Evaluating the Clinical Impact of CYP2C19 and CYP2D6 on Amitriptyline Outcomes in a Real-World Chronic Pain Cohort
Uckac, B.; Ceja, Z.; Ogonowski, N. S.; Lind, P.; Nyholt, D.; Martin, N.; Medland, S.; Renteria, M. E.; Ferreira, G.
Show abstract
Amitriptyline is commonly prescribed for chronic pain, yet treatment response and tolerability vary substantially. Genetic variation in CYP2C19 and CYP2D6 influences amitriptyline metabolism, but evidence linking pharmacogene status to clinical outcomes in chronic pain is limited. Amitriptyline is typically prescribed for chronic pain at lower doses than for depression, which may reduce pharmacogenomic effects on clinical outcomes. We analysed 1,146 participants with chronic pain from the Australian Genetics of Depression Study who reported amitriptyline use, treatment outcomes, and genotype data. Metaboliser phenotypes were assigned using PharmCAT. Associations with self-reported effectiveness and discontinuation due to side effects were examined using regression models adjusted for age and sex. Only CYP2C19 intermediate metabolisers showed nominally lower odds of discontinuation and reduced likelihood of reporting moderate effectiveness. Overall, pharmacogenetic phenotypes were not significantly associated with patient-reported amitriptyline outcomes in chronic pain, potentially reflecting the lower doses typically prescribed for pain management.
Matching journals
The top 12 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Whole-genome sequencing analysis of clozapine-induced myocarditis 91%
- Investigating an in-silico approach for prioritizing antidepressant drug prescription based on drug-induced expression profiles and predicted gene expression 91%
- Implementation of Pre-emptive Pharmacogenomics Testing in Outpatient Clinics in Asia (IMPT study) 89%
Similar papers in this journal
- A novel preclinical secondary pharmacology resource illuminates target-adverse drug reaction associations of marketed drugs 93%
- Clinical Impact of Pharmacogenetic Risk Variants in a Large Chinese Cohort 93%
- Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial 91%
Similar papers in this journal
- Trends of long-term opioid therapy and subsequent discontinuation among people with chronic non-cancer pain in UK primary care: a retrospective cohort study 94%
- A large Australian longitudinal cohort registry demonstrates sustained safety and efficacy of oral medicinal cannabis for at least two years 92%
- A Multi-Centre, Tolerability Study of a Cannabidiol-enriched Cannabis Herbal Extract for Chronic Headaches in Adolescents: the CAN-CHA Protocol 92%
Similar papers in this journal
- Sociodemographic, clinical, and genetic factors associated with self-reported antidepressant response outcomes in the UK Biobank 93%
- Longitudinal impact of different treatment sequences of second-generation antipsychotics on metabolic outcomes: a study using targeted maximum likelihood estimation 91%
- Antipsychotic Polypharmacy and Adverse Drug Reactions Among Adults in a London Mental Health Service, 2008-2018 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.