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Clinical Policy Bulletin:
Naltrexone Implants
Number: 0878


Aetna considers naltrexone implants experimental and investigational for treatment of alcohol addiction, narcotic addiction, and all other indications because of insufficient evidence in the peer-reviewed published medical literature of their safety and effectiveness.


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.

CPT Codes / HCPCS Codes / ICD-9 Codes
Naltrexone Implants:
No specific code
ICD-9 codes not covered for indications listed in the CPB (not all inclusive):
303.00 - 303.93 Alcohol dependence syndrome
304.00 - 304.93 Drug dependence

The above policy is based on the following references:
  1. 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.
  2. National Health and Medical Research Council (NHMRC). Naltrexone implant treatment for opioid dependence. NHMRC Literature Review. Canberra, ACT: NHMRC; 2011.
  3. 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.
  4. 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.
  5. Gibson AE, Degenhardt LJ, Hall WD. Opioid overdose deaths can occur in patients with naltrexone implants. Med J. Australia..2007;186:152-153.
  6. Gibson AE, Degenhardt LJ, Mortality related to pharmacotherapies for opioid dependence: A comparative analysis of coronial records. Drug Alcohol Rev. 2007;26:405-410.
  7. Olivier P. Fatal opiate overdose following regimen changes in naltrexone treatment. Addiction. 2005;100:560–563.
  8. 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. 
  9. Lobmaier P, Kornør H, Kunøe N, Bjørndal A. Sustained-release naltrexone for opioid dependence. Cochrane Database Syst Rev. 2008;(2):CD006140.
  10. Lobmaier PP, Kunøe N, Gossop M, Waal H. Naltrexone depot formulations for opioid and alcohol dependence: A systematic review. CNS Neurosci Ther. 2011;17(6):629-636.
  11. 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.
  12. 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.

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Copyright Aetna Inc. All rights reserved. Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.
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