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Meta-Analysis
. 2008 Apr 16;2008(2):CD006140.
doi: 10.1002/14651858.CD006140.pub2.

Sustained-release naltrexone for opioid dependence

P Lobmaier  1 , H Kornør, N Kunøe, A Bjørndal
Affiliations
Meta-Analysis

Sustained-release naltrexone for opioid dependence

P Lobmaier et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Naltrexone is an opioid antagonist which effectively blocks heroin effects. Since opioid dependence treatment with naltrexone tablets suffers from high dropout rates, several depot injections and implants are under investigation. Sustained-release formulations are claimed to be effective, but a systematic review of the literature is lacking.

Objectives: To evaluate the effectiveness of sustained-release naltrexone for opioid dependence and its adverse effects in different study populations.

Search strategy: The following databases were searched from their inception to November 2007: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, LILACS, PsycINFO, ISI Web of Science, trial database at http://clinicaltrials.gov, available NIDA monographs, CPDD and AAAP conference proceedings. The reference lists of identified studies, published reviews and relevant web sides were searched manually. Study authors and drug companies were contacted to obtain any unpublished material or missing data.

Selection criteria: To evaluate effectiveness only RCTs were included. To evaluate safety, any clinical trial reporting adverse effects was assessed. Treatment condition was extended to include alcohol dependent subjects and healthy volunteers.

Data collection and analysis: Reviewers independently evaluated the reports, rated methodological quality and extracted data. Analyses were performed separately for opioid dependent, alcohol dependent and healthy participants.

Main results: Foe effectiveness, one report met inclusion criteria. Two dosages of naltrexone depot injections (192 and 384 mg) were compared to placebo. High-dose significantly increased days in treatment compared to placebo (WMD 21.00, 95% CI 10.68 to 31.32, p<0.0001). High-dose compared to low-dose significantly increased days in treatment (WMD 12.00, 95% CI 1.69 to 22.31, p=0.02). Number of patients retained in treatment did not show significant differences between groups. For adverse effects, seventeen reports met inclusion criteria analyses, six were RCTs. Side effects were significantly more frequent in naltrexone depot groups compared to placebo. In alcohol dependent samples only, adverse effects appeared to be significantly more frequent in the low-dose naltrexone depot groups compared to placebo (RR 1.18, 95% CI 1.02 to 1.36, p=0.02). In the opioid dependent sample, group differences were not statistically significant. Reports on systematic assessment of side effects and adverse events were scarce.

Authors' conclusions: There is insufficient evidence to evaluate the effectiveness of sustained-release naltrexone for treatment of opioid dependence. For naltrexone injections, administration site-related adverse effects appear to be frequent, but of moderate intensity and time limited. For a harm-benefit evaluation of naltrexone implants, more data on side effects and adverse events are needed.

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Conflict of interest statement

None

Figures

1
1
1.1
1.1. Analysis
Comparison 1 effectiveness outcomes treatment vs. control, Outcome 1 treatment retention in high‐dose depot vs. placebo.
1.2
1.2. Analysis
Comparison 1 effectiveness outcomes treatment vs. control, Outcome 2 treatment retention in low‐dose depot vs. placebo.
1.3
1.3. Analysis
Comparison 1 effectiveness outcomes treatment vs. control, Outcome 3 treatment retention in high‐dose vs. low‐dose depot.
1.4
1.4. Analysis
Comparison 1 effectiveness outcomes treatment vs. control, Outcome 4 time to drop out in high‐dose depot vs. placebo.
1.5
1.5. Analysis
Comparison 1 effectiveness outcomes treatment vs. control, Outcome 5 time to drop out in high‐dose vs. low‐dose depot.
1.6
1.6. Analysis
Comparison 1 effectiveness outcomes treatment vs. control, Outcome 6 time to drop out in low‐dose depot vs. placebo.
2.1
2.1. Analysis
Comparison 2 safety outcomes treatment vs. control, Outcome 1 high‐dose depot vs. placebo in opioid dependence.
2.2
2.2. Analysis
Comparison 2 safety outcomes treatment vs. control, Outcome 2 high‐dose depot vs. placebo in alcohol dependence.
2.3
2.3. Analysis
Comparison 2 safety outcomes treatment vs. control, Outcome 3 low‐dose depot vs. placebo in opioid dependence.
2.4
2.4. Analysis
Comparison 2 safety outcomes treatment vs. control, Outcome 4 low‐dose depot vs. placebo in alcohol dependence.
2.5
2.5. Analysis
Comparison 2 safety outcomes treatment vs. control, Outcome 5 low‐dose depot vs. placebo in healthy volunteers.
2.6
2.6. Analysis
Comparison 2 safety outcomes treatment vs. control, Outcome 6 high‐dose vs. low‐dose depot in opioid dependence.
2.7
2.7. Analysis
Comparison 2 safety outcomes treatment vs. control, Outcome 7 high‐dose vs. low‐dose depot in alcohol dependence.
2.8
2.8. Analysis
Comparison 2 safety outcomes treatment vs. control, Outcome 8 one or more adverse effects in liver impaired vs. healthy controls.
2.9
2.9. Analysis
Comparison 2 safety outcomes treatment vs. control, Outcome 9 mortality in naltrexone implant vs. methadone maintenance.
See this image and copyright information in PMC

