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Naltrexone is an opioid receptor antagonist that blocks the reinforcing effects of opioids and reduces alcohol consumption and craving. It has no abuse potential, mild and transient side effects, and thus appears an ideal pharmacotherapy for opioid dependence. Its effectiveness in alcohol dependence is less evident, but compliance with naltrexone combined with psychosocial support has been repeatedly shown to improve drinking outcomes. Limited compliance with oral naltrexone treatment is a known drawback. Several naltrexone implant and injectable depot formulations are being investigated and provide naltrexone release for at least 1 month. Studies among opioid-dependent patients indicate significant reductions in heroin use, but sample sizes are usually small. In alcohol dependence, two large multicenter trials report alcohol and craving reductions for naltrexone and placebo groups, indicating a significant but moderate effect. The pharmacokinetic profile of the injectable formulation indicates reliable naltrexone release over 1 month at therapeutic levels. Implant formulations releasing naltrexone up to 7 months are reported. Findings on safety and tolerability confirm the generally mild adverse effects described for naltrexone tablets. However, further research on therapeutic levels (i.e., opioid blocking) is warranted. The majority of naltrexone implants lacks approval for regular clinical use and larger longitudinal studies are needed. The available naltrexone depot formulations have the potential to significantly improve medication compliance in opioid and alcohol dependence. In certain circumstances, they may constitute a promising new treatment option., (© 2010 Blackwell Publishing Ltd.)

Background: Naltrexone's usefulness in the treatment of opioid dependence stems from its ability to block the action of heroin and other opioids. However, many patients are ambivalent towards naltrexone and often drop out of treatment with orally administered naltrexone. Sustained release naltrexone seems promising in reducing opioid use, but the extent to which patients remain in treatment beyond the first dosage of naltrexone is not clear., Methods: Patients (n=61) receving treatment with sustained release naltrexone implants were offered a second naltrexone implant after 6 months. Patients who remained in treatment were compared to those who did not, on drug use, mental health, and social problems before and during naltrexone implant treatment. Information was obtained on other treatments sought by patients who discontinued naltrexone. Blood samples were used to verify naltrexone release, and hair samples to confirm opioid intake., Results: Of the patients who received the first naltrexone implant, 51% (n=31) remained in naltrexone implant treatment. Among those who discontinued treatment, 21% expressed a wish to reimplant but failed to attend for reimplantation and 28% declined reimplantation: 6 non-retained patients initiated maintenance or residential treatment. Remaining in naltrexone treatment was related to pre-study length of employment, illicit drug use, and concern for family problems. Higher levels of substance misuse and criminal activity during naltrexone treatment were negatively related to subsequent retention., Conclusion: Rates of retention among opioid-dependent patients receiving naltrexone implant treatment are encouraging and support this as a feasible long-term treatment option., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Aims: Naltrexone is a competitive opioid antagonist that effectively blocks the action of heroin and other opioid agonists. Sustained-release naltrexone formulations are now available that provide long-acting opioid blockade. This study investigates the use of heroin and other opioids among opioid-dependent patients receiving treatment with long-acting naltrexone implants, their subjective experience of drug 'high' after opioid use, and factors associated with opioid use., Methods: Participants (n = 60) were opioid-dependent patients receiving treatment with naltrexone implants. Outcome data on substance use, drug 'high', depression and criminal activity were collected over a 6-month period. Blood samples were taken to monitor naltrexone plasma levels, and hair samples to verify self-reported opioid use., Findings: More than half [n = 34 or 56%; 95% confidence interval (CI) 44-68%)] the patients challenged the blockade with illicit opioids during the 6-month treatment period; 44% (n = 26; 95% CI 32-56%) were abstinent from opioids. Mean opioid use was reduced from 18 [standard deviation (SD)13] days during the month preceding treatment to 6 days (SD 11) after 6 months. Of the respondents questioned on opioid 'high' (n = 31), nine patients (30%; 95% CI 16-47%) reported partial drug 'high' following illicit opioid use, and three (12%; 95% CI 3-26%) reported full 'high'. Opioid use was associated with use of non-opioid drugs and criminal behaviour., Conclusions: Challenging naltrexone blockade with heroin on at least one occasion is common among sustained-release naltrexone patients, but only a minority of patients use opioids regularly. Challenges represent a warning sign for poor outcomes and often occur in the context of polydrug use and social adjustment problems.

