Naltrexone with or without guanfacine for preventing relapse to opiate addiction in St.-Petersburg, Russia

Abstract Background Stress is a key precipitant to discontinuing naltrexone and relapsing to opiate abuse. Alpha-2 adrenergic agonists like guanfacine may reduce stress induced craving and have reduced opiate relapse in small clinical trials. Methods This randomized, double blind double dummy placebo-controlled 6-month trial tested oral naltrexone with or without guanfacine for reducing stress and preventing opiate relapse. We randomized 301 patients to: naltrexone 50 mg/day + guanfacine 1 mg/day ( n = 75) (N/G), naltrexone + guanfacine placebo (N/P) ( n = 76), naltrexone placebo + guanfacine ( n = 75) (P/G), and double placebo ( n = 75) (P/P). Results Among the 75 patients in each group the percentage still retained on naltrexone treatment at six months was: N/G 26.7%, N/P 19.7% ( p = 0.258 to N/G), P/G 6.7% ( p < 0.05 to both N groups), and P/P 10.7% ( p = 0.013 to N + G). Guanfacine reduced the severity of stress particularly at weeks 10 and 18. Adverse events (AE) were infrequent (4.7%) without group differences, with most common AEs: headache, poor appetite, insomnia, and dizziness. Conclusions Adding guanfacine to naltrexone did not improve treatment retention or opiate free urines, but it reduced both stress and craving at later time points in treatment, which may be related to stress-induced craving and the animal model of incubation of reinstatement. During treatment, HIV risk, anxiety, and depression reduced among all patients in treatment, regardless of group.