Study: Methadone Dosing Needs to be More Precise

Talal, professor of medicine in the Division of Gastroenterology, Hepatology and Nutrition, is lead author of a paper that focuses on genetic and non-genetic differences in how methadone is metabolized in specific patient populations.

“Methadone prescription has really not changed in the past 50 years since the medication was originally discovered,” says Talal, a physician with UBMD Internal Medicine.

“The issue with methadone prescribing is that it is very difficult to accurately predict what the correct dose is, and the outcomes can be catastrophic,” Talal adds. “If too much is given, it can be fatal, and too little can lead to withdrawal symptoms and potentially the need to use illicit drugs — such as heroin — to diminish the symptoms.”

He describes the process of trying to determine the appropriate dose as “laborious and time-consuming.” Dosing usually begins with a low, standardized dose that is then titrated to increasingly higher doses as needed.

“This is a time-consuming and complex process from both the patient and provider standpoint,” Talal says.

The study was conducted on 97 participants. The majority of participants were either African American or Hispanic and more than half were male.

The research was motivated by a desire to bring “personalized medicine” to methadone prescribing, meaning that a patient’s optimal dose will be determined according to characteristics specific to that patient.

“According to the study’s findings, gender, body mass index and ethnic background through encoding of different metabolizing enzymes can all affect how a patient metabolizes methadone,” Talal says.

The study demonstrates that different ethnicities may encode different forms of the enzyme that metabolizes methadone so that some people metabolize it quickly while others are slow metabolizers, Talal explains. Without measurement of these different enzyme forms, patients may be susceptible to using too much or too little of a dose and the symptoms and signs associated with each.

“In this study, we found that the individual genotype of the liver enzyme that is responsible for methadone metabolism can have a direct effect on whether a patient is a slow or rapid methadone metabolizer,” Talal says.

The next step is to do larger studies in more racially and ethnically diverse patient populations. Ultimately, the goal is to develop methadone-dosing algorithms that can be applied clinically.

“Our ultimate goal is to decrease the incidence of deaths due to opioid overdoses, improve symptom control, and increase patient satisfaction,” Talal says.

Arpan Dharia, PhD, research scientist in medicine, is a co-author.

Other UB co-authors are:

• Lindsay M. Chakan, PhD, project staff associate in the Office of Research Advancement
• Yuxin Ding, PhD, who earned a doctoral degree in biostatistics in 2020
• Marianthi Markatou, PhD, professor of biostatistics in the School of Public Health and Health Professions
• Gene D. Morse, PharmD, SUNY Distinguished Professor of pharmacy practice in the School of Pharmacy and Pharmaceutical Sciences

Other co-authors are from Duke University, the University of Rochester and START Treatment and Recovery Centers.

The study was supported, in part, by an administrative supplement from the University of Rochester Center for AIDS Research and the Troup Fund of the Kaleida Health Foundation. Several National Institutes of Health grants also supported the research. The study also received support from Echosens with the donation of Fibroscan for measurement of hepatic fibrosis and steatosis.