Subjective symptoms and serum methadone concentrations: what should guide dose adjustments in methadone maintenance treatment? A naturalistic cohort study from Norway

Fatemeh Chalabianloo,Lars Thore Fadnes,Else-Marie Løberg,Gudrun Høiseth,Christer Aas,Jørgen G Bramness,Jørn Henrik Vold,Kjell Arne Johansson,Christian Ohldieck

doi:10.1186/s13011-021-00367-w

Abstract

BackgroundThere is little evidence-based guidance on how to optimize methadone dosages 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 concentrations and the role that these variables could play in clinical decisions on dose adjustments.MethodsThis naturalistic prospective cohort study included clinical and laboratory measurements from 83 patients undergoing MMT in outpatient clinics in Bergen, Norway, from May 2017 to January 2020. Information on age, gender, methadone daily doses and serum concentrations, subjective opioid withdrawal symptoms using 16 items Subjective Opioid Withdrawal Scale (SOWS) questionnaire, self-reported adverse effects, and substance use was obtained. Linear mixed modelling was used for analyzing the data.ResultsThe mean age of the participants was 45 years, and 33% were women. Almost half reported mild to moderate subjective opioid withdrawal symptoms, and all had experienced at least one subjective adverse effect. The use of at least one substance was reported by 88% of the participants. Serum concentration-to-dose ratios were lower among those who had reported subjective opioid withdrawal symptoms (p) = 0.039). The total SOWS score (p < 0.001); the specific subjective withdrawal symptoms of anxiety (p = 0.004), bone and muscle aches (p = 0.003), restlessness (p = 0.017), and (slightly) shaking (p = 0.046), also use of heroin (p = 0.015) and alcohol (p = 0.011) were associated with lower methadone concentrations. Cannabis use was slightly related to higher methadone concentrations (p = 0.049).ConclusionsThe findings suggest that the patient’s self-perceived symptoms and current clinical condition are related to the serum concentrations of methadone. This interpretation supports dose adjustments based on patient-reported symptoms. In some aberrant cases, measurement of serum concentrations together with other individual assessments may be considered to support the clinical decision.

Highlights

There is little evidence-based guidance on how to optimize methadone dosages among patients with opioid addiction undergoing methadone maintenance treatment (MMT)
The aim of this study is to investigate whether selfperceived opioid withdrawal symptoms, adverse effects, and substance use in patients on MMT are related to serum methadone concentrations and the role that these variables should play in clinical decisions on dose adjustments
In the unadjusted Linear mixed model (LMM) analysis (Table 2), we found statistically significant inverse associations, weak to moderate correlations, between serum methadone concentrations and total Subjective Opioid Withdrawal Scale (SOWS) scores (p = 0.011), and for the specific symptoms of anxiety (p = 0.009), bone and muscle aches (p = 0.007), and restlessness (p = 0.021) out of the 16 subjective opioid withdrawal symptoms based on the SOWS questionnaire, as well as for use of heroin (p = 0.028) and alcohol (p = 0.008)

Summary

Introduction

There is little evidence-based guidance on how to optimize methadone dosages among patients with opioid addiction undergoing methadone maintenance treatment (MMT). Understanding factors that may influence treatment satisfaction and continuity – and preventing a relapse to illicit opioid use and the subsequent risk of overdose and death – is crucial Such factors may be opioid withdrawal symptoms and adverse effects related to inappropriate methadone dosages. Some researchers have shown that factors other than the dose – such as the patient’s expectations and medication preferences, as well as the patient’s total physical and mental health condition or improvements in psychosocial functioning – may influence treatment satisfaction [9, 10]. These findings add to the complexity of the issue challenging clinicians regarding how to cope with suboptimal treatment outcomes: should the dose be adjusted, or should other problems instead be addressed?

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