Oxcarbazepine--efficacy and tolerability during treatment of alcohol withdrawal: a double-blind, randomized, placebo-controlled multicenter pilot study. A double-blind comparison of abecarnil and diazepam in the treatment of uncomplicated alcohol withdrawal. The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial. Divalproex sodium (Depakote) for alcohol withdrawal and relapse prevention. [Gamma-hydroxybutyrate for treatment of alcohol withdrawal syndrome in intensive care patients. A comparison between with two symptom-oriented therapeutic concepts]. Carbamazepine versus oxazepam in the treatment of alcohol withdrawal: a double-blind study. Divalproex sodium in alcohol withdrawal: a randomized double-blind placebo-controlled clinical trial. Treatment of acute alcohol withdrawal with gabapentin: results from a controlled two-center trial. Double-blind controlled trial comparing carbamazepine to oxazepam treatment of alcohol withdrawal. Oxcarbazepine versus carbamazepine in the treatment of alcohol withdrawal. Gamma-hydroxybutyric acid (GHB) in the treatment of alcohol withdrawal syndrome: a randomized comparative study versus benzodiazepine. Treating alcohol withdrawal with oral baclofen: a randomized, double-blind, placebo-controlled trial. Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial. Clonidine vs chlordiazepoxide in the management of acute alcohol withdrawal syndrome. Treatment of alcohol withdrawal: chlormethiazole vs. carbamazepine and the effect on memory performance--a pilot study. Gamma-hydroxybutyric acid versus clomethiazole for the treatment of alcohol withdrawal syndrome in a medical intensive care unit: an open, single-center randomized study. Enlarged double-blind randomised trial of benzodiazepines against psychotropic analgesic nitrous oxide for alcohol withdrawal. Double-blind comparison of lorazepam and chlordiazepoxide in the treatment of the acute alcohol abstinence syndrome. Double-blind study of alprazolam, diazepam, clonidine, and placebo in the alcohol withdrawal syndrome: preliminary findings. Tiapride and chlordiazepoxide in acute alcohol withdrawal. A controlled clinical trial. Emergency department treatment of alcohol withdrawal seizures with phenytoin. Ambulant treatment of alcohol withdrawal symptoms with carbamazepine: a formal multicentre doubl-blind comparison with placebo. Gamma-hydroxybutyrate reduces both withdrawal syndrome and hypercortisolism in severe abstinent alcoholics: an open study vs. diazepam. Effects of beta-blocking drugs in alcohol withdrawal: a double-blind comparative study with propranolol and diazepam. A double-blind comparison of carbamazepine and clomethiazole in the treatment of alcohol withdrawal syndrome. A pilot open randomized trial of valproate and phenobarbital in the treatment of acute alcohol withdrawal. Oxcarbazepine in combination with Tiaprid in inpatient alcohol-withdrawal--a RCT. Alcohol withdrawal: effects of clonidine treatment on sympathetic activity, the renin-aldosterone system, and clinical symptoms. Divalproex in the treatment of alcohol withdrawal. Comparison of chlormethiazole (Heminevrin) and chlordiazepoxide (Librium) in the treatment of acute alcohol withdrawal. Antiglutamatergic strategies for ethanol detoxification: comparison with placebo and diazepam. A comparison of the efficacy and tolerability of clobazam and chlordiazepoxide in the treatment of acute withdrawal from alcohol in patients with primary alcoholism. Alcohol withdrawal severity is decreased by symptom-orientated adjusted bolus therapy in the ICU. Double blind study on the efficacy and safety of tetrabamate and chlordiazepoxide in the treatment of the acute alcohol withdrawal syndrome. Therapy of alcohol withdrawal syndrome in intensive care unit patients following trauma: results of a prospective, randomized trial. Piracetam and chlormethiazole in acute alcohol withdrawal: a controlled clinical trial. Second-line anticonvulsant treatment of neonatal seizures: a video-EEG monitoring study. Halazepam in the management of acute alcohol withdrawal syndrome. Gamma-hydroxybutyric acid for treatment of alcohol withdrawal syndrome. Alcohol withdrawal treatment in intoxicated vs non-intoxicated patients: a controlled open-label study with tiapride/carbamazepine, clomethiazole and diazepam. Treatment of alcohol withdrawal symptoms in hospitalized patients. A randomized, double-blind comparison of carbamazepine (Tegretol) and barbital (Diemal). A randomized, double-blind comparison of lorazepam and chlordiazepoxide in patients with uncomplicated alcohol withdrawal. A double-blind comparison of the efficacy and safety of lorazepam and diazepam in the treatment of the acute alcohol withdrawal syndrome. Safety and efficacy of vigabatrin and carbamazepine in newly diagnosed epilepsy: a multicentre randomised double-blind study. Vigabatrin European Monotherapy Study Group. Self-reported sleep, sleepiness, and repeated alcohol withdrawals: a randomized, double blind, controlled comparison of lorazepam vs gabapentin. Treatment of acute alcohol withdrawal syndrome with carbamazepine: a double-blind comparison with tiapride. A randomized, open-label, controlled trial of gabapentin and phenobarbital in the treatment of alcohol withdrawal. 