(B-240) Treatment-Resistant Depression (TRD) in Children and Adolescents and its Life-Course Determinants

Background: Treatment-resistant depression (TRD) refers to failure to achieve remission or inadequate response to a first-line antidepressant monotherapy trial. While TRD has been extensively studied in adults, its prevalence and associated factors in paediatric and adolescent populations within real-wolrd settings remain poorly understood.

Objectives: This study aimed to estimate rates of TRD in children/adolescents and identify key life-course factors associated with TRD.

Methods: We included children born to women with mental illnesses (depression, anxiety and eating disorders) before or during pregnancy enrolled in the Norwegian Mother, Father and Child Cohort Study (MoBa). We further limited our study population to those having records of depression diagnosis and at least one antidepressant dispensation prior to September 2022. Two types of TRD were assessed: (i) antidepressant switching and/or an antipsychotic augmentation (S/A); (ii) extended monotherapy lasting over a year (EM). Forward Stepwise Modified Poisson Regression models were used to identify individual, maternal and paternal factors associated with TRD, performed separately for each set of factors adjusted for key covariates. Missing data on covariates were handled using Multiple Imputation by Chained Equations.

Results: The study included 221 children/adolescents, of whome 75% were females. Nearly half (47.5%) met criteria for TRD. Of these, 21.7% (N=48) were S/A and 25.8% (N=57) were EM. Individuals with TRD were younger at first antidepressant prescription (EM: 14 yrs, S/A: 14 yrs, non-TRD: 16 yrs). Psychiatrists initiated nearly two-thirds of initial antidepressant prescriptions. Key TRD determinants included male sex (EM: RR=1.21, 95% CI: 1.10-1.33), age at first antidepressant (S/A: RR=0.84, 95% CI: 0.82-0.86; EM: RR=0.81, 95% CI: 0.80-0.82), prescriptions from psychiatrists (S/A: RR=0.75, 95% CI: 0.68-0.83; EM: RR=0.88, 95% CI: 0.80-0.97), maternal depression prepregnancy (S/A: RR=1.36, 95% CI: 1.21-1.52), maternal anxiety in early pregnancy (S/A: RR=1.26, 95% CI: 1.09-1.46; EM: RR=2.07, 95% CI: 1.82-2.36), and paternal severe depression/anxiety symptoms in early pregnancy (EM: RR=1.66, 95% CI: 1.39-1.98).

Conclusions: mong children/adolescents with depression – born to mothers with a mental illness participating in MoBa study – who received antidepressant treatment during childhood/adolescence, half of them were classified as having TRD. Several individual and parental factors were associated with the risk of TRD in this population. Our study findings are useful for early intervention and personalised counselling plans to optimize management strategies and improve treatment outcomes.