Drug and Alcohol Findings home page in a new window EFFECTIVENESS BANK BULLETIN 27 February 2012

The entries below are our accounts of documents collected by Drug and Alcohol Findings as relevant to improving outcomes from drug or alcohol interventions in the UK. The original documents were not published by Findings; click on the Titles to obtain copies. Free reprints may also be available from the authors. If displayed, click prepared e-mail to adapt the pre-prepared e-mail message or compose your own message. The Summary is intended to convey the findings and views expressed in the document. Below may be a commentary from Drug and Alcohol Findings.


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Groundbreaking naltrexone implants studies from Norway

All five entries (the first an update of one first released in 2009) document the groundbreaking randomised controlled trials conducted in Norway of naltrexone implants which block the effects of heroin and other opiate-type drugs for up to six months. Implants work by depriving the addict of the choice to experience opiate-type effects – a curtailment which at the same time makes them effective and controversial. Short of surgical removal, in theory for several months the procedure irreversibly prevents heroin addicts experiencing the desired effects of the drug, providing an extended opiate-free space during which a new non-opiate focused life can be constructed.

The Norwegian studies tested implants against normal aftercare for patients leaving inpatient treatment, and against methadone maintenance as a bridge to community treatment for formerly dependent prisoners coming to the end of their sentences. They showed that implants can be an effective and lasting aid to curbing opiate use for a small minority of patients motivated to aim for opiate abstinence and prepared to accept that opiate effects may be unavailable to them for six months.

Implants help sustain heroin abstinence after detoxification ...

Implants equal methadone as a prison-community bridging treatment ...

False confidence leads formerly addicted prisoners to reject in-prison treatment ...

Despite implants a quarter of patients repeatedly used opiates ...

Half implanted patients opt for a second implant ...


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

Kunøe N., Lobmaier P., Vederhus J.K. et al.
British Journal of Psychiatry: 2009, 194, p. 541–546.
Unable to obtain a copy by clicking title? Try asking the author for a reprint by adapting this prepared e-mail or by writing to Dr KunKunøe at nikolaj.kunoe@medisin.uio.no.

In the first randomised trial, implants which block opiate-type drugs for months helped heroin addicts in Norway avoid relapse after detoxification. If these or allied products gain a UK licence, they could help pave the way to abstinence for the minority of suitable addicts.

Summary Naltrexone is a medication which blocks the effects of heroin and other opiate-type drugs. Its considerable potential in helping to prevent post-detoxification relapse has not been realised because patients generally refuse to take it or quickly discontinue. However, these limitations apply to the oral formulation which has be taken daily. Longer-lasting formulations in the form of a depot injection or an implant inserted under the skin avoid the need to take the medication daily. This is the first randomised trial of an implant whose opiate-blocking effects last for about six months.

Over 18 months from January 2006, staff at inpatient drug clinics in south-eastern Norway invited opiate-dependent patients on abstinenceľoriented programmes to participate in the study. Patients who agreed were contacted by researchers at the end of their detoxification or residential treatment. The 56 who joined the study were told that for the first six months they would be randomly allocated to the implant or to usual aftercare arrangements, but that then all would be offered (re)implantation. Typically they were male injectors in their 30s who had used heroin for on average seven years; nearly all also used other drugs.

Average proportion days using opiate-type drugs

Three of the implant group left the clinic before they could be implanted and another three had the implants removed. All but three Follow-up results for these patients were assumed to be the same as the last time they were assessed, presumably the initial baseline assessment. of the surviving (there were two deaths) patients were reassessed six months later. The main analysis included all the patients whether or not they had received or retained their implants. Over the six months of the follow-up, usual-care patients recalled using opiate-type drugs on average on 97 days, the implant group on just 37 days chart. This differential remained in the last month of the follow-up, when the corresponding figures were 17 and six days, a statistically significant difference. Average frequency of use was also significantly higher among the usual-care patients. At the six-month follow-up assessment, 18 out of 27 usual-care patients but just 9 of the 29 implant patients continued to meet criteria for opioid dependence. In line with this, implant patients were much less likely to experience craving. Nevertheless, during the study over half (18 of 29) tried opioids at least once.

In the last month of the follow-up, implant patients scored significantly lower on an index of multiple drug use and injected less often, but there were no significant differences in drinking or use of non-opioid drugs. Over the follow-up, usual-care patients averaged significantly more repeat detoxifications (0.71 versus 0.21); there were no significant differences in outpatient treatment attendance or use of aftercare services. By the end of the follow-up, implant patients expressed greater satisfaction with their lives but there were no significant differences in levels of depression, work, or criminal activity.

One patient in the implant group reported three non-fatal overdoses (there were four in the usual-care group) while using combinations of opioids, amphetamines and benzodiazepines. Three had implants removed due to infection, discomfort or side-effects. In another two, wound-opening required antibiotic treatment, and three had allergic reactions treated with antihistamines. The single death among patients allocated to implants was an overdose prior to implantation. There was also one overdose death among the usual-care patients.

The authors concluded that naltrexone implants safely and significantly reduced opioid use in a motivated population of patients.


Findings logo commentary In the UK, neither implants nor depot injections of naltrexone have been licensed for medical use; they can still be (and have been; 1 2 Revill J. "A Comparative study of the protective benefits of oral and implanted naltrexone in a British NHS general practice." Abstracts from 7th International Conference 2002. Stapleford Trust. 3 Daly M. "Implant progress blocked." Druglink: September/October 2004, p. 12–13. 4) used, but patient and doctor have to accept the added responsibility of a product which has not yet been shown to meet the safety and efficacy requirements involved in licensing.

As with oral naltrexone, the main limitation of the treatment is its acceptability to patients. In Norway acceptability will have been heightened by restricted access to substitute prescribing programmes, particularly for people unwilling to contract to forgo not just heroin, but persistent substance use of any kind. Nevertheless, recruitment to the study seems to have been slow. Just 56 out of 667 assessed for the study were recruited over 18 months at two (or possibly more) clinics, a throughput of at best just over two a month per clinic. The 56 out of 667 patients who joined the study were probably unusually highly motivated Most of the 611 patients who did not join the study did not complete their initial treatments or were planning to continue care at other clinics or in maintenance treatments. Another 131 who might have joined the study simply refused. The 56 left had completed the initial treatment and were prepared to countenance a relatively untried follow-on procedure which (barring surgical or self-removal) blocked opiate effects for six months. As the authors pointed out, the absence of self-removal attempts and the high retention rate seem further signs of high motivation and compliance. to sustain abstinence from opiates, yet over half the implant patients tried resuming opiate use. Though the implant was expected to render such use futile, repeated use did happen: on average the 12 of 23 followed-up implant patients who used opioids had used these drugs on about 38 days out of the roughly 180 days of the study, figures were skewed by some very frequent users. This degree of persistence seems incompatible with the implant having among these patients totally eliminated opiate-type effects.

