Pregabalin and Methadone Plasma Levels in Patients Receiving Methadone Maintenance Treatment: An Observational Study

The combination of pregabalin and opioid usage is a known risk for fatalities. The pregabalin misuse rate among patients in methadone maintenance treatment (MMT) is reported to be high. However, pregabalin's risk among MMT patients, specifically concerning methadone dose and plasma level, is not yet determined. We aimed to study retention, survival, and whether pregabalin misuse is related to methadone dose and plasma level in MMT patients.

An observational study was conducted on 273 patients at the MMT clinic in Tel Aviv, Israel. Inclusion criteria required having urine drug-screening results for pregabalin when evaluated for methadone plasma levels. Methadone dose and plasma level, drug in urine, sociodemographic, and addiction variables were taken from patients' records.

Patients with positive urine for pregabalin (n = 50) were comparable to 223 negative patients tested in methadone dose (124.3 ± 30.7 vs. 117.1 ± 42.5, p = 0.3) but had higher methadone plasma levels (693.8 ± 327.6 vs. 572.3 ± 286.5 ng/ml, p = 0.009) and QTc intervals on ECG (422.8 ± 31.8 vs. 412.1 ± 29.8 ms, p = 0.03). Logistic regression model found pregabalin tested positive as more likely to test positive for benzodiazepine (OR = 9.1), methylphenidate (OR = 5.5), and fentanyl (OR = 5.9), and to have higher methadone plasma levels (OR = 1.002). Cumulative retention (p < 0.001) and survival (p = 0.007) since admission to MMT were both shorter in the pregabalin group.

Patients who tested positive for pregabalin presented high methadone plasma levels, even though they were treated with normal or low methadone doses. This phenomenon highlights the importance of monitoring methadone levels, which is not a routine procedure, to reduce patients' risk.