Clinical UM Guideline



Subject: Naltrexone (Vivitrol®) Injections for the Treatment of Alcohol and Opioid Dependence
Guideline #:  CG-DRUG-21 Current Effective Date:    09/27/2017
Status: Reviewed Last Review Date:    08/03/2017

Description

This document addresses extended-release, injectable naltrexone (Vivitrol, Alkermes, Inc., Cambridge, MA). Naltrexone is an opioid antagonist that binds to opioid receptors, blocking the euphoric effects of exogenous opioids in those who are opioid or alcohol dependent.

This document does not address the oral formulation of naltrexone (Revia® , Duramed Pharmaceuticals Inc., Pomona, NY) or compounded implantable naltrexone pellets.

Note: Please see the following related documents for additional information:

Clinical Indications

Medically Necessary:

I.  Alcohol Dependence (Alcohol Use Disorder):

Injectable naltrexone (Vivitrol) is considered medically necessary for the treatment of alcohol dependence (alcohol use disorder) when the individual:

  1. Is being treated for alcohol dependence (alcohol use disorder); and
  2. Is not actively drinking at the time of initial injectable naltrexone (Vivitrol) administration; and
  3. Is able to abstain from alcohol for at least 7 days in an outpatient setting prior to treatment initiation; and
  4. Actively participates in a comprehensive rehabilitation program that includes psychosocial support; and
  5. Is not:   
    1. Currently on opioid analgesics for pain management; or
    2. Currently on opioid agonists for the treatment of opioid dependence (opioid use disorder) (for example, buprenorphine and methadone); or
    3. Physiologically dependent on opioids; or
    4. Currently in acute opioid withdrawal; and
  6. Does not have:
    1. A positive urine screen for opioids; or
    2. A failed naloxone challenge test; or
    3. Acute hepatitis; or
    4. Liver failure; or
    5. Previous hypersensitivity to naltrexone, 75:25 polylactide-co-glycolide (PLG), carboxymethylcellulose or any other component of the diluent.

II.  Opioid Dependence (Opioid Use Disorder):

Injectable naltrexone (Vivitrol) is considered medically necessary for the prevention of relapse to opioid dependence (opioid use disorder) following detoxification when the individual:

  1. Is being treated for opioid dependence (opioid use disorder ); and
  2. Has successfully completed an opioid detoxification program; and
  3. Has been opioid-free (including buprenorphine and methadone) for at least 7 days prior to initiating treatment with naltrexone (Vivitrol) injection; and
  4. Actively participates in a comprehensive rehabilitation program that includes psychosocial support; and
  5. Is not:
    1. Currently on opioid analgesics for pain management; or
    2. Currently in acute opioid withdrawal; and
  6. Does not have:
    1. A positive urine screen for opioids; or
    2. A failed naloxone challenge test; or
    3. Acute hepatitis; or
    4. Liver failure; or
    5. Previous hypersensitivity to naltrexone, 75:25 polylactide-co-glycolide (PLG), carboxymethylcellulose or any other component of the diluent.

Not Medically Necessary:

Injectable naltrexone (Vivitrol) is considered not medically necessary for the treatment of alcohol dependence (alcohol use disorder) or opioid dependence (opioid use disorder) when the criteria above are not met and for all other indications.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

HCPCS  
J2315 Injection, naltrexone, depot form, 1 mg [Vivitrol® ]
   
ICD-10 Diagnosis  
F10.10-F10.19 Alcohol abuse
F10.20-F10.29 Alcohol dependence
F10.92-F10.99 Alcohol use, unspecified
F11.10-F11.19 Opioid abuse
F11.20-F11.29 Opioid dependence
F11.90-F11.99 Opioid use, unspecified
Z71.41 Alcohol abuse counseling and surveillance of alcoholic
   
Discussion/General Information

According to the 2014 National Survey on Drug Use and Health (NSDUH), approximately 21.5 million Americans met the diagnostic criteria for a substance use disorders; 17 million of which had an alcohol use disorder and 7.1 million had an illicit drug use disorder (2.6 million had co-occurring alcohol and illicit drug use disorders) (Substance Abuse and Mental Health Services Administration [SAMHSA], 2014). The Diagnostic and Statistical Manual, 5th Edition (DSM-5), introduced in 2013, simplified the diagnosis of drug and alcohol problems to substance use disorders. The updated diagnostic terminology, alcohol use disorder (moderate to severe subtype) and opioid use disorder (moderate to severe subtype), subsume alcohol dependence and opioid dependence, respectively (American Psychiatric Association [ASA], 2013; American Society of Addiction Medicine [ASAM], 2015; SAMHSA, 2015a; SAMHSA, 2015b).

