Naltrexone Implants

Number: 0878

Table Of Contents

Applicable CPT / HCPCS / ICD-10 Codes


Scope of Policy

This Clinical Policy Bulletin addresses naltrexone implants.

  1. Experimental and Investigational

    Aetna considers naltrexone implants experimental and investigational for the treatment of the following (not an all-inclusive list) because of insufficient evidence in the peer-reviewed published medical literature and the safety and effectiveness of this approach have not been established:

    1. Alcohol addiction;
    2. Amphetamine use;
    3. Autism spectrum disorders;
    4. Buprenorphine dependence;
    5. Impulse control disorders in Parkinson disease;
    6. Narcotic addiction;
    7. Prolactinoma (prolactin-secreting pituitary tumor);
    8. Trichotillomania.

      Note: This CPB does not apply to Vivitrol Injections (J2315).


CPT Codes / HCPCS Codes / ICD-10 Codes

Code Code Description

Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":

Naltrexone Implants:

No specific code

ICD-10 codes not covered for indications listed in the CPB (not all inclusive):

D35.2 Benign neoplasm of pituitary gland
F10.20 - F10.29 Alcohol dependence
F11.20 - F11.29, F12.20 - F12.29, F13.20 - F13.29, F14.20 - F14.29, F15.20 - F15.29, F16.20 - F16.29, F18.20 - F18.29, F19.20 - F19.29 Drug dependence
F15.10 - F15.19 Stimulant abuse [amphetamine]
F63.3 Trichotillomania
F84.0 - F84.9 Pervasive development disorders
G20 - G21.9 Parkinson's disease [impulse control disorder]


Naltrexone is a drug used in the management of alcohol and opioid dependence.  When taken, naltrexone attaches to the opiate receptors in the brain and blocks them, preventing the euphoric effect from the opiate.

Naltrexone is available in oral, ‘depot’ (slow-release) injection or implant preparations, however only the oral and depot forms of naltrexone have been approved for use by the Food and Drug Administration (FDA).  The potential benefits of a naltrexone implant include less frequent dosage and reduced rates of withdrawal and relapse between doses.

An assessment by the Australian National Health and Medical Research Council (NHMC, 2011) concluded that.naltrone implants are unproven for treatment of opioid dependence.  The review concluded that evidence is currently at an early stage and as such, naltrexone implants remain an experimental product and should only be used within a research setting.  Until the relevant data are available and validated, the efficacy of the treatment, alone or in comparison to best practice, cannot be determined (NHMC, 2011).  NHMRC’s position on naltrexone implants is that further research on adverse effects is required before a statement on safety can be confidently made.

Specifically regarding the use of the naltrexone implant for alcoholism, a systematic evidence review concluded that larger longitudinal studies of the naltrexone implants are needed (Lobmaier et al, 2011).

World Journal of Biological Psychiatry Guidelines on the Treatment of Substance Use and Related Disorders (2011) state: "Naltrexone implants cannot yet be recommended for clinical use because although there are promising efficacy data for them, safety concerns remain and require further evaluation".   

However, since then, some randomized controlled clinical trials of naltrexone implants have been published examining the effectiveness of the naltrexone implants for narcotic addictions.  Limitations include the fact that these studies were not U.S. based, they examined short-term impact, and compared the implants to oral naltrexone rather than the depot injection (Vivitrol) that has been approved by the FDA. 

Kelty and Hulse (2012) have reported on the mortality in cohorts of patients treated with oral and implant naltrexone.  Some concerns with the methodology of this study have been raised including the comparison used; it was suggested that comparison with currently accepted modes of treatment such as opioid substitution treatment would be more appropriate (Hickman et al, 2012).

There are some published reports of deaths attributable to naltrexone implants (Gibson et al, 2007a; Gibson et al, 2007b; Olivier, 2005) and other reports claiming significantly reduced mortality (Ngo et al., 2008).  Further research is needed to establish the risk of mortality during and after treatment with naltrexone implants and other treatment approaches.

