Fatemeh Chalabianloo: Making methadone treatment better

Methadone maintenance treatment (MMT) has been used as an effective therapy in heroin-addicted patients for several decades. It has been shown to reduce mortality, morbidity, and criminality, as well as reducing illicit opioid use and the risk of overdose. MMT gives opioid users a chance to undergo social rehabilitation and to become more integrated in society. Optimal dosing is important as too high serum concentrations of methadone are thought to contribute to adverse effects, whereas too low concentrations may lead to lack of therapeutic effects, such as experiencing withdrawal symptoms. However, optimal dosing is challenging as knowledge remains limited concerning methadone’s pharmacokinetics (the drug’s behaviour in the body), as well as other potentially influencing factors relating to its dosing such as age, gender, and the use of different co-medications. Identifying valid and reliable predictors for optimal treatment outcomes would be of high clinical importance.

Genotype effects

In paper 1, Chalabianloo was examining specific enzymes involved in the metabolism (breakdown) of methadone in the body. People having certain genotypes (genes producing specific enzymes involved in methadone metabolism) had higher or lower methadone concentration to dose ratios (increased dose ratios may lead to undesirable side effects). In this paper, Chalabianloo and collaborators concluded that genotyping for this gene together with engaging in therapeutic drug monitoring, could be useful for assessing dose requirements for patients.

Other influencing factors

In paper 2, Chalabianloo and collaborators aimed to investigate effects of age, gender, and various co-medications on the methadone serum concentration-to dose ratio in a naturalistic setting. The results showed that gender differences should be taken into consideration, as well as the potential impacts of drug-drug interactions when determining an optimal therapeutic dose that avoids adverse effects.

Clinical tools

In paper 3, Chalabianloo and collaborators investigated possible associations between serum concentrations and subjective opioid withdrawal symptoms in MMT patients. They aimed to show whether the self-perceived, subjective side effects of the treatment or illicit opioid use were related to methadone serum concentrations. They used therapeutic drug monitoring (TDM), which measures steady state methadone serum concentrations 24 h after dose ingestion. This measurement might be a better indicator of drug amounts at the effect site than dose, due to inter-individual differences in methadone pharmacokinetics and disposition. As such TDM could be useful as a supplementary tool in clinical assessments evaluating the adequacy of the MMT.

Chalabianloo is currently wrapping up her analyses and finishing writing her papers. Papers 1 and 2 are published. She has plans for a fourth paper looking further into liver function and genotypes. Chalabianloo plans to finish and defend her work in 2022.