The United States (U.S.) Food & Drug Administration (FDA) approved extended-release, injectable naltrexone (Vivitrol) for treatment of alcohol dependence (2006) for individuals who are able to abstain from alcohol in an outpatient setting prior to initiation of treatment with Vivitrol. Naltrexone was later FDA approved for preventing opioid dependence relapse, following opioid detoxification (2010). Vivitrol is administered via intramuscular injection (IM) and generally produces a sufficiently sustained effect for approximately 30 days (FDA PI Label, 2015). Vivitrol is the only FDA approved medication indicated for both alcohol dependence (alcohol use disorder) and opioid dependence (opioid use disorder). Although the prescribing information for Vivitrol is based on a diagnosis of alcohol or opioid dependence, treatment with Vivitrol should be available to individuals given a diagnosis of alcohol or opioid use disorder when guideline criteria apply.

Naltrexone is an opioid antagonist that binds to the opioid receptors, blocking the euphoric effects of exogenous opioids in those who are opioid dependent. The neurobiological mechanism by which it reduces alcohol consumption in alcohol dependent individuals is not entirely understood, but clinical data suggests that there is involvement of the endogenous opioid system (SAMHSA, 2015b).

Alcohol and opioid dependence (use disorders) can be treated by rehabilitation and medication. In some cases, oral medication does not achieve optimum therapeutic effect and for some individuals, this may be related to poor compliance in taking an oral drug.

Alcohol Dependence (Alcohol Use Disorder)

Alcohol use disorder is the cluster of cognitive, behavioral and physiological symptoms that replace alcohol abuse and alcohol dependence found in prior diagnostic categories. Symptoms of alcohol use disorder include symptoms related to tolerance and withdrawal.

The efficacy of injectable Vivitrol for the treatment of alcohol dependence (alcohol use disorder) was evaluated in a 24-week, placebo-controlled, multi-center, double-blind, randomized trial. The dose escalation study included 624 alcohol dependent subjects who were randomized into three outpatient treatment groups. Two treatment groups received monthly injections; one group received Vivitrol 190 mg (n=210) and the other group received Vivitrol 380 mg (n=205). The third group (n=209) received a matching volume placebo. Both treatment and placebo groups received psychosocial intervention. Compared with placebo, the group receiving Vivitrol 380 mg demonstrated a statistically significant 25% reduction in the event rate of heavy drinking days while the group receiving 190 mg of Vivitrol resulted in a 17% decrease. Gender and pretreatment abstinence each showed significant impact with the medication group on treatment outcome. Males and those who were alcohol abstinent for 7 consecutive days prior to treatment exhibited greater treatment effects. In contrast, the treatment effect was not evident in those who were actively drinking at the start of treatment (Garbutt, 2005).

Vivitrol is marketed as providing increased compliance as compared to the oral formulation of naltrexone. However, there are no trials to substantiate the claim that increased compliance leads to better outcomes through either increased rates of abstinence or increased time to a first heavy drinking day. A heavy drinking day is defined as five or more standard drinks consumed on a given day for males and four or more standard drinks consumed on a given day for females. The monthly injection method of administration addresses non-compliance which hampers efficacy of the oral medication regimen. Furthermore, the injection method reduces the first-pass delay imposed by hepatic metabolism necessitated by oral ingestion of the drug.

For many individuals, oral medication and rehabilitation successfully treat alcohol dependence (alcohol use disorder). The oral medications work in different ways:

When an individual who is on oral medication therapy fails to achieve and maintain alcohol abstinence, Vivitrol, the injectable form of naltrexone given monthly by a healthcare provider, may be an option. The Center for Substance Abuse Treatment (2009) notes Vivitrol is appropriate for individuals who "experience relatively low therapeutic effects from oral naltrexone, suggesting that a trial with an injectable preparation be done to rule out fluctuating blood levels of naltrexone as a possible cause."

