Methods of detoxification and their role in treating patients with opioid dependence.

OPIOID DEPENDENCE AND ITS ASSOCIATED MORBIDity, mortality, and social costs continue to plague societies around the world. Opioid dependence is characterized by physical dependence as evidenced by tolerance and withdrawal and by behavioral problems, including the inability to control opioid use, opioid use despite adverse consequences, and social dysfunction. The 2003 National Survey on Drug Use and Health reported that 3.7 million Americans had used heroin at some time in their lives. The Monitoring the Future Survey noted that approximately 1.2% of 10thand 12th-graders reported ever using heroin in 2004. In addition, the recent trend of increasing abuse of prescription opioids including oxycodone, propoxyphene, hydrocodone, hydromorphone, and meperidine has been a major concern since the late 1990s. The National Survey on Drug Use and Health estimated that as of 2003, more than 31.2 million Americans had used narcotic pain relievers in a “nonmedicinal” manner sometime in their lives and 11.7 million were “past year” nonmedicinal users in 2003. The Monitoring the Future Survey indicated that 6.2% of 10th-graders and 9.3% of 12th-graders used hydrocodone and 3.5% of 10thgraders and 5.0% of 12th-graders used oxycodone in 2004. These statistics and the overall lack of access to highquality treatment resources for opioid-dependent individuals point directly to the urgent need to develop new treatment strategies for opioid dependence while expanding access to established treatment approaches known to be effective. Medication-basedtreatment foropioiddependenceconsists of2distinctapproaches:detoxificationandmaintenance. Detoxification involves the use of medications to bring a patient from an opioid-dependent to an opioid-free state. The medications used are designed to decrease withdrawal-related discomfort andcomplications.Maintenance therapy involves the substitutionofanabusedopioid suchasheroinornarcotic analgesics, which are often used intravenously or intranasally several times a day, by a medically prescribed opioid such as methadone or buprenorphine that can be taken orally and administered once a day in combination with counseling. Detoxification-based treatments for opioid dependence have been studied over many decades. Among the early treatment approaches were some in which opioid withdrawal occurred in patients who were rendered unconscious during detoxification. These treatments included “bromide sleep treatment,” “hibernation therapy,” and “insulin-induced hypoglycemia” and were subsequently noted to be ineffective and dangerous. More rational approaches using methadone and clonidine were demonstrated to be relatively safe and effective in the short term (measured in days) but of questionable long-term value due to exceedingly high dropout and relapse rates following detoxification. More recently, “rapid” detoxification techniques in which opioid withdrawal is precipitated by opioid antagonists such as naloxone or naltrexone have attempted to speed up the detoxification process to improve retention in withdrawal treatment and initiate induction of naltrexone to prevent relapse. Naltrexone, an orally administered opioid antagonist, is designed to prevent relapse by blocking the effects of opioids. The US Food and Drug Administration (FDA) approval of buprenorphine in 2002 for the treatment of opioid dependence (for both detoxification and maintenance) offers a new option for opioid detoxification, although data concerning its long-term effectiveness in detoxification are also lacking. In fact, all detoxification approaches are only partially effective in controlling the symptoms of opioid withdrawal and are often not followed with effective relapse prevention treatment. In a relatively new approach for treating opioid dependence, “ultrarapid” opioid detoxification is induced with an opioid antagonist while the patient is under anesthesia or heavy sedation. This approach offers patients the possibility of a rapid and “painless” withdrawal under anesthesia, after which they awaken in a non–opioid-dependent state, thereby, at least in theory, avoiding the discomfort of withdrawal. Thus, like the other “sleep” and “hibernation” therapies of the past, anesthesia-assisted detoxification is designed to limit patients’ withdrawal-related discomfort by rendering them unconscious during withdrawal. However, the effectiveness and safety of anesthesiaassisted detoxification have been called into question. A systematic review published in 1998 noted a lack of evidence to support this approach: of the 9 studies published in peerreviewed journals, only 3 included a control group, only 2