The pharmacological treatment of depression consists of stages of trial and error, with less than 40% of patients achieving remission during first medication trial. However, in a large, randomized-controlled trial (RCT) in the U.S. ("GUIDED"), significant improvements in response and remission rates were observed in patients who received treatment guided by combinatorial pharmacogenomic testing, compared to treatment-as-usual (TAU). Here we present results from the Canadian "GAPP-MDD" RCT. This 52-week, 3-arm, multi-center, participant- and rater-blinded RCT evaluated clinical outcomes among patients with depression whose treatment was guided by combinatorial pharmacogenomic testing compared to TAU. The primary outcome was symptom improvement (change in 17-item Hamilton Depression Rating Scale, HAM-D17) at week 8. Secondary outcomes included response (≥50% decrease in HAM-D17) and remission (HAM-D17 ≤ 7) at week 8. Numerically, patients in the guided-care arm had greater symptom improvement (27.6% versus 22.7%), response (30.3% versus 22.7%), and remission rates (15.7% versus 8.3%) compared to TAU, although these differences were not statistically significant. Given that the GAPP-MDD trial was ultimately underpowered to detect statistically significant differences in patient outcomes, it was assessed in parallel with the larger GUIDED RCT. We observed that relative improvements in response and remission rates were consistent between the GAPP-MDD (33.0% response, 89.0% remission) and GUIDED (31.0% response, 51.0% remission) trials. Together with GUIDED, the results from the GAPP-MDD trial indicate that combinatorial pharmacogenomic testing can be an effective tool to help guide depression treatment in the context of the Canadian healthcare setting (ClinicalTrials.gov NCT02466477).
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8921325 | PMC |
| http://dx.doi.org/10.1038/s41398-022-01847-8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Pharmacogenomics in psychiatry: Practice recommendations from an Asian perspective (2024).
Ann Acad Med Singap
December 2024
Institute of Mental Health, Singapore.
Introduction: Pharmacogenomic testing in psychiatry is an emerging area with potential clinical application of guiding medication choice and dosing. Interest has been fanned by commercial pharmacogenomic providers who have commonly marketed combinatorial panels that are direct-to-consumer. However, this has not been adopted widely due to a combination of barriers that include a varying evidence base, clinician and patient familiarity and acceptance, uncertainty about cost-effectiveness, and regulatory requirements.
View Article and Find Full Text PDFImmunobiology of biliary tract cancer and recent clinical findings in approved and upcoming immune checkpoint inhibitors.
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.
Fc-enhanced anti-CTLA-4, anti-PD-1, doxorubicin, and ultrasound-mediated blood-brain barrier opening: A novel combinatorial immunotherapy regimen for gliomas.
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.
Article Synopsis
- Glioblastoma is a challenging brain cancer that often resists standard immunotherapy, but Botensilimab, a specialized antibody, has shown potential in treating this type of cancer.
- In preclinical studies, a mouse version of Botensilimab demonstrated effectiveness when used alone or with doxorubicin combined with ultrasound techniques, leading to significant immune responses in treatment-resistant glioblastoma.
- Results indicated that this combination therapy not only effectively targeted and reduced tumor-associated immune cells but also fostered a strong infiltration of harmful T cells, achieving a remarkable cure rate in mice and suggesting promising implications for human treatments.
Pharmacogenomic Clinical Support Tools for the Treatment of Depression.
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.
Tissue-specific atlas of trans-models for gene regulation elucidates complex regulation patterns.
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.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!