Adjusting Methadone Dose Based on Plasma R-Methadone Levels Does Not Improve Retention

Methadone is a racemic mixture comprised of 50% R-methadone and 50% S-methadone. R-methadone is considered to be responsible for the mu-opioid agonist properties of methadone, while S-methadone blocks the N-methyl-D-Aspartate receptor and may be responsible for adverse effects. Researchers sought to determine whether providing doses such that patients’ plasma levels of R-methadone remained within a target therapeutic window of 80-250ng/mL improved treatment retention at 6 and 12 months. They randomized 308 patients receiving methadone from 13 treatment centers in Italy. Intervention participants had their methadone dose titrated weekly based on plasma R-methadone concentrations while the control participants received dose titration as usual. Participants were not blinded.

• Treatment retention at 6 and 12 months was high in both groups, but not better in the intervention group than control (81% and 72% in intervention, 91% and 80% in control at 6 and 12 months, respectively).
• Participants with R-methadone levels in the target range at baseline and 6 months had significantly better treatment retention at 12 months than those who did not (94% versus 80%).
• Correlation between methadone dose and plasma R-methadone concentration was low.

Comments: Although patients with plasma R-methadone levels in a range of 80-250ng/mL were more likely to be retained in treatment, dose adjustments based on plasma concentrations of R-methadone did not improve and may have worsened retention. The clinical utility of R-methadone plasma testing to determine dose remains unproven.

Payel J. Roy, MD† & Alexander Y. Walley, MD, MSc

† Contributing editorial intern and addiction medicine fellow, Boston Medical Center, Boston, MA, USA

Reference: Mannaioni G, Lanzi C, Lotti M, et al. Methadone dose adjustments, plasma R-methadone levels and therapeutic outcome of heroin users: a randomized clinical trial. Eur Addict Res. 2018;24(1):9–18.