Clonidine in treatment of mixed abusers (Ethanol + benzodiazepines).

Fråga: Clonidine in treatment of mixed abusers (Ethanol + benzodiazepines).

Sammanfattning: In summary: clonidine appears to be effective in controling some signs and symptoms of alcohol withdrawal, especially blood pressure and pulse rate. However, patients who are predisposed to alcohol withdrawal seizures should be treated with prophylactic anticonvulsants during clonidine treatment.

The effectiveness of clonidine in the treatment of withdrawal from drugs other than narcotics or alcohol cannot be evaluated at this time due to lack of data.

Svar: Eventhough the use of clonidine in the treatment of narcotic withdrawal is well documented, there are only a few studies of the use of this drug in alcohol withdrawal (1-4) and only one case report of clonidine in benzodiazepine withdrawal (5) to-date. There is one report on the use of clonidine in mixed-drug withdrawal which urges caution as clonidine "masked the signs of sedative withdrawal" (6). Since this report will not be available in print till November 1985, further comments can not be made about the use of clonidine in mixed-drug withdrawal.

Björkqvist (1) compared the effects of placebo and clonidine 0.15 mg at bedtime, 3 times daily, twice daily, and at bedtime on days 1, 2, 3 and 4 respectively. In addition to clonidine the patients with history of seizures received phenytoin and all patients received a combination hypnotic (diphenhydramine 25 mg and methaqualone 250 mg) at bedtime. The severity of withdrawal before treatment or history of withdrawal is not mentioned. Björkqvist observed that the clonidine group had significantly better scores on day 2 and 3 in the following respects: anxiety, tremor, palpitations, shortness of breath, sweating and some other subjective symptoms. Clonidine was more effective than placebo in lowering systolic blood pressure. There were no differences in nausea, abdominal pain, hallucinations, sleep disturbances (which were present despite the use of a hypnotic?!) between the clonidine and placebo groups.

Wilkins´ study (2) of 11 patients in alcohol withdrawal of unknown severity and time of onset showed that one dose of clonidine 5 ug/kg was more effective than placebo in decreasing blood pressure, tremor, heart rate, and reducing anxiety according to a subjective anxiety score. Patients with grand mal convulsions or severe concurent illness which justified immediate use of other therapy were excluded from the study.

Manhem (3) compared the effects of clonidine 0.15-0.3 mg four times a day and chlormethiazole 500-1000 mg 4x daily in a 4 day study in 20 patients withdrawing from ethanol. All patients received carbamazepine 200 mg twice daily from the time of admission. Two patients who progressed to a "delirious state" were excluded after the start of the study. Other exclusion criteria were not stated. In this study clonidine was observed to be as effective as chlormethiazole in supressing the signs and symptoms of ethanol withdrawal. In addition, clonidine was more effective in reducing blood pressure, pulse rate and correcting tachycardia.

Cushman (4) reported similar results as Björkqvist, using lofexidine, a new alpha-adrenergic agonist (not available in Sweden yet). Lofexidine is also more effective than placebo in lowering blood pressure and tremors, but no difference was observed on diaphoresis, restlessness, sleep duration, and alcohol craving.

Keshavan (5) reported a case where clonidine was used "successfully" in the management of lorazepam withdrawal. However, insufficient information was given in this report to evaluate the potential use of this drug in withdrawal from benzodiazepines.