Kelly et al (2013) examined self-reported abstinence from amphetamines following treatment with a sustained release naltrexone preparation in patients with self and clinically identified problems with amphetamine use and the relationship between naltrexone blood levels and abstinence from amphetamines.  A total of 44 patients with problematic amphetamine use, who were treated with a naltrexone implant, completed an interview evaluating self-reported reduction in amphetamine use following treatment.  Additional data were collected from the patients' clinical treatment files.  Of the 44 subjects, 29 (65.9 %) interviewed reported that following treatment they ceased using and maintained abstinence from amphetamines for at least 1 month. Of these patients, 14 (48.3 %) were reportedly still abstinent at 6 months.  Rates of abstinence were found to be 2.27 times higher (95 % % confidence interval (CI): 1.38 to 3.74) in patients when blood naltrexone levels were above 2 ng/ml, with rates as high as 100 % and 90.9 % for greater than or equal to 5 and greater than or equal to 2 ng/ml, respectively, compared with 42.9 % for 1 to 2 ng/ml and 38.9 % low less than 1 ng/ml.  The authors concluded that although this study has several limitations, the findings provided preliminary data in support of the use of implant naltrexone for the treatment of problematic amphetamine use and suggested that naltrexone levels above 2 ng/ml should be targeted for use in patients.  Moreover, they stated that further research is needed.

Larney et al (2014) systematically reviewed the literature to evaluate the safety and effectiveness of naltrexone implants for treating opioid dependence.  Studies were eligible if they compared naltrexone implants with another intervention or placebo.  Examined outcomes were induction to treatment, retention in treatment, opioid and non-opioid use, adverse events, non-fatal overdose and mortality.  Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach.  Data from randomized studies were combined using meta-analysis.  Data from non-randomized studies were presented narratively.  A total of 5 randomized trials (n = 576) and 4 non-randomized studies (n = 8,358) were eligible for review.  The quality of the evidence ranged from moderate to very low.  Naltrexone implants were superior to placebo implants [risk ratio (RR): 0.57; 95 % confidence interval (CI): 0.48 to 0.68; k = 2] and oral naltrexone (RR: 0.57; 95 % CI: 0.47 to 0.70; k = 2) in suppressing opioid use.  No difference in opioid use was observed between naltrexone implants and methadone maintenance (standardized mean difference: -0.33; 95 % CI: -0.93 to 0.26; k = 1); however, this finding was based on low-quality evidence from 1 study.  The authors stated that the evidence on safety and effectiveness of naltrexone implants is limited in quantity and quality, and the evidence has little clinical utility in settings where effective treatments for opioid dependence are used.  They concluded that better designed research is needed to establish the safety and effectiveness of naltrexone implants; until such time, their use should be limited to clinical trials.

Autism Spectrum Disorders

Roy and colleagues (2015) stated that autism spectrum conditions (ASC) may result from a failure of striatal beta endorphins to diminish with maturation. Many symptoms of ASC resemble behaviors induced in animals or humans by opiate administration, including decreased socialization, diminished crying, repetitive stereotypies, insensitivity to pain and motor hyperactivity.  Naltrexone, an opioid antagonist, has been used in the management of children with ASC and can produce a clinically significant reduction in the serious and life-threatening behavior of self-injury for individuals who have not been responsive to any other type of treatment and is important for this reason.  In a systematic review, these researchers reviewed the available evidence regarding the use of opioid antagonists in attenuating the core symptoms of ASC in children.  Four electronic databases were searched for relevant journal articles.  In addition, cross-referencing of pertinent reviews and a hand-search for articles in major international intellectual disability (ID) journals between the years 2010 and 2012 was carried out to ensure that all relevant articles were identified.  These investigators also searched databases for unpublished clinical trials to overcome publication bias.  Each database was searched up to present (February 2013) with no restrictions on the date of publication.  The search terms consisted of broad expressions used to describe ID and autistic spectrum disorder (ASD) as well as terms relating to opioid antagonists and specific drugs.  All studies identified by the electronic database search and hand-search were examined on the basis of title alone for relevance and duplication.  The abstracts of the remaining papers were then scrutinized against the inclusion criteria.  Where abstracts failed to provide adequate information, the full texts for these papers were obtained.  All the full texts were then evaluated against the inclusion proforma.  Two reviewers carried out all the stages of the process independently.  The reviewers met to discuss their selections and where disagreements arose, these were settled by discussion with a member of the study group.  Data from each study meeting the inclusion criteria were extracted on a pre-piloted data extraction form.  The quality of each study was further assessed using the Jadad scale, a tool developed to assess the quality of randomised controlled trials.  A total of 155 children participated in 10 studies; 27 received placebo.  Of the 128 that received naltrexone, 98 (77 %) showed statistically significant improvement in symptoms of irritability and hyperactivity.  Side effects were mild and the drug was generally well-tolerated.  The authors concluded that naltrexone may improve hyperactivity and restlessness in children with autism but there was insufficient evidence that it had an impact on core features of autism in majority of the participants.  They stated that it is likely that a subgroup of children with autism and abnormal endorphin levels may respond to naltrexone and identifying the characteristics of these children must become a priority.

