James Potts
Investigating the Factors That Impact Duloxetine Efficacy in Fibromyalgia Patients
Mentor: Ken Johnson, MD, MS
Department: Anesthesiology
Background:
Fibromyalgia, affecting 2-3% of the American population, is a chronic pain syndrome with symptoms including persistent, widespread musculoskeletal pain, sleep disturbances, and cognitive difficulties. Duloxetine, a serotonin-norepinephrine reuptake inhibitor, is FDA-approved to treat fibromyalgia but shows variable treatment response. The variability may be explained by genetic differences in cytochrome P450 enzymes CYP2D6 and CYP1A2, which metabolize the drug. Patients are categorized according to their metabolizer phenotype (Table 1), impacting treatment efficacy and adverse effects. The frequency of these phenotypes in the American population is shown in Table 2. Additionally, enzyme inducers or inhibitors can affect duloxetine plasma concentrations, altering its efficacy and side effects. Understanding pharmacogenetics and pharmacokinetics can lead to personalized medicine by predicting individual treatment responses. This study aims to investigate duloxetine plasma concentrations, genetic phenotypes of CYP2D6 and CYP1A2, and the impact of enzyme inducers and inhibitors in fibromyalgia patients.
Methods:
We will enroll 100 patients from the University of Utah Pain Management Center who are 18 years or older, diagnosed with fibromyalgia, and on 60 mg/day of duloxetine for at least eight weeks. Exclusion criteria include impaired kidney or liver function, pregnancy, need for an interpreter, and additional progressive illnesses with chronic pain. Participants will complete demographic and health questionnaires, the Revised Fibromyalgia Impact Questionnaire (FIQR), and the American College of Rheumatology (ACR) 2016 diagnostic criteria. On the study day, participants will fast, and blood samples will be collected six hours after the morning dose to measure peak plasma duloxetine concentrations and perform genotyping for CYP2D6 and CYP1A2. Data analysis will compare duloxetine concentrations across metabolizer phenotypes, assess the impact of enzyme inducers and inhibitors, and correlate findings with patient-reported outcomes.
Future Plans for the Study:
We are awaiting IRB approval for recruitment and enrollment. Preliminary data will guide a larger, observational study to characterize genotype, phenotype, and treatment response profiles in fibromyalgia patients. This research will support the development of clinical trials aimed at personalizing therapy, optimizing outcomes, and improving cost-effectiveness.
