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 2015 and December 2021. Data on methadone treatment and polygraph recording, including the apnea-hypopnea index (AHI) were collected.

Findings: A total of 40 patients, mostly male (72.5%), with a mean age of 35±6.7 years and a mean body mass index (BMI) of 25.1±4.5 kg/m² were included. The daily dose of methadone was significantly associated with an AHI≥15 events/h as well as an AHI≥30 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≥15 events/h. The best sensitivity and specificity for the prediction of AHI≥15 events/h and AHI≥30 events/h were obtained with daily methadone doses of≥72.5 mg and 77.5 mg, respectively.

Conclusion: In this sample of MMT patients, methadone doses of 72.5 mg and 77.5 mg were the best cut-off values for predicting AHI≥15 and≥30 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.