Opioid Dependence (Opioid Use Disorder) 

The 2013 NSDUH further found that 1.9 million persons in America met DSM-4 criteria for opioid dependence (opioid use disorder) associated with prescribed opioids, and more than 0.5 million additional people met DSM-4 criteria for opioid dependence (opioid use disorder) associated with heroin use (ASAM, 2015). Opioid use is associated with an increased risk of mortality from overdose, trauma and depending on the route of administration, exposure to Human Immunodeficiency Virus (HIV), viral hepatitis and other infections agents.

The Vivitrol FDA labeled indication was expanded to include prevention of relapse to opioid dependence (opioid use disorder) following opioid detoxification by FDA approval on October 12, 2010. The product information label (2015) indicates prior to initiation of Vivitrol, the individual should be opioid-free for a "Minimum of 7-10 days, to avoid precipitation of opioid withdrawal that may be severe enough to require hospitalization." The manufacturer proposed that there is a need for a product to treat opioid dependency (opioid use disorder) that is not a controlled substance like methadone or buprenorphine both of which are agonist treatments. The approval was based on results from a double-blind randomized controlled trial (RCT; n=250). Enrollment criteria included no opioid use for at least 7 consecutive days prior to participation in the trial. A naloxone challenge test was performed prior to randomization. The group was either treated with Vivitrol (n=126) or placebo (n=124). In the study populations, 51% of the Vivitrol-treated individuals and 65% of the placebo-treated individuals did not complete the full 24 weeks of treatment. The common reason for discontinuation was lack of efficacy. Other reasons for discontinuation differed between the Vivitrol and placebo group, including withdrawal of consent (14%, 10%; respectively) and positive naloxone challenge testing (1%, 14%; respectively). The results showed that the percentages of individuals opioid free for 20 weeks were 23% for the placebo group and 36% for the Vivitrol group (p=0.022). Although the Vivitrol group had more participants with shorter duration of opioid dependence at baseline than those in the placebo group, a subgroup analysis showed a consistent treatment effect across both groups (Krupitsky, 2011). In an updated publication of this trial, authors report follow-up data 1 year after an open-label phase was initiated (18 months after trial inception). A total of 47 participants remained enrolled from the placebo arm and were switched to treatment at initiation of the open-label phase; 67 remaining in the treatment group continued. In total, 114 were enrolled in this phase; 71 were available for analysis at study end (37 from the original treatment arm and 32 from the original placebo arm). Authors reported of the 62.3% who completed the phase, 50.9% remained abstinent from opioids. No new safety concerns were observed (Krupitsky, 2013).

Injectable naltrexone was addressed in a feasibility study by Comer and colleagues (2006). The study (n=60) was a multicenter, randomized, double-blind, placebo-controlled, parallel-group, 8-week clinical trial. Participants received an initial inpatient detoxification, then oral naltrexone for 3 consecutive days to ensure participants were willing and able to tolerate the effects of injectable naltrexone. Participants were then randomized into groups receiving placebo, 192 mg or 384 mg naltrexone twice at 4 week intervals. The groups had physical evaluations twice weekly for treatment response and adverse events. Psychosocial evaluations were conducted twice during the study period. The highest percentage of negative urine samples occurred in the 384 mg group followed by the 192 mg group. Heroin craving was high in all three groups at the study's onset. Those who received either dose of naltrexone reported needing heroin less than the placebo group (p<0.001). The authors noted that opioid dependents pose a greater risk for Vivitrol adverse events than alcoholic individuals in that opioid abuse can involve injectable routes of administration increasing the chance of acquisition of HIV and thus the potential for compromised immunity is also elevated in this population. They also acknowledged that larger studies with more diverse populations are needed.

In a recent randomized, placebo-controlled trial (Sullivan, 2015) four treatment groups were studied to evaluate treatment retention following inpatient detoxification and oral naltrexone induction (n=125). The four treatment groups included (1) behavioral naltrexone therapy (BNT)+Vivitrol (n=23); (2) BNT+placebo injection (n=21); (3) compliance enhancement (CE)+Vivitrol (n=24); and (4) CE+placebo injection (n=21). BNT consisted of a manual-guided therapy incorporating motivational and cognitive-behavioral techniques that have been empirically validated for the treatment of substance use disorders. CE is also a manual-guided intervention but was delivered by a trained research psychiatrist and incorporates basic medication management, psychoeducation, problem-solving and 12-step principles. The study found that for low-severity heroin users, a single dose of Vivitrol improved the long-term retention of oral naltrexone treatment when coupled with BNT. Larger trials are warranted to evaluate the use of Vivitrol in this treatment approach to enhance compliance with oral naltrexone in heroin users.

In the guidelines published by SAMSHA (2015) on the clinical use of Vivitrol for opioid use disorder (dependence), the following guidance is given:

All medications for the treatment of the opioid use disorder should be prescribed as part of a comprehensive treatment approach that includes counseling and other psychosocial therapies delivered by a psychiatrist, psychologist, or professional counselor, as well as social support through participation in Narcotics Anonymous (NA) and other mutual help programs.

It additionally states,

Naltrexone functions as an opioid antagonist, whereas methadone is an opioid agonist and buprenorphine is an opioid partial agonist. Patients should abstain from using any opioids, including opioid-containing medicines, for a minimum of 7 to 10 days before starting extended-release injectable naltrexone to avoid precipitation of opioid withdrawal. Patients transitioning from buprenorphine or methadone may be vulnerable to precipitation of withdrawal symptoms for as long as 2 weeks.

Use of Vivitrol is not without complications. Unlike oral medication, when an adverse event occurs, the oral medication is discontinued. However, when an adverse event occurs with an extended-release injectable drug, stopping the drug action is much more difficult. In a review by Johnson (2006), it was noted the "…depot formulation cannot be removed from the body once injected and any allergic-type reactions that developed would be prolonged due to its long duration of action…". There is a receptor blockade drop off prior to subsequent Vivitrol injections making opioid receptors vulnerable if the individual ingests opioids. Pain management poses a problem when narcotics are necessary during Vivitrol treatment. Inadvertent drug withdrawal or overdose can occur.

Adverse Events and Warnings
Warnings and precautions from the FDA Product Information Label (2015) include the following:

Definitions

Agonist: A drug that binds to a receptor of a cell and triggers a response by the cell. An agonist often mimics the action of a naturally occurring substance.

Antagonist: A substance that tends to nullify the action of another, as a drug that binds to a cell receptor without eliciting a biological response, blocking binding of substances that could elicit such responses.

Detoxification: The medically supported transition to an alcohol or opioid-free state.

Endogenous: Originating or produced within the body.

Exogenous: Originating from outside the body; derived externally.

First-pass hepatic metabolism: When an oral medication undergoes passage through the gut and liver before reaching the systemic circulation; the concept provides information about the therapeutic effect of an orally administered drug versus administration via intramuscular or intravenous injection. 

Naloxone challenge test: A test in which naloxone is administered to verify current opioid dependence. Withdrawal symptoms evoked by naloxone's antagonist interaction with opioids confirm an individual's current dependence.

Opioid: Natural or synthetic substances that act at one of the three main opioid receptor systems (mu, kappa, delta). Opioids can have analgesic and central nervous system (CNS) depressant effects as well as the potential to cause euphoria.

References

Peer Reviewed Publications:

  1. Anton RF, O'Malley SS, Ciraulo DA, et al. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA. 2006; 295(17):2003-2017.
  2. Ciraulo DA, Dong Q, Silverman BL, et al. Early treatment response in alcohol dependence with extended-release naltrexone. J Clin Psychiatry. 2008; 69(2):190-195.
  3. Comer SD, Sullivan MA, Yu E, et al. Injectable, sustained-release naltrexone for the treatment of opioid dependence: a randomized, placebo-controlled trial. Arch Gen Psychiatry. 2006; 63(2):210-218.
  4. Dunbar JL, Turncliff RZ, Dong Q, et al. Single- and multiple-dose pharmacokinetics of long-acting injectable naltrexone. Alcohol Clin Exp Res. 2006; 30(3):480-490.
  5. Garbutt JC, Kranzler HR, O'Malley SS, et al. Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial. JAMA. 2005; 293(13):1617-1625.
  6. Johnson, BA. A synopsis of the pharmacological rationale, properties and therapeutic effects of depot preparations of naltrexone for treating alcohol dependence. Expert Opin Pharmacother. 2006; 7(8):1065-1073.
  7. Krupitsky E, Nunes EV, Ling W, et al. Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial. Lancet. 2011; 377(9776):1506-1513.
  8. Lee JD, Friedmann PD, Kinlock TW, et al. Extended-Release Naltrexone to Prevent Opioid Relapse in Criminal Justice Offenders. N Engl J Med. 2016. 31; 374(13):1232-1242.
  9. 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.
  10. Lucey MR, Silverman BL, Illeperuma A, O'Brien CP. Hepatic safety of once-monthly injectable extended-release naltrexone administered to actively drinking alcoholics. Alcohol Clin Exp Res. 2008; 32(3):498-504.
  11. O'Malley SS, Garbutt JC, Gastfriend DR, et al. Efficacy of extended-release naltrexone in alcohol-dependent patients who are abstinent before treatment. J Clin Psychopharmacol. 2007; 27(5):507-512.
  12. Pal R, Mendelson JE, Flower K, et al. Impact of prospectively determined A118G polymorphism on treatment response to injectable naltrexone among methamphetamine-dependent patients: an open-label, pilot study. J Addict Med. 2015; 9(2):130-135.
  13. Sullivan MA, Bisaga A, Glass A. Opioid use and dropout in patients receiving oral naltrexone with or without single administration of injection naltrexone. Drug Alcohol Depend. 2015; 147:122-129.
  14. Swainston Harrison T, Plosker GL, Keam SJ. Extended-release intramuscular naltrexone. Drugs. 2006; 66(13):1741-1751.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Agency for Healthcare Research and Quality (AHRQ). Pharmacotherapy for Adults with Alcohol-Use Disorders in Outpatient Settings; 2014. Available at: http://www.effectivehealthcare.ahrq.gov/ehc/products/477/1908/alcohol-misuse-drug-therapy-report-140513.pdf. Accessed on July 1, 2017.
  2. American Psychiatric Association (ASA). Substance-related and addictive disorders. 2013. Available at: http://www.dsm5.org/Documents/Substance%20Use%20Disorder%20Fact%20Sheet.pdf. Accessed on July 1, 2017.
  3. American Society of Addiction Medicine (ASAM) Federal guidelines for opioid treatment programs. 2015. Available at: http://store.samhsa.gov/shin/content//PEP15-FEDGUIDEOTP/PEP15-FEDGUIDEOTP.pdf. Accessed on July 1, 2017.
  4. Centers for Medicare and Medicaid Services. National Coverage Determination: outpatient hospital services for treatment of alcoholism. NCD #130.2, 130.6. Effective date not posted. Available at: http://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?NCDId=27&ncdver=1&DocID=130.2&from2=index_chapter_list.asp&list_type=&bc=gAAAAAgAAAAA&. Accessed on July 1, 2017.
  5. Center for Substance Abuse Treatment. Incorporating alcohol pharmacotherapies into medical practice: a review of the literature. Substance Abuse and Mental Health Services Administration (SAMHSA); 2009. (Treatment Improvement Protocol (TIP) Series, No. 49s.). Available at: http://www.ncbi.nlm.nih.gov/books/NBK65180/pdf/TOC.pdf. Accessed on July 1, 2017.
  6. Lobmaier P, Kornor H, Kunoe N, Bjorndal A. Sustained-release naltrexone for opioid dependence. Cochrane Database Syst Rev. 2008; (2):CD006140.
  7. Kampman K, Jarvis M. American Society of Addiction Medicine (ASAM) National practice guideline for the use of medications in the treatment of addiction involving opioid Use. 2015. Available at: http://www.asam.org/docs/default-source/practice-support/guidelines-and-consensus-docs/asam-national-practice-guideline-supplement.pdf?sfvrsn=24#search="naltrexone". Accessed on July 1, 2017.
  8. Naltrexone. In: DrugDex® Evaluations (electronic version). Truven Health Analytics, Greenwood Village, CO. Updated March 27, 2017. Available at: http://www.micromedexsolutions.com. Accessed on June 30, 2017.
  9. Naltrexone Monograph. Lexicomp® Online, American Hospital Formulary Service® (AHFS® ) Online, Hudson, Ohio, Lexi-Comp., Inc. Last revised June 01, 2016. Accessed on June 06, 2016.
  10. Substance Abuse and Mental Health Services Administration (SAMHSA). Behavioral health trends in the United States: Results from the 2014 National Survey on Drug Use and Health; 2014. Available at: http://www.samhsa.gov/data/sites/default/files/NSDUH-FRR1-2014/NSDUH-FRR1-2014.pdf. Accessed on June 30, 2017. 
  11. Substance Abuse and Mental Health Services Administration (SAMHSA). Clinical use of extended-release injectable naltrexone in the treatment of opioid use disorder: A brief guide. 2015a. Available at: http://store.samhsa.gov/shin/content/SMA14-4892/SMA14-4892.pdf.  Accessed on June 30, 2017.
  12. Substance Abuse and Mental Health Services Administration (SAMHSA). Medication for the treatment of alcohol use disorder: A brief guide. 2015b. Available at: http://store.samhsa.gov/shin/content/SMA15-4907/SMA15-4907.pdf. Accessed on June 30, 2017.
  13. World Health Organization (WHO). Guidelines for the psychosocially assisted pharmacological treatment of opioid dependence. 2009. Available at: http://www.who.int/substance_abuse/activities/treatment_opioid_dependence/en/. Accessed on June 30, 2017. 
  14. Vivitrol [Product information], Cambridge, MA. Alkermes, Inc.; December 01, 2015. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021897s029lbl.pdf. Accessed on June 30, 2017.
Websites for Additional Information
  1. National Institutes of Health (NIH) National Institute on Alcohol Abuse and Alcoholism (NIAAA): Naltrexone or specialized alcohol counseling an effective treatment for alcohol dependence when delivered with medical management. May 2, 2006. Available at: http://www.nih.gov/news/pr/may2006/niaaa-02.htm. Accessed on June 30, 2017.
  2. Substance Abuse and Mental Health Services Administration's (SAMHSA). Available at: http://www.dpt.samhsa.gov/medications/naltrexone.aspx. Accessed on June 30, 2017.
Index

