The opioid withdrawal syndrome can easily be suppressed by administering any opioid with significant same-receptor agonism as the drug that originally produced the addiction. However, it is more useful to prevent opioid withdrawal symptoms pharmacologically with a nonaddicting drug. This approach furthers the goals of detoxification and abstinence. When circumstances force addicts to treat their withdrawal symptoms without opioids, they most commonly use alcohol and/or benzodiazepines. The main disadvantage to this approach is that because of the lack of cross-tolerance between opioids and alcohol/benzo-diazepines, blockade of withdrawal symptoms requires the ingestion of large amounts of these sedatives to achieve suppression. Clonidine, a presynaptic alpha2 agonist originally marketed as an antihypertensive, represents an effective and safer alternative for the treatment of opiate withdrawal symptoms (Koob & Bloom, 1988; O'Connor et al., 1995). It can partially suppress many (but not all) elements of opioid withdrawal, so that the risk of immediate relapse is reduced (Jasinski, Johnson, & Kocher, 1985). Clonidine is most effective for those motivated persons who are involved in their overall treatment program and are using small amounts of opioid (Kleber et al., 1985). Outpatients who are on less than 20 mg of methadone per day and detoxifying at rates approaching 1 mg per day make ideal candidates for the adjunctive use of clonidine. These individuals can be given 0.1 to 0.3 mg up to three or four times a day throughout the withdrawal period, with good effect. Sometimes only small amounts of clonidine (on the order of 0.1 mg per day) may be useful, to be administered at the time of day that is most difficult for the patient. Clonidine is not generally useful beyond 2 weeks after the last dose of methadone (Gold, Pottash, Sweeney, & Kleber, 1980). A transdermal delivery system (Catapres-TTS), which is active over a 7-day period, is useful in the outpatient setting, because the indiscriminate use of large amounts of clonidine by the individual can be avoided, thus limiting the risk of adverse reactions (Spencer & Gregory, 1989). Hypotension and bradycardia are major side effects of clonidine, and can be profound. Lethargy is also common, but this effect can be useful at night.

In a hospital setting, clonidine has been used in concert with abstinence and an opioid antagonist to produce tolerable withdrawal and detoxification in a short period (5-6 days) for persons on methadone doses of 50 mg or less; various protocols exist (Charney, Heninger, & Kleber, 1986). This treatment can be complicated by delirium and/or psychosis (Brewer, Rezae, & Bailey, 1988). The treatment involves sudden cessation of opioid ingestion, precipitation of an acute abstinence syndrome with an opioid antagonist, and aggressive treatment of the withdrawal symptoms with large doses of clonidine throughout the day and benzodiazepines at night. Over the 5- to 6-day course, the clonidine and opioid blocker are tapered. Naltrexone with buprenorphine has been used successfully (Cheskin, Fudala, & Johnson, 1994; Gerra et al., 1995), and this combination produces the shortest and least severe withdrawal interval. Benzo-diazepines are not routinely used after the second or third night, and there is a risk of synergistic respiratory suppression in the coadministration of benzo-diazepines and full or partial opiate agonists. A more time-consuming approach would involve abstinence not precipitated suddenly by an opioid blocker and more aggressive use of clonidine than would be practical in an outpatient setting. These approaches are appropriate for those individuals who are highly motivated to become drug-free quickly in a controlled manner, for reasons related to employment or to impending incarceration.

It is generally recognized that abrupt withdrawal from opioids is almost always followed by relapse. The risk of relapse is less with a rational plan for detoxification, using decreasing amounts of an opioid over time. In this way, the withdrawal syndrome is minimized, rendering the individual more responsive to other, nonpharmacological therapies during this high-risk phase of treatment. In the United States, the usual first step toward detoxification is to switch the addicted individual to a longer acting opioid. Methadone is the obvious choice, with a half-life of 15-25 hours in comparison to 2-3 hours for morphine, heroin, and many other commonly available opioids. In addition to methadone, LAAM was approved in 1993 as a maintenance treatment agent for opioid dependence; however, because of growing awareness of life-threatening arrhythmias, it is no longer used. Generally speaking, for every 2 mg of heroin, 1 mg of methadone may be substituted. The same is true for 4 mg of morphine, 20 mg of meperidine, 50 mg of codeine, and 12 mg of oxycodone. Other equivalencies are available in standard pharmacology texts.

Usually, it is not possible to know how much heroin a user is actually administering in a 24-hour period because of the impure nature of the product available on the street. Experience shows that an initial dose of 20-30 mg of methadone will block most withdrawal symptoms in moderate to heavy users who may inject from four to 12 or more times in 24 hours. For those who inject two to three times per day, a starting dose of 10-20 mg of methadone is usually sufficient. Methadone may be given every 24 hours, and the dose may be adjusted daily up or down by 5- to 10-mg increments, based on observable symptoms of withdrawal or intoxication. The peak plasma levels from metha-done occur between 2 and 6 hours after ingestion. Over time, methadone becomes tissue-bound throughout the body, creating a buffer against significant withdrawal in those persons who occasionally miss a daily dose. This phenomenon also facilitates a smooth detoxification over time as daily dosage is reduced. Stabilization on methadone can usually be accomplished with 20-50 mg daily. Detoxification may then begin. Federal law allows the use of opiates for detoxification only when doses are dispensed directly by the provider. Of course, methadone may only be dispensed for the treatment of opiate addiction by a licensed clinic.

For the hospitalized patient, federal law allows the administration of opiates for a maximum of 3 days, or longer as required, if the patient is primarily admitted for a general medical condition. Any opiate may be selected, but common choices are methadone, buprenorphine, or propoxyphene.

Regulations at the various levels of government historically mandated that outpatient detoxification be accomplished within 21 days. Unfortunately, this period was too short for all but the most minimally addicted individuals and frequently resulted in relapse. Fortunately, the regulations have been liberalized, largely because of recognition that HIV/AIDS is spread very rapidly among intravenous drug abusers who share needles. Changes in the regulations are intended to allow more addicts to enter and stay in treatment. As a practical matter, 30 days is the minimum amount of time required for successful detoxification, and often 45 days or more may be needed; relapse still is a definite risk. For those individuals with long abuse histories and high doses of opioids, 6 months or more may be required. Veteran opioid users are extremely sensitive to even small reductions in their daily dose of methadone. The critical stage of detoxification occurs below 20 mg of methadone daily, and the use of clonidine is helpful in blocking withdrawal symptoms. In some individuals, detoxification is successful, but symptoms of insomnia, malaise, irritability, fatigue, gastrointestinal hypermotility, and even premature ejaculation may persist for months. Clonidine is less effective in this situation.

Ultrarapid detoxification (URD) under anesthesia, which has received a great deal of recent attention and controversy, is not generally accepted as cost-effective in the long term but may be useful in special cases (Hensel & Kox, 2000). Naltrexone maintenance, which probably is underutilized as a general treatment technique, has been utilized in follow-up after URD (Rabinowitz, Cohen, & Atias, 2002).

Acupuncture may be helpful in detoxification, as well as maintenance, although scientific studies are limited (Otto, 2003).

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