Ultra Rapid Detoxification (UROD)

Number: 0317

Policy

Aetna considers ultra rapid detoxification (UROD) experimental and investigational as a clinical detoxification treatment and for all other indications because its effectiveness has not been established.

Background

Detoxification, although important, is only the first step in long-term relapse prevention treatment of opiate addiction.  Proven detoxification procedures presently involve a gradual withdrawal followed by medication and long-term psychosocial support in producing long-term abstinence from illicit opioid use.

In the ultra rapid detoxification (UROD) procedure, opiate detoxification is induced by the use of a bolus injection of very high doses of an opiate antagonist (naloxone) under general anesthesia or heavy sedation followed by a slow infusion of low-dose naloxone.  The 4-hour procedure is carried out in an intensive care unit and the patient requires 1 to 2 days of hospitalization for a full treatment protocol.  Proponents of the procedure claim that complete accelerated detoxification is attained, the patient experiences no withdrawal symptoms, physical dependency is eliminated, and the psychological craving for drugs is greatly reduced.  However, experts prominent in the field of opiate addiction in 1996 reported their concerns about UROD stating that detoxification is not a cure for opiate addiction and that medication without psychosocial support has little impact on opiate addiction.

There is no scientifically-based evidence in the medical literature to substantiate that UROD is safe and effective as a clinical detoxification treatment.  There is a reported risk of serious adverse events, including death with the use of anesthetics, making the risk:benefit ratio of this detoxification procedure unacceptable.  Besides direct causality associated with inadvertent anesthetic over-dose, there is also the risk of indirect causality related to possible aspiration and choking from emesis that may occur when an anesthetized or heavily sedated individual is detoxified while asleep.

To date, only 1 double-blind study and few research reports have systematically documented the nature of the UROD procedure and its safety and efficacy for both immediate detoxification and longer term relapse prevention.  No double-blind studies indicate that ultra-short detoxification procedures are more successful in decreasing relapse to opiates than longer duration treatments.

The California Technology Assessment Forum (CTAF, 2002) has determined that rapid and ultra rapid opiate detoxification does not meet CTAF's assessment criteria.  The CTAF assessment concluded: "Existing published studies of rapid detoxification and ultra rapid detoxification have raised the prospect of new approaches to opioid detoxification.  However, methodological limitations limit the generalizability of the studies, and thus these techniques, to widespread clinical application.  Lack of randomization and blinding, sample size variations, different clinical profiles of studied patients, and diverse pharmacologic treatment used and clinical settings, preclude comparisons between studies and the drawing of any firm conclusions regarding the efficacy and safety of these procedures.  The post-detoxification relapse rate for these techniques appears to be quite variable.  The most suitable patients for these procedures must still be defined.  Both rapid and ultra rapid opioid detoxification must undergo further scientific evaluation in randomized, controlled trials to determine whether their clinical effectiveness and safety outweigh their risks.  Further research is also warranted to evaluate longer-term outcomes and compare these methods with other treatments for opioid addiction such as methadone maintenance supervised methadone taper, naltrexone maintenance, counseling-supported abstinence, and toxicological surveillance."

A structured evidence review by Gowing et al (2010) reached the following conclusions about UROD: "Heavy sedation compared to light sedation does not confer additional benefits in terms of less severe withdrawal or increased rates of commencement on naltrexone maintenance treatment.  Given that the adverse events are potentially life-threatening, the value of antagonist-induced withdrawal under heavy sedation or anaesthesia is not supported.  The high cost of anaesthesia-based approaches, both in monetary terms and use of scarce intensive care resources, suggest that this form of treatment should not be pursued."

An UpToDate review on “Opioid detoxification during treatment for addiction” (Weaver and Hopper, 2013) stated that “Serious complications have been reported with anesthesia-assisted rapid detoxification, and a randomized trial did not find it to be superior to buprenorphine-assisted rapid detoxification, or clonidine-assisted detoxification.  In this study, the three detoxification strategies resulted in no differences in rates of completion of inpatient detoxification or completion of the treatment program at 12 weeks; the overall dropout rate was 82 percent.  There were three serious adverse events, all occurring in the anesthesia group.  A systematic review of five randomized trials found that the potential serious harms and costs of heavy sedation or anesthesia, and lack of benefit from this procedure, do not support this method of detoxification.  We believe that ultrarapid opiate detoxification is not a medically sound therapy and should be avoided".

