Philipp Lobmaier

The pharmacological treatment of opioid addiction—a clinical perspective

This article reviews the main pharmacotherapies that are currently being used to treat opioid addiction. Treatments include detoxification using tapered methadone, buprenorphine, adrenergic agonists such as clonidine and lofexidine, and forms of rapid detoxification. In opioid maintenance treatment (OMT), methadone is most widely used. OMT with buprenorphine, buprenorphine-naloxone combination, or other opioid agonists is also discussed. The use of the opioid antagonists naloxone (for the treatment of intoxication and overdose) and oral and sustained-release formulations of naltrexone (for relapse prevention) is also considered. Although recent advances in the neurobiology of addictions may lead to the development of new pharmacotherapies for the treatment of addictive disorders, a major challenge lies in delivering existing treatments more effectively. Pharmacotherapy of opioid addiction alone is usually insufficient, and a complete treatment should also include effective psychosocial support or other interventions. Combining pharmacotherapies with psychosocial support strategies that are tailored to meet the patients’ needs represents the best way to treat opioid addiction effectively.

Naltrexone implants after in-patient treatment for opioid dependence: randomised controlled trial

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 Implants Compared to Methadone: Outcomes Six Months after Prison Release

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.

Naltrexone Depot Formulations for Opioid and Alcohol Dependence: A Systematic Review

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.

Retention in naltrexone implant treatment for opioid dependence

BACKGROUND Naltrexones 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.

Injectable and implantable sustained release naltrexone in the treatment of opioid addiction

Sustained release technologies for administering the opioid antagonist naltrexone (SRX) have the potential to assist opioid‐addicted patients in their efforts to maintain abstinence from heroin and other opioid agonists. Recently, reliable SRX formulations in intramuscular or implantable polymers that release naltrexone for 1–7 months have become available for clinical use and research. This qualitative review of the literature provides an overview of the technologies currently available for SRX and their effectiveness in reducing opioid use and other relevant outcomes. The majority of studies indicate that SRX is effective in reducing heroin use, and the most frequently studied SRX formulations have acceptable adverse events profiles. Registry data indicate a protective effect of SRX on mortality and morbidity. In some studies, SRX also seems to affect other outcomes, such as concomitant substance use, vocational training attendance, needle use, and risk behaviour for blood‐borne diseases such as hepatitis or human immunodeficiency virus. There is a general need for more controlled studies, in particular to compare SRX with agonist maintenance treatment, to study combinations of SRX with behavioural interventions, and to study at‐risk groups such as prison inmates or opioid‐addicted pregnant patients. The literature suggests that sustained release naltrexone is a feasible, safe and effective option for assisting abstinence efforts in opioid addiction.

Treatment research in prison: Problems and solutions in a randomized trial

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.

Rapid widespread distribution of intranasal naloxone for overdose prevention

BACKGROUND Take home naloxone programs have been successful internationally in training bystanders to reverse an opioid overdose with naloxone, an opioid antagonist. A multi-site naloxone distribution program began in Norway in 2014 as part of a national overdose prevention strategy. The aim of this study was to a) describe the program, and b) present findings from the government-supported intervention. METHODS From July 2014 to December 2015, staff from multiple low-threshold facilities trained clients on how to use intranasal naloxone. Distribution occurred without an individual prescription or physician present. Questionnaires from initial and refill trainings were obtained, and distribution rates were monitored. RESULTS There were 2056 naloxone sprays distributed from one of the 20 participating facilities, with 277 reports of successful reversals. Participants exhibited known risks for overdosing, with injecting (p=0.02, OR=2.4, 95% CI=1.14, 5.00) and concomitant benzodiazepine use (p=0.01, OR=2.6, 95% CI=1.31, 5.23) being significant predictors for having had high rates of previous overdoses. Suggested target coverage for large-scale programs was met, with an annual naloxone distribution rate of 144 per 100,000 population, as well as 12 times the cities mean annual number of opioid-related deaths. CONCLUSION A government-supported multisite naloxone initiative appears to achieve rapid, high volume distribution of naloxone to an at-risk population.

Circumstances surrounding non-fatal opioid overdoses attended by ambulance services

Abstract Introduction and Aims Opioid overdose fatalities are a significant concern globally. Non‐fatal overdoses have been described as a strong predictor for future overdoses, and are often attended by the ambulance services. This paper explores characteristics associated with non‐fatal overdoses and aims to identify possible trends among these events in an urban area in Norway. Design and Methods This is a retrospective analysis of non‐fatal overdoses from Bergen ambulance services from 2012 to 2013. Demographic, temporal and geographic data were explored. Results During the two years, 463 non‐fatal opioid overdoses were attended by ambulance services. Ambulance call‐outs occurred primarily during the late afternoon and evening hours of weekdays. Summer months had more overdoses than other seasons, with a peak in August. Overdoses were nearly twice as likely to occur in a public location in August (risk ratio 1.92, P = 0.042). Ambulance response times were more likely to be longer to private locations, and these victims were more likely to be treated and left at the scene. There was no difference in arrival time for drug‐related and non‐drug related dispatch. Discussion and Conclusions The temporal patterns suggest that non‐fatal overdoses occur during non‐recreational time periods. The longer ambulance response time and disposition for private addresses indicate potential opportunities for peer interventions. Our analysis describes circumstances surrounding non‐fatal overdoses and can be useful in guiding relevant, targeted prevention interventions. [Madah‐Amiri D, Clausen T, Myrmel L, Brattebø G, Lobmaier P. Circumstances surrounding non‐fatal opioid overdoses attended by ambulance services. Drug Alcohol Rev 2017;36:288‐294]

Substance use and problem awareness among drug-involved prisoners in Norway

A sample of 110 drug-involved offenders from two prisons was assessed regarding drug and alcohol consumption, problem awareness, ambivalence and treatment readiness. Of these, 56% reported hazardous alcohol consumption and 53% highly problematic drug use. Highly problematic users reported more problem awareness and more cognitive dissonance regarding change. Treatment readiness was rated higher by problematic users as compared to users reporting fewer problems. The influence of prison environment on ambivalence needs to be studied longitudinally after imprisonment. Identification of drug-involved prisoners should be done systematically, including assessment of alcohol consumption. Opportunities for substance misuse treatment in prisons should be increased.