Subanalysis of the CYP-GUIDES Trial: CYP2D6 Functional Stratification and Operational Timeline Selection.

CYP-GUIDES (Cytochrome Psychotropic Genotyping Under Investigation for Decision Support) was a Randomized Controlled Trial comparing 2 outcomes in hospitalized patients with major depressive disorder treated according to the patient's CYP2D6 genotype and functional status versus standard psychotropic therapy. The primary outcome was hospital Length of Stay (LOS) and the secondary was Re-Admission Rate (RAR) 30 days after discharge. Methodology, total results and database of the trial have been published. Here we present a subanalysis that isolated 3 confounders to assess the impact of CYP2D6 therapeutic guidance on LOS: a single Electronic Medical Record, a minimum 3-day LOS, and CYP2D6 functional stratification of patients. CYP2D6 functional stratification enabled subgrouping patients and comparing outcomes according to CYP2D6 functionality within Group G and Group S. Subfunctional patients evidenced a 2-day shorter LOS in Group G compared to Group S. Drug administration for subfunctional patients in Group S evidenced a higher percentage of CYP2D6 substrate psychotropics being prescribed as well as a greater number of prescriptions than in functional patients. We conclude that there was an effect of pharmacogenetic clinical decision support that reduced LOS in patients with CYP2D6 subfunctional status and reduced prescribing of CYP2D6 substrate dependent drugs.

Clinical database of the CYP-guides trial: An open data resource on psychiatric hospitalization for severe depression.

CYP-GUIDES (Cytochrome Psychotropic Genotyping Under Investigation for Decision Support ) is a randomized controlled trial (RCT) of pharmacogenetic decision support in the psychotropic treatment of hospitalized patients with major depressive disorder or severe depression. Patients were treated according to their CYP2D6 functional status or empirically and compared for both their Length of Stay (LOS, primary outcome) at the hospital and Re-Admission Rate (RAR, secondary outcome) 30 days after discharge. The trial was conducted at the Institute of Living (Hartford Hospital, Hartford CT). CYP2D6 genotyping was implemented to infer the functional status of the CYP2D6 enzyme and classify it as sub-normal, normal or supra-normal. The electronic medical record (EMR) transmitted to the physician the indicated drug prescribing guidance. During the RCT, 1500 patients were recruited and 1459 genotyped for CYP2D6. A 1:2 randomization assigned 477 patients to standard therapy (Group S) and 982 to genetically-guided therapy (Group G). In Group S, standard empiric treatment was indicated for all patients. In Group G, medications primarily metabolized by the CYP2D6 enzyme were proscribed for patients with sub- or supra-normal CYP2D6 function. The clinical course, therapeutic guidance, and drug treatment for each patient are being published in this article and deposited in Mendeley Data. These data should be valuable to assess the impact of clinical decision support on utilization of psychiatric resources for treatment of severe depression requiring hospitalization.

Results of the CYP-GUIDES randomized controlled trial: Total cohort and primary endpoints.

CYP-GUIDES (Cytochrome Psychotropic Genotyping Under Investigation for Decision Support) is a randomized controlled trial (RCT) comparing 2 outcomes in hospitalized patients with major depressive disorder (MDD) treated according to the patient's CYP2D6 genotype and functional status versus standard psychotropic therapy. The primary outcome was hospital Length of Stay (LOS) and the secondary outcome was the Re-Admission Rate (RAR) 30 days after discharge. The trial setting was the Institute of Living at Hartford Hospital. CYP2D6 genotyping was implemented to detect common polymorphisms resulting in an enzyme with sub-normal, normal or supra-normal function. The electronic medical record (EMR) was utilized to transmit clinically actionable drug prescribing guidance based on the patient's CYP2D6 genotype to the physician. The RCT recruited 1500 patients, genotyped CYP2D6 in 1459, and randomized 477 to standard therapy (Group S), for whom treatment-as-usual guidance was delivered without consideration of patient CYP2D6 genotype, and 982 to genetically-guided therapy (Group G) where CYP2D6-based treatment recommendations were provided via EMR to physicians. For inpatients in Group G whose CYP2D6 function was sub- or supra-normal, medications primarily metabolized by the CYP2D6 enzyme were proscribed. The RCT developed a database of potential benefit to the field. The genetic, pharmacologic and clinical information is being simultaneously published. Results did not reveal differences in LOS or RAR between Group G and Group S, but confounders may have obscured the effects of pharmacogenetic guidance. We present strategies to assess effects of pharmacogenetic guidance on the most vulnerable patients at either extreme of CYP2D6 function treated with multiple psychotropics.