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. Treatment of the alcohol withdrawal syndrome is best accomplished using pharmacologic agents that have minimal interaction with alcohol, have limited adverse effects, and are without abuse potential. The partial benzodiazepine receptor agonist beta-carboline compound, abecarnil, has been shown in animal and human studies to possess a number of these characteristics and to be useful in the reduction of alcohol withdrawal convulsions in mice. In this study, 49 alcohol-dependent inpatients who exhibited at least moderate symptoms of uncomplicated alcohol withdrawal were treated over a 5-day detoxification period with abecarnil or diazepam and rated daily for alcohol withdrawal symptoms and adverse events. Both the abecarnil and diazepam treatment groups exhibited a similar marked reduction in withdrawal symptoms over time. In addition, similar rates of successful treatment and improvement were observed after 1 day of treatment and at termination in alcoholics treated with either medication. Overall, rates of adverse events and changes in liver enzymes were similar in both treatment groups and were generally benign. Because of the unique pharmacologic profile of abecarnil in animal and in non-clinical human studies, including anticonvulsant action, low abuse liability, and a favorable side effect profile, further study of compounds of the partial benzodiazepine receptor agonist type in the treatment of alcohol withdrawal syndromes seems warranted. Benzodiazepines are the mainstay of treatment for mild-to-moderate alcohol withdrawal in outpatient settings, but they can interact with alcohol, cause motor incoordination, or be abused. This study compared the therapeutic responses of the benzodiazepine lorazepam and the anticonvulsant carbamazepine for the outpatient treatment of acute alcohol withdrawal in terms of patients' previous detoxification histories, and compared the effects of these 2 medications on drinking behaviors in the immediate postdetoxification period.
                This was a randomized double-blind trial comparing patient responses to carbamazepine and lorazepam across 2 levels of detoxification histories (0-1 or >or=2 previous medicated detoxifications).
                A university medical center substance abuse clinic in Charleston, SC.
                One hundred thirty-six patients in moderate alcohol withdrawal were randomized. Major exclusions were significant hepatic or hematologic abnormalities and use of medications that could alter withdrawal symptoms.
                Patients received 600-800 mg of carbamazepine or 6-8 mg of lorazepam in divided doses on day 1 tapering to 200 mg of carbamazepine or 2 mg of lorazepam.
                The Clinical Institute Withdrawal Assessment for Alcohol-Revised was used to assess alcohol withdrawal symptoms on days 1 through 5 and postmedication at days 7 and 12. Daily drinking was measured by patient report using a daily drinking log and a breath alcohol level with each visit. Side effects were recorded daily.
                Carbamazepine and lorazepam were equally effective at decreasing the symptoms of alcohol withdrawal. In the post-treatment period, 89 patients drank on at least 1 day; on average, carbamazepine patients drank less than 1 drink per drinking day and lorazepam patients drank almost 3 drinks per drinking day (P =.003). Among those with multiple past detoxifications, the carbamazepine group drank less than 1 drink per day on average and the lorazepam group drank about 5 drinks per day on average (P =.033). Lorazepam-treated patients had a significant rebound of alcohol withdrawal symptoms post-treatment (P =.007) and the risk of having a first drink was 3 times greater (P =.04) than for carbamazepine-treated patients. Twenty percent of lorazepam-treated patients had dizziness, motor incoordination, or ataxia and did not recognize their impairment. Twenty percent of carbamazepine-treated patients reported pruritus but no rash.