Background: After prison release, offenders with heroin use problems are at high risk of relapse and overdose death. There is a particular need for treatments that can be initiated in prison and continued after release into the community. Methadone maintenance treatment has been shown to reduce heroin use, criminality and mortality. Naltrexone implant treatment has not previously been evaluated in prison settings., Methods: This study compares the effects of naltrexone implants and methadone treatment on heroin and other illicit drug use, and criminality among heroin-dependent inmates after release from prison., Results: Forty-six volunteers were randomly allocated to naltrexone implants or methadone before release. Intention-to-treat analyses showed reductions in both groups in frequency of use of heroin and benzodiazepines, as well as criminality, 6 months after prison release., Conclusions: Naltrexone implants may be a valuable treatment option in prison settings., (2010 S. Karger AG, Basel.)

Background: Naltrexone has considerable potential in helping to prevent relapse in heroin dependency. A longer-lasting formulation for naltrexone treatment is desirable to further reduce non-adherence and relapse during treatment of opiate dependence., Aims: To evaluate the safety and effectiveness of a 6-month naltrexone implant in reducing opioid use after in-patient treatment., Method: A group of 56 abstinence-oriented patients who completed in-patient treatment for opioid dependence were randomly and openly assigned to receive either a 6-month naltrexone implant or their usual aftercare. Drug use and other outcomes were assessed at 6-month follow-up., Results: Patients receiving naltrexone had on average 45 days less heroin use and 60 days less opioid use than controls in the 180-day period (both P<0.05). Blood tests showed naltrexone levels above 1 ng/ml for the duration of 6 months. Two patients died, neither of whom had received an implant., Conclusions: Naltrexone implant treatment safely and significantly reduces opioid use in a motivated population of patients.

Naltrexone blocks opioid effects effectively, but poor compliance limits the clinical usefulness in the treatment of opioid dependence. Long-acting implanted formulations might increase the clinical feasibility. Several implants have been produced, but few clinical reports have been published. This paper describes an open trial with an Australian implant. This implant is claimed to have duration of up to six months with double implants and acceptable levels of side effects. This was explored in the present pilot study with 13 opioid-dependent patients. By single implant of 1.8 g naltrexone the duration judged by naltrexone plasma levels above 1 ng/ml naltrexone was between 2 and 4 months. Double implants maintained such plasma levels for 5-6.5 months. Clinically, the implants appeared promising. Side effects were minimal. During the period with adequate plasma levels of naltrexone, use of opioids was absent and use of other psychoactive drugs reduced. At 1-year follow-up, the patients rated the implants highly positively.

Aims: To evaluate individual variations in plasma concentrations over time in patients with naltrexone implants., Methods: Ten opioid-dependent patients received up to four implants. Plasma samples were collected regularly for the analyses of naltrexone and the metabolite beta-naltrexol., Results: The median naltrexone C(max) was 12.3 (range 5.8-22.1) ng ml(-1), the median T(max) was 1 day (range 3 h to 35 days), and the median length of time that plasma concentrations were above 1 ng ml(-1) was 55 (range 30-80) days. Two patients reported heroin use without experiencing any effect. Tissue reactions were recorded in two patients after repeated implantation., Conclusion: Marked individual and intraindividual variations in naltrexone concentrations were observed. Further studies should be performed to evaluate the need for therapeutic drug monitoring during naltrexone implant treatment.