References

References to studies included in this review

Carreno 2003 {published data only}
    1. LinksCarreño JE, Alvarez CE, Narciso GI, Bascarán MT, Díaz M, Bobes J. Maintenance treatment with depot opioid antagonists in subcutaneous implants: an alternative in the treatment of opioid dependence. Addict Biol 2003;8(4):429‐38. - PubMed
Comer 2002 {published data only}
    1. Comer SD, Collins ED, Kleber HD, Nuwayser ES, Kerrigan JH, Fischman MW. Depot naltrexone: long‐lasting antagonism of the effects of heroin in humans. Psychopharmacology 2002;159(4):351‐60. - PMC - PubMed
Comer 2006 {published data only}
    1. Comer SD, Sullivan MA, Yu E, Rothenberg JL, Kleber HD, Kampman K, et al. Injectable, sustained‐release naltrexone for the treatment of opioid dependence: a randomised, placebo‐controlled trial. Archives of General Psychiatry 2006;63(2):210‐8. - PMC - PubMed
Dunbar 2006 {published data only}
    1. Dunbar JL, Turncliff RZ, Dong Q, Silverman BL, Ehrich EW, Lasseter KC. Single‐ and multiple‐dose pharmacokinetics of long‐acting injectable naltrexone. Alcoholism: Clinical & Experimental Research 2006;30(3):480‐90. - PubMed
Foster 2003 {published data only}
    1. Foster J, Brewer C, Steele T. Naltrexone implants can completely prevent early (1‐month) relapse after opiate detoxification: a pilot study of two cohorts totaling 101 patients with a note on naltrexone blood levels. Addiction Biology 2003;8(2):211‐7. - PubMed
Galloway 2005 {published data only}
    1. Galloway GP, Koch M, Cello R, Smith DE. Pharmacokinetics, safety, and tolerability of a depot formulation of naltrexone in alcoholics: an open‐label trial. BMC Psychiatry 2005;5(1):18. - PMC - PubMed
Garbutt 2005 {published data only}
    1. Garbutt JC, Kranzler HR, O'Malley SS, Gastfriend DR, Pettinati HM, Silverman BL, et al. Efficacy and Tolerability of Long‐Acting Injectable Naltrexone for Alcohol Dependence: A Randomized Controlled Trial. JAMA 2005;293(13):1617‐25. - PubMed
    1. O'Malley SS, Garbutt JC, Gastfriend DR, Dong Q, Kranzler HR. Efficacy of extended‐release naltrexone in alcohol‐dependent patients who are abstinent before treatment.. Journal of Clinical Psychopharmacology 2007;5:507‐12. - PubMed
Gölz 2000 {published and unpublished data}
    1. Gölz J, Partecke G. Catamnestic development of opiate addicts after Naltrexone induced detoxification under anaesthesia, Naltrexone supported relapse prevention and psychosocial outpatient aftercare [Katamnestische Entwicklung Opiatabhängiger nach Naltrexoninduziertem Entzug unter Narkose, naltrexongestützter Rückfallprophylaxe und ambulanter psychosozialer Nachsorge]. Suchttherapie 2000;1(3):166‐72.
Hulse 2005 {published data only (unpublished sought but not used)}
    1. Hulse GK, Tait RJ, Comer SD, Sullivan MA, Jacobs IG, Arnold‐Reed D. Reducing hospital presentations for opioid overdose in patients treated with sustained release naltrexone implants. Drug and Alcohol Dependence 2005;79(3):351‐7. - PMC - PubMed
Johnson 2004 {published data only}
    1. Johnson BA, Ait‐Daoud N, Aubin HJ, BW, Guzzetta R, Loewy J, et al. A pilot evaluation of the safety and tolerability of repeat dose administration of long‐acting injectable naltrexone (Vivitrex) in patients with alcohol dependence. Alcoholism: Clinical & Experimental Research 2004;28(9):1356‐61. - PubMed
Kranzler 1998 {published data only}
    1. Kranzler HR, Modesto‐Lowe V, Nuwayser ES. Sustained‐release naltrexone for alcoholism treatment: a preliminary study. Alcoholism: Clinical & Experimental Research 1998;22(5):1074‐9. - PubMed
Kranzler 2004 {published data only}
    1. Kranzler HR, Wesson DR, Billot L, DrugAbuse Sciences Naltrexone Depot Study Group. Naltrexone Depot for Treatment of Alcohol Dependence: A Multicenter, Randomized, Placebo‐Controlled Clinical Trial. Alcoholism: Clinical & Experimental Research 2004;28(7):1051‐9. - PubMed
Sullivan 2006 {published data only}
    1. Sullivan MA, Vosburg SK, Comer SD. Depot naltrexone: antagonism of the reinforcing, subjective, and physiological effects of heroin. Psychopharmacology 2006;189(1):37‐46. - PubMed
Tait 2007 {published data only}
    1. Tait RJ, Ngo HT, Hulse GK. Mortality in heroin users 3 years after naltrexone implant or methadone maintenance treatment. Journal of Substance Abuse Treatment in press. - PubMed
Turncliff 2005 {published data only}
    1. Turncliff RZ, Dunbar JL, Dong Q, Silverman BL, Ehrich EW, Dilzer SC, et al. Pharmacokinetics of long‐acting naltrexone in subjects with mild to moderate hepatic impairment. Journal of Clinical Pharmacology 2005;45(11):1259‐67. - PubMed
Waal 2003 {published and unpublished data}
    1. Olsen L, Christophersen AS, Frogopsahl G, Waal H, Morland J. Plasma concentrations during naltrexone implant treatment of opiate‐dependent patients. British journal of clinical pharmacology 2004;58(2):219‐22. - PMC - PubMed
    1. Waal H, Christophersen AS, Frogopsahl G, Olsen LH, Morland J. [Naltrexone implants‐‐a pilot project]. The Journal of the Norwegian Medical Association 2003;123(12):1660‐1. - PubMed
Waal 2006 {published data only}
    1. Waal H, Frogopsahl G, Olsen L, Christophersen AS, Morland J. Naltrexone implants ‐ duration, tolerability and clinical usefulness. A pilot study. European Addiction Research 2006;12(3):138‐44. - PubMed

