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.

International Collaboration in HIV Prevention Research: Evidence from a Research Seminar in Russia

“…34 The extended release injectable naltrexone (one injection has a 1 month effect) has demonstrated better results than oral or implantable naltrexone, with low rates of complications. 35,36 Although additional research is necessary, the preliminary data are promising. Injectable naltrexone may have greater efficacy and may be the most cost-effective treatment option to reduce drug use and consequently reduce HIV risk and transmission in this highest risk population group.…”

“…Several studies suggest that the efficacy of oral naltrexone therapy may be improved by using extended-release implantable or injectable naltrexone instead of oral naltrexone, or by combining naltrexone treatment with behavioral counseling. [34][35][36] Data indicate that oral naltrexone produces an up to 33% reduction in drug use and drug risk: however, low compliance is a major barrier and may significantly reduce effectiveness. 34 Implantable naltrexone has a more prolonged effect (up to 3 months) and higher drug use reduction than oral naltrexone.…”

“…[34][35][36] Dr. Krupitsky estimates that there are between 1.6 and 4 million opiate users in Russia. The majority of these are IDUs, and many are HIV infected.…”

A pharmacogenetic analysis of dopaminergic and opioidergic genes in opioid addicts treated with the combination of naltrexone and guanfacine

“…На протяжении 6-месячного пе-риода пациенты должны были приходить в клинику 1 раз в 2 нед для получения фармакотерапии, психо-логического консультирования, контроля мочи на наркотики, контроля приема пероральных лекар-ственных форм по рибофлавину в моче, регистра-ции побочных эффектов и проведения психометри-ческих оценок [20].…”

Stabilization of remission in patients with opioid dependence with naltrexone implant: a pharmacogenetic approach

“…Пероральная лекарственная форма налтрексона является достаточно эффективным средством для стабилизации ремиссий опийной наркомании толь-ко при условии контроля приверженности терапии (комплаенса) родственниками больных [2][3][4], од-нако это далеко не всегда возможно, низкий ком-плаенс существенно ограничивает эффективность лечения.…”