Pharmacogenetic Decision Support IT System for Psychiatric Hospitalization: RCT

Summary

This Randomized Clinical Trial (RCT) compares outcomes in patients with major depressive disorder (MDD) treated according to the patient's CYP2D6 genotype status versus empiric "standard-of-care" psychotropic therapy. The hypothesis is that provision of medication based on the functional status of the patient's CYP2D6 enzyme inferred from genotype results within 48 hours of admission to treating clinicians will, through refined selection of psychotropic medication during hospitalization, decrease length of psychiatric hospitalization stay and decrease the rate of 30 day re-admission.

The trial setting is the Hartford Hospital Institute of Living (IOL). The IOL operated the Clinical Evaluation and Monitoring System (CEMS), an innovative electronic messaging system developed by Co-Investigator Dr. J.W. Goethe. The Hartford Hospital Genetics Research Center (GRC) performs the genotype testing. CYP2D6 genotype analysis detects all known polymorphisms that result in an enzyme with sub-normal or supra-normal function. In this study, CEMS transmits clinically actionable guidance based on the patient's genotype to the clinician, advancing the medication alerts in real time.

The RCT will test the effects of timely incorporation of medication recommendations based on CYP2D6 genotype into CEMS. The RCT randomizes patients to standard therapy (Group S) for whom CYP2D6 genetic information is determined but not transmitted to the treating clinician, allowing psychotropic therapy to be empirically determined, and to genetically guided therapy (Group G) where genotyping result and treatment recommendations are furnished via CEMS to the clinician within 48 hours of admission. For patients in Group G who are poor or rapid metabolizers, medications primarily metabolized by the CYP2D6 enzyme are proscribed.

The primary outcome is hospital length of stay and the secondary outcome, the frequency of 30 day hospital readmission. Additional genetic stratification of both Group S and Group G will allow investigation of specific psychotropic usage.

The expected benefits are (1) quantitative understanding of the effect of providing CYP2D6 pharmacogenetic information on length of hospitalization, 30 day readmission rate, and associated costs; and (2) objective benchmarking for the comparative effectiveness of CYP2D6 genotyping for guiding psychotropic therapy.

Conditions

• Major Depressive Disorder

Interventions

OTHER

Genotype-guided care

Pharmacogenetic alerts are furnished to the clinician within 2 days of admission. Buccal cell DNA is analyzed for 21 common CYP2D6 polymorphisms and results quantified into a drug metabolism reserve index to establish levels of sub-normal function (poor metabolizer) or supra-normal function (rapid metabolizer). For the estimated 50% of patients who are poor or rapid metabolizers, CEMS will proscribe medications which are major CYP2D6 substrates.

Sponsors & Collaborators

• Agency for Healthcare Research and Quality (AHRQ)

  collaborator FED

• Hartford Hospital

  lead OTHER

Principal Investigators

• Gualberto Ruano, M.D., Ph.D. · Hartford Hospital Genetics Research Center

• John W Goethe, M.D. Retired · Institute of Living, Hartford Healthcare

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

95 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-03-31

Primary Completion

2018-08-31

Completion

2019-10-31

Countries

• United States

Study Locations