References to studies excluded from this review

Albanese 2000 {published data only}
    1. Albanese AP, Gevirtz C, Oppenheim B, Field JM, Abels I, Eustace JC. Outcome and six month follow up of patients after Ultra Rapid Opiate Detoxification (UROD). Journa of Addictive Diseases 2000;19(2):11‐28. - PubMed
Brewer 2001 {published data only}
    1. Brewer C. Naltrexone implants for opiate addiction: New life for a middle‐aged drug. Pharmaceutical Journal 2001;267(7162):260.
Brewer 2002 {published data only}
    1. Brewer C. Serum naltrexone and 6‐beta‐naltrexol levels from naltrexone implants can block very large amounts of heroin: a report of two cases. Addiction Biology 2002;7(3):321‐3. - PubMed
Brewer 2004 {published data only}
    1. Brewer C, Wong VS. Naltrexone: Report of lack of hepatotoxicity in acute viral hepatitis, with a review of the literature. Addiction Biology 2004;9(1):81‐7. - PubMed
Carreno 2002 {published data only}
    1. Carreno JE, Bobes J, Brewer C, Alvarez CE, San Narciso GI, Bascaran MT, et al. 24‐Hour opiate detoxification and antagonist induction at home‐‐the 'Asturian method': a report on 1368 procedures. Addiction Biology 2002;7(2):243‐50. - PubMed
Chiang 1984 {published data only}
    1. Chiang CN, Hollister LE, Kishimoto A, Barnett G. Kinetics of a naltrexone sustained‐release preparation. Clinical Pharmacology and Therapeutics 1984;36(5):704‐8. - PubMed
Chiang 1985a {published data only}
    1. Chiang CN, Hollister LE, Gillespie HK, Foltz RL. Clinical evaluation of a naltrexone sustained‐release preparation. Drug and Alcohol Dependence 1985;16(1):1‐8. - PubMed
Chiang 1985b {published data only}
    1. Chiang CN, Kishimoto A, Barnett G, Hollister LE. Implantable narcotic antagonists: a possible new treatment for narcotic addiction. Psychopharmacology Bulletin 1985;21(3):672‐5. - PubMed
Collins 2005 {published data only}
    1. Collins ED, Kleber HD, Whittington RA, Heitler NE. Anesthesia‐assisted vs buprenorphine‐ or clonidine‐assisted heroin detoxification and naltrexone induction: a randomised trial. JAMA 2005;294(8):903‐13. - PubMed
Colquhoun 2005 {published data only}
    1. Colquhoun R, Tan DY, Hull S. A comparison of oral and implant naltrexone outcomes at 12 months. Journal of Opioid Management 2005;1(5):249‐56. - PubMed
Dean 2005 {published data only}
    1. Dean RL. The preclinical development of Medisorb Naltrexone, a once a month long acting injection, for the treatment of alcohol dependence. Frontiers in Bioscience 2005;10:643‐55. - PubMed
Dean 2006 {published data only}
    1. Dean AJ, Saunders JB, Jones RT, Young RM, Connor JP, Lawford BR. Does naltrexone treatment lead to depression? Findings from a randomised controlled trial in subjects with opioid dependence. Journal of Psychiatry and Neuroscience 2006;31(1):38‐45. - PMC - PubMed
Garcia‐Alonso 1989 {published data only}
    1. Garcia‐Alonso F, Gutierrez M, San L, Bedate J, Forteza‐Rei J, Rodriguez‐Artalejo F, et al. A multi centre study to introduce naltrexone for opiate dependence in Spain. Drug and Alcohol Dependence 1989;23(2):117‐21. - PubMed
Gooberman 1998 {published data only}
    1. Gooberman LL, Bradway DW. Depot naltrexone vs oral naltrexone post detoxification. Journal of Addictive Diseases 1998;17(2):150.
Grusser 2006 {published data only}
