Objective: Evaluate the clinical utility of combinatorial pharmacogenomic testing for informing medication selection among older adults who have experienced antidepressant medication failure for major depressive disorder (MDD).
Design: Post hoc analysis of data from a blinded, randomized controlled trial comparing two active treatment arms.
Setting: Psychiatry specialty and primary care clinics across 60 U.S. community and academic sites.
Participants: Adults age 65 years or older at baseline (n = 206), diagnosed with MDD and inadequate response to at least one medication on the combinatorial pharmacogenomic test report during the current depressive episode.
Intervention: Combinatorial pharmacogenomic testing to inform medication selection (guided-care), compared with treatment as usual (TAU).
Outcomes: Mean percent symptom improvement, response rate, and remission rateat week 8, measured using the 17-item Hamilton Depression Rating Scale; medication switching; and comorbidity moderator analysis.
Results: At week 8, symptom improvement was not significantly different for guided-care than for TAU (∆ = 8.1%, t = 1.64, df = 187; p = 0.102); however, guided-care showed significantly improved response (∆ = 13.6%, t = 2.16, df = 187; p = 0.032) and remission (∆ = 12.7%, t = 2.49, df = 189; p = 0.014) relative to TAU. By week 8, more than twice as many patients in guided-care than in TAU were on medications predicted to have no gene-drug interactions (χ = 19.3, df = 2; p <0.001). Outcomes in the guided-care arm showed consistent improvement through the end of the open-design 24-week trial, indicating durability of the effect. Differences in outcomes between arms were not significantly impacted by comorbidities.
Conclusions: Combinatorial pharmacogenomic test-informed medication selection improved outcomes over TAU among older adults with depression.
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http://dx.doi.org/10.1016/j.jagp.2020.05.005 | DOI Listing |
Expert Opin Biol Ther
December 2024
S.S.D. C.O.r.O. Bed Management Presa in Carico, TDM, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy.
Introduction: Recently, immunotherapy has offered new hope for treating biliary tract cancer (BTC). However, several issues are to be considered, including the lack of validated predictive biomarkers that could help to identify patient groups which are most likely to benefit from such therapeutic approaches.
Areas Covered: In the current article, we will provide an overview of recent results and ongoing and future research directions of immunotherapy in BTC, with a special focus on recently published, practice-changing data, and ongoing active and recruiting clinical trials.
Neuro Oncol
November 2024
Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Am J Psychiatry
July 2024
Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston (Baum); Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis (Widge); Butler Hospital Neuromodulation Research Facility, Providence, R.I., and Department of Psychiatry and Human Behavior, Alpert Medical School, Brown University, Providence, R.I. (Carpenter); Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta (McDonald); Department of Psychiatry and Program for Neuropsychiatric Research, McLean Hospital, Harvard Medical School, Belmont, Mass. (Cohen); Department of Psychiatry and Behavioral Sciences, Dell Medical School, University of Texas, Austin (Nemeroff).
Objective: In this review, the authors update the 2018 position statement of the American Psychiatric Association Council of Research Workgroup on Biomarkers and Novel Treatments on pharmacogenomic (PGx) tools for treatment selection in depression.
Methods: The literature was reviewed for new clinical trials and meta-analyses, published from 2017 to 2022, of studies using PGx tools for treatment selection in depression. The blinding and control conditions, as well as primary and secondary outcomes and post hoc analyses, were summarized.
BMC Genomics
April 2024
McWilliams School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX, USA.
Background: Deciphering gene regulation is essential for understanding the underlying mechanisms of healthy and disease states. While the regulatory networks formed by transcription factors (TFs) and their target genes has been mostly studied with relation to cis effects such as in TF binding sites, we focused on trans effects of TFs on the expression of their transcribed genes and their potential mechanisms.
Results: We provide a comprehensive tissue-specific atlas, spanning 49 tissues of TF variations affecting gene expression through computational models considering two potential mechanisms, including combinatorial regulation by the expression of the TFs, and by genetic variants within the TF.
J Child Adolesc Psychopharmacol
February 2024
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, USA.
Combinatorial pharmacogenetic testing panels are widely available in clinical practice and often separate medications into columns/bins associated with low, medium, or high probability of gene-drug interactions. The objective of the Adolescent Management of Depression (AMOD) study was to determine the clinical utility of combinatorial pharmacogenetic testing in a double-blind, randomized, controlled effectiveness study by comparing patients who had genetic testing results at time of medication initiation to those that did not have results until week 8. The objective of this analysis was to assess and report additional outcomes with respect to significant gene-drug interactions (i.
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