NCDEU Poster Session 2012

The Clinical Impact of an Antidepressant Pharmacogenomic Algorithm

Kevin M. Furmaga, PharmD, BCPP; Eric Achtyes, MD; and LeAnn Smart, BA
From Pine Rest Christian Mental Health Services, Grand Rapids, Michigan (Drs Achtyes and Furmaga and Ms Smart); Department of Psychiatry, Michigan State University College of Human Medicine, East Lansing (Drs Achtyes and Furmaga); and the Department of Pharmacy, Saint Mary’s Health Care, Grand Rapids, and the University of Michigan College of Pharmacy, Ann Arbor (Dr Furmaga).

This poster presentation was funded by AssureRx Health, Inc., the Pine Rest Foundation, and Priority Health.

Background: Genes linked to metabolism (CYP450 2D6, 2C19, and 1A2), efficacy (SLC6A4), and tolerability (5HTR2A) of antidepressants may inform treatment selection. Published case reports suggest that pharmacogenomic (PGx) testing may improve outcomes in drug treatment of depression. This prospective randomized double-blind pilot study evaluated the clinical impact of a 5-gene PGx algorithm and interpretive report on antidepressant selection and treatment outcomes in depressed outpatients.

Methods: Depressed adult outpatients were randomized to a PGx-testing (PGxT, n = 25) or treatment as usual (TAU, n = 24) arm. Depression severity and medication side effects were assessed at baseline and 2, 4, and 8 weeks after a routine clinic visit using the HAM-D and the Frequency, Intensity, and Burden of Side Effects Rating Scale (FIBSER), respectively. Treating clinician use of the report was optional. Study subjects and their raters were blinded to treatment arm. Treating clinicians were surveyed regarding the influence of PGxT on antidepressant selection.

Results: Subjects in the PGxT arm had a greater decrease in HAM-D mean change scores from baseline than subjects in the TAU arm at week 4 (p =0.029) but not at weeks 2 and 8 (p=0.22 and p=0.27). Thirteen PGxT vs 6 TAU subjects were responders (p=0.055) and 8 PGxT vs 1 TAU subject were remitters during the study (p=0.012). No difference in side effect burden was detected between treatment arms. The PGx report had a high/moderate and low/no level of influence on treatment decisions in 15 (60%) and 10 (40%) PGxT subjects, respectively.

Conclusions: This is the first prospective randomized study designed to evaluate the impact of PGx testing on antidepressant treatment. Though patient group sizes were small, and application of the PGx test was uncontrolled, clinical improvement was found, and a greater number of PGxT subjects remitted vs TAU subjects. Treatment decisions were highly or moderately influenced by the PGx report in a majority of PGxT subjects. An additional prospective, double-blind, TAU-controlled clinical study of PGx testing is warranted to evaluate its effect on response and remission during antidepressant therapy.

Learning Objectives:
Describe the impact of PGx testing on treatment outcomes in depressed outpatients.

Characterize the influence of PGx testing on antidepressant selection.

References
Black JL, O’Kane DJ, Mrazek DA. The impact of CYP allelic variation on antidepressant metabolism: a review. Expert Opin Drug Metab Toxicol. 2007;3(1):21–31. PubMed

Serretti A, Kato M, De Ronchi D, et al. Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with selective serotonin reuptake inhibitor efficacy in depressed patients. Mol Psychiatry. 2007;12(3):247–257. PubMed

Murphy GM, Kremer C, Rodrigues HE, et al. Pharmacogenetics of antidepressant medication intolerance. Am J Psychiatry. 2003;160(10):1830–1835. PubMed

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