                Carbamazepine and lorazepam were both effective in decreasing the symptoms of alcohol withdrawal in relatively healthy, middle-aged outpatients. Carbamazepine, however, was superior to lorazepam in preventing rebound withdrawal symptoms and reducing post-treatment drinking, especially for those with a history of multiple treated withdrawals. This pilot study evaluates the safety and efficacy of divalproex sodium (Depakote) for alcohol withdrawal and relapse prevention. Sixteen patients in moderate alcohol withdrawal were randomized to receive a standard benzodiazepine detoxification, depakote detoxification, or depakote detox plus maintenance. Symptom reduction occurred more rapidly and consistently in the depakote treated patients than in the benzodiazepine control group, and at six-week follow up a greater percentage of patients in the depakote maintenance group were completely abstinent than either detox-only group. There were no significant differences in sociodemographic or drinking data amongst the three cohort samples at baseline. Our findings suggest that the anticonvulsant divalproex sodium (Depakote) may be a safe and efficacious alternative to benzodiazepines for the treatment of alcohol withdrawal. It may be an advantageous alternative for outpatient detoxification, as it has no abuse potential, pharmacologic synergy with alcohol, or substantial cognitive or psychomotor side effects. Seeing as gamma-hydroxybutyrate (GHB) and benzodiazepines interact with the GABA-transmitter system, we investigated whether GHB can replace the conventional therapy, which uses benzodiazepines in the treatment of alcohol withdrawal syndrome in ICU settings.
                42 chronic alcoholics were included in this prospective and randomized study. Following the development of alcohol withdrawal syndrome, the patients were randomly allocated to the GHB or to the flunitrazepam group. In addition to this, clonidine was administered in order to treat autonomic signs of withdrawal. In cases were hallucinations occurred, haloperidol was administered.
                There was no significant difference in the efficacy of treatment used in the duration of mechanical ventilation and intensive care unit stay between groups. The patients in the GHB-group required significantly higher dosages of haloperidol and significantly lower dosages of clonidine. 14 out of 21 patients from the GHB-group developed hypernatriaemia and 15 out of 21 developed a metabolic alkalosis.
                Symptoms of the autonomic nervous system were more effectively prevented by GHB as evident in the lower dosage requirement of clonidine. However, GHB may not sufficiently block the hyperactivity of the dopaminergic system or may have an hallucinogenic effect itself. This may be evident from the higher dosages of haloperidol which were necessary. Due to the latter fact, the administration of GHB cannot be recommended in all patients suffering from AWS in ICU settings. 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. Divalproex sodium, an anticonvulsant and antikindling agent and gamma-aminobutyric acid enhancer, has been proposed as an alternative to benzodiazepines for treating alcohol withdrawal. This study reports on a randomized, double-blind, placebo-controlled trial of divalproex sodium in acute alcohol withdrawal.
                Thirty-six hospitalized patients experiencing moderate alcohol withdrawal as measured by a score of at least 10 on the revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar) were randomized to receive either divalproex sodium 500 mg three times per day for 7 days or matched placebo in a double-blind manner. All subjects received a baseline dose of oxazepam and had additional oxazepam available as a rescue medication in accordance with a standard, symptom-triggered detoxification protocol. Mean total milligrams of oxazepam received, progression of withdrawal symptoms, psychological distress as measured by the Symptom Checklist-90, side effects, and adverse outcomes were compared between groups.
                Use of divalproex sodium resulted in less use of oxazepam (p < 0.033). Group differences seemed primarily driven by those subjects who experienced symptoms above threshold level (CIWA-Ar >or=10) after 12 hr. The progression in severity of withdrawal symptoms (increase in CIWA-Ar above baseline) was also significantly greater in the placebo group (p < 0.05).