    1. Grusser SM, Thalemann CN, Platz W, Golz J, Partecke G. A new approach to preventing relapse in opiate addicts: A psychometric evaluation. Biological Psychology 2006;71(3):231‐5. - PubMed
Hamilton 2002 {published data only}
    1. Hamilton RJ, Olmedo RE, Shah S, Hung OL, Howland MA, Perrone J, et al. Complications of ultrarapid opioid detoxification with subcutaneous naltrexone pellets. Academic emergency medicine 2002;9(1):63‐8. - PubMed
Harrison 2006 {published data only}
    1. Harrison TS, Plosker GL, Keam SJ. Extended‐release intramuscular naltrexone. Drugs 2006;13:1741‐51. - PubMed
Heading 2006 {published data only}
    1. Heading CE. Vivitrex (Alkermes/Cephalon). Current Opinion in Investigational Drugs 2006;7(1):81‐8. - PubMed
Hulse 2002a {published data only}
    1. Hulse G, O'neil G. Using naltrexone implants in the management of the pregnant heroin user. Australian & New Zealand Journal of Obstetrics & Gynaecology 2002;42(5):569‐73. - PubMed
Hulse 2002b {published data only}
    1. Hulse GK, O'Neill G. A possible role for implantable naltrexone in the management of the high‐risk pregnant heroin user. Australian & New Zealand Journal of Obstetrics & Gynaecology 2002;42(1):93‐4. - PubMed
Hulse 2003a {published data only}
    1. Hulse GK, Tait RJ. A pilot study to assess the impact of naltrexone implant on accidental opiate overdose in 'high‐risk' adolescent heroin users. Addiction Biology 2003;8(3):337‐42. - PubMed
Hulse 2003b {published data only}
    1. Hulse GK, O'neil G, Hatton M, Paech MJ. Use of oral and implantable naltrexone in the management of the opioid impaired physician.[see comment]. Anaesthesia & Intensive Care 2003;31(2):196‐201. - PubMed
Hulse 2003c {published data only}
    1. Hulse GK, Arnold‐Reed DE, O'Neil G, Hansson RC. Naltrexone implant and blood naltrexone levels over pregnancy. Australian & New Zealand Journal of Obstetrics & Gynaecology 2003;43(5):386‐8. - PubMed
Hulse 2004a {published data only}
    1. Hulse GK, Arnold‐Reed DE, O'Neil G, Chan CT, Hansson R, O'Neil P. Blood naltrexone and 6‐beta‐naltrexol levels following naltrexone implant: comparing two naltrexone implants. Addiction Biology 2004;9(1):59‐65. - PubMed
Hulse 2004b {published data only}
    1. Hulse GK, Arnold‐Reed DE, O'Neil G, Chan CT, Hansson RC. Achieving long‐term continuous blood naltrexone and 6‐beta‐naltrexol coverage following sequential naltrexone implants. Addiction Biology 2004;9(1):67‐72. - PubMed
Hulse 2004c {published data only}
    1. Hulse GK, O'neil G, Arnold‐Reed DE. Methadone maintenance vs. implantable naltrexone treatment in the pregnant heroin user. International Journal of Gynaecology & Obstetrics 2004;85(2):170‐1. - PubMed
Hulse 2004d {published data only}
    1. Hulse GK, O'neil G, Arnold‐Reed DE. Management of an opioid‐impaired anaesthetist by implantable naltrexone. Journal of Substance Use 2004;9(2):86‐90.
Iversen 2005 {published data only}
    1. Iversen L. Addiction. Drug Discovery Today: Therapeutic Strategies 2005;2(1):v.
Jasinski 2006 {unpublished data only}
    1. Jasinski DR. Clinical Studies of a Long‐Acting Naltrexone Implant for Opioid Addiction. http://www.valerapharma.com/.
Jeffrey 2007 {published data only}
    1. Jeffrey GP, MacQuillan G, Chua F, Galhenage S, Bull J, Young E, et al. Hepatitis C virus eradication in intravenous drug users maintained with subcutaneous naltrexone implants.[see comment]. Hepatology 2007;45(1):111‐7. - PubMed
