Kimberly Ann Yonkers1, Ariadna Forray2, Charla Nich3, Kathleen M Carroll3, Cristine Hine4, Brian C Merry2, Howard Shaw5, Julia Shaw6, Mehmet Sofuoglu3. 1. Departments of Psychiatry, Obstetrics and Gynecology and School of Epidemiology and Public Health, Yale University School of Medicine,40 Temple Street, Suite 6B, New Haven, Connecticut, USA 06510. 2. Department of Psychiatry, Yale University School of Medicine,40 Temple Street, Suite 6B, New Haven, Connecticut, USA 06510. 3. Department of Psychiatry, Yale University School of Medicine, VA CT Healthcare System, 950 Campbell Avenue, West Haven, CT 06516. 4. Department of Psychiatry, Yale University School of Medicine,40 Temple Street, Suite 6B New Haven, Connecticut, USA 06510. 5. Department of Obstetrics and Gynecology, Yale New Haven Hospital, 1450 Chapel Street, New Haven, CT 06511. 6. Department of Obstetrics and Gynecology, Yale University School of Medicine, 20 York St, New Haven, CT 06511.
Abstract
BACKGROUND:Progesterone modulates multiple brain functions implicated in the pathogenesis ofdrug addiction. During high endogenous progesterone states, women reduce use of cocaine. We sought to test whether progesterone replacement reduces cocaine use in postpartum women with a cocaine use disorder (CUD). METHODS: A 12-week, double-blind, parallel, randomized, placebo-controlled pilot trial with a 3-month post trial follow-up. 25 women within 12 weeks of deliverywere randomized toplaceboand 25 to100 mgs of oral micronized progesterone, administered twice daily. Participants were recruited from obstetrical clinics. Randomization and allocation were performed by the study biostatistician. Attrition was 18% and the analysis included all50participants. Outcomes were self-reported days of cocaine use and positive urine toxicology assays for cocaine metabolites. FINDINGS: Participants randomized to placebo compared to progesterone had increased likelihood of cocaine use per week (RR=1·19; 95% confidence interval (CI)=1·05 to 1·36; p<0·01). At the three-month post trial visit the difference between groups was not significant (Likelihood RatioΧ2 =5·16; P=·08). There were no group differences in rates of submission of a positive urine test. A post hoc analysis showed a higher rate of relapse for participants randomized to placebo (HR=4·71; 95% CI= 1·09 to 20·5). We did not observe groups differences in the rate of adverse events. INTERPRETATION: These preliminary findings support the promise of progesterone treatment in postpartum women with a CUD and could constitute a therapeutic break through. FUNDING: US National Institute on Drug Abuse; Veterans Administration.
RCT Entities:
BACKGROUND:Progesterone modulates multiple brain functions implicated in the pathogenesis ofdrug addiction. During high endogenous progesterone states, women reduce use of cocaine. We sought to test whether progesterone replacement reduces cocaine use in postpartum women with a cocaine use disorder (CUD). METHODS: A 12-week, double-blind, parallel, randomized, placebo-controlled pilot trial with a 3-month post trial follow-up. 25 women within 12 weeks of deliverywere randomized to placeboand 25 to100 mgs of oral micronized progesterone, administered twice daily. Participants were recruited from obstetrical clinics. Randomization and allocation were performed by the study biostatistician. Attrition was 18% and the analysis included all50participants. Outcomes were self-reported days of cocaine use and positive urine toxicology assays for cocaine metabolites. FINDINGS:Participants randomized to placebo compared to progesterone had increased likelihood of cocaine use per week (RR=1·19; 95% confidence interval (CI)=1·05 to 1·36; p<0·01). At the three-month post trial visit the difference between groups was not significant (Likelihood RatioΧ2 =5·16; P=·08). There were no group differences in rates of submission of a positive urine test. A post hoc analysis showed a higher rate of relapse for participants randomized to placebo (HR=4·71; 95% CI= 1·09 to 20·5). We did not observe groups differences in the rate of adverse events. INTERPRETATION: These preliminary findings support the promise of progesterone treatment in postpartum women with a CUD and could constitute a therapeutic break through. FUNDING: US National Institute on Drug Abuse; Veterans Administration.
Entities:
Keywords:
Cocaine Abuse; Cocaine Dependence; Cocaine Use Disorder; Obstetrics and Gynecology; Postpartum; Progesterone; Women
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