Wastewater-based evidence of pregabalin misuse in Türkiye: implications for drug policy and surveillance

Pregabalin has increasingly attracted attention in Türkiye due to rising concerns around non-medical use despite regulatory controls on prescribing. Evidence describing its population-level consumption, however, remains largely dependent on administrative data sources. This study applied wastewater-based epidemiology (WBE) to assess community pregabalin use and to compare wastewater-derived estimates with pharmacy sales data.

A total of 882 influent wastewater samples were collected from 31 major cities (42 WWTPs) between June and December 2022 and analysed using a validated LC-MS/MS. Population-normalised daily intake (PNDI) was calculated and assessed for seasonal and within-week variation and for agreement with dispensing indicators.

Influent concentrations ranged 0.11-1.92 µg/L (mean 0.84 ± 0.45). PNDI ranged 53.4-2604 mg/1000p/day (mean 591 ± 355; median 503). Seasonal differences were observed (p < 0.001), while weekday-weekend differences were not (p = 0.67). Wastewater and sales indicators showed a moderate correlation (r = 0.437, p = 0.014). Ten cities (32%) fell within the 0.8-1.2 agreement band, 13 (42%) were <0.8, and 8 (26%) were >1.2.

Wastewater analysis provides an independent, population-level perspective on pregabalin use that is not fully captured by prescription, records alone. Because WBE cannot distinguish therapeutic from non-therapeutic use and influent loads may include unquantified direct disposal, wastewater-sales discrepancies should be interpreted cautiously. When triangulated with pharmacy sales, such discrepancies can help flag locations where dispensing indicators may underestimate community exposure, consistent with potential diversion or unrecorded access, supporting evidence-based drug policy and public health surveillance.