Detoxification: Long-term, Short-term, Rapid and Ultra-rapid - Opioid Use Disorders

Detoxification: Long-term, Short-term, Rapid and Ultra-rapid

Detoxification from opioids, for most patients, is only the first phase of a longer treatment process. Most patients seeking treatment have been addicted to heroin or other opioids for 2 to3 years, and some for 30 years or more. Thus, treatment usu-ally involves changes in individuals’ lifestyles. Though generally ineffective in achieving sustained remission unless combined with long-term pharmacological, psychosocial, or behavioral therapies, detoxification alone continues to be widely used. It is sometimes the only option available for individuals who do not meet the Food and Drug Administration (FDA) criteria for, do not desire, or do not have access to agonist medications such as methadone or methadyl acetate (LAAM).

Pharmacologic detoxification is generally ineffective in achieving sustained remission unless combined with long-term pharmacologic, psychosocial, or behavioral therapies.

The detoxification process may include use of opioid ago-nists (e.g., methadone); partial agonists (e.g., buprenorphine); an-tagonists (e.g., naloxone, naltrexone); or nonopioid alternatives such as clonidine, benzodiazepines, or nonsteroidal anti-inflam-matory agents. In many cases, one or more medications are com-bined, such as naloxone with clonidine and a benzodiazepine. The choice of detoxification medication and the duration of the process depend on numerous factors including patient prefer-ence, clinician expertise and experience, type of treatment facil-ity, licensing and available resources. Ultimately, however, the goal of detoxification is the achievement (and maintenance) of a drug-free state while minimizing withdrawal. Unfortunately de-toxification for some individuals appears to be used in a punitive manner or as an expedient means to achieve a drug-free state rap-idly with no follow-up pharmacological or behavioral therapy.

Opioid detoxification paradigms are frequently catego-rized according to their duration: long-term (typically 180 days), short-term (up to 30 days), rapid (typically 3–10 days) and ultra-rapid (1–2 days). These temporal modifiers provide only a coarse description of the paradigm; they do not provide other important information such as the medications used or whether postdetoxi-fication pharmacological, psychosocial, or behavioral therapy is provided. However, some general guidelines typically apply.

The most common detoxification protocols, and those for which the most data are available, are the long-term (typically 180 days) and short-term (up to 30 days) paradigms involving the use of methadone. Unfortunately, these strategies have not gen-erally been associated with acceptable treatment response using relapse to opioid use as an outcome criterion. Results from more rapid detoxification evaluations using short- or even intermediate term (up to 70 days) medication-tapering protocols are even less encouraging and have an unfortunately low success rate. It should be noted, however, that provision of additional services such as counseling, behavioral therapy, treatment of underlying psychopathologies, job skills training and family therapy to ad-dress concomitant treatment needs can improve outcome though success rates remain low, even with these services.

Rapid detoxification involves the use of an opioid antago-nist, typically naltrexone or naloxone, in combination with other medications (such as clonidine and benzodiazepines) to mitigate the precipitated withdrawal syndrome. The procedure is intended to expedite and compress withdrawal in order to minimize dis-comfort and decrease treatment time. Ultra-rapid detoxification also utilizes other medications, along with an opioid antagonist, to moderate withdrawal effects. However, rather than individuals being awake as they are during the rapid detoxification process, they are placed under general anesthesia or, alternatively, deeply sedated. A recently published study (Hensel and Kox, 2000) in which ultra-rapid detoxification was followed by naltrexone maintenance and supportive psychotherapy, indicated that 49 ofpatients were opioid abstinent 12 months following detoxifica-tion. However this study and other studies involved self-selected individuals thus making it impossible to know the overall effec-tiveness of this type of intervention.

A major concern regarding ultra-rapid detoxification is the occurrence of potentially serious adverse effects, such as respira-tory distress or other pulmonary and renal complications dur-ing or immediately following the procedure. A high frequency of vomiting has also been reported. The degree to which serious adverse events occur has not yet been determined. In spite of the emerging evidence about serious adverse events, ultra-rapid de-toxification may be appropriate for highly selected individuals based on considerations of previous treatment history, economic factors and patient choice. However, patients seeking this treat-ment must be thoroughly informed that serious adverse events, including sudden unexpected deaths, have occurred in associa-tion with this procedure and its use should probably be limited to inpatient settings where monitoring by anesthesiologists and other highly trained staff is available.

Buprenorphine, a μ-opioid partial agonist, has also been used as a detoxification agent. Results from inpatient studies have shown that it is safe, well tolerated and mitigates opioid withdrawal signs and symptoms over a range of doses and detoxi-fication schedules. Clonidine, an alpha-2-adrenergic agonist, has been shown to suppress many of the autonomic signs and symp-toms of opioid withdrawal. It can cause sedation and hypotension but has been used with few problems when appropriate monitor-ing is available. It does not suppress the subjective discomfort of withdrawal and, probably for that reason, is not well accepted by most patients.

Other alpha-2-adrenergic agonists have also been evalu-ated in order to find agents that are as or more effective, but less sedating and hypotensive than clonidine. Lofexidine, a medica-tion that was originally promoted as an antihypertensive but was shown to lack clinically significant hypotensive effects, has been the most studied. When compared with clonidine, it has been found equally to suppress autonomic signs and symptoms of opioid withdrawal but with less sedation and hypotension. When compared with methadone dose tapering, lofexidine detoxifica-tion was associated with opioid withdrawal effects that peaked sooner, but resolved to negligible levels more rapidly. Data re-garding the potential effectiveness of guanabenz and guanfacine have also been reported, but further studies are required to as-sess the potential utility of these medications. In summary, recent studies have shown that lofexidine is likely to be a useful opioid detoxification agent whose efficacy approximates that of cloni-dine but with fewer side effects.