Methadone trough levels in pregnancy

This study was undertaken to determine (1) the methadone serum trough level adequate to prevent withdrawal symptoms in heroin-addicted pregnant women and (2) whether the methadone serum trough level in symptomatic women with withdrawal symptoms differs from that of asymptomatic women.

Pregnant women addicted to heroin were followed up prospectively between March 1, 1999, and March 1, 2000, in a specialized multidisciplinary methadone program after in-hospital stabilization. After counseling, women signing Institutional Review Board-approved informed consent had their methadone serum trough (20-24 hours after last dose) level checked at regular intervals throughout pregnancy. Methadone levels were kept blinded from clinicians. Methadone doses were increased only according to withdrawal symptoms. Methadone levels of asymptomatic (without withdrawal symptoms) women were compared with methadone serum trough levels of symptomatic (with withdrawal symptoms) women.

Mean methadone serum trough level was 0.295 +/- 0.16 mg/L in asymptomatic women (n = 44) and 0.175 +/- 0.11 mg/L in symptomatic (n = 58) women (P <.001). The mean methadone dose in asymptomatic patients was 101 +/- 42 mg versus 114 +/- 43 mg in symptomatic patients (P =.1). No patient had a toxic-range methadone trough level (all <0.7 mg/L). By receiver operating characteristic curve, the best differentiating methadone trough level between asymptomatic and symptomatic women was 0.24 mg/L. These differences in methadone serum trough levels between asymptomatic and symptomatic women were not influenced by continuing drug abuse, maternal weight, or gestational age when methadone serum trough level was drawn.

Mean methadone serum trough level in asymptomatic pregnant women is approximately 0.3 mg/L, and levels of 0.24 mg/L or greater should be considered adequate to prevent withdrawal symptoms in pregnancy. Knowledge of these levels will help management of the frequently noncompliant heroin-addicted pregnant woman. Appropriate daily dosing to achieve these levels is usually between 50 and 150 mg methadone, with the occasional need for even higher doses in the third trimester.