Christian S Hendershot1,2,3,4,5, Sarah S Dermody6, Jeffrey D Wardell1,2,3, Michelle J Zaso7, James L Kennedy1,3, Susan A Stoner8. 1. From the, Campbell Family Mental Health Research Institute, (CSH, JDW, JLK), Centre for Addiction and Mental Health, Toronto, ON, Canada. 2. Institute for Mental Health Policy Research, (CSH, JDW), Centre for Addiction and Mental Health, Toronto, ON, Canada. 3. Department of Psychiatry, (CSH, JDW, JLK), University of Toronto, Toronto, ON, Canada. 4. Department of Psychology, (CSH), University of Toronto, Toronto, ON, Canada. 5. Department of Pharmacology and Toxicology, (CSH), University of Toronto, Toronto, ON, Canada. 6. School of Psychological Science, (SSD), Oregon State University, Corvallis, Oregon. 7. Clinical and Research Institute on Addictions, (MJZ), University at Buffalo, Buffalo, New York. 8. Alcohol and Drug Abuse Institute, (SAS), University of Washington, Seattle, Washington.
Abstract
BACKGROUND: Initial evidence that OPRM1 genotype moderates the clinical response to naltrexone has not been replicated in prospective clinical trials. However, the use of traditional statistical analyses and clinical endpoints might limit sensitivity for studying pharmacogenetic associations, whereas the use of intensive daily assessments and person-centered analytic methods might increase sensitivity. This study leveraged person-centered analyses and daily measures of alcohol use, craving, and medication adherence to investigate OPRM1 as a moderator of changes in clinical outcomes during naltrexone treatment. METHODS: Treatment-seeking participants with alcohol use disorder (n = 58; Mage = 38 years; 71% male) provided daily cell phone reports of craving and consumption while taking naltrexone as part of a mobile health trial. Daily medication adherence was measured remotely using electronic pill cap recordings. Multilevel modeling and multilevel structural equation modeling analyses evaluated the hypotheses that OPRM1 genotype would moderate prospective reductions in daily alcohol use and craving, and would also moderate within-person associations of daily adherence with same-day craving and consumption. RESULTS: OPRM1 genotype moderated the association of daily adherence with reduced same-day consumption (p = 0.007) and craving (p = 0.06), with these associations being stronger for participants with the 118G variant. OPRM1 genotype did not moderate changes in craving and consumption over time. CONCLUSIONS: These findings suggest that high-density assessments and person-centered analytic approaches, including modeling within-person variation in medication adherence, could be advantageous for pharmacogenetic studies.
BACKGROUND: Initial evidence that OPRM1 genotype moderates the clinical response to naltrexone has not been replicated in prospective clinical trials. However, the use of traditional statistical analyses and clinical endpoints might limit sensitivity for studying pharmacogenetic associations, whereas the use of intensive daily assessments and person-centered analytic methods might increase sensitivity. This study leveraged person-centered analyses and daily measures of alcohol use, craving, and medication adherence to investigate OPRM1 as a moderator of changes in clinical outcomes during naltrexone treatment. METHODS: Treatment-seeking participants with alcohol use disorder (n = 58; Mage = 38 years; 71% male) provided daily cell phone reports of craving and consumption while taking naltrexone as part of a mobile health trial. Daily medication adherence was measured remotely using electronic pill cap recordings. Multilevel modeling and multilevel structural equation modeling analyses evaluated the hypotheses that OPRM1 genotype would moderate prospective reductions in daily alcohol use and craving, and would also moderate within-person associations of daily adherence with same-day craving and consumption. RESULTS: OPRM1 genotype moderated the association of daily adherence with reduced same-day consumption (p = 0.007) and craving (p = 0.06), with these associations being stronger for participants with the 118G variant. OPRM1 genotype did not moderate changes in craving and consumption over time. CONCLUSIONS: These findings suggest that high-density assessments and person-centered analytic approaches, including modeling within-person variation in medication adherence, could be advantageous for pharmacogenetic studies.
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