The devastating costs of opioid abuse and dependence underscore the need for effective treatments for these disorders. At present, several different maintenance medications exist for treating opioid dependence, including methadone, buprenorphine and naltrexone. Of these, naltrexone is the only one that possesses no opioid agonist effects. Instead, naltrexone occupies opioid receptors and prevents or reverses the effects produced by opioid agonists. Despite its clear pharmacologic effectiveness, its clinical effectiveness in treating opioid dependence has been disappointing, primarily due to non-compliance with taking the medication. However, the recent availability of sustained-release formulations of naltrexone has renewed interest in this medication. The present paper describes the development of sustained-release naltrexone formulations and discusses the clinical issues associated with their use in treating opioid dependence.
"In an effort to abrogate the problem of patient noncompliance with oral dosing, extended-release, injectable (depot) formulations of the antagonist naltrexone have been developed by three companies. Such an approach would seem to be a desirable method for delivering an opioid antagonist to opioid-dependent patients.34 "
[Show abstract][Hide abstract] ABSTRACT: The United States Food and Drug Administration (FDA) approved naltrexone, a synthetic competitive antagonist at opioid receptors, in oral form in 1984 for use in the management of opioid abuse and addiction. Because naltrexone and its major metabolite, 6-β-naltrexone, are both competitive antagonists at opioid receptors - and thereby inhibit opioid agonist-induced effects including those desired by abusers - it was hypothesized that once maintained on naltrex-one, opioid-induced desirable effects would be diminished to the point that relapse to illicit use would decline because it was no longer rewarding. However, good medication compliance is a requisite for such a strategy to be effective and a systematic review of oral naltrexone concluded that this method of treatment was not superior for any outcomes measured (ie, retention, abstinence, or side effects) to placebo, psychotherapy, benzodiazepines, or buprenorphine treatment. In addition, the retention rate on oral naltrexone was very low (less than 30%). Recently, the FDA approved an extended-release formulation (intramuscular depot injection) of naltrexone for prevention of relapse to opioid dependence following opioid detoxification and to be used along with counseling and social support. Since it needs to be administered only monthly, as opposed to the daily administration required for the oral formulation, naltrexone injection has the potential for increasing adherence and retention rates. Concerns include liver damage at high doses (oral formulation) and possible opioid overdose if an attempt is made to surmount receptor antagonism by taking higher doses of an opioid agonist or if opioid receptors become "sensitized" under long-term antagonism. The focus of the present review is the current information regarding the safety and efficacy of naltrexone extended-release therapy.
"Several injectable suspension formulations of naltrexone for extended release (XR-NTX) have been developed to reduce the frequency of dosing and improve adherence (Comer et al., 2007). Evaluations with an investigational XR-NTX formulation, Depotrex®, showed that XRNTX can provide long-lasting opioid blockade and may be useful in the treatment of opioid addiction (Comer et al., 2002; 2006). "
[Show abstract][Hide abstract] ABSTRACT: Naltrexone provides excellent opioid blockade, but its clinical utility is limited because opioid-dependent patients typically refuse it. An injectable suspension of naltrexone for extended release (XR-NTX) was recently approved by the FDA for treatment of opioid dependence. XR-NTX treatment may require concurrent behavioral intervention to maximize adherence and effectiveness, thus we sought to evaluate employment-based reinforcement as a method of improving adherence to XR-NTX in opiate dependent adults.
Opioid-dependent adults (n=38) were detoxified and inducted onto oral naltrexone, then randomly assigned to contingency or prescription conditions. Participants received up to six doses of XR-NTX at four-week intervals. All participants could earn vouchers for attendance and performance at a therapeutic workplace. Contingency participants were required to accept XR-NTX injections to access the workplace and earn vouchers. Prescription participants could earn vouchers independent of their acceptance of XR-NTX injections.
Contingency participants accepted significantly more naltrexone injections than prescription participants (87% versus 52%, p=.002), and were more likely to accept all injections (74% versus 26%, p=.004). Participants in the two conditions provided similar percentages of samples negative for opiates (72% versus 65%) and for cocaine (58% versus 54%). Opiate positivity was significantly more likely when samples were also cocaine positive, independent of naltrexone blockade (p=.002).
Long-term adherence to XR-NTX in unemployed opiate dependent adults is low under usual care conditions. Employment-based reinforcement can maintain adherence to XR-NTX. Ongoing cocaine use appears to interfere with the clinical effectiveness of XR-NTX on opiate use.
Drug and alcohol dependence 07/2011; 120(1-3):48-54. DOI:10.1016/j.drugalcdep.2011.06.023 · 3.42 Impact Factor
"However, care should be taken to implement graded exposure techniques so as not to overwhelm patients and provoke an opioid relapse. Switching from orally administered naltrexone to long-acting injectable naltrexone formulations (Comer et al., 2007) may also enhance treatment success by providing a longer period of nonreinforcement where stress resiliency can be enhanced through psychotherapeutic interventions. For those opioid dependent individuals who are unable to directly inhibit maladaptive/avoidant coping reactions, our data suggest that simply enhancing social support may temper maladaptive/avoidant coping and lead to stress reduction. "
[Show abstract][Hide abstract] ABSTRACT: Stress is known to increase addiction vulnerability and risk of relapse to substance use. PURPOSE & METHOD: We compared opioid dependent individuals entering naltrexone treatment (n = 57) with healthy controls (n = 75) on measures of stress, coping, and social support and examined the relative contribution of group membership, coping, and social support to stress within the sample. Analyses of variance (ANOVA) and covariance (ANCOVA), and stepwise multiple regression were conducted.
Compared with controls, opioid dependent subjects reported greater stress, less use of adaptive coping, but comparable use of maladaptive/avoidant coping. No group differences were found with respect to social support. Perceived stress was predicted by group membership, low social support, and greater use of maladaptive/avoidant coping, and the prediction by social support and maladaptive/avoidant coping did not differ by group.
Opioid dependent individuals entering naltrexone treatment experience higher levels of stress and report less use of adaptive coping strategies when compared with controls. Group membership, maladaptive/avoidant coping, and social support independently contribute to perceived stress. Findings suggest that novel treatment approaches that decrease maladaptive/avoidant coping and improve social support are important aspects of decreasing stress during early recovery from opioid addiction.
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