                This placebo-controlled pilot study suggests that divalproex sodium significantly affects the course of acute alcohol withdrawal and reduces the need for treatment with a benzodiazepine. A more aggressive loading dose strategy may demonstrate a more robust or earlier response. A few case reports and data from animal experiments point to a possible efficacy of gabapentin (GP) in the treatment of alcohol withdrawal syndrome (AWS). Because of ethical considerations, the efficacy of GP in acute AWS was tested in an add-on fashion to clomethiazole (CLO). Given that the symptom-triggered amount of CLO required to limit AWS within the first 24 hours is related to the severity of AWS, we tested this amount of CLO during placebo (P) or GP (400 mg qid) under double blind, randomized conditions. Sixty-one patients (P = 29/GP = 32) suffering from alcohol dependence (ICD-10) and without any other psychiatric condition or psychotropic medication were included. The groups were not significantly different in baseline characteristics (eg, demographic data, severity of AWS). Both ITT and completer analyses revealed no significant differences between the groups considering the primary effectiveness measure: amount of CLO required in the first 24 hours (P = 6.1 +/- 5.4/GP = 6.2 +/- 4.7 capsules). In addition, premature discontinuations (P = 3/GP = 2) and decreases in Mainz Alcohol Withdrawal Scores were not significantly different in the first 48 hours of AWS (secondary effectiveness measures). Tolerability of combined CLO/GP was studied throughout the whole treatment comprising a 5-day lasting reduction part subsequent to the first 48 hours. Throughout the whole 7-day treatment a total of 5 and 2 patients dropped out and 6 and 5 patients reported adverse clinical events in the P and GP groups, respectively. All together, GP (400 mg qid) was no better than P in saving initial consumption of CLO or decreasing initial Mainz Alcohol Withdrawal Scores suggesting that GP was ineffective in the management of acute AWS in this model. The combination of GP and CLO was safe. Of 86 alcoholic men with severe alcohol withdrawal who began a double-blind controlled study comparing carbamazepine, 800 mg/day, to oxazepam, 120 mg/day, 66 (carbamazepine, N = 32; oxazepam, N = 34) completed the 7-day trial. In general, the drugs were found to be equally efficacious in treating the withdrawal syndrome and not significantly different with respect to side effects. The subjects taking oxazepam had an increase in global psychological distress from day 3 to day 7, and those taking carbamazepine exhibited a decline. The study suggests that carbamazepine is as effective and safe as benzodiazepine treatment for alcohol withdrawal. In a single-blinded and randomized pilot study efficacy and tolerability of oxcarbazepine versus carbamazepine were investigated in 29 patients during therapy of alcohol withdrawal. No initial differences were found regarding sociodemographic data and alcohol-related parameters, indicating successful randomization. The oxcarbazepine group showed a significant decrease of withdrawal symptoms and reported significantly less 'craving for alcohol' compared to the carbamazepine group. Subjectively experienced side effects, normalization of vegetative parameters and improvement in the cognitive processing speed did not reveal differences for both groups. Therefore, oxcarbazepine might be an interesting alternative to carbamazepine, and having almost no addictive potential, no clinically relevant interaction with alcohol and no prominent sedatory effect, possibly also to other drugs such as benzodiazepines or clomethiazole, in the treatment of alcohol withdrawal syndrome. Benzodiazepine has been shown to be one of the most effective class of drugs in the management of alcohol withdrawal syndrome (AWS). Gamma-hydroxybutyric acid (GHB) has recently been introduced in the treatment of alcohol problems, including AWS. At present there are no comparative studies between benzodiazepines and GHB in AWS treatment. The aim of the present randomized, controlled, single-blind study was to evaluate the efficacy and safety of GHB compared with diazepam in the treatment of AWS.
                Sixty alcoholics affected by AWS were enrolled in the study. Diazepam (0.5-0.75 mg/kg body weight for 6 days, tapering the dose 25% daily until day 10) was administered orally to 30 patients (25 males, 5 females; mean age 44.3 +/- 10.9 years); GHB (50 mg/kg body weight for 10 days) was administered orally to 30 patients (26 males,4 females; mean age 41.7 +/- 10.4 years). The Clinical Institute Withdrawal Assessment for Alcohol-revised scale (CIWA-Ar) was used to evaluate the AWS physical symptoms. The State Anxiety Inventory test for current anxiety assessment and the Zung self-rating Depression Scale for current depression assessment were performed.
