Oxcarbazepine--efficacy and tolerability during treatment of alcohol withdrawal: a double-blind, randomized, placebo-controlled multicenter pilot study. Carbamazepine versus oxazepam in the treatment of alcohol withdrawal: a double-blind study. Effects of beta-blocking drugs in alcohol withdrawal: a double-blind comparative study with propranolol and diazepam. Treating alcohol withdrawal with oral baclofen: a randomized, double-blind, placebo-controlled trial. Enlarged double-blind randomised trial of benzodiazepines against psychotropic analgesic nitrous oxide for alcohol withdrawal. Double-blind study of alprazolam, diazepam, clonidine, and placebo in the alcohol withdrawal syndrome: preliminary findings. Ambulant treatment of alcohol withdrawal symptoms with carbamazepine: a formal multicentre doubl-blind comparison with placebo. Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial. Comparison of two benzodiazepines in the treatment of alcohol withdrawal: effects on symptoms and cognitive recovery.
Alcohol withdrawal syndrome (AWS) is a serious complication of alcohol dependence and often requires intensive medical treatment. Antiepileptic drugs (AEDs) have been shown to be as efficacious in the treatment of AWS in several controlled trials as benzodiazepines and superior to placebo in relieving alcohol withdrawal symptoms. Oxcarbazepine (OXC), a newer anticonvulsive drug, has a favorable safety profile over carbamazepine (CBZ) and other older AEDs due to its excellent efficacy and better side-effect profile.
                The efficacy and tolerability of OXC versus placebo were investigated in 50 inpatients during a 6-day treatment of alcohol withdrawal in a 4-site, double-blind, randomized, placebo-controlled pilot study. The amount of rescue medication of clomethiazole (CLO) capsules needed was chosen as the primary variable. The data were collected between May 2003 and September 2004.
                No initial differences were found regarding sociodemographic data and alcohol-related parameters, indicating successful randomization. No differences were found in the need for rescue medication CLO, decrease of withdrawal symptoms, or craving for alcohol between the OXC and the placebo group. Subjectively experienced side effects, normalization of vegetative parameters, craving, or improvement of psychopathological parameters were not different between the groups.
                Despite the negative finding, which may be attributable to the design of the study, OXC still poses an interesting alternative to CBZ and other drugs because other studies have found it not only as efficient but also as having no addictive potential, while additionally possessing an anti-craving effect. Therefore, well-designed investigations with larger cohorts are required to further elucidate this issue. The use of more than 130 drugs and drug combinations against the alcohol withdrawal syndrome reflects the fact that views on its treatment are far from being unequivocal. Benzodiazepines are the first choice treatment but it should not be disregarded that they have side effects and, above all, a varying risk of dependency themselves. In recent years many trials have focused on carbamazepine in this respect. Its efficacy was proven in various open and double-blind studies, most of them using concomitant sedative drugs, thereby diminishing the reliability of the results. In a double-blind study we compared the efficacy of carbamazepine with that of oxazepam, in 60 in-patients suffering from alcohol withdrawal syndrome. The main rating instrument was the Clinical Institute Withdrawal Scale--Alcohol (CIWA-A). The 7-day trial showed equal efficacy of carbamazepine and oxazepam during the first 5 days and a statistically significant superiority of carbamazepine on days 6 and 7. Four patients in each group had to be dropped from the study due to side effects or after having withdrawn informed consent. There was no decrease in white blood counts under carbamazepine. The experiences with carbamazepine up to now suggest a more widespread use, especially in non-delirious withdrawal states. Alcohol withdrawal is associated with a decrease in gamma-aminobutyric acid neurotransmission. This explains the efficacy of benzodiazepines. However, an increase in adrenergic activity may also play a part in alcohol withdrawal symptoms, suggesting a potential efficacy of beta-blocking drugs. A double-blind comparative study of propranolol and diazepam was carried out in 28 patients suffering from moderate uncomplicated alcohol withdrawal. Patients were treated for 15 days with either 75 mg of propranolol or 30 mg of diazepam. The results show that both drugs at the dosages used are equipotent in reducing physical withdrawal symptoms and anxiety symptoms. This suggests that most likely the central as well as the peripheral effects determine the clinical usefulness of propranolol in the management of alcohol withdrawal. However, propranolol is ineffective in preventing major motor seizures, suggesting that different neurobiological mechanisms underlie the alcohol withdrawal symptoms. Abrupt cessation of alcohol intake causes habituated drinkers to experience symptoms of alcohol withdrawal syndrome (AWS).
                To determine the effect of the gamma-aminobutyric acid (GABA)-B agonist baclofen on the course of acute symptomatic AWS.
                Prospective, randomized, double-blind, placebo-controlled clinical study.
                Two tertiary-care hospitals in Duluth, Minnesota.
                Inpatient adults admitted for any reason (including AWS) judged to be at high risk for AWS.
                Inpatients who developed symptoms of AWS received symptom-triggered benzodiazepine treatment using lorazepam by standard protocol, and were randomized to receive baclofen 10 mg or placebo, 3 times per day, orally.
                AWS severity was assessed using the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar); lorazepam dose was monitored.
                Seventy-nine subjects were enrolled. The 44 subjects who developed symptoms of AWS were randomized to baclofen or placebo. Thirty-one subjects (18 baclofen, 13 placebo) completed 72 hours of assessments, either entirely as inpatients or with outpatient follow-up. The need for high doses of benzodiazepines (20 mg or more of lorazepam over 72 hours) to control AWS was less likely in the baclofen treatment group (1 of 18) than in the placebo-treated group (7 of 13) (P = 0.004).