Johnson 2006 {published data only}
    1. Johnson BA. A synopsis of the pharmacological rationale, properties and therapeutic effects of depot preparations of naltrexone for treating alcohol dependence. Expert Opinion on Pharmacotherapy 2006;7(8):1065‐73. - PubMed
Lerner 1992 {published data only}
    1. Lerner A, Sigal M, Bacalu A, Shiff R, Burganski I, Gelkopf M. A naltrexone double blind placebo controlled study in Israel. The Israel journal of psychiatry and related sciences 1992;29(1):36‐43. - PubMed
Marlowe 2006 {published data only}
    1. Marlowe DB. Depot naltrexone in lieu of incarceration: A behavioral analysis of coerced treatment for addicted offenders. Journal of Substance Abuse Treatment 2006;31(2):131‐9. - PubMed
Martin 1974 {published data only}
    1. Martin WR, Sandquist VL. A sustained release depot for narcotic antagonists. Arch Gen Psychiatry 1974;30(1):31‐3. - PubMed
Modesto‐Lowe 2002 {published data only}
    1. Modesto‐Lowe V. Naltrexone depot Drug Abuse Sciences. IDrugs 2002;5(8):835‐8. - PubMed
Ngo 2007 {published data only}
    1. Ngo HT, Tait RJ, Arnold‐Reed DE, Hulse GK. Mental health outcomes following naltrexone implant treatment for heroin‐dependence. Progress in Neuro‐Psychopharmacology & Biological Psychiatry 2007;31(3):605‐12. - PubMed
NRCC report 1978 {published data only}
    1. NRCC report 1978. Clinical evaluation of naltrexone treatment of opiate‐dependent individuals. Report of the National Research Council Committee on Clinical Evaluation of Narcotic Antagonists. Archives of General Psychiatry 1978;35(3):335‐40. - PubMed
O'Brien 2005 {published data only}
    1. O'Brien CP. Efficacy and tolerability of long‐acting injectable naltrexone for alcohol dependence. Current Psychiatry Reports 2005;7(5):327‐8. - PubMed
O'Brien 2006 {published data only}
    1. O'Brien B, Cody C. Analgesia and sedation in the presence of a naltrexone implant: A novel pharmacological challenge. European Journal of Emergency Medicine 2006;13(5):315‐6. - PubMed
O'Malley 1992 {published data only}
    1. O'Malley SS, Jaffe AJ, Chang G, Schottenfeld RS, Meyer RE, Rounsaville B. Naltrexone and coping skills therapy for alcohol dependence. A controlled study. Archives of General Psychiatry 1992;49(11):881‐7. - PubMed
Oliver 2005 {published data only}
    1. Oliver P, Horspool M, Keen J. Fatal opiate overdose following regimen changes in naltrexone treatment [1]. Addiction 2005;100(4):560‐1. - PubMed
Pekta 1998 {published data only}
    1. Pekta SNO, Kalyonko ÖA, Mirsal H, Pektas A, Gooberman LL, Beyazyürek M. Different forms (Oral or implant) Of naltrexone use in relapse prevention on heroin addicts: A controlled clinical trial up to 6 months follow‐up. XXIst Collegium Internationale Neuro psychopharmacologicum, Glasgow, Scotland 12th 16th July, 1998. 1998.
Pitt 1981 {published data only}
    1. Pitt CG, Marks TA, Schindler A. Biodegradable drug delivery systems based on aliphatic polyesters: application to contraceptives and narcotic antagonists. NIDA Research Monograph 1981;28:232‐53. - PubMed
Poser 1996 {published data only}
    1. Poser W, Ehrenreich H. Naltrexone‐‐prevention of recurrence in narcotic dependence and in alcoholism. Internist 1996;37(10):1061‐7. - PubMed