The reduction in multiple drug use seems to have been mainly due to the effect on opiate use, since drinking and use of other drugs were not significantly affected. As this study shows, implants and depot injections do not guarantee abstinence. Implants can be removed and both these and depot injections can be sidestepped by turning to non-opiate drugs (as may have happened in Australia) or overridden by very high doses of opiate-type drugs, attempts which risk overdose.

The implants were compared against relatively weak The usual aftercare against which the implants were compared does not appear to have been a continued service from the clinics, but external counselling and other services which (if necessary with help from the clinics) patients would have had to arrange for themselves. aftercare arrangements; more active and structured aftercare (for example, regular monitoring, continued well organised care from the initial service, or active referral) might have narrowed the differences between the groups. However, highly motivated patients and imperfect aftercare arrangements probably reflect the conditions in which implants would be deployed in normal practice, Where the study departed most from normal practice was in holding out to the usual-care group the prospect of an implant in six months time, a prospect which (as the authors commented) may have helped keep them in the study and possibly also given them an incentive not to become so dependent that implantation would be ruled out. as does the fact that patients knew whether they had an active implant; unlike some other studies, there was no placebo comparison group.

Of the 26 patients who were implanted, eight (nearly 1 in 3) experienced complications which led three to have the implant removed. One other potential problem is that implants impede opiate-based pain relief. To cater for this, participants were given a card to carry which specified the presence of a naltrexone implant, its expected duration, possible pain relief options, and contact details for study staff. Without this (as reported in Australia) hospital staff sometimes make futile attempts to relieve pain using opiate-type medications. The same report of hospital admissions after implantation identified severe withdrawal symptoms after rapid detoxification to the point where hospitalisation was required. Long-acting naltrexone means one effective way of relieving these symptoms (using opiate-type drugs) is denied to the patient, though others Patients can be sedated (in an intensive care unit if necessary) and given clonidine, octreotide and other anti-withdrawal drugs while the objective withdrawal symptoms decline, as they do within hours. Personal communication from Dr Colin Brewer August 2012. remain.

Norwegian prison study

Other related reports from Norway have also been analysed by Findings. Two concerned a sister study from the same research team of prisoners dependent on opiates before their sentence who in their final month in prison were randomly allocated to naltrexone implants or methadone maintenance to promote continuity of treatment on release and avoid relapse. One focused on the acceptability of the attempt to randomly allocate prisoners, while a second focused on drug use and other outcomes after six months.

The prison study found that inmates refused treatment usually because they misjudged their ability to maintain abstinence on release. At the same time this misplaced confidence and features of the prison environment impeded treatment entry. Motivating inmates to accept treatment in prison involves cooperation between prison health services, criminal justice staff and (to ensure continuity and support on release) community treatment providers, as well as researchers if the treatment offer is part of a study. For methadone in particular, continuity often could not be arranged. Unless removed, naltrexone implants automatically continued on release, but fewer inmates were prepared to go through with this treatment.

Despite the fact that 17 of the 44 patients did not initiate treatment in prison, compared to the six months before their imprisonment, on average in the six months after release frequency of use of heroin and illicit benzodiazepines had significantly declined. From using heroin nearly every day before prison, after release use was down to 15–20 days a month. Days per month on which crimes were committed also fell significantly by 4–5 days a month to on average every other day. Neither on these measures nor on the days the former prisoners 'survived' before relapsing to heroin use were there any significant differences between prisoners allocated to methadone versus those allocated to naltrexone.

Data from implanted patients in these and another Norwegian study have been amalgamated in a report which assessed the degree to which the implants actually did block the effects of opiate-type drugs and prevent opiate use. Drawing on data from the same patients, a further report assessed how many would continue the treatment by having a second implant after six months.

Amalgamated findings from Norway

From all these Norwegian reports it seems that six-month naltrexone implants can be an effective and lasting aid to curbing opiate use for the minority of patients motivated to aim for opiate abstinence and prepared to accept that opiate effects may be unavailable to them for six months. Because it does not require the patient to choose to enter aftercare treatment, the option may have a particular role in safeguarding patients emerging opiate-free from prison or other protected environments such as inpatient detoxification centres. However, and despite being motivated to sustain abstinence and being implanted, many if not most patients try opiates again and some do so repeatedly. Details below.

As in the featured study, recruitment in prison seems to have been very slow and no patient volunteered as opposed to being referred by staff. In both studies the minority of potential participants who joined were probably highly motivated to sustain abstinence from opiates because they were prepared to risk random allocation to a procedure which promised to enforce this for up to six months. In the aftercare study they had just completed abstinence-oriented residential care and in the prison study were keen to sustain their enforced abstinence on release.

Across the Norwegian studies implant patients substantially reduced their opiate use during the six months the initial implants were active and in the aftercare study, did so substantially and significantly more than patients allocated to normal aftercare arrangements. However, even among this selected and presumably motivated set of patients, the implants did not totally abolish use of opiate-type drugs and nor did they reduce some other forms of drug use. Just over half the implant patients tested the naltrexone blockade by using opiate-type drugs, and about a quarter of the sample did so repeatedly. Most of this opioid use occurred when naltrexone levels were above those known to block the pleasurable effects of heroin and few patients experienced the usual opiate-induced euphoria or 'high'. Perhaps because nearly a third allocated to implants refused these, in the prison study in particular, the reduction in opiate use was on average modest and no greater than among patients allocated to methadone maintenance.

Of the 61 patients implanted in all the studies, three had the initial implant removed. After six months, 44 said they wanted to be re-implanted and 31 actually were, showing that for some patients the implants can be a long-term treatment rather than simply an enforced break from opiates.

Other studies

In studies a minority of patients experience complications at the insertion site which lead the implant to be removed. Another potential problem is that implants impede opiate-based pain relief. Other occasionally severe reactions to implants and injections have been observed, but generally side effects are mild and/or short-lived and treatable. As with any abstinence-based treatment, overdose due to lost tolerance to opiate-type drugs is a serious concern. However, the few studies to date suggest these products protect against overdose while they are active, and that in caseloads prepared to undertake these procedures, opiate overdose reductions can outlast the active period of the implants. These findings are consistent with findings from Britain (1) and elsewhere (1 2 3 Maksoud N.A. "Experience with detox and naltrexone implants in Egypt." Abstracts from 7th International Conference 2002. Stapleford Trust. 4 5) tentatively suggesting that long-acting naltrexone can be used to create an opiate-free period which extends beyond the initial blockade, sometimes aided by further administrations (1 2). See background notes for more on these important issues of adverse effects and overdose protection.

Another randomised trial of a different long-acting form of naltrexone has been conducted in the USA. Compared to placebo, this injection lasting four weeks nearly doubled the time heroin dependent patients were retained in aftercare following inpatient detoxification. On the credible assumption that drop-outs relapsed, there was a similar impact on heroin use. At the four-week choice point when the naltrexone patients could have refused the second set of injections, few did so, most committing themselves to another period without (or with reduced) opiate effects. Though encouraging, multiple exclusions (such as psychiatric conditions or dependence on other drugs) and the recruitment procedures (partly through newspaper ads) meant the patients may not have been typical of usual caseloads.

A criticism of trials to date is that they included highly selected patients. However, in this they may have reflected normal practice. Patients will only opt for such procedures if they are prepared (irreversibly in the case of depot injections) to commit to weeks or months without the effects of heroin or other opiate-type drugs, or with severely attenuated effects requiring higher than usual doses. From the control groups in naltrexone implant/depot studies, we know that even in these caseloads, treatment drop-out and relapse are common. Long-acting naltrexone helps these highly motivated patients sustain their resolve. The clearest candidates for the treatment are patients who are motivated to return to a life without opiate-type drugs (including prescribed substitutes), have the resources, stability and support to sustain this, are unlikely to simply use other drugs instead, but who when free to experience heroin and allied drugs cannot resist using them, possibly reflected in their poor compliance with oral naltrexone regimens. The treatment may also be considered for unstable patients at very high risk of overdose, but who will not accept or do poorly in substitute prescribing programmes.

Thanks for their comments on this entry in draft to Nikolaj KunKunøe of the Norwegian Centre for Addiction Research, Liv Langberg of the Drammen Council Drug Addiction Prevention Centre in Norway, and Duncan Raistrick of the Leeds Addiction Unit. Commentators bear no responsibility for the text including the interpretations and any remaining errors.

Last revised 28 August 2012. First uploaded

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STUDY 2011 Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial

STUDY 2010 Challenges to antagonist blockade during sustained-release naltrexone treatment

STUDY 2010 Naltrexone implants compared to methadone: outcomes six months after prison release

STUDY 2015 Opioid treatment at release from jail using extended-release naltrexone: a pilot proof-of-concept randomized effectiveness trial

STUDY 2010 Retention in naltrexone implant treatment for opioid dependence

STUDY 2010 Favorable mortality profile of naltrexone implants for opiate addiction

STUDY 2009 The Drug Treatment Outcomes Research Study (DTORS): final outcomes report

STUDY 2011 Outpatient versus inpatient opioid detoxification: a randomized controlled trial

STUDY 2010 Ultra-rapid opiate detoxification followed by nine months of naltrexone maintenance therapy in Iran

STUDY 2010 Treatment research in prison: problems and solutions in a randomized trial





Naltrexone implants compared to methadone: outcomes six months after prison release.

Lobmaier P.P., Kunøe N., Waal H.
European Addiction Research: 2010, 16(3), p. 139–145.
Unable to obtain a copy by clicking title? Try asking the author for a reprint by adapting this prepared e-mail or by writing to Dr Lobmaier at p.p.lobmaier@medisin.uio.no.

In the first study of its kind opiate-dependent prisoners in Norway were randomly allocated to a six-month implant which blocks the effects of heroin or to methadone which substitutes for heroin as a way of bridging the period after release. Among the few interested in either option, they led to equivalent reductions in opiate use and crime.

Summary This account draws on another report on the study analysed by Findings.

In five Norwegian prisons the study aimed to randomly allocate prisoners who had been dependent on opiates before starting their sentences to either methadone maintenance or to a naltrexone implant as a way of promoting continuity of treatment on release and avoiding relapse to heroin use. Treatments were started about a month before their release date. No attempt was made to 'blind' staff or patients to which treatment they had been allocated to.

Pharmacologically the two treatments are at opposite poles; methadone is an agonist which has effects similar to heroin; naltrexone is an antagonist which has no psychoactive effects of its own but blocks the effects of heroin and other opiate-type drugs. In prison methadone doses were gradually increased to 80–130mg per day, normally considered high-dose therapy. The implant form of naltrexone is inserted under the skin. In the form used in the study, blocking effects last for five to six months, avoiding the need to take the medication daily and in theory overcoming the main shortcoming of oral naltrexone – that patients usually stop taking the pills and resume heroin use.

Over one and a half years to January 2007 the study was publicised directly to inmates through prison health services and referrals were also sought from criminal justice staff, prison health services and social workers. Prisoners were free to accept or decline participation with no impact on their sentences.

Of the 111 inmates who agreed to see the researchers and were found to qualify for the trial, most (65 before and two after random allocation) subsequently declined to participate, leaving 44 who were included in the analyses. All but a few of the 111 intended to build on their enforced break from opiates in prison by remaining abstinent on release, and this was the main reason for refusing treatment.

Six months after their release from prison, an attempt was made to follow-up all the patients whether or not they had started treatment in prison. Those who could not be contacted were assumed to have relapsed immediately after release.

Main findings

Seven of the 23 patients allocated to naltrexone refused implantation because they wanted methadone or some other treatment. Ten of the 21 allocated to methadone did not start treatment, most because they were unable to arrange continuity of treatment from community social services. The upshot was that 11 started methadone treatment in prison (of whom two stopped before release due to side effects) and 16 were implanted with naltrexone – in total 27 of the 111 patients seen by researchers and who had had been opiate dependent before entering prison. None of the 16 implants were removed.

