Withdrawal syndrome

The abrupt cessation of a repeatedly or continuously administered opioid agonist, or the administration of an antagonist typically results in the withdrawal syndrome. Signs and symptoms include sweating, tachycardia, hypertension, diarrhea, hyperventilation, and hyperre-flexia. 

An important initial intervention for a minority of alcohol-dependent patients is the management of alcohol withdrawal through detoxification. The objectives in treating alcohol withdrawal are relief of discomfort, prevention or treatment of complications, and preparation for rehabilitation. Successful management of the alcohol withdrawal syndrome is generally necessary for subsequent efforts at rehabilitation to be successful treatment of withdrawal alone is usually not sufficient, because relapse occurs commonly. 

Dobrydnjov I, Axelsson K, Berggren L, et al Intrathecal and oral clonidine as prophylaxis for postoperative alcohol withdrawal syndrome a randomized double-blinded study. Anesth Analg 98 738—744, 2004... 

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A protracted abstinence syndrome may follow the acute opioid withdrawal syndrome and last for many weeks (Martin et al. 1973). In one study ofher-oin addicts detoxified with methadone, withdrawal distress peaked at day 20,... 

Personality variables, state of mind at time of withdrawal, and expectations of severity of symptoms all may affect withdrawal severity (Kleber 1981). One study found that merely providing addicts information about the withdrawal syndrome resulted in lower levels of withdrawal symptoms (Green and Gos-sop 1988). Naloxone rapidly induces a severe withdrawal syndrome, which peaks within 30 minutes and then declines rapidly. Until the antagonist is eliminated, only partial suppression of the withdrawal syndrome is possible, and then only by using very high opioid doses, which may cause respiratory depression when naloxone is metabolized. 

Methadone is a p receptor agonist with special properties that make it particularly useful as a maintenance agent. Rehably absorbed orally, it does not reach peak concentration until about 4 hours after administration and maintains a large extravascular reservoir (Kreek 1979). These properties minimize acute euphoric effects. The reservoir results in a plasma half-life of 1—2 days, so there are usually no rapid blood level drops that could lead to withdrawal syndromes between daily doses. Effective blood levels are in the range of 200-500 ng/mL. Trough levels of 400 ng/mL are considered optimal (Payte and Khouri 1993). There is wide variability among individuals in blood levels with identical doses (Kreek 1979), and some have inadequate levels even with doses as high as 200 mg/day (Tennant 1987 Tenore 2003). 

Gossop M, Bradley B, Phillips GT An investigation of withdrawal symptoms shown by opiate addicts during and subsequent to a 21 -day in-patient methadone detoxification procedure. Addict Behav 12 1-6, 1987 GreenJ, Jaffe JH Alcohol and opiate dependence. J Stud Alcohol 38 1274-1293,1977 Green L, Gossop M Effects of information on the opiate withdrawal syndrome. Br J Addict 83 305-309, 1988... 

A rebound sleep disturbance has been found after only 7—10 days of treatment with therapeutic doses of triazolam (Greenblatt et al. 1987). Others have described a withdrawal syndrome after substitution of a short-acting benzodiazepine for a long-acting benzodiazepine (Conell and Berhn 1983). Rebound insomnia may occur with zolpidem. 

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Sellers EM Alcohol, barbiturate and benzodiazepine withdrawal syndromes clinical management. CMAJ 139 113—120, 1988... 

An initial examination of the extent to which lithium may prevent cannabis withdrawal in rats was conducted by Cui et al. (2001), who reported that, at clinically relevant serum levels, lithium prevented the appearance of the cannabis withdrawal syndrome. The authors also noted that these effects were accompanied by a release of oxytocin, which they conclude is responsible for suppression of the withdrawal signs. 

Cornelius JR, Salloum IM, EhlerJG, et al Fluoxetine in depressed alcoholics a doubleblind, placebo-controlled trial. Arch Gen Psychiatry 54 700—705, 1997 Cornelius JR, Salloum IM, Haskett RF, et al Fluoxetine versus placebo for the marijuana use of depressed alcoholics. Addict Behav 24 111—114, 1999 Cui S-S, Bowen RC, Gu G-B, et al Prevention of cannabinoid withdrawal syndrome by lithium involvement of oxytocinergic neuronal activation. J Neurosci 21 9867— 9876, 2001... 

Lichtman AH, Martin BR Marijuana withdrawal syndrome in the animal model. J Clin Pharmacol 42 S20-S27, 2002... 

Wiesbeck GA, Shuckit MA, Kalmijn JA, et al An evaluation of the history of a marijuana withdrawal syndrome in a large population. Addiction 91 1469-1478, 1996... 

Dependence and withdrawal can occur with all of the stimulants. Cocaine is one of the most strongly reinforcing drugs in self-administration paradigms in animals and also has a psychological withdrawal syndrome. A typical pattern of withdrawal includes a ravenous appetite, exhaustion, and mental depression, which may last for several days after the drug is withdrawn. Because tolerance develops quickly, abusers may take large doses, compared with those used medically, for example, as anorexiants. 

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