                Eight patients (26.6%) in the diazepam group and 4 patients (13.3%) in the GHB group dropped out. Both treatments were effective in reducing AWS. No significant difference was found between the groups in CIWA-Ar total score at baseline and at the different times of observation. Considering the CIWA-Ar subscore and Zung scale, a significant reduction of anxiety on day 4 (p < 0.02), agitation on day 5 (p < 0.02) and time of recovery of depression on day 5 (p < 0.02) was observed in the GHB group with respect to the diazepam group. Drowsiness and vertigo developed after initial drug administration in the GHB (19.2%) and diazepam (36.4%) groups and quickly resolved in both groups.
                GHB is as effective in the management of AWS as benzodiazepine and it seems to be quicker in reducing anxiety, agitation, and depression. Both drugs are safe and well-tolerated in AWS management. 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. 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. To our knowledge, this is the first reported comparison of clonidine with benzodiazepine in the management of acute alcohol withdrawal syndrome. In a double-blind trial, 61 men experiencing acute alcohol withdrawal were randomly assigned to receive clonidine or chlordiazepoxide over a 60-hour treatment period. Clonidine was more effective than chlordiazepoxide at reducing alcohol withdrawal scale scores, systolic blood pressures, and heart rates over the entire study period. Clonidine was as good as chlordiazepoxide at improving Cognitive Capacity Screening Exam, Hamilton Anxiety Rating Scale, and Self-Rating Scale scores. Adverse drug reactions reported by each group were similar, though less nausea and vomiting were observed in the clonidine group. Clonidine may represent a new alternative agent for the management of acute alcohol withdrawal syndrome. Although relatively little attention has been paid to the question how acute alcohol withdrawal might affect cognitive functions, this factor remains of particular interest because it influences psychotherapeutic treatment during detoxification. The clinical outcome and neuropsychological state of 37 inpatients with alcohol withdrawal was investigated in a randomized single-blind approach. Two different medical strategies [chlormethiazole (CMZ) vs. carbamazepine (CBZ)] in the treatment of inpatients with alcohol withdrawal syndrome were compared. Among comparable groups (related to gender, age, initial alcohol level, severity of abuses, severity of initial withdrawal symptoms such as tremor, perspiration, psychomotor agitation, hallucinations, orientation, intelligence, patient demographics), CBZ is just as potent as CMZ in therapy of withdrawal symptoms (circulatory function, vegetative function, psychomotor activity). Patients in both groups showed initial impairments in some neuropsychological tests (d2, Zahlen-Verbundings test, Beck Depression Inventory, Anxiety Sensitivity Index) with significant improvement during detoxification. Additionally, CBZ-treated patients showed significantly better verbal memory performance during the first days of treatment. Without any addictive potential, CBZ therapy could be very supportive in alcohol detoxification. In addition a higher verbal memory performance state could be favourable for a psychotherapeutic approach. Clomethiazole (CLO) has been shown to be effective in treating alcohol withdrawal syndrome (AWS). Gamma-Hydroxybutyric acid (GHB) has also been introduced in the treatment of alcoholic patients and is effective in surgical intensive care unit (ICU) patients in preventing and treating AWS. There are no comparative studies between CLO and GHB in a medical ICU setting.
                Twenty-six alcoholic patients with severe AWS and concomitant medical diseases were randomally enrolled in the study. CLO was given orally to 12 patients in a dosage of 250 mg every 4 hours as a liquid; GHB (initially 30 mg/kg body weight (BW) followed by 15 mg/kg BW) was administered intravenously to 14 patients. Four major AWS symptoms (tremor, sweating, nausea, restlessness) were scored, and the administration of additional medication was registered.
                GHB was more effective in treating AWS symptoms. In the GHB group, AWS score dropped from 6.6 +/- 2.6 to 1.8 +/- 2.1 (p <.01), while in the CLO group, the score dropped from 6 +/- 2.5 to 4.1 +/- 2.4 (n. s.). Differences between groups were significant (p =.021, two-way ANOVA). The treatment did not alter outcome or the duration of ICU stay. No serious side effects were detected.