Despite the fact that 17 of the 44 patients did not initiate treatment in prison, compared to the six months before their imprisonment, on average in the six months after release the frequency of use of heroin and illicit benzodiazepines had significantly declined. From using heroin nearly every day before prison, after release use was down to 15–20 days a month. Days per month on which crimes were committed also fell significantly by 4–5 days a month to on average every other day. Neither on these measures nor on the days the former prisoners 'survived' before relapsing to heroin use were there any significant differences between prisoners allocated to methadone versus those allocated to naltrexone.

Over half the implanted patients experienced headaches, poor appetite, nausea, sleep disorders, restlessness or irritability . Though possibly related to the naltrexone, generally these maladies were minor and transient, and none of the 16 implants was surgically removed due to site reactions or patient request. None of the patients who had started treatment in prison died during the follow-up period.

The authors' conclusions

As assessed at the six-month follow-up, allocating prisoners to either of the two treatments led to comparable reductions in illicit drug use and crime. There were differences in treatment entry and retention. Naltrexone was more often refused but (by the nature of a long-lasting implant) also more often continued to exert its effects over the six months after release from prison. Methadone was acceptable to more prisoners but harder to initiate because of the need to arrange post-prison treatment, and harder to stick with after prison, possibly because of the requirement that patients attend the clinic every day. These results should be seen in the light of the fact that many formerly opiate-dependent prisoners were not willing to join the study, leaving a selected minority who may have been unusually willing to countenance long-term blockade of the effects of opiate-type drugs.

For inmates who accept and initiate this treatment in prison, compared to methadone or oral naltrexone, naltrexone implants reliably bridge the vulnerable prison-community transfer period, potentially helping avoid what are otherwise frequent overdose deaths.


Findings logo commentary In the UK, neither implants nor depot injections of naltrexone have been licensed for medical use; they can still be (and have been; 1 2 Revill J. "A Comparative study of the protective benefits of oral and implanted naltrexone in a British NHS general practice." Abstracts from 7th International Conference 2002. Stapleford Trust. 3 Daly M. "Implant progress blocked." Druglink: September/October 2004, p. 12–13. 4) used, but patient and doctor have to accept the added responsibility of a product which has not yet been shown to meet the safety and efficacy requirements involved in licensing.

Other related reports have also been analysed by Findings. Another report from the same study focused on the acceptability of the attempt to randomly allocate prisoners to the treatments. It found that inmates refused treatment in prison usually because they misjudged their ability to maintain abstinence on release. At the same time this misplaced confidence and features of the prison environment impeded treatment entry. Motivating inmates to accept treatment in prison involves cooperation between prison health services, criminal justice staff and (to ensure continuity and support on release) community treatment providers, as well as researchers if the treatment offer is part of a study. For methadone in particular, continuity often could not be arranged. Unless removed, naltrexone implants automatically continued on release, but fewer inmates were prepared to go through with this treatment.

A sister study from the same research team tested naltrexone implants versus normal aftercare for opiate-dependent patients leaving Norwegian inpatient treatment centres.

Data from implanted patients in these and another Norwegian study have been amalgamated in a report which assessed the degree to which the implants actually did block the effects of opiate-type drugs and prevent opiate use. Drawing on data from the same patients, a further report assessed how many would continue the treatment by having a second implant after six months.

Findings from Norway

From these Norwegian reports it seems that six-month naltrexone implants can be an effective and lasting aid to curbing opiate use for the minority of patients motivated to aim for opiate abstinence and prepared to accept that opiate effects may be unavailable to them for six months. Because it does not require the patient to choose to enter aftercare treatment, the option may have a particular role in safeguarding patients emerging opiate-free from prison or other protected environments such as inpatient detoxification centres. However, and despite being motivated to sustain abstinence and being implanted, many if not most patients try opiates again and some do so repeatedly. Details below.

As with oral naltrexone, the main limitation of implant treatment is its acceptability to patients. In Norway acceptability will have been heightened by restricted access to substitute prescribing programmes, particularly for people unwilling to contract to forgo not just heroin, but persistent substance use of any kind. Nevertheless, recruitment to both studies seems to have been slow. The minority of potential participants who joined were probably highly motivated to sustain abstinence from opiates because they were prepared to risk random allocation to a procedure which promised to enforce this for up to six months. In the aftercare study they had just completed abstinence-oriented residential care and in the prison study were keen to sustain their enforced abstinence on release.

Across the Norwegian studies implant patients substantially reduced their opiate use during the six months the initial implants were active and in the aftercare study, did so substantially and significantly more than patients allocated to relatively weak The usual aftercare against which the implants were compared does not appear to have been a continued service from the clinics, but external counselling and other services which (if necessary with help from the clinics) patients would have had to arrange for themselves. normal aftercare arrangements. However, even among this selected and presumably motivated set of patients, the implants did not totally abolish use of opiate-type drugs and nor did they reduce some other forms of drug use. Just over half the implant patients tested the naltrexone blockade by using opiate-type drugs, and about a quarter of the sample did so repeatedly. Most of this opioid use occurred when naltrexone levels were above those known to block the pleasurable effects of heroin and few patients experienced the usual opiate-induced euphoria or 'high'. Perhaps because nearly a third allocated to implants refused these, in the prison study in particular, the reduction in opiate use was on average modest and no greater than among patients allocated to methadone maintenance.

Of the 61 patients implanted in all the studies, three had the initial implant removed. After six months, 44 said they wanted to be re-implanted and 31 actually were, showing that for some patients the implants can be a long-term treatment rather than simply an enforced break from opiates.

Other studies

In studies a minority of patients experience complications at the insertion site which lead the implant to be removed. Another potential problem is that implants impede opiate-based pain relief. To cater for this, patients have been given cards to carry which specify the presence of a naltrexone implant, its expected duration, possible pain relief options, and contact details for staff responsible for the implant. Without this (as reported in Australia) hospital staff sometimes make futile attempts to relieve pain using opiate-type medications.

Other occasionally severe reactions to implants and injections have been observed, but generally side effects are mild and/or short-lived and treatable. As with any abstinence-based treatment, overdose due to lost tolerance to opiate-type drugs is a serious concern. However, the few studies to date suggest these products protect against overdose while they are active, and that in caseloads prepared to undertake these procedures, opiate overdose reductions can outlast the active period of the implants. These findings are consistent with findings from Britain (1) and elsewhere (1 2 3 Maksoud N.A. "Experience with detox and naltrexone implants in Egypt." Abstracts from 7th International Conference 2002. Stapleford Trust. 4 5) tentatively suggesting that long-acting naltrexone can be used to create an opiate-free period which extends beyond the initial blockade, sometimes aided by further administrations (1 2). See background notes to an earlier Findings analysis for more on these important issues of adverse effects and overdose protection.