Impulse Control Disorders in Parkinson Disease

In a placebo-controlled study, Papay et al (2014) determined the tolerability and effectiveness of naltrexone for the treatment of impulse control disorders (ICDs) in Parkinson’s disease (PD). Patients with PD (n = 50) and an ICD were enrolled in an 8-week, randomized (1:1), double-blind, placebo-controlled study of naltrexone 50 to 100 mg/day (flexible dosing).  The primary outcome measure was response based on the Clinical Global Impression-Change score, and the secondary outcome measure was change in symptom severity using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) ICD score.  A total of 45 patients (90 %) completed the study.  The Clinical Global Impression-Change response rate difference favoring naltrexone in completers was 19.8 % (95 % CI: -8.7 % to 44.2 %).  While this difference was not significant (odds ratio [OR] = 1.6, 95 % CI: 0.5 to 5.2, Wald χ2 [df] = 0.5 [1], p = 0.5), naltrexone treatment led to a significantly greater decrease in QUIP-RS ICD score over time compared with placebo (regression coefficient for interaction term in linear mixed-effects model = -7.37, F[df] = 4.3 [1, 49], p = 0.04).  The estimated changes in QUIP-RS ICD scores from baseline to week 8 were 14.9 points (95 % CI: 9.9 to 19.9) for naltrexone and 7.5 points (95 % CI: 2.5 to 12.6) for placebo.  The authors concluded that naltrexone treatment was not effective for the treatment of ICDs in PD using a global assessment of response, but findings using a PD-specific ICD rating scale support further evaluation of opioid antagonists for the treatment of ICD symptoms in PD.


In a double-blind, placebo-controlled study, Grant et al (2014) examined the effectiveness of naltrexone in adults with trichotillomania (TTM) who had urges to pull their hair.  A total of 51 individuals with TTM were randomized to naltrexone or placebo in an 8-week, double-blind trial.  Subjects were assessed with measures of TTM severity and selected cognitive tasks.  Naltrexone failed to demonstrate significantly greater reductions in hair pulling compared to placebo.  Cognitive flexibility, however, significantly improved with naltrexone (p = 0.026).  Subjects taking naltrexone with a family history of addiction showed a greater numerical reduction in the urges to pull, although it was not statistically significant.  The authors concluded that future studies are needed to examine if pharmacological modulation of the opiate system may provide promise in controlling pulling behavior in a subgroup of individuals with TTM.

Buprenorphine Dependence

Jhugroo and associates (2014) stated that although substitution therapy with opiate agonist treatments such as methadone and buprenorphine has resulted in a reduction of illicit drug use related harm, such treatment has also resulted in severe problems in some countries where opioid-dependent individuals now inject illicitly sold buprenorphine or buprenorphine-naloxone instead of heroin.  There is no approved treatment for buprenorphine dependence.  Naltrexone is an opioid antagonist that has been used for the treatment of both alcohol and opioid dependencies.  Although both buprenorphine and heroin resemble each other concerning their effects, buprenorphine has a higher affinity to opioid receptors than heroin.  Thus, it is unclear if naltrexone can block the psychoactive effects of buprenorphine as it does for heroin.  The authors presented observational case-series data on the use of a sustained-release naltrexone implant for the treatment of buprenorphine dependence.  To the authors' knowledge, this was the 1st use of sustained-release naltrexone for this indication.  The use of naltrexone implants for the treatment of buprenorphine dependence needs to be further investigated.

