitoring and safety of adolescents at risk of suicide.

Innovative strategies have emerged to address suicidal behaviors. Until recently, it was rare for clinical trials to focus on suicidal thoughts and behaviors as primary outcomes. One promising approach involves the application of repetitive TMS. For the sake of simplicity and clarity, TMS refers to repetitive TMS in this manuscript unless stated otherwise. TMS is a non-invasive brain stimulation intervention for the treatment of major depressive disorder (MDD), with minimal adverse effects (Lefaucheur et al., 2020). International research labs and clinics have employed TMS protocols for MDD for more than two decades (Horvath et al., 2010).

Recent systematic reviews and meta-analyses have examined the putative effectiveness of TMS interventions for reducing suicidal ideation (Bozzay et al., 2020; Cui et al., 2021; Godi et al., 2021; Mehta et al., 2022). However, large effectiveness studies of TMS for suicidal ideation examining optimal parameters for treatment are still lacking (Weissman et al., 2018). Furthermore, research with adolescents and TMS interventions for suicidal thoughts and behaviors is only slowly developing. Existing studies addressing suicidal thoughts and behaviors with TMS treatments have primarily focused on high-frequency TMS administered to the left dorsolateral prefrontal cortex (DLPFC) in adolescents (Croarkin et al., 2018; Pan et al., 2018; Zhang et al., 2021).

High-frequency TMS interventions are thought to have excitatory effects on cortical neurophysiology and therapeutic mechanisms that involve long-term potentiation (LTP)-like activity (Hoogendam et al., 2010; Karabanov et al., 2015; Kimbrell et al., 1999). The application of high-frequency TMS to the left DLPFC is based on the theory that the left DLPFC is hypoactive in patients with depression (Brunoni et al., 2017). Conversely, low-frequency TMS protocols are thought to have inhibitory effects. Therapeutic effects of low frequency TMS are thought to be mediated through long-term depression (LTD)-like activity (Kimbrell et al., 1999). It is important to emphasize that these theories involving high and low-frequency TMS interventions are oversimplifications of complex processes. For example, some prior research demonstrated excitatory effects of low frequency TMS (Gilio et al., 2003; Schambra et al., 2003). These contrasting outcomes underscore the importance of accounting for individual variability (Hoogendam et al., 2010).

Low-frequency TMS interventions have been studied less for depression and suicidal thoughts/behaviors (Brunoni et al., 2017; Hecht, 2010). A systematic review of the effects of low-frequency TMS in adolescents with depression found that low-frequency TMS applied to the right DLPFC was effective and safe (Zheng et al., 2023). Evidence also shows that TMS treatments have global brain effects related to transsynaptic activity (Wassermann et al., 1998). It is unknown whether low-frequency TMS may have favorable specific or global cerebral effects for the treatment of suicidal thoughts and behaviors in adolescents. To our knowledge, no study has compared the effectiveness of different frequencies of TMS in adolescents with suicidal ideation. This exploratory study examined the effectiveness of 1 Hz and 10 Hz frequencies of TMS on reducing suicidal ideation in adolescents with MDD. Our hypothesis was that 1 Hz and 10 Hz treatments would have similar effects in reducing suicidal ideation in adolescents with MDD.