Last revised 24 February 2012

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Top 10 most closely related documents on this site. For more try a subject or free text search

STUDY 2010 Treatment research in prison: problems and solutions in a randomized trial

STUDY 2015 Opioid treatment at release from jail using extended-release naltrexone: a pilot proof-of-concept randomized effectiveness trial

DOCUMENT 2013 Community loses from failure to offer maintenance prescribing in prisons

REVIEW 2012 The effectiveness of opioid maintenance treatment in prison settings: a systematic review

STUDY 2011 Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial

STUDY 2009 The Drug Treatment Outcomes Research Study (DTORS): final outcomes report

REVIEW 2009 Pharmacotherapies for the treatment of opioid dependence: efficacy, cost-effectiveness and implementation guidelines

STUDY 2010 Favorable mortality profile of naltrexone implants for opiate addiction

HOT TOPIC 2016 Opiate-blocking implants: magic bullet or dangerous experiment?

STUDY 2012 A randomized trial of methadone initiation prior to release from incarceration





Treatment research in prison: problems and solutions in a randomized trial.

Lobmaier P.P., Kunøe N., Waal H.
Addiction Research and Theory: 2010, 18(1), p. 1–13.
Unable to obtain a copy by clicking title? Try asking the author for a reprint by adapting this prepared e-mail or by writing to Dr Lobmaier at p.p.lobmaier@medisin.uio.no.

In the first study of its kind, as a way of bridging the period after release opiate-dependent prisoners in Norway were randomly allocated to a six-month implant which blocks the effects of heroin or to methadone which substitutes for heroin. Many prisoners rejected treatment, wrongly believing they would sustain abstinence on release.

Summary This Norwegian study aimed to randomly allocate prisoners who had been dependent on opiates before starting their sentence to either methadone maintenance or to a naltrexone implant as a way of promoting continuity of treatment on release and avoiding relapse to heroin use. Pharmacologically the two treatments are at opposite poles; methadone is an agonist which has effects similar to heroin; naltrexone is an antagonist which has no psychoactive effects of its own but blocks the effects of heroin and other opiate-type drugs. The implant form of naltrexone is inserted under the skin. In the form used in the study blocking effects last for five to six months, avoiding the need to take the medication daily and in theory overcoming the main shortcoming of naltrexone – that patients usually stop taking the pills and resume heroin use.

In five prisons over one and a half years to January 2007 the study was publicised directly to inmates through prison health services and referrals were also sought from criminal justice staff, prison health services and social workers. Prisoners were free to accept or decline participation with no impact on their sentences. The featured report focuses on the acceptability of the attempt to randomly allocate prisoners to the treatments.

Main findings

Very few inmates contacted the trial directly. Nearly all had been referred by staff. Of the 111 inmates who agreed to see the researchers and were found to qualify for the trial, most (65) subsequently declined to participate, leaving 46 who were randomly allocated to methadone or naltrexone. All but a few of the 111 intended to and were confident that they could build on their enforced break from opiates in prison by remaining abstinent on release, and this was the main reason for refusing treatment.

A third of the 24 patients allocated to naltrexone withdrew from the study because they wanted methadone. Three of the 22 allocated to methadone withdrew because they wanted naltrexone and another because they had arranged drug-free treatment on release. Other methadone patients were unable to get the required support from community social services and one preferred buprenorphine. The upshot was that 11 started methadone treatment in prison and 16 were implanted with naltrexone – in total 27 of the 111 patients seen by researchers and who had had been opiate dependent before entering prison.

An attempt was made to follow-up the patients six months after their release from prison. Of the 11 methadone starters in prison, six were known to have relapsed to frequent heroin use as were four of the 16 implanted with naltrexone, though none of the 16 had had their implants removed. Of the 19 prisoners who had been allocated to but not started treatment in prison, all 10 who could be traced had relapsed to frequent heroin use.

The authors' conclusions

Despite intending to remain abstinent on release, relapse was the norm (and possibly universal) among patients who did not start treatment in prison; inmates misjudged their ability to maintain abstinence without treatment. At the same time this misplaced confidence and features of the prison environment impeded treatment entry. Motivating inmates to accept treatment in prison involves cooperation between prison health services, criminal justice staff and (to ensure continuity and support on release) community treatment providers, as well as researchers if the treatment offer is part of a study. Prisoners must feel confident that their disclosure of a treatment need will remain confidential. Enrolment in the study was possibly depressed because prisoners could receive methadone treatment in the normal way in the prisons without having to accept the risk of random allocation.

Importantly, none of the prisoners to whom the trial was explained declined it because it involved possible allocation to naltrexone, and two thirds actually allocated to this treatment accepted it. This suggests that implants may have a role in bridging the prison-community transfer period. However, among those prepared to start treatment in prison, methadone was slightly more often the preferred option. Post-prison relapse despite starting methadone in prison may have been partly due to newly released prisoners finding it difficult to comply with the need for daily attendance at the clinic and being discharged from treatment.

The implications of the study are that in-prison treatment should be tailored to the preferences of the prisoner, and that prisoners should be counselled realistically about their chances of remaining heroin-free on release, and told that these chances are improved if they initiate treatment in prison which is continued on release.


Findings logo commentary In the UK, neither implants nor depot injections of naltrexone have been licensed for medical use; they can still be (and have been; 1 2 Revill J. "A Comparative study of the protective benefits of oral and implanted naltrexone in a British NHS general practice." Abstracts from 7th International Conference 2002. Stapleford Trust. 3 Daly M. "Implant progress blocked." Druglink: September/October 2004, p. 12–13. 4) used, but patient and doctor have to accept the added responsibility of a product which has not yet been shown to meet the safety and efficacy requirements involved in licensing.

Other related reports from Norway have also been analysed by Findings. Among these is another report from the same study which focused on drug use and other outcomes after six months. Despite the fact that 17 of the 44 patients did not initiate treatment in prison, it found that (compared to the six months before their imprisonment) on average in the six months after release frequency of use of heroin and illicit benzodiazepines had significantly declined. From using heroin nearly every day before prison, after release use was down to 15–20 days a month. Days per month on which crimes were committed also fell significantly by 4–5 days a month to on average every other day. Neither on these measures nor on the days the former prisoners 'survived' before relapsing to heroin use were there any significant differences between prisoners allocated to methadone versus those allocated to naltrexone.