                We found that the use of baclofen was associated with a significant reduction in the use of high doses of benzodiazepine (lorazepam) in the management of symptomatic AWS. The use of low-dose baclofen in the management of AWS deserves further study, as reduced dependence on high-dose benzodiazepines in AWS management could improve patient safety.
                Copyright © 2011 Society of Hospital Medicine. We report a randomised double-blind controlled study with an enlarged cohort of participants (N = 51) using psychotropic analgesic nitrous oxide (PAN) versus benzodiazepines (BZs) for treating acute alcoholic withdrawal states. An additional 28 participants having received a BZ the night previous to the study were pooled with the previously analysed 23 (with no additional BZ). These pooled results showed that PAN is superior to a BZ regimen at P = .05 level, despite additional BZs. Our work provides further support for previous findings that show that PAN is a safe, rapid, and effective therapy for acute mild to moderately severe withdrawal states. Both a reduction in the inhibitory effects of GABA (disinhibition) and activation of the sympathetic nervous system are manifested during the alcohol withdrawal syndrome. This study was designed to explore the relative efficacy of medications that differentially affects these two biological systems: the benzodiazepines, which attenuate GABAergic disinhibition, and the alpha 2-adrenergic receptor agonists, which decrease sympathetic activation. The benzodiazepine diazepam (n = 6), the alpha 2-receptor agonist clonidine (n = 7), the benzodiazepine alprazolam (this is also purported to have alpha 2-receptor agonist properties) (n = 6), and placebo (n = 6) were evaluated in their effectiveness in decreasing signs and symptoms of alcohol withdrawal. Drug-free, alcohol-dependent patients were administered 1 of the 4 medications in a double-blind design until symptoms of withdrawal, as measured by the Clinical Instrument Withdrawal Assessment for Alcohol-Revised, were successfully treated. Alprazolam was significantly more efficacious than both clonidine and placebo in decreasing withdrawal symptoms. Diazepam was more effective than clonidine and placebo on some measures of withdrawal. Clonidine decreased systolic blood pressure significantly more than the other two active drugs and placebo, but was no more effective than placebo in decreasing other symptoms of withdrawal. Alprazolam did not significantly decrease blood pressure compared with diazepam or placebo. Despite the small sample size, these preliminary findings suggest that the efficacy of alprazolam in the treatment of alcohol withdrawal is related to its effect at the benzodiazepine receptor and not its alpha 2-receptor agonist properties. One hundred male out-patients were treated for alcohol withdrawal symptoms with either carbamazepine or placebo in a double-blind, multicentre trial carried out a five Finnish A-clinics (alcoholism treatment centres) in different parts of the country. In both the carbamazepine and the placebo groups two thirds of the patients completed the 7-day treatment successfully, and the final treatment results were considered equally good in both groups. However, the withdrawal symptoms, especially the sleep disturbances, subsided faster in the carbamazepine group than in the placebo group. The change in the total symptom score from the first day of treatment to the second was significantly greater in the carbamazepine group than in the placebo group. The patients' ability to work improved significantly faster in the carbamazepine group. In alcohol withdrawal, fixed doses of benzodiazepine are generally recommended as a first-line pharmacologic approach. This study determines the benefits of an individualized treatment regimen on the quantity of benzodiazepine administered and the duration of its use during alcohol withdrawal treatment.
                We conducted a prospective, randomized, double-blind, controlled trial including 117 consecutive patients with alcohol dependence, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, entering an alcohol treatment program at both the Lausanne and Geneva university hospitals, Switzerland. Patients were randomized into 2 groups: (1) 56 were treated with oxazepam in response to the development of signs of alcohol withdrawal (symptom-triggered); and (2) 61 were treated with oxazepam every 6 hours with additional doses as needed (fixed-schedule). The administration of oxazepam in group 1 and additional oxazepam in group 2 was determined using a standardized measure of alcohol withdrawal. The main outcome measures were the total amount and duration of treatment with oxazepam, the incidence of complications, and the comfort level.
                A total of 22 patients (39%) in the symptom-triggered group were treated with oxazepam vs 100% in the fixed-schedule group (P<.001). The mean oxazepam dose administered in the symptom-triggered group was 37.5 mg compared with 231.4 mg in the fixed-schedule group (P<.001). The mean duration of oxazepam treatment was 20.0 hours in the symptom-triggered group vs 62.7 hours in the fixed-schedule group (P<.001). Withdrawal complications were limited to a single episode of seizures in the symptom-triggered group. There were no differences in the measures of comfort between the 2 groups.
                Symptom-triggered benzodiazepine treatment for alcohol withdrawal is safe, comfortable, and associated with a decrease in the quantity of medication and duration of treatment. Forty newly admitted alcohol-dependent patients were randomly allocated to equivalent 6-day regimes of either lorazepam or diazepam, to compare involvement in physical, emotional and cognitive state during the first 8 days in hospital. Diazepam provided a more comfortable withdrawal period and was associated with slightly better cognitive functioning on the eighth day.
Benzodiazepines showed a protective benefit against alcohol withdrawal symptoms, in particular seizures, when compared to placebo and a potentially protective benefit for many outcomes when compared with other drugs. Nevertheless, no definite conclusions about the effectiveness and safety of benzodiazepines was possible, because of the heterogeneity of the trials both in interventions and the assessment of outcomes.