Acamprosate
Naltrexone
Vivitrol
XR-NTX (extended-release naltrexone)

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Document History
Status Date Action
Reviewed 08/03/2017 Medical Policy & Technology Assessment Committee (MPTAC) review.
Reviewed 07/21/2017 Behavioral Health Subcommittee Review. References section updated.
Revised 08/04/2016 MPTAC review.
Revised 07/29/2016 Behavioral Health Subcommittee Review. Removal of oral naltrexone trial from MN criteria and added clarifying statements. Formatting in Clinical Indications section, Coding, Discussion/General Information and References sections updated.
Reviewed 02/04/2016 MPTAC review.
Reviewed 01/29/2016 Behavioral Health Subcommittee Review. Discussion/General Information and References sections updated. Removed ICD-9 codes from Coding section.
Revised 02/05/2015 MPTAC review.
Revised 01/30/2015 Behavioral Health Subcommittee Review. Clarified Criteria, Description, Discussion/General Information and References sections updated.
Reviewed 02/13/2014 MPTAC review.
Reviewed 02/07/2014 Behavioral Health Subcommittee Review. Discussion/General Information and References sections updated.
Reviewed 02/14/2013 MPTAC review.
Reviewed 02/08/2013 Behavioral Health Subcommittee Review. Discussion/General Information and References updated.
Reviewed 02/16/2012 MPTAC review.
Reviewed 02/10/2012 Behavioral Health Subcommittee Review. Discussion/General Information and References updated.
Revised 02/17/2011 MPTAC review.
Revised 02/11/2011 Behavioral Health Subcommittee Review. Medically necessary criteria revised to reflect FDA approval for opioid dependence. Description, Coding, Discussion and References updated.
Reviewed 05/13/2010 MPTAC review. References updated.
Reviewed 05/21/2009 MPTAC review. Place of service deleted, references updated.
Reviewed 05/15/2008 MPTAC review. References updated.
New 05/17/2007 MPTAC review. Initial guideline development.