A sister study from the same research team tested naltrexone implants versus normal aftercare for opiate-dependent patients leaving Norwegian inpatient treatment centres.

Data from implanted patients in these and another Norwegian study have been amalgamated in a report which assessed the degree to which the implants actually did block the effects of opiate-type drugs and prevent opiate use. Drawing on data from the same patients, a further report assessed how many would continue the treatment by having a second implant after six months.

Findings from Norway

From these Norwegian reports it seems that six-month naltrexone implants can be an effective and lasting aid to curbing opiate use for the minority of patients motivated to aim for opiate abstinence and prepared to accept that opiate effects may be unavailable to them for six months. Because it does not require the patient to choose to enter aftercare treatment, the option may have a particular role in safeguarding patients emerging opiate-free from prison or other protected environments such as inpatient detoxification centres. However, and despite being motivated to sustain abstinence and being implanted, many if not most patients try opiates again and some do so repeatedly. Details below.

As with oral naltrexone, the main limitation of implant treatment is its acceptability to patients. In Norway acceptability will have been heightened by restricted access to substitute prescribing programmes, particularly for people unwilling to contract to forgo not just heroin, but persistent substance use of any kind. Nevertheless, recruitment to both studies seems to have been slow. The minority of potential participants who joined were probably highly motivated to sustain abstinence from opiates because they were prepared to risk random allocation to a procedure which promised to enforce this for up to six months. In the aftercare study they had just completed abstinence-oriented residential care and in the prison study were keen to sustain their enforced abstinence on release.

Across the Norwegian studies implant patients substantially reduced their opiate use during the six months the initial implants were active and in the aftercare study, did so substantially and significantly more than patients allocated to relatively weak The usual aftercare against which the implants were compared does not appear to have been a continued service from the clinics, but external counselling and other services which (if necessary with help from the clinics) patients would have had to arrange for themselves. normal aftercare arrangements. However, even among this selected and presumably motivated set of patients, the implants did not totally abolish use of opiate-type drugs and nor did they reduce some other forms of drug use. Just over half the implant patients tested the naltrexone blockade by using opiate-type drugs, and about a quarter of the sample did so repeatedly. Most of this opioid use occurred when naltrexone levels were above those known to block the pleasurable effects of heroin and few patients experienced the usual opiate-induced euphoria or 'high'. Perhaps because nearly a third allocated to implants refused these, in the prison study in particular, the reduction in opiate use was on average modest and no greater than among patients allocated to methadone maintenance.

Of the 61 patients implanted in all the studies, three had the initial implant removed. After six months, 44 said they wanted to be re-implanted and 31 actually were, showing that for some patients the implants can be a long-term treatment rather than simply an enforced break from opiates.

Other studies

In studies a minority of patients experience complications at the insertion site which lead the implant to be removed. Another potential problem is that implants impede opiate-based pain relief. To cater for this, patients have been given cards to carry which specify the presence of a naltrexone implant, its expected duration, possible pain relief options, and contact details for staff responsible for the implant. Without this (as reported in Australia) hospital staff sometimes make futile attempts to relieve pain using opiate-type medications.

Other occasionally severe reactions to implants and injections have been observed, but generally side effects are mild and/or short-lived and treatable. As with any abstinence-based treatment, overdose due to lost tolerance to opiate-type drugs is a serious concern. However, the few studies to date suggest these products protect against overdose while they are active, and that in caseloads prepared to undertake these procedures, opiate overdose reductions can outlast the active period of the implants. These findings are consistent with findings from Britain (1) and elsewhere (1 2 3 Maksoud N.A. "Experience with detox and naltrexone implants in Egypt." Abstracts from 7th International Conference 2002. Stapleford Trust. 4 5) tentatively suggesting that long-acting naltrexone can be used to create an opiate-free period which extends beyond the initial blockade, sometimes aided by further administrations (1 2). See background notes to an earlier Findings analysis for more on these important issues of adverse effects and overdose protection.

Last revised 24 February 2012

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Top 10 most closely related documents on this site. For more try a subject or free text search

STUDY 2010 Naltrexone implants compared to methadone: outcomes six months after prison release

DOCUMENT 2009 Guidelines for the psychosocially assisted pharmacological treatment of opioid dependence

STUDY 2015 Opioid treatment at release from jail using extended-release naltrexone: a pilot proof-of-concept randomized effectiveness trial

HOT TOPIC 2016 Opiate-blocking implants: magic bullet or dangerous experiment?

STUDY 2010 The SUMMIT Trial: a field comparison of buprenorphine versus methadone maintenance treatment

STUDY 2015 Extended-release naltrexone for alcohol and opioid problems in Missouri parolees and probationers

DOCUMENT 2013 Community loses from failure to offer maintenance prescribing in prisons

REVIEW 2012 The effectiveness of opioid maintenance treatment in prison settings: a systematic review

DOCUMENT 2013 Rewarding virtue

HOT TOPIC 2016 Should we offer prizes for not using drugs?





Challenges to antagonist blockade during sustained-release naltrexone treatment.

Kunøe N., Lobmaier P.P., Vederhus J.K. et al.
Addiction: 2010, 105, p. 1633–1639.
Unable to obtain a copy by clicking title? Try asking the author for a reprint by adapting this prepared e-mail or by writing to Dr Kunøe at nikolaj.kunoe@medisin.uio.no. You could also try this alternative source.

Despite being motivated to sustain abstinence and implanted with a drug which should have blocked the effects of opiates, in Norwegian studies most opiate-dependent patients used opiates and about a quarter did so repeatedly.

Summary This account draws on Findings analyses of the two main source studies set in prison and inpatient services respectively.

The featured report recruited opiate-dependent patients allocated to naltrexone implants in three Norwegian studies. Naltrexone is an antagonist which has no psychoactive effects of its own but blocks the effects of heroin and other opiate-type drugs. The implant form of naltrexone is inserted under the skin. In the form used in the studies, blocking effects last for five to six months, avoiding the need to take the medication daily and in theory overcoming the main shortcoming of oral naltrexone – that patients usually stop taking the pills and resume heroin use.

One of the source studies involved prisoners dependent on opiates before their sentence. Sixteen of the 24 who had been allocated to naltrexone were actually implanted before release after being randomly allocated to this or to methadone maintenance to promote continuity of treatment on release and avoid relapse. They were the minority prepared to accept random allocation (most potentially eligible prisoners did not) and who accepted the treatment to which they had been allocated (eight refused the implant).

In a second study, 56 inpatients (of 667 who might have qualified for the study) coming towards the end of their detoxification or residential treatment agreed to be randomly allocated to the implant or to usual aftercare arrangements; 26 of 29 allocated to naltrexone were actually implanted. A third study involved a further six implanted patients.

From these studies 60 implanted patients were recruited for the featured study to assess the degree to which over six months the implants actually did block the effects of opiate-type drugs and prevent opiate use. Of the 60, 42 came from treatment and 18 from criminal justice settings. All but five completed follow-up interviews and for the missing five data was collected from contacts such as families or treatment staff.

Main findings

All the blood samples taken at the end of month five and all but three taken in month six revealed that naltrexone levels had remained above that normally associated with a blocking effect.

Over half (34) of the 60 patients had used illicit opiate-type ('opioid') drugs during the six months when the implants were active; 14 did so on just one or two days, while at the other extreme, nine did so on average at least every other day. Across all the patients, from an average of 18 days per months before implantation, illicit opiate use fell to six days in the final month of the six months of the implant, having risen from even lower levels over the preceding months.

Patients who had tried opioids in the first month of their implants were more likely to try again later. During the six-month follow-up, patients who took opioids were also more likely to be using other types of drugs including benzodiazepines, cocaine, amphetamines and cannabis, more likely to have injected drugs, and more involved with the criminal justice system. By the end of the six months, patients who had avoided opioids were more satisfied with their quality of life and housing, less anxious or depressed, and had found more and better work.

Of the 34 patients who had tried opiate-type drugs, 31 told researchers how it had felt; 22 felt no definite euphoria or 'high' and nine some effect, of whom three said this was a fully fledged high on at least one occasion. The greater the high they had experienced, the more often patients used opioids and also benzodiazepines.

Two patients had sought to overcome the blockade by taking unusually high doses of opiate-type drugs. Among these was one of the two who experienced non-fatal overdoses; the other patient's overdoses were due to use of non-opiate drugs. No further serious adverse events were reported.

The authors' conclusions

On average opioid-dependent patients who received sustained-release naltrexone implants substantially reduced their opioid use but this reduction was unevenly distributed. Almost half did not use at all, while at some point just over half tested the naltrexone blockade, and about a quarter of the sample did so repeatedly. Yet most of this opioid use occurred when naltrexone levels were above those shown previously to block the pleasurable effects of heroin. This repeated use cannot generally be attributed to successful overcoming of the blockade. Many patients confirmed the blocking properties of naltrexone by administering heroin or other illicit opioids, sometimes at high doses, to no effect. Few who tested the blockade reported repeatedly having experienced a full-blown 'high'. When some degree of euphoria was experienced, this may have been due to concurrent use of other types of drugs or due to expectations and conditioned responses.

Whatever the reasons for using heroin or other opioids while on naltrexone, this was associated with poor outcomes. By the end of the six months, patients who had repeatedly tested the blockade had returned to pre-treatment levels of opioid use. Patients who tested the blockade were also more likely to be using non-opioid drugs and to have social adjustment problems, including a more serious involvement in crime.

Rather than being of no significance or a salutary (non)experience, these findings suggest that use of opioids during implant treatment is indicative of the need for urgent clinical attention. In the present study, even patients who used opioids only once or twice tended to report more problem behaviours relative to abstinent patients. Repeated use (with or without reported 'highs') is a warning sign that the patient is at risk of relapsing to a lifestyle involving polydrug use and crime. Services should monitor patients for injecting polydrug use before and during sustained-release naltrexone treatment and where required, offer supplemental interventions to address the wider context of substance use for the individual.

Clinicians who provide this type of medication can expect that many patients will test the blockade by using opioids, some frequently, and some experiencing what they interpret as an opioid 'high'. The latter may warrant blood or urine testing to check naltrexone levels.


Findings logo commentary Other reports from the Norwegian implant studies have also been analysed by Findings, in analyses which details the findings, place these in the context of related research, and explore UK regulations and experience related to naltrexone implants. Two concerned one of the main source studies for the featured report conducted in prison. One focused on the acceptability of the attempt to randomly allocate prisoners to the treatments, while the second focused on drug use and other outcomes after six months. From the same research team, the other main source study for the featured report tested naltrexone implants versus normal aftercare for opiate-dependent patients leaving Norwegian inpatient treatment centres.

As well as the featured report, data from implanted patients in these and another Norwegian study have been amalgamated in a report on how many of the patients continued the treatment by having a second implant after six months. About half did so.

From these Norwegian reports it seems that six-month naltrexone implants can be an effective and lasting aid to curbing opiate use for the minority of patients motivated to aim for opiate abstinence and prepared to accept that opiate effects may be unavailable to them for six months. Because it does not require the patient to choose to enter aftercare treatment, the option may have a particular role in safeguarding patients emerging opiate-free from prison or other protected environments such as inpatient detoxification centres. However, and despite being motivated to sustain abstinence and being implanted, many if not most patients try opiates again and some do so repeatedly.

Last revised 24 February 2012

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Top 10 most closely related documents on this site. For more try a subject or free text search

STUDY 2010 Retention in naltrexone implant treatment for opioid dependence

STUDY 2009 Naltrexone implants after in-patient treatment for opioid dependence: randomised controlled trial

STUDY 2011 Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial

STUDY 2010 Naltrexone implants compared to methadone: outcomes six months after prison release

HOT TOPIC 2016 Opiate-blocking implants: magic bullet or dangerous experiment?

STUDY 2015 Opioid treatment at release from jail using extended-release naltrexone: a pilot proof-of-concept randomized effectiveness trial

DOCUMENT 2012 An introduction to extended-release injectable naltrexone for the treatment of people with opioid dependence

STUDY 2010 Favorable mortality profile of naltrexone implants for opiate addiction

REVIEW 2011 Oral naltrexone maintenance treatment for opioid dependence

REVIEW 2009 Pharmacotherapies for the treatment of opioid dependence: efficacy, cost-effectiveness and implementation guidelines





Retention in naltrexone implant treatment for opioid dependence.

