Trends in Prescription Medications Reflect the Current Substance Misuse Trends

Background: In Israel, fentanyl and pregabalin prescription rates for pain management have increased over the years. However, Health Maintenance Organizations (HMOs) implemented restrictions on opioid prescribing in 2022, potentially reducing fentanyl availability while pregabalin prescribing remained unrestricted. We aimed to examine temporal trends in fentanyl and pregabalin misuse between 2021 and 2025 among individuals receiving methadone maintenance treatment (MMT) in Tel Aviv, in the context of changes in opioid prescribing policies, and to characterize fentanyl misuse groups. Methods: In this prospective descriptive study, between February 2021 and December 2025, patients (ranging from 291 to 311) were screened three to four times annually for fentanyl and pregabalin, in addition to other routine urine tests for substance use. Trends in positive urine screens for pregabalin and fentanyl were compared. Additionally, methadone doses and serum methadone levels were compared among patients who consistently tested positive for fentanyl (n = 15), tested negative for fentanyl (n = 202), or Stopped/Started fentanyl Use (n = 22) between 2023 and 2025. Results: Pregabalin positivity ranged between 11.2% and 15.9%, with no temporal trend. The fentanyl positivity rate increased from 9.8% in October 2021 to 15.1% in March 2023 and subsequently decreased to 7.5% in March 2025, paralleling the reported reduction in fentanyl availability following HMO restrictions. The methadone dose among patients testing positive for fentanyl was higher, whether they discontinued or continued fentanyl use, than among patients who consistently tested negative for fentanyl. Conclusions: Fentanyl positivity decreased following HMO restrictions and the associated reduction in fentanyl availability, whereas pregabalin positivity remained stable during the study period. Further research is needed to identify the distinct drivers of pregabalin misuse and evaluate appropriate prevention and prescribing strategies. Patients with fentanyl-positive urine screens may require higher methadone doses.