Guidelines from the National Institute for Health and Clinical Excellence (2007) stated that "Ultra-rapid and rapid detoxification using precipitated withdrawal should not be routinely offered.  This is because of the complex adjunctive medication and the high level of nursing and medical supervision required".  The guidelines also stated that "Ultra-rapid detoxification under general anaesthesia or heavy sedation (where the airway needs to be supported) must not be offered.  This is because of the risk of serious adverse events, including death".

Blum et al (2015) noted that over the past 20 years, the prescription of high dose opiate therapy has continued to accelerate in an attempt to treat patients with chronic pain.  This presents a substantial challenge when patients on high dose opiate therapy require surgery, as opiate pain relief is a cornerstone of post-operative pain management.  These patients have exceptionally challenging pain to control.  This is likely due to down-regulation of existing opiate receptors and the reluctance of clinicians to increase doses of opiates to exceptionally high levels to facilitate pain relief.  These researchers hypothesized that using the method of UROD, it would be possible to rapidly increase the number of opiate receptors and return patients to a more naive state, which would be susceptible to exogenous opiate administration.  Validation of this hypothesis is supported by 2 mechanisms, the first of which were reports of patients that underwent UROD for opiate addiction that subsequently suffer respiratory arrests when beginning to rapidly abuse opiates shortly after treatment.  Additionally there were data demonstrating the tapering of opiate therapy prior to elective surgery resulted in better pain control.  The authors concluded that they hypothesized that patients on chronic high dose opiates could obtain substantially better pain relief if they underwent UROD prior to surgery.  This technique could be administered shortly before surgery and may dramatically improve the patients' recoveries.  This hypothesis need to be tested in well-designed studies.

Qiu et al (2016) examined alterations of resting brain function in codeine-containing cough syrups (CCS) dependent individuals before and after UROD under general anesthesia combined with naltrexone treatment (NMT).  A total of 14 CCS-dependent individuals were scanned using resting-state fMRI.  After UROD and 2 weeks of NMT, CCS-dependent individuals were re-scanned; 14matched controls were studied at baseline and compared.  The amplitude of low frequency fluctuations (ALFF) and seed-based functional connectivity (FC) were used to characterize resting-state cerebral function.  After UROD and 2 weeks of NMT, CCS-dependent individuals had increased ALFF in the bilateral para-hippocampal gyrus and right medial orbito-frontal cortex (mOFC), decreased ALFF in the left post-central gyrus (PoCG), left middle occipital cortex (MOC) and left dorsal lateral prefrontal cortex (DLPFC), and reduced FC between right mOFC and right DLPFC, and between left DLPFC and left inferior parietal lobe relative to pre-treatment.  Decreased ALFFs in the left PoCG and left MOC were associated with decreased withdrawal syndrome severity in CCS-dependent individuals.  The authors concluded that they provided the first report describing how regional and integral synchronous neural activity occurred after UROD and short-term NMT, accompanied by decreased withdrawal syndrome severity.  They stated that these findings contributed to the understanding of complex systems involved in UROD-NMT effects.  This was a small study (n = 14 in the treatment group), and its findings were confounded by the combinational use of UROD and NMT. 

The Canadian Agency for Drugs and Technologies in Health’s guideline on “Rapid and ultra-rapid detoxification in adults with opioid addiction” (2016) stated that “Overall, the evidence on clinical effectiveness and safety of UROD and evidence-based guidelines associated with the use of UROD in adults with opioid addiction were limited and of low quality …. The included guideline recommended against the use of UROD, due to high risk for adverse events.  No evidence on ROD or on cost-effectiveness of ROD and UROD was identified”.


Table: 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 "+":

Ultra rapid detoxification:

No specific code

Other HCPCS codes related to the CPB:

J2310 Injection, naloxone HCl, per 1 mg [not covered when used for UROD]

ICD-10 codes not covered for indications listed in CPB:

F11.10 - F11.19 Opioid abuse
F11.20 - F11.29 Opioid dependence
T40.0X1+ - T40.0X4+
T40.1X1+ - T40.1X4+
T40.2X1+ - T40.2X4+
T40.3X1+ - T40.3X4+
T40.4X1+ - T40.4X4+
T40.601+ - T40.604+
T40.691+ - T40.694+
Poisoning by opiates and related narcotics
T40.0X5+
T40.2X5+
T40.4X5+
T40.605+
T40.695+
Adverse effects of other opiates and related narcotics
T40.3X5+ Adverse effects of methadone

The above policy is based on the following references:

  1. National Institute on Drug Abuse (NIDA). NIDA Scientific Report of Ultra Rapid Detoxification with Anesthesia (UROD): Opinion of the Consultants and Criteria Relating to Evaluating the Safety and Efficiency of UROD. Bethesda, MD: National Institutes of Health (NIH); February 23, 1996.
  2. Mannelli P, De Risio S, Pozzi G, et al. Serendipitous rapid detoxification from opiates: The importance of time-dependent processes. Addiction. 1999;94(4):589-591.
  3. Lawental E. Ultra rapid opiate detoxification as compared to 30-day inpatient detoxification program -- a retrospective follow-up study. J Subst Abuse. 2000;11(2):173-181.
  4. O'Connor PG, Kosten TR. Rapid and ultrarapid opioid detoxification techniques. JAMA. 1998;279(3):229-234.
  5. Rosenberg H, Melville J, McLean PC. Acceptability and availability of pharmacological interventions for substance misuse by British NHS treatment services. Addiction. 2002;97(1):59-65.
  6. Badenoch J. A death following ultra-rapid opiate detoxification: The General Medical Council adjudicates on a commercialized detoxification. Addiction. 2002;97(5):475-477.
  7. American Society of Addiction Medicine. Public policy statement on opioid antagonist agent detoxification under sedation or anesthesia (OADUSA). J Addictive Dis. 2000;19:109-112.
  8. Gowing L, Ali R, White J. Opioid antagonists with minimal sedation for opioid withdrawal. Cochrane Database Syst Rev. 2009;(4):CD002021.
  9. Gowing L, Ali R, White J. Opioid antagonists under heavy sedation or anaesthesia for opioid withdrawal. Cochrane Database Syst Rev. 2010;(1):2022. 
  10. California Technology Assessment Forum (CTAF). Rapid and ultrarapid opiate detoxification. Technology Assessment. San Francisco, CA: CTAF; June 12, 2002.
  11. Jhirwal OP, Basu D. Ultra-rapid opioid detoxification procedures in India: How far they are ethical? Indian J Med Sci. 2004;58(3):132-133.
  12. Camarasa X, Khazaal Y, Besson J, Zullino DF. Naltrexone-assisted rapid methadone discontinuation: A pilot study. Eur Addict Res. 2007;13(1):20-24.
  13. Naderi-Heiden A, Naderi A, Naderi MM, et al. Ultra-rapid opiate detoxification followed by nine months of naltrexone maintenance therapy in Iran. Pharmacopsychiatry. 2010;43(4):130-137.
  14. National Collaborating Centre for Mental Health. Drug misuse: Opioid detoxification. National Clinical Guideline 52. London, UK: National Institute for Health and Clinical Excellence (NICE); July 2007.
  15. Sigmon SC, Bisaga A, Nunes EV, et al. Opioid detoxification and naltrexone induction strategies: Recommendations for clinical practice. Am J Drug Alcohol Abuse. 2012;38(3):187-199.
  16. Weaver MF, Hopper JA. Opioid detoxification during treatment for addiction. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed February 2013.
  17. Fontaine E, Godfroid IO, Guillaume R. Ultra-rapid detoxification of opiate dependent patients: Review of the literature, critiques and proposition for an experimental protocol. Encephale. 2001;27(2):187-193.
  18. Salimi A, Safari F, Mohajerani SA, et al. Long term relapse of ultra-rapid opioid detoxification. J Addict Dis. 2014;33(1):33-40.
  19. Blum JM, Biel SS, Hilliard PE, Jutkiewicz EM. Preoperative ultra-rapid opiate detoxification for the treatment of post-operative surgical pain. Med Hypotheses. 2015;84(6):529-531.
  20. Forozeshfard M, Hosseinzadeh Zoroufchi B, Saberi Zafarghandi MB, et al. Six-month follow-up study of ultrarapid opiate detoxification with naltrexone. Int J High Risk Behav Addict. 2014;3(4):e20944.
  21. Qiu YW, Jiang GH, Su HH, et al. Short-term UROD treatment on cerebral function in codeine-containing cough syrups dependent male individuals. Eur Radiol. 2016;26(9):2964-2973.
  22. Canadian Agency for Drugs and Technologies in Health (CADTH). Rapid and ultra-rapid detoxification in adults with opioid addiction: A review of clinical and cost-effectiveness, safety, and guidelines. CADTH Rapid Response Reports. Ottawa, ON: CADTH; January 2016.