Background: Naltrexone is a well-known opioid antagonist that has attracted increased attention with respect to new techniques in detoxification, methods for improving compliance, and new indications. Naltrexone 50 mg Revia recently obtained registration in Norway as a pharmaceutical product. A review of its pharmacological properties and documentation of clinical use is merited., Methods: Basic neurobiological descriptions are cited from review publications. In addition, Medline, Embase and the Cochrane library have been searched for evidence-based evaluations., Results and Interpretation: The basic antagonist effect is proven beyond doubt. Clinical dosages give few and moderate side effects. The drug's two properties, blocking for exogenic opioid and modulating the endogenic opioid system, are both therapeutically useful. Its use in the treatment of heroin addiction is hampered by poor compliance; this might be improved by formulations with prolonged duration or by special therapeutic techniques. Usefulness in treatment of alcohol problems is documented but effect size is moderate and partly dependent on psychosocial therapeutic techniques. There is interesting but undocumented reports on usefulness with nicotine and cocaine addiction, with gambling problems, in impulsive behaviour and in several other areas.

Background: The study explores the use of naltrexone as an adjuvant therapy for psychosocial treatment in a unit for young heroin addicts with frequent relapses., Material and Method: Naltrexone was introduced through discussions in the therapeutic community. 16 patients elected to participate in a six-month trial. Side effects were recorded daily, then weekly, and patient reactions by weekly self-ratings. At end point patient and counsellor independently scored estimated utility. The group was followed up at four years., Results and Interpretation: Staff and patients developed an increasing degree of consensus during the project. Naltrexone is a useful adjuvant therapy. Several short-term goals were reached; side effects were minimal. Four out of 16 patients completed the full six-month treatment. 11 patients judged the use of naltrexone as somewhat or very positive. Therapists judged naltrexone to be beneficiary for 10. At four years follow up, six patients were rehabilitated without illegal substance use and two were substantially improved. Four of these were, however, on methadone maintenance. Naltrexone is useful as an adjuvant therapy to increase therapeutic potency in comprehensive therapeutic units for heroin addicts. The long-term effects are limited. Therapeutic units for heroin addicts should integrate both agonists and antagonists in their psychosocial programs.

Background: An increasing number of Norwegian heroin addicts have had naltrexone implants abroad without proper documentation. The authors established a joint project to study duration and safety., Material and Methods: Methodology to measure naltrexone in plasma was developed. 10 patients had 21 implants. Plasma samples were collected before, one and three hours after implantation, daily for one week, then weekly. Patient satisfaction, side effects and unwanted medical events were recorded., Results: Patients had a protective level of naltrexone for 35-80 days. Side effects were few. Two patients had abstinence reactions caused by insufficient detoxification. Two patients had their repeat implants removed because of tissue reactions. One patient developed hepatitis C infection in the second week after implantation. One had transient increase in transaminases after heavy multi-drug use. The others were without signs of hepatic toxicity., Interpretation: Use of implants secures a prolonged period of naltrexone protection. Implants are mostly well tolerated, but tissue reactions to repeat implants could be a problem. Evaluation of the patients should be thorough and the treatment integrated in a competent follow up.

Opioid-dependent individuals are frequently incarcerated and relapse rates following their release are high. Evidence of the effectiveness of prison-based treatments and community aftercare is limited. We report the preliminary findings of a randomized controlled trial that encountered specific challenges inherent in prison research. Naltrexone implants were compared with methadone maintenance treatment among pre-release inmates. Naltrexone implants have not previously been evaluated in prison settings. Approximately 41% of eligible inmates volunteered to participate; 27 of the total 46 participants commenced treatment according to the protocol. Although most inmates intended to remain abstinent from heroin after their release, the relapse rates among individuals who had not commenced treatment were high. Naltrexone implants were regarded as a valuable treatment option. During the study, several problems were encountered regarding enrollment, treatment initiation and aftercare. These findings have important implications for future prison research. Random allocation to the fixed interventions was inefficient in limiting the risk of selection bias. Alternative approaches should be considered, such as sequential multiple assignment randomized trials. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Naltrexone Implants After In-Patient Treatment for Opioid Dependence: Randomised Controlled Trial," by N. Kunøe and colleagues which appeared in a 2009 issue.