(PS3-10) Effectiveness Study of Pharmacogenetics Testing to Inform the Treatment of Depression

Introduction

Combinatorial pharmacogenomics (PGx) provides data about how genes, mostly involved in metabolism, affect drug-gene interactions. PGx has been used to guide clinicians who prescribe antidepressants to minimize side effects and guide dosing. The gap in PGx is that it is unclear if clinicians who use PGx get better outcomes. In this study, we examined the effectiveness of adding PGx testing to guideline-informed treatment compared to guideline-informed treatment only in improving wellness and general quality of life in individuals with depression. We also investigated if clinicians prescribed medications consistent with the PGx recommendations within each group.

Methods

Participants were recruited and randomized to PGx plus guideline-informed treatment or guideline-informed treatment only. All study clinicians were trained on the CANMAT guidelines for management of depression. All participants underwent genetic testing; however, those in the PGx-guided group received their PGx testing results immediately to inform their treatment while the guideline-informed treatment only group received the results after completing the study. Wellness was the primary outcome assessed by The World Health Organization Well-Being Index (WHO-5). We also explored how treatment congruence profiles changed over the study period by group. Participants in both groups received GeneSight reports that categorized the probability drug-gene interactions (low, medium and high risk of drug-gene interactions) with the prescribed medications and indicated if there was increased risk of side effects or a need for dose adjustments.  Treatment was considered congruent if the prescribed medications had no significant drug-gene interaction as per the PGx results (i.e: no high-risk medications prescribed). Additional covariates included age, gender identity, race, education and study site.

Results

Two hundred and one participants were randomized to the PGx-guided (n=102; mean age=41.0; F:77%) or the guideline-informed groups (n=99; mean age=41.4; F:82.5%) and followed for 12 months. Although both groups experienced improvement in overall well-being (i.e., WHO-5; the primary outcome) over the 12-month study period, there were no group differences (PGx-guided versus guideline-informed group difference in slopes per log(week) [95% CI]: -0.63 [-1.75, 0.49], p=0.270). The proportion of participants with congruent (only low and medium risk) medications ranged from 72-82%, across groups and over time. There was no difference in the proportion of high-risk medications prescribed over time in either group. However, there was an increase in prescription of low-risk medications over time within the PGx testing plus guideline-informed treatments group.

Conclusion

This study compared PGx testing plus guideline-informed treatments to guideline-informed treatment alone, on the primary outcome of well-being. These findings suggest that PGx-guided treatment offers no further advantage in outcomes. One possible explanation is that the guideline-informed treatments had a ceiling effect and the addition of PGx did not improve those outcomes.