Prolactinoma (Prolactin-Secreting Pituitary Tumor)

Maglakelidze and colleagues (2017) stated that prolactinoma (prolactin-secreting pituitary adenomas) is the most common pituitary tumors in humans.  Animal studies have identified aggressive prolactinoma development in fetal alcohol exposed rats.  These researchers have recently identified a combination treatment of a μ opioid receptor antagonist naltrexone and a δ opioid receptor agonist D-Ala2-,N-Me-Phe4,Gly-ol Enkephalin (DPDPE) increases innate immune function.  In this study, these investigators  examined if naltrexone and DPDPE combination therapy is useful to control pituitary tumor growth.  Fetal alcohol exposed and control Fischer 344 female rats at 60 days of age were ovariectomized and received an estrogen implant to induce prolactinomas.  Six weeks after the estrogen implant, these animals received treatments of naltrexone and DPDPE or saline.  The growth of the pituitary tumor prior to and after opioidergic agent treatments was visualized using magnetic resonance imaging (MRI).  At the end of the treatment, pituitary weights, plasma prolactin and splenic levels of cytotoxic factors were determined.  Both imaging data and weight data indicated that the volume and the weight of the pituitary were increased more after estrogen treatment in animals exposed to fetal alcohol than control.  Naltrexone and DPDPE treatment reduced the weight and volume of the pituitary gland and plasma levels of prolactin in both fetal alcohol exposed and control-fed animals.  The treatment of opioidergic agents also increased the levels of cytotoxic factors in the spleen.  The authors concluded that these data provided a novel possibility in treating pituitary tumors using a combination therapy of naltrexone and DPDPE.

Opioid Use Disorder

Strang and colleagues (2019) noted that people recovering from heroin addiction need better treatments than are currently offered.  The chronic relapsing nature of drug dependence means that helping a patient to achieve abstinence is often difficult.  Naltrexone blocks the effects of ingested heroin; however, evidence is conflicting regarding the best delivery method.  In a 3-year, 3-center, 3-arm, parallel group, placebo-controlled, double-blind, double-dummy, randomized controlled trial (RCT), these researchers examined the clinical effectiveness and cost-effectiveness of extended-release naltrexone versus standard oral naltrexone versus relapse prevention therapy without medication for opioid use disorder (OUD).  The setting was at 2 specialist NHS out-patient addiction clinics: 1 in London and 1 in Birmingham.; the planned study sample was 300 adult patients with OUD who had completed detoxification.  One iGen / Atral-Cipan extended release naltrexone device (iGen/Atral-Cipan, Castanheira do Ribatejo, Portugal) (765 mg naltrexone or placebo) at day 0 of study week 1.  Three weekly directly observed active or placebo oral naltrexone tablets (2 × 50 mg, Monday and Wednesday; 3 × 50 mg, Friday) at day 0 of study week 1 (for 4 weeks) and then an 8-week regimen of patient-administered dosing at the same dosing level.  The primary outcome measure was the proportion of heroin-negative urine drug screen (UDS) results at the end of the 12-week post-randomization time-point.  A total of 6  patients were recruited and randomized to receive study interventions; 2 patients had no positive UDS samples for heroin during the 12-week treatment period, 1 patient had only 1 positive UDS sample and the remaining patients had 2, 6, and 8 positive UDS results for heroin.  All patients had at least 1 missed clinic visit (range of 1 to 14).  The authors concluded that considerable problems were encountered with the stipulated requirement of a validated "detoxified" status prior to the initiation of the study naltrexone; the requirement for a consent cooling-off period; and delays awaiting the surgical implant procedure.  Major upheaval to the organization and delivery of NHS community treatment services across England led to extremely poor levels of actual entry of patients into the trial.  Research-vital clinical and procedural requirements were, thus, more challenging to implement.  These researchers stated that the potential therapeutic value of the opioid antagonist naltrexone still needs clear investigation, including comparison of the established oral form with the new ultra-long-acting depot implant formulations (for which no licensed products exist in Europe).  Despite the small number of subjects (n = 6), some tentative conclusions could be reached, relevant to potential future work.  The blinding of the active/placebo medications appeared to be good.  Self-report was insufficient to detect instances of heroin use.  Self-report plus UDS information provided a fuller picture.  Instances of lapsed heroin use were not necessarily followed by full relapse, and future work should consider the lapse-relapse relationship.  The prison release setting also warrants special consideration.  In the future, investigators should consider seeking ethics approval for studies in which clinical procedures to accelerate the treatment process are permitted, even if outside orthodox clinical practice, if they address a clinical need at the time of challenge and clinical risk.  In addition, it may be appropriate to seek exemption from the ordinary requirement of a cooling-off period after securing consent because it is often essential to initiate treatment promptly.

