Subjective Symptoms and Serum Methadone Concentration: What Should Guide Dose Adjustments in Methadone Maintenance Treatment? A Naturalistic Cohort Study From Norway

Abstract

BackgroundThere is little evidence-based guidance on how to optimize methadone dosage among patients with opioid addiction undergoing methadone maintenance treatment (MMT). This study aims to investigate whether self-perceived opioid withdrawal symptoms, adverse effects and self-reported substance use in patients on MMT are related to serum methadone concentration and what role these could play in clinical decisions on dose adjustments.MethodsIn this naturalistic cohort study clinical and laboratory measurements from 83 patients undergoing MMT in outpatient clinics in Bergen, Norway during May 2017-January 2020 were included. Information on age, gender, methadone daily doses and serum concentrations, subjective opioid withdrawal symptoms (SOWS), self-reported adverse effects and substance use were obtained. Linear mixed modelling was used for analyzing the data.ResultsMean age was 45 years and 34% were women. 55% reported subjective opioid withdrawal symptoms, and all had experienced at least one subjective adverse effect. Self-reported substance use was recorded in 88% of the interviews. Total SOWS score (P<0.001), and the specific subjective withdrawal symptoms of anxiety (P=0.004), bone- and muscle ache (P=0.003), restlessness (P=0.017) and shaking (P=0.046) out of the 16 symptoms in standard SOWS questionnaire, as well as the use of heroin (P=0.015) and alcohol (P=0.011) were associated with lower methadone concentrations, whereas cannabis use was associated with higher methadone concentrations (P=0.049). Conclusions More subjective opioid withdrawal symptoms and more self-reported use of heroin and alcohol were associated with lower serum methadone concentrations. More use of cannabis was related to higher serum methadone concentrations. These findings suggest that patient's self-perceived symptoms and current clinical condition can be applied as the main guide in methadone dose adjustments. In some aberrant cases, measurement of serum concentration together with other individual assessments may be considered to support the clinical decision.