Methadone Dose and Timing of Administration as Predictors of Sleep Apnea Syndrome During Methadone Maintenance Treatment: A Retrospective Cross-sectional Study

Background: This study aimed to assess the association of sleep apnea syndrome (SAS) with methadone dose and timing of administration in patients receiving methadone maintenance treatment (MMT) for opioid use disorder (OUD).Methods: This retrospective cross-sectional study was conducted on adult patients receiving MMT who had a nocturnal respiratory polygraphy between November ۲۰۱۵ and December ۲۰۲۱. Data on methadone treatment and polygraph recording, including the apnea-hypopnea index (AHI) were collected.Findings: A total of ۴۰ patients, mostly male (۷۲.۵%), with a mean age of ۳۵±۶.۷ years and a mean body mass index (BMI) of ۲۵.۱±۴.۵ kg/m² were included. The daily dose of methadone was significantly associated with an AHI≥۱۵ events/h as well as an AHI≥۳۰ events/h, even after adjustment for age, gender, BMI, and benzodiazepine use. However, these associations were not preserved when the time of administration (day vs evening) was considered, while the evening administration was significantly associated with an AHI≥۱۵ events/h. The best sensitivity and specificity for the prediction of AHI≥۱۵ events/h and AHI≥۳۰ events/h were obtained with daily methadone doses of≥۷۲.۵ mg and ۷۷.۵ mg, respectively.Conclusion: In this sample of MMT patients, methadone doses of ۷۲.۵ mg and ۷۷.۵ mg were the best cut-off values for predicting AHI≥۱۵ and≥۳۰ events/h, respectively, especially when taken in the evening. These results should draw clinicians’ attention to the importance of SAS screening, and further studies are needed, notably comparisons with buprenorphine.

Keywords:

Opioid-related disorders , Methadone , Sleep apnea syndrome