Rabinowitz 1998 {published data only}
    1. Rabinowitz J, Cohen H, Kotler M. Outcomes of ultrarapid opiate detoxification combined with naltrexone maintenance and counseling. American Journal on Addictions 1998;49(6):831‐3. - PubMed
Ramenskaya 2005 {published data only}
    1. Ramenskaya GV, Shikh EV, Arzamastsev AP, Kukes VG. Molecular‐biological problems of drug design and mechanism of drug action ‐ Pharmacokinetic study of the new domestic hypodermic form of naltrexone: Prodetoxon depot tablets. Pharmaceutical Chemistry Journal 2005;1:1‐3.
Rawson 2000 {published data only}
    1. Rawson RA, McCann MJ, Hasson AJ, Ling W. Addiction pharmacotherapy 2000: new options, new challenges. Journal of Psychoactive Drugs 2000;32(4):371‐8. - PubMed
Reece 2007 {published data only}
    1. Reece AS. Psychosocial and treatment correlates of opiate free success in a clinical review of a naltrexone implant program. Subst Abuse Treat Prev Policy 2007;2(1):35. - PMC - PubMed
Resnick 1977 {published data only}
    1. Resnick RB. Prospects, problems, side effects, and safety of narcotic antagonists. International Journal of the Addictions 1977;12(7):863‐7. - PubMed
Reuning 1976 {published data only}
    1. Reuning RH, Malspeis L, Frank S, Notari RE. Testing of drug delivery systems for use in the treatment of narcotic addiction. NIDA 1976;4:43‐5. - PubMed
Riddle 2001 {published data only}
    1. Riddle MA, Kastelic EA, Frosch E. Pediatric psychopharmacology. Journal of Child Psychology & Psychiatry & Allied Disciplines 2001;42(1):73‐90. - PubMed
Schwope 1975 {published data only}
    1. Schwope AD, Wise DL, Howes JF. Lactic/glycolic acid polymers as narcotic antagonist delivery systems. Life Sciences 1975;17(12):1877‐85. - PubMed
Sobel 2001 {published data only}
    1. Sobel BFX, Liesbon IA, Bigelow GE. Prolonged opioid blockade by depot naltrexone. Drug and Alcohol Dependence 2001;63(Suppl 1):148.
Suhaida 2004 {published data only}
    1. Suhaida MG, Yahya IB, Darmawati MY. Preparation of naltrexone hydrochloride loaded poly (DL‐lactide‐co‐glycolide) microspheres and the effect of polyvinyl alcohol (PVA) as surfactant on the characteristics of the microspheres. Medical Journal of Malaysia 2004;59(Supplement B):63‐4. - PubMed
Teagle 2007 {published data only}
    1. Teagle S. Depot naltrexone appears safe and effective for heroin addiction. Nida Notes 2007;21(3):7.
Warhaft 2003 {published data only}
    1. Warhaft N. Naltrexone implants. Anaesthesia & Intensive Care 2003;31(5):592‐3. - PubMed
Wesson 2003 {published data only}
    1. Wesson DR, Kranzler HR, Kusmierek J. A placebo‐controlled, clinical trial of naltrexone depot in treatment of alcohol dependence: Results at 9 and 12 months. Journal of Addictive Diseases 2003;22(2):121.
Willette 1978 {published data only}
    1. Willette RE. The development of sustained action preparations of narcotic antagonists. NIDA Research Monograph 1978;19:333‐9. - PubMed
Willette 1981 {unpublished data only}
    1. Willette RE, Barnett G editors. Narcotic antagonists: naltrexone pharmacochemistry and sustained‐release preparations. NIDA Research Monograph. Vol. 28, Washington, D.C: U.S. Government, 1981:1‐273. - PubMed
Wodak 2001 {published data only}
    1. Wodak A. Drug treatment for opioid dependence. Australian Prescriber 2001;24(1):4‐6.

