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Background <p>As aging is associated with physiological changes, patients in methadone maintenance treatment (MMT) may require an adequate methadone dose adjustment. We aimed to study the relationship between aging and methadone dose and plasma level.</p> Methods <p>Patients with two methadone plasma level results, above one year apart, were included. Methadone dose and plasma levels, as well as their changes over time, were studied by age group.</p> Results <p>318 patients, 36.5% aged &lt;50 years, 53.5% 50–64, and 10.1% aged ≥65 years, were compared. Methadone dose did not differ between groups (120.8±38.6 mg/day); however, methadone plasma levels were lowest in the &lt;50y group (580.9±270.9 ng/ml), followed by the 50–64y group (715.4±345.1 ng/ml), and highest in the ≥65y group (893.1±379 ng/ml, p&lt;0.001). This was also reflected in the proportion of patients with (≥1000 ng/ml methadone plasma levels): 6.9%, 18.8%, and 37.5%, respectively (p&lt;0.001). Groups also differed in BMI, which was lowest in the ≥65 years group (24.8±3.9), compared to 26.0±5.5 in the &lt;50 and 26.9±5.1 in the 50–64.9 age group (p=0.053). Methadone plasma levels still significantly differed by age group (p&lt;0.001) after controlling for methadone dose (p&lt;0.001) and BMI (p=0.02) (ANOVA, corrected model p&lt;0.001, F=37.8). Following 4.6±1 years, at the latest evaluation, both methadone doses (Repeated Measures p(Time)=0.004) and plasma levels (p(Time)=0.002) were reduced, with no interaction by age group (p(Time*Group)=0.4 and 0.5, respectively), but only methadone plasma levels differed by age groups (p(Group)&lt;0.001). The proportion of ≥1000 ng/ml methadone plasma levels remained significantly higher among the older age group.</p> Conclusions <p>Although the dose of methadone does not require elevation over the years, due to aging, methadone plasma level evaluation should be considered to avoid excessively high methadone plasma levels. However, as the older group represented a small subgroup, additional larger cohort studies and future follow-up are needed to confirm our preliminary findings.</p>

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The relationship between methadone dosage and plasma level changes with aging in methadone maintenance treatment (MMT) patients

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  • 发表日期：

    2026年2月19日

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  • Anat Sason,
  • Miriam Adelson,
  • Shaul Schreiber,
  • Einat Peles

摘要

Background

As aging is associated with physiological changes, patients in methadone maintenance treatment (MMT) may require an adequate methadone dose adjustment. We aimed to study the relationship between aging and methadone dose and plasma level.

Methods

Patients with two methadone plasma level results, above one year apart, were included. Methadone dose and plasma levels, as well as their changes over time, were studied by age group.

Results

318 patients, 36.5% aged <50 years, 53.5% 50–64, and 10.1% aged ≥65 years, were compared. Methadone dose did not differ between groups (120.8±38.6 mg/day); however, methadone plasma levels were lowest in the <50y group (580.9±270.9 ng/ml), followed by the 50–64y group (715.4±345.1 ng/ml), and highest in the ≥65y group (893.1±379 ng/ml, p<0.001). This was also reflected in the proportion of patients with (≥1000 ng/ml methadone plasma levels): 6.9%, 18.8%, and 37.5%, respectively (p<0.001). Groups also differed in BMI, which was lowest in the ≥65 years group (24.8±3.9), compared to 26.0±5.5 in the <50 and 26.9±5.1 in the 50–64.9 age group (p=0.053). Methadone plasma levels still significantly differed by age group (p<0.001) after controlling for methadone dose (p<0.001) and BMI (p=0.02) (ANOVA, corrected model p<0.001, F=37.8). Following 4.6±1 years, at the latest evaluation, both methadone doses (Repeated Measures p(Time)=0.004) and plasma levels (p(Time)=0.002) were reduced, with no interaction by age group (p(Time*Group)=0.4 and 0.5, respectively), but only methadone plasma levels differed by age groups (p(Group)<0.001). The proportion of ≥1000 ng/ml methadone plasma levels remained significantly higher among the older age group.

Conclusions

Although the dose of methadone does not require elevation over the years, due to aging, methadone plasma level evaluation should be considered to avoid excessively high methadone plasma levels. However, as the older group represented a small subgroup, additional larger cohort studies and future follow-up are needed to confirm our preliminary findings.