Clonidine

While not itself life-threatening, the opioid WITHDRAWAL syndrome is extremely unpleasant and contributes to further opioid use and relapse. HEROIN addicts report that the acute withdrawal syndrome begins in approximately eight hours after their last injection andincludes the following: craving for the drug, anxiety, perspiration, perspiration with hot and cold flashes, tearing of the eyes and nose, restlessness, problems sleeping, problems falling asleep, goose bumps, aching bones and muscles, loss of appetite, nausea, vomiting, diarrhea, abdominal cramps, spontaneous yawning, and a group of symptoms called flu-like.

During the later years of the nineteenth century and early years of the twentieth, some cures for this opioid withdrawal syndrome have been far worse than the withdrawal itself—with some actually causing death. Soon after it became available in the mid-nineteenth century, injectable MORPHINE was proposed as a treatment for opium eating; then heroin or COCAINE were, in the late nineteenth century, proposed as cures for morphine addiction. From the mid-twentieth century until the 1970s, most medical treatment of the opioid withdrawal syndrome involved either gradual reduction of the dose of opioid or the substitution of METHADONE, followed by its gradual reduction. In 1978, Gold and coworkers proposed that the nonopiate antihypertensive clonidine could be an effective nonopiate treatment for opiate withdrawal distress. The scientific basis for the proposition that clonidine would be useful was based on the hypothesis that the opiate withdrawal syndrome was caused by hyperactivity or hyperexcitability of a specific brain nucleus composed of noradrenergic neurons, called the locus coeruleus (LC). There was considerable neuroscientific research to support this withdrawal hypothesis and the rationale for the efficacy of clonidine.

Since 1977/78, clonidine has been tried in numerous inpatient and outpatient opioid addict populations worldwide and studied by researchers in numerous well-controlled studies. In virtually all studies, clonidine has been shown to be a safe and effective nonopioid treatment that could control several aspects of opioid withdrawal. Clonidine, while having opiate-like effects in reversing several aspects of opiate withdrawal, is not an opiate and is therefore not subject to the burdensome regulatory CONTROLS that have been placed on the use of opioids. Clonidine has its most demonstrable effects on autonomic elements of opioid withdrawal: sweating, gastrointestinal complaints (cramps, diarrhea, nausea), and elevated blood pressure. It does not have substantial capacity to alleviate muscle aches, insomnia, or craving for opioids.

Research and clinical experiences since the original discoveries have (1) supported the notion of LC hyperactivity as one of the neural substrates for the opioid withdrawal syndrome; (2) supported the ef-ficacy of clonidine—establishing clonidine detoxi-fication as one of the standard treatments for adult opioid addicts—and extended it to neonates (newborns) and to alcohol, nicotine, and other drug withdrawals that share a preponderance of behaviours with opioid withdrawal; (3) demonstrated that abstinence could be maintained by some opioid addicts and that others could benefit from antagonist therapy with NALTREXONE, thanks to clonidine or accelerated clonidine-naltrexone detoxification; (4) led to considerable progress in the understanding of the critical cellular event causing LC hyperactivity in opioid withdrawal and hypoactivity in the presence of clonidine or opioid agonists; and (5) led to the rapidly expanding clinical armamentarium available to treat addicts on the basis of rodent and primate studies.

Detoxification of opioid addicts with clonidine has been used to facilitate the transition from chronic opioid administration to naltrexone (a long-acting opioid ANTAGONIST) or to drug-free status. Naltrexone possesses opioid-blocking action at all opioid-receptor sites in the body and brain, rather than having an affinity for a specific type of opioid receptor. It is a useful medication for those patients willing to take it to prevent relapse. When recovering addicts take naltrexone, they make opioid effects unavailable to themselves. The affinity of naltrexone for the receptors is such that they are unable to feel the effects of heroin, methadone, or other exogenous opioids. While the original cloni-dine treatment protocol of Gold and his colleagues (1978a, b) facilitated the initiation of naltrexone by avoiding the extra ten-day wait required after the last methadone, an accelerated detoxification protocol has been developed using naltrexone and clonidine simultaneously. Since clonidine reduces precipitated withdrawal as well as the withdrawal that results from simply discontinuing chronic opioid administration, total withdrawal and naltrexone induction time has been shortened to six days with little loss in success rate (Charney, Heninger, & Kleber, 1986).

Clonidine has been tried with varying success in a number of medical problems where the behaviors, signs, and/or symptoms resemble those seen in opiate withdrawal or following LC electrical or chemical stimulation to a certain degree. Clonidine has also been tried in humans on the basis of noradrenergic hyperactivity in generalized and panic ANXIETY; obsessive-compulsive symptomatology; Gilles de La Tourette's syndrome; mania; ATTEN-TION DEFICIT DISORDER; narcolepsy; neuroleptic-induced akathisia; ALCOHOL withdrawal and NIC-OTINE withdrawal; and phaeochromocytoma. Clonidine's ANALGESIC effects have been rediscovered and given orally, transdermally (skin patches), epidurally (into the area around the spinal canal), and parenterally (by injection)—to decrease anesthetic requirements and to effect less respiratory depression than OPIOIDS alone.

Using clonidine for withdrawal distress allows the brain to reestablish normal homeostatic patterns when given as part of a long-term recovery program. It allows patients sufficient motivation to achieve and sustain drug-free existence.

Opioid Complications and Withdrawal)

CHARNEY, D. S., HENINGER, G. R., & KLEBER, H.D. (1986). The combined use of clonidine and naltrexone as a rapid, safe and effective treatment of abruptwithdrawal from methadone. American Journal of Psychiatry, 143, 817-831.

GOLD, M. S. (1991). The good news about drugs and alcohol. New York: Villard Books.

GOLD, M. S., REDMOND, D. E., & KLEBER, H. D. (1978a). Clonidine in opiate withdrawal. Lancet I, 929-930.

GOLD, M. S., REDMOND, D. E., & KLEBER, H. D. (1978). Clonidine blocks acute opiate symptoms. Lancet II, 599-602.

JAFFE J. H. (1990). Drug addiction and drug abuse. InA. G. Gilman, et al. (Eds.), Goodman and Gilman's the pharmacological basis of therapeutics, 8th ed. New York: Pergamon.

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