References to ongoing studies

Hulse {published data only}
    1. Hulse GK, Arnold‐Reed D, Bulsara M. A randomised, double‐blind, placebo‐controlled clinical trial of naltrexone implants for the treatment of heroin addiction. personal communication.
Kunøe {published data only}
    1. Kunøe. Naltrexone Naltrexone Implants as an Aid in Preventing Relapse Following Inpatient Treatment for Opioid Addiction ‐ a Randomised Study Naltrexone Naltrexone Implants as an Aid in Preventing Relapse Following Inpatient Treatment for Opioid Addiction ‐ a Randomised Study. http://clinicaltrials.gov identifier: NCT00521157.
Lobmaier {published data only}
    1. Lobmaier P. Naltrexone Implants ‐ a Treatment Alternative for Heroin Dependent Prisoners?. http://clinicaltrials.gov identifier: NCT00204243.
Nunes 2002 {published data only}
    1. Nunes E. Behavioral Naltrexone Therapy: A Novel Treatment for Heroin Dependence. http://clinicaltrials.gov identifier NCT00332228.
Nunes 2008 {published data only}
    1. Nunes E. Behavioral Naltrexone Therapy (BNT) for Promoting Adherence to Oral Naltrexone (BNT‐Oral) vs Extended Release Injectable Depot Naltrexone (Depot‐BNT); a Randomized Trial. Clinicaltrial.gov reference: NCT00577408.
Tiihonen {published data only}
    1. Tiihonen J. Naltrexone depot implant in the treatment of co‐morbid amphetamine and opioid dependence: a double‐blind, randomised, placebo‐controlled trial. http://www.controlled‐trials.com/. [ISRCTN88905555]
Woody {published data only}
    1. Woody G. Addiction Treatment in Russia: Oral and Depot Naltrexone. http://clinicaltrials.gov identifier NCT00218426.