Darke and associates (2019) stated that naltrexone is used as a maintenance drug for the treatment of opioid dependence and in opioid withdrawal regimens.  These researchers examined the clinical characteristics and circumstances of death of individuals undergoing naltrexone treatment for opioid dependence; and determined the blood toxicology of cases including naltrexone concentrations, the presence of other drugs and a comparison of morphine concentrations in the presence and absence of naltrexone.  This was a retrospective study of all deaths among individuals undergoing naltrexone treatment for opioid dependence retrieved from the National Coronial Information System (Australia), 2000 to 2017.  A total of 74 cases, with a mean age of 32.5 years; 81.1 % male.  Information was collected on demographics, manner of death, naltrexone treatment history, toxicology and major organ pathology.  Death was attributed to opioid toxicity in 86.5 % of cases: accidental (79.7 %), and deliberate (6.8 %).  In 55.4 % of all cases the decedent was maintained on oral naltrexone and 32.4 % had a recent naltrexone implant.  In 5 cases the decedent was undergoing opioid detoxification.  Among those screened for naltrexone, naltrexone was present in the blood or urine of 52.5 % (15.8 % of oral maintenance cases, 85.7 % of implant cases); 14 cases were known to have died from opioid toxicity with naltrexone present in their blood or urine.  The median blood naltrexone concentrations were within the reported therapeutic range.  The authors concluded that the primary cause of death among individuals undergoing naltrexone treatment for opioid dependence in Australia from 2000 to 2017 was opioid toxicity, the majority of cases having been maintained on oral naltrexone.  Cases in which naltrexone was not detected indicated the importance of treatment compliance.  Deaths due to opioid toxicity where naltrexone was present indicated the possibility of over-dose while naltrexone medication was maintained.

Roache et al (2021) noted that the comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT) trial showed that following induction, treatment with the sublingual agonist (buprenorphine-naloxone, BUP-NX) or injected antagonist (extended-release naltrexone, XR-NTX) produced similar reductions in opioid relapse in injection users with OUD.  Because XR-NTX reduces drinking in alcohol use disorder (AUD), these researchers carried out a secondary analysis of the X:BOT sample of patients successfully inducted onto treatment to determine whether XR-NTX (n = 204) was superior to BUP-NX (n = 270) in reducing drinking or heavy drinking in patients with OUD.  Standard drink units consumed were measured using the Timeline Follow-back method.  Mixed-models regression was used to examine the monthly frequency of any drinking and heavy drinking over 6 months of treatment.  These investigators used a proportional hazard survival analysis to examine the time to 1st drink.  Both treatment groups reduced drinking from baseline to post-treatment (small to medium effect), but no differences between groups were detected.  However, only 29 % (n = 136) of the sample had AUD and 19 % (n = 26/136) of those were abstinent before treatment.  Analysis of a sub-sample enriched for possible drinking included 136 individuals with an AUD diagnosis plus 43 who did not have AUD; but reported at least 1 day of heavy drinking before the study.  However, this sub-sample reported only 32 % of days of any drinking with a median of only 13 % of days designated as "heavy".  Within this sub-sample, at baseline, the BUP-NX group reported more mean drinks per drinking day than the XR-NTX group (p = 0.03); however, there were no other significant group differences on drinking observed before, during, or at the end of treatment.  The authors concluded that there was an overall reduction in drinking during treatment of OUD using both agonist and antagonist medications, so that the hypothesis that XR-NTX would be superior to BUP-NX was not supported.  Moreover, these researchers stated that this study was limited by low levels of co-morbid AUD or heavy drinking observed in X:BOT trial participants seeking treatment for OUD.

In a retrospective study, Erdogan et al (2022) compared the effectiveness of XR-NTX implant and BUP-NX in relapse prevention in OUD.  Medical records of 400 patients who were treated for OUD between 2016 and 2020 were examined concerning socio-demographic and clinical characteristics and abstinence duration with either BUP-NX (192 patients) or XR-NTX (208 patients) as maintenance treatments.  The median age of patients using BUP-NX was 25.00 years, and the median age of patients using XR-NTX was 25.50 years (p = 0.785).  The ratio of female patients in the BUP-NX group and the XR-NTX group was 7.3 % (n = 14) and 6.7 % (n = 14), respectively.  A significantly higher abstinence time was observed in the BUP-NX group (median = 4 months) than in the XR-NTX group (median = 3 months) (p = 0.015).  Liver function tests were within the normal ranges at the 3 time-points, which were just before the beginning and in the 1st and 3rd months of treatment.  The authors concluded that these findings suggested that BUP-NX might be more effective than XR-NTX in preventing relapse in OUD and both drugs are safe for the liver.  Moreover, these researchers stated that prospective randomized studies are needed to validate these findings.

Wang et al (2022) stated that chronic pain is highly prevalent among patients with OUD; however, little is known regarding how pharmacotherapies for OUD (e.g., XR-NTX and BUP-NX) affect pain.  These investigators carried out a secondary analysis of pain data on a large prospective 24-week, open-label, randomized-controlled comparative effectiveness trial of XR-NTX versus BUP-NX (the X:BOT Trial).  Subjects' pain status was evaluated by the EuroQol (EQ-5D).  Based on their responses to the pain question at baseline, subjects were divided into "Pain" versus "No Pain" categories.  Subject's pain status was examined every 4 weeks.  A mixed effects longitudinal logistic regression model was fitted to assess the differential effect of XR-NTX versus BUP-NX on pain, modeling pain at all available follow-up assessments, adjusted for age, sex, and baseline pain.  A total of 474 individuals who were successfully inducted onto their assigned medications were included in this analysis.  Among subjects endorsing pain at baseline, substantial reductions in pain were observed over the course of the study in both treatment groups.  However, reduction in pain was slightly greater in the group treated with XR-NTX than the one treated with BUP-NX (OR = 1.60; 95 % CI: 1.07 to 2.40, p = 0.023).  The authors concluded that future research using instruments and design specifically focused on pain could extend the present observations and evaluate their clinical significance.


The above policy is based on the following references:

  1. Darke S, Farrell M, Duflou J, et al. Circumstances of death of opioid users being treated with naltrexone. Addiction. 2019;114(11):2000-2007.
  2. Donoghue K, Elzerbi C, Saunders R, et al. The efficacy of acamprosate and naltrexone in the treatment of alcohol dependence, Europe versus the rest of the world: A meta-analysis. Addiction. 2015;110(6):920-930.
  3. Erdogan A, Topcuoglu M, Coskun MN, et al. Comparison of naltrexone implant and oral buprenorphine-naloxone in the treatment of opiate use disorder. Hum Psychopharmacol. 2022;37(2):e2813.
  4. Gibson AE, Degenhardt LJ, Hall WD. Opioid overdose deaths can occur in patients with naltrexone implants. Med J. Australia..2007;186:152-153.
  5. Gibson AE, Degenhardt LJ, Mortality related to pharmacotherapies for opioid dependence: A comparative analysis of coronial records. Drug Alcohol Rev. 2007;26:405-410.
  6. Grant JE, Odlaug BL, Schreiber LR, Kim SW. The opiate antagonist, naltrexone, in the treatment of trichotillomania: Results of a double-blind, placebo-controlled study. J Clin Psychopharmacol. 2014;34(1):134-138.
  7. Hickman M, Degenhardt L, Farrell M, Hall W. Commentary on Kelty & Hulse (2012): Is the comparison of mortality between patients prescribed implanted or oral naltrexone an unbiased and unconfounded comparison? Addiction. 2012,107:1825-1826.
  8. Jhugroo A, Ellayah D, Norman A, Hulse G. Naltrexone implant treatment for buprenorphine dependence -- Mauritian case series. J Psychopharmacol. 2014;28(8):800-803.
  9. Kelty E, Hulse G. A retrospective cohort study of obstetric outcomes in opioid-dependent women treated with implant naltrexone, oral methadone or sublingual buprenorphine, and non-dependent controls. Drugs. 2017;77(11):1199-1210.
  10. Kelty E, Hulse G. Examination of mortality rates in a retrospective cohort of patients treated with oral or implant naltrexone for problematic opioid use. Addiction. 2012;107:1817-1824.
  11. Kelty E, Hulse G, Joyce D. A comparison of blood toxicology in fatalities involving alcohol and other drugs in patients with an opioid use disorder treated with methadone, buprenorphine, and implant naltrexone. Am J Drug Alcohol Abuse. 2020;46(2):241-250.
  12. Kelty E, Thomson K, Carlstein S, et al. A retrospective assessment of the use of naltrexone implants for the treatment of problematic amphetamine use. Am J Addict. 2013;22(1):1-6.
  13. Krupitsky E, Blokhina E, Zvartau E, et al. Slow-release naltrexone implant versus oral naltrexone for improving treatment outcomes in people with HIV who are addicted to opioids: A double-blind, placebo-controlled, randomised trial. Lancet HIV. 2019;6(4):e221-e229.
  14. Krupitsky E, Zvartau E, Blokhina E, et al. Randomized trial of long-acting sustained-release naltrexone implant vs oral naltrexone or placebo for preventing relapse to opioid dependence. Arch Gen Psychiatry. 2012;69(9):973-981.
  15. Larney S, Gowing L, Mattick RP, et al. A systematic review and meta-analysis of naltrexone implants for the treatment of opioid dependence. Drug Alcohol Rev. 2014;33(2):115-128.
  16. Lobmaier P, Kornor H, Kunoe N, Bjorndal A. Sustained-release naltrexone for opioid dependence. Cochrane Database Syst Rev. 2008;(2):CD006140.
  17. Lobmaier PP, Kunoe N, Gossop M, Waal H. Naltrexone depot formulations for opioid and alcohol dependence: A systematic review. CNS Neurosci Ther. 2011;17(6):629-636.
  18. Maglakelidze G, Wynne O, Sarkar DK. A combined opiate agonist and antagonist treatment reduces prolactin secreting pituitary tumor growth. J Cell Commun Signal. 2017;11(3):227-232.
  19. Mayor S. Meta-analysis finds no evidence for efficacy of nalmefene in treating alcohol dependence. BMJ. 2015;351:h6988.
  20. National Health and Medical Research Council (NHMRC). Naltrexone implant treatment for opioid dependence. NHMRC Literature Review. Canberra, ACT: NHMRC; 2011.
  21. Ngo HT, Tait RJ, Hulse GK. Comparing drug-related hospital morbidity following heroin dependence treatment with methadone maintenance or naltrexone implantation. Arch Gen Psychiatry. 2008;65(4):457-465. 
  22. Olivier P. Fatal opiate overdose following regimen changes in naltrexone treatment. Addiction. 2005;100:560–563.
  23. Palpacuer C, Laviolle B, Boussageon R, et al. Risks and benefits of nalmefene in the treatment of adult alcohol dependence: A systematic literature review and meta-analysis of published and unpublished double-blind randomized controlled trials. PLoS Med. 2015;12(12):e1001924.
  24. Papay K, Xie SX, Stern M, et al. Naltrexone for impulse control disorders in Parkinson disease: A placebo-controlled study. Neurology. 2014;83(9):826-833.
  25. Roache JD, Pavlicova M, Campbell A, et al. Is extended release naltrexone superior to buprenorphine-naloxone to reduce drinking among outpatients receiving treatment for opioid use disorder? A secondary analysis of the CTN X:BOT trial. Alcohol Clin Exp Res. 2021;45(12):2569-2578.
  26. Roy A, Roy M, Deb S, et al. Are opioid antagonists effective in attenuating the core symptoms of autism spectrum conditions in children: A systematic review. J Intellect Disabil Res. 2015;59(4):293-306.
  27. Soyka M, Friede M, Schnitker J. Comparing nalmefene and naltrexone in alcohol dependence: Are there any differences? Results from an indirect meta-analysis. Pharmacopsychiatry. 2016;49(2):66-75.
  28. Soyka M, Kranzler HR, van den Brink W, et al.; WFSBP Task Force on Treatment, Guidelines for Substance Use Disorders. The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of substance use and related disorders. Part 2: Opioid dependence. World J Biol Psychiatry. 2011;12(3):160-187.
  29. Strang J, Kelleher M, Mayet S, et al. Extended-release naltrexone versus standard oral naltrexone versus placebo for opioid use disorder: The NEAT three-arm RCT. Health Technol Assess. 2019;23(3):1-72.
  30. Tiihonen J, Krupitsky E, Verbitskaya E, et al. Naltrexone implant for the treatment of polydrug dependence: A randomized controlled trial. Am J Psychiatry. 2012;169(5):531-536.
  31. Wang A-L, Shulman M, Choo T-H, et al. Baseline- and treatment-associated pain in the X:BOT comparative effectiveness study of extended-release naltrexone versus buprenorphine-naloxone for OUD. Addict Biol. 2022;27(2):e13112.