                GHB effectively controls AWS symptoms in medical ICU patients. The rapid initial treatment response of GHB in contrast to CLO has no influence on duration of patient withdrawal. 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. The anxiolytic efficacy and safety of lorazepam and chlordiazepoxide were evaluated and compared during a five-day double-blind trial in 50 male inpatients who were experiencing acute alcohol withdrawal symptoms. The total daily doses of lorazepam and chlordiazepoxide were tapered from 6 to 2 mg and from 150 to 50 mg, respectively, during the first four days; no medication was given on day 5. Drug effectiveness was measured by improvements in the total severity assessment score (TSAS), in the three composite TSAS factors, and by the physician's global rating. No drug-related adverse effects occurred during treatment. Vital signs remained stable, and laboratory test results remained within normal limits. The results indicate that lorazepam was as effective as chlordiazepoxide in reducing the symptoms of acute alcohol withdrawal. Because of its simpler and more predictable metabolic pathway and its insignificant accumulation in plasma during multiple-dose therapy, lorazepam may be the drug of choice if benzodiazepine therapy is required for chronic alcoholics with acute withdrawal symptoms. 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. The efficacy of chlordiazepoxide and tiapride in the management of acute alcohol withdrawal syndrome was compared in a randomized, parallel-group, double-blind trial. The mean daily dose for both preparations on the first two days was four capsules, i.e., 200 mg for chlordiazepoxide and 400 mg for tiapride. Thereafter the patients were treated according to the relief of symptoms obtained. The treatment periods lasted 3-5 days. Both drugs effectively alleviated alcohol withdrawal symptoms, especially anxiety, fear, hallucinations, insomnia, sweating, tremor, abdominal pain and vertigo. Seventy percent of the patients in the chlordiazepoxide and 42% in the tiapride group considered the drug effective. The difference was statistically significant in favour of chlordiazepoxide (p less than 0.05). Tiapride is an alternative drug in the treatment of this condition, if benzodiazepines are to be avoided. Prevention of recurrent alcohol withdrawal seizures is a common emergency department problem. A prospective, randomized, placebo-controlled, double-blind study of adequate size was designed to assess the efficacy of phenytoin in preventing recurrence of alcohol withdrawal seizures.
                Fifty-five patients who had seized from alcohol withdrawal were randomly assigned to treatment with IV phenytoin or placebo. Patients with known seizure disorders and those receiving any anticonvulsant were excluded. The study was terminated after seizure recurrence or passage of a six-hour, high-risk seizure interval.
                Six of 28 phenytoin-treated patients (21%) had recurrent seizures compared with five of 27 placebo-treated patients (19%). The 95% confidence interval for the difference in response probabilities was +16% to -20%. There was no statistically significant difference between the response rates for the two treatments (P greater than .05).
                Phenytoin does not show significant benefit over placebo in preventing recurrence of alcohol withdrawal seizures. 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 42 alcoholic inpatients we performed an open randomized study to compare the effects of diazepam and gamma-hydroxybutyrate (GHB) on the suppression of severe alcohol withdrawal syndrome and hypercortisolism. Both diazepam (.5 mg/kg bodyweight, q.i.d.) and GHB (50 mg/kg bodyweight, q.i.d.) were orally administered for three weeks. During all study period, GHB was more able than diazepam in reducing both withdrawal syndrome and hypercortisolism. These effects were evident during the first week of treatment and persisted throughout the study period. The results confirm a strict correlation between high levels of plasma cortisol and alcohol withdrawal symptoms and they show a slight superiority of GHB over diazepam in the suppression of both ethanol withdrawal and hypercortisolism. Taken together, our data suggest that GHB may act as potent anti-withdrawal agent in severe abstinent alcoholics. 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. The efficacy and tolerability of carbamazepine and clomethiazole in the treatment of alcohol withdrawal symptoms were compared in a double-blind study with 68 hospitalized patients. Target withdrawal symptoms, the patient's subjective feeling and unwanted effects were recorded daily during the 1 week-treatment period. No significant differences between the two treatments could be demonstrated in the parameters studied. It appears that carbamazepine, which is widely used as an antiepileptic drug, well tolerated and not likely to produce any addiction as such, might offer a valuable alternative treatment for the symptoms of alcohol withdrawal. The authors conducted a randomized, open comparison of the GABAergic anticonvulsant sodium valproate (divalproex sodium; Depakote) and phenobarbital as an active control in the management of acute withdrawal from alcohol. Repeated measures ANOVA was used to assess treatment effects in the first 37 inpatients, evaluating mood, hