Age-Dependent Sex Differences in the Prevalence of Selective Serotonin Reuptake Inhibitor Treatment: A Retrospective Cohort Analysis.

Background: Antidepressants are among the most prescribed medications in the United States. The aim of this study was to explore the prevalence of antidepressant prescriptions and investigate sex differences and age-sex interactions in adults enrolled in the Right Drug, Right Dose, Right Time: Using Genomic Data to Individualize Treatment (RIGHT) study. Materials and Methods: We conducted a retrospective analysis of the RIGHT study. Using electronic prescriptions, we assessed 12-month prevalence of antidepressant treatment. Sex differences and age-sex interactions were evaluated using multivariable logistic regression and flexible recursive smoothing splines. Results: The sample consisted of 11,087 participants (60% women). Antidepressant prescription prevalence was 22.24% (27.96% women, 13.58% men). After adjusting for age and enrollment year, women had significantly greater odds of antidepressant prescription (odds ratio = 2.29; 95% confidence interval = 2.07, 2.54). Furthermore, selective serotonin reuptake inhibitors (SSRIs) had a significant age-sex interaction. While SSRI prescriptions in men showed a sustained decrease with age, there was no such decline for women until after reaching ∼50 years of age. There are important limitations to consider in this study. Electronic prescription data were cross-sectional; information on treatment duration or adherence was not collected; this cohort is not nationally representative; and enrollment occurred over a broad period, introducing confounding by changes in temporal prescribing practices. Conclusions: Underscored by the significant interaction between age and sex on odds of SSRI prescription, our results warrant age to be incorporated as a mediator when investigating sex differences in mental illness, especially mood disorders and their treatment.

A Randomized Controlled Trial of Combinatorial Pharmacogenetics Testing in Adolescent Depression.

OBJECTIVE: Numerous commercial pharmacogenetics panels are now widely available for clinical use in psychiatric practice. However, there is a paucity of literature evaluating the use of combinatorial pharmacogenetics panels to enhance outcomes in the treatment of adolescents with depression. This study sought to prospectively evaluate the clinical impact of combinatorial pharmacogenetics testing in a double-blind, randomized, controlled effectiveness study for the pharmacologic treatment of adolescents with depression. METHOD: Adolescents aged 13 to 18 years (N = 176) with moderate to severe major depressive disorder (MDD) were randomized to treatment arm guided by testing in which pharmacogenetic testing results were available at the baseline visit (GENE arm, n = 84) or a treatment-as-usual arm (TAU arm, n = 92) in which testing results were not available until an 8-week visit. Raters, participants, and families were blinded to group allocation. Symptom improvement, side effects, and satisfaction were assessed throughout the study at 4 weeks, 8 weeks, and 6 months. RESULTS: There were no differences between the GENE and TAU arms at 8 weeks or 6 months for symptom improvement, side effect burden, or satisfaction. Selective serotonin reuptake inhibitors were prescribed at higher rates in the TAU arm compared to the GENE arm (p = .024). CONCLUSION: Combinatorial pharmacogenetics-guided treatment did not demonstrate improved outcomes compared to TAU in adolescents with MDD. Future research should examine how specific medication-gene pairs may affect clinical outcomes in the treatment of adolescents with depression and how best to integrate pharmacogenetics into clinical practice. CLINICAL TRIAL REGISTRATION INFORMATION: A PK/PD Genetic Variation Treatment Algorithm Versus Treatment As Usual for Adolescent Management Of Depression; https://www.clinicaltrials.gov; NCT02286440.