EXPLORATION OF THE APPLICATION OF PHARMACOGENETICS IN THE MANAGEMENT OF DEPRESSION

Abstract

Genetic factors have been reported as playing an important role in the treatment efficacy of antidepressants (ADs). Studies report up to 55 % of patients experience AD treatment failure. The aim of this research was to explore the role of pharmacogenetics (PGx) in the management of major depressive disorder (MDD) as well as the potential for its application in the Middle East and North Africa (MENA) region. The first phase of this research consisted of a systematic review (SR) to summarize, update, and assess the quality of the available evidence regarding the clinical utility of PGx testing in the management of depression. The second phase entailed conducting a qualitative study utilizing semi-structured interviews with mental health prescribers from the MENA region to assess their perceptions, level of education, and experience with genetic testing. The third phase involved conducting a prospective cohort study to assess the genetic and environmental associations with response to selective serotonin reuptake inhibitors in Arabs diagnosed with MDD. Results of the SR highlighted that PGx testing showed positive but inconsistent effects on efficacy outcomes, and further research is still required to evaluate its impact on safety outcomes. Five overarching major themes, and 11 subthemes, emerged from 18 interviews with psychiatrists from the MENA region regarding PGx testing in mental health. The major themes include: 1. Overall perceptions and attitudes. 2. Knowledge and awareness. 3. Education, training, and professional experience. 4. Facilitators and barriers, and 5. Ethical dilemmas. A total of 56 patients were recruited for the prospective study, which demonstrated a lack of significant associations between genetic variants on CYP2C19, HTR2A, and GRIK4 and clinical outcomes of MDD. Additionally, vitamin D3 levels and caffeine were identified as significant predictors for safety outcomes. The findings from the three phase investigations revealed that PGx showed promise in improving MDD outcomes based on international data. Psychiatrists expressed high awareness and positive perceptions towards its adoption in the health systems of the MENA region. However, supporting strategies are needed to facilitate its implementation. Additionally, genetic association studies with longer durations are warranted to further explore how genetic variants affect clinical endpoints in Arabs with MDD.