Esketamine Youth

The literature contains limited evidence on the treatment and management of adolescent treatment-resistant depression, making it a condition that often remains difficult to resolve (Zhou et al., 2014). Despite advancements in treatment modalities and interventions, the management of MDD with suicide ideation and TRD in adolescents continues to present significant clinical and therapeutic challenges. Given these ongoing difficulties, there is growing interest in exploring innovative treatments such as ketamine and esketamine

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In adolescents, ketamine’s neurobiological effects have been studied with a focus on brain entropy and neurotrophic molecular markers [Roy et al., 2021]. It was found that ketamine treatment increased brain entropy, suggesting enhanced neuroplasticity and brain function adaptability. Additionally, a significant rise in BDNF levels post-treatment indicated the promotion of neuronal growth and synaptic plasticity, correlating with clinical improvements in depressive symptoms (Roy et al., 2021) In another study, fMRI was used to observe changes in brain activity in adolescents with treatment-resistant depression before and after ketamine treatment [Thai et al., 2020]. Significant alterations were noted in the prefrontal cortex and amygdala, correlating with reductions in depressive symptoms and improvements in cognitive functions and overall behavior. Clinically, it is crucial that we address adolescent depression promptly not only to alleviate suffering and improve quality of life but also because untreated depression significantly increases the risk of suicide among this age group. Studies have shown that depression is a major risk factor for suicidal ideation and attempts in adolescents (Aalsma et al., 2020). The approval of esketamine, the S-enantiomer of ketamine, by major regulatory authorities such as the FDA and EMA for TRD has indeed been a significant advancement in the treatment of TRD. Several studies have demonstrated esketamine efficacy and safety in adults, even in the long term (Daly et al., 2018). Other reviews have investigated the general efficacy of ketamine in treating adolescent and pediatric depression, predominantly focusing on the use of intravenous ketamine at varying doses, highlighting its potential as a rapidly acting antidepressant (Ryan et al., 2023). A recent review investigated the role of ketamine for mood disorders, anxiety, and suicidality in children and adolescents, highlighting that ketamine may be safe and effective for these conditions in youth [Bruton et al., 2024].

 

Why esketamine intervention for depression in young adults matters

Especially the transition phase between adolescence and adulthood is important, ranging from 18 to 30 years old. Young adults experience high rates of mental health problems. Depression is of particular importance in this developmental period. Unlike anxiety disorders, which typically emerge in childhood and early adolescence, the peak age of onset for depression is 19-20 years of age (Solmi et al., 2022) – making young adulthood a critical period for depression prevention

and early intervention. Also this group isn’t represented enough in research.

In the Netherlands we have an ongoing data collection of adults 18-65 who use esketamine for TRD. We will compare the group of young adults 18-30 to the adults, and describe the group on clinical relevant factors. How is the efficacy? Side effects? Duration and dosage? And what covariates determine outcome?

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Researchers:

Anja Lok

Viktoria Janke

Sem Cohen

Ghita Benjelloun

Dominique Scheepens

Ellen Rooda (Youz)

Armin Shazad (Youz)

Jolien Veraart (PsyQ)

ENC-NL working group