Kunøe N., Lobmaier P.P., Vederhus J.K. et al.
Drug and Alcohol Dependence: 2010, 111, p. 166–169.
Unable to obtain a copy by clicking title? Try asking the author for a reprint by adapting this prepared e-mail or by writing to Dr Kunøe at nikolaj.kunoe@medisin.uio.no. You could also try this alternative source.

In Norway over half the opiate dependent patients implanted with the opiate blocking drug naltrexone opted for another implant after six months when the first had worn off, giving themselves a year in which to construct a life no longer reliant on the effects of heroin.

Summary This account draws on Findings analyses of two of the three source studies set in prison and inpatient units respectively.

The featured report recruited opiate-dependent patients allocated to naltrexone implants in three Norwegian studies. Naltrexone is an antagonist which has no psychoactive effects of its own but blocks the effects of heroin and other opiate-type ('opioid') drugs. The implant form of naltrexone is inserted under the skin. In the form used in the studies, blocking effects last for five to six months, avoiding the need to take the medication daily and in theory overcoming the main shortcoming of oral naltrexone – that patients usually stop taking the pills and resume heroin use.

One of the source studies involved prisoners dependent on opiates before their sentence. Sixteen of the 24 who had been allocated to naltrexone were actually implanted before release after being randomly allocated to this or to methadone maintenance to promote continuity of treatment on release and avoid relapse. They were the minority prepared to accept random allocation (most potentially eligible prisoners did not) and who accepted the treatment to which they had been allocated (eight refused the implant).

In a second study, 56 patients (of 667 who might have qualified for the study) coming towards the end of their detoxification or residential treatment agreed to be randomly allocated to the implant or to usual aftercare arrangements; 26 of 29 allocated to naltrexone were actually implanted.

From these and a third study, 61 implanted patients were recruited for the featured study to assess how many would continue the treatment by having a second implant after six months. Four to eight weeks before the end of the six months, patients were phoned and offered the second implant. Those who declined were reminded of the dangers of overdose and encouraged to initiate other treatment. Those who accepted but missed the initial appointment were re-contacted up to three times to check their wishes.

Main findings

Blood tests showed that all but a few patients had sufficient naltrexone circulating to block the effects of opiates for almost the entire six months of the initial implant.

Of the 61 patients, three had had the initial implant removed. After six months, 44 said they wanted to be re-implanted and 31 actually were. Six of the remaining 30 patients who were not re-implanted had started alternative treatments for their opiate dependence and another five were considered recovered from their addiction. Before treatment, patients who later did not accept a second implant had better employment records, had injected less often, and worried more often about family problems. During the initial implant the same patients had more often used opiates and other types of drugs, been more involved in crime, and had experienced more mental health problems and a lower quality of life than patients who were re-implanted.

The authors' conclusions

The results of this study suggest it is feasible to treat opioid dependent patients with repeated administrations of sustained release naltrexone implants. About half those initially implanted were re-implanted six months later (much better retention than on oral naltrexone) and only about a quarter clearly turned down the offer. The remainder – about a fifth – expressed a wish to be re-implanted but did not attend for this procedure despite repeated efforts by the clinical team. Together with the low incidence of implant removals, this suggests that most patients who start this treatment can remain in it for 10–12 consecutive months. Retained patients are likely to continue to experience previously reported benefits including reduced risk of relapse to regular opioid use, fewer opioid overdoses, and fewer deaths.

As with oral naltrexone, a longer pre-treatment employment history, concern about family problems, and less intense pre-treatment injecting drug use were associated with retention in treatment. Patients who during the initial implant period used illicit opioids or other drugs and/or engaged in more criminal activity, were less likely to be re-implanted, suggesting a return to a heroin-related lifestyle incompatible with a re-commitment to naltrexone-assisted abstinence.


Findings logo commentary The encouraging implications of this study are that patients who do relatively well on an initial implant will be willing to have a second one, giving them up to a year during which to construct a life no longer based on opiate use, and that this can be as many as half those initially implanted. These findings must be set in the context of what was a highly selected and probably highly motivated caseload.

Other reports from the Norwegian implant studies have also been analysed by Findings, in analyses which details the findings, place these in the context of related research, and explore UK regulations and experience related to naltrexone implants. Two concerned one of the main source studies for the featured report conducted in prison. One focused on the acceptability of the attempt to randomly allocate prisoners to the treatments, while the second focused on drug use and other outcomes after six months. From the same research team, the other main source study for the featured report tested naltrexone implants versus normal aftercare for opiate-dependent patients leaving Norwegian inpatient treatment centres.

As well as the featured report, data from implanted patients in these and another Norwegian study have been amalgamated in a report on the degree to which the implants actually did block the effects of opiate-type drugs and prevent opiate use.

From these Norwegian reports it seems that six-month naltrexone implants can be an effective and lasting aid to curbing opiate use for the minority of patients motivated to aim for opiate abstinence and prepared to accept that opiate effects may be unavailable to them for six months. Because it does not require the patient to choose to enter aftercare treatment, the option may have a particular role in safeguarding patients emerging opiate-free from prison or other protected environments such as inpatient detoxification centres. However, and despite being motivated to sustain abstinence and being implanted, many if not most patients try opiates again and some do so repeatedly.

Last revised 24 February 2012

Comment/query to editor
Back to contents list at top of page
Give us your feedback on the site (two-minute survey)
Open Effectiveness Bank home page
Add your name to the mailing list to be alerted to new studies and other site updates


Top 10 most closely related documents on this site. For more try a subject or free text search

STUDY 2010 Challenges to antagonist blockade during sustained-release naltrexone treatment

STUDY 2009 Naltrexone implants after in-patient treatment for opioid dependence: randomised controlled trial

STUDY 2011 Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial

STUDY 2015 Opioid treatment at release from jail using extended-release naltrexone: a pilot proof-of-concept randomized effectiveness trial

STUDY 2010 Naltrexone implants compared to methadone: outcomes six months after prison release

STUDY 2015 Extended-release naltrexone for alcohol and opioid problems in Missouri parolees and probationers

HOT TOPIC 2016 Opiate-blocking implants: magic bullet or dangerous experiment?

STUDY 2010 Favorable mortality profile of naltrexone implants for opiate addiction

STUDY 2010 The SUMMIT Trial: a field comparison of buprenorphine versus methadone maintenance treatment

STUDY 2011 Outpatient versus inpatient opioid detoxification: a randomized controlled trial





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