Additional references

Amato 2005
    1. Amato L, Davoli M, Perucci A, Ferri M, Faggiano F, Mattick P. An overview of systematic reviews of the effectiveness of opiate maintenance therapies: available evidence to inform clinical practice and research. Journal of Substance Abuse Treatment 2005;28(4):321‐9. - PubMed
Chiang 1985
    1. Chiang CN, Hollister LE, Gillespie HK, Foltz RL. Clinical evaluation of a naltrexone sustained‐release preparation. Drug and Alcohol Dependence 1985;16(1):1‐8. - PubMed
Comer 2007
    1. Comer SD, Sullivan MA, Hulse GK. Sustained‐release naltrexone: novel treatment for opioid dependence. Expert Opin Investig Drugs 2007;16(8):1285‐94. - PubMed
Cornish 1997
    1. Cornish JW, Metzger D, Woody GE, Wilson D, McLellan AT, Vandergrift B, et al. Naltrexone pharmacotherapy for opioid dependent federal probationers. Journal of Substance Abuse Treatment 1997;14(6):529‐34. - PubMed
EMCDDA 2006
    1. EMCDDA. 11th annual report 2006. http://ar2006.emcdda.europa.eu/download/ar2006‐en.pdf. EMCDDA, (accessed 31 August 2007).
Ginzburg 1984
    1. Ginzburg HM, Glass WJ. The role of the National Institute on Drug Abuse in the development of naltrexone. Journal of Clinical Psychiatry 1984;45(9):4‐6. - PubMed
Gonzalez 1988
    1. Gonzalez JP, Brogden RN. Naltrexone. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the management of opioid dependence. Drugs 1988;35(3):192‐213. - PubMed
Guo 2001
    1. Guo S, Jiang Z, Wu Y. Efficacy of naltrexone hydrochloride for preventing relapse among opiate‐dependent patients after detoxification. Hong Kong Journal of Psychiatry 2001;11(4):2‐8.
Higgins 2006
    1. Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions 4.2.5 [updated May 2005].. The Cochrane Library, Issue 2.. Chichester, UK:: John Wiley & Sons, Ltd. Cochrane Collaboration, 2006., 2006.
Krupitsky 2007
    1. Krupitsky EM, Burakov AM, Tsoy MV, Egorova VY, Slavina TY, Grinenko AY, et al. Overcoming opioid blockade from depot naltrexone (Prodetoxon). Addiction 2007;102(7):1164‐5. - PubMed
Maksoud 2006
    1. Maksoud NA. Evolution of Techniques over 10 years and 10000 cases. 3rd Berlin Stapleford International Addiction Conference. 2006.
Martin 1973
    1. Martin WR, Jasinski DR, Mansky PA. Naltrexone, an antagonist for the treatment of heroin dependence. Effects in man. Archives of General Psychiatry 1973;28(6):784‐91. - PubMed
Mattick 2003
    1. Mattick RP, Breen C, Kimber J, Davoli M. Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database of Systematic Reviews 2003, Issue 2. [DOI: 10.1002/14651858] - DOI - PubMed
McLellan 2000
    1. McLellan AT, Lewis DC, O'Brien CP, Kleber HD. Drug dependence, a chronic medical illness: implications for treatment, insurance, and outcomes evaluation. JAMA 2000;284(13):1689‐95. - PubMed
Minozzi 2006
    1. Minozzi S, Amato L, Vecchi S, Davoli M, Kirchmayer U, Verster A. Oral naltrexone maintenance treatment for opioid dependence. Cochrane Database of Systematic Reviews 2006, Issue 1. [DOI: 10.1002/14651858] - DOI - PubMed
Moran 2007
    1. Moran W. Naltrexone Implant ‐ Improved Long Term Extended Release Naltrexone Implant Model 2 eu. personal communication 2007.
Navaratnam 1994
    1. Navaratnam V, Jamaludin A, Raman N, Mohamed M, Mansor SM. Determination of naltrexone dosage for narcotic agonist blockade in detoxified Asian addicts. Drug & Alcohol Dependence 1994;34(3):231‐6. - PubMed
OAS 2005
    1. Substance Abuse and Mental Health Services Administration. Results from the 2004 National Survey on Drug Use and Health: National Findings. http://oas.samhsa.gov/nsduh/ (accessed 14 February 2006).
Partecke 2007
    1. Partecke G. Cravex. personal communication 2007.
Preston 1999
    1. Preston KL, Silverman K, Umbricht A, DeJesus A, Montoya ID, Schuster CR. Improvement in naltrexone treatment compliance with contingency management. Drug and Alcohol Dependence 1999;54(2):127‐35. - PubMed
San 1991
    1. San L, Pomarol G, Peri JM, Olle JM, Cami J. Follow‐up after a six‐month maintenance period on naltrexone versus placebo in heroin addicts. British Journal of Addiction 1991;86(8):983‐90. - PubMed
van den Brink 2006
    1. Brink W, Haasen C. Evidenced‐based treatment of opioid‐dependent patients. Canadian Journal of Psychiatry 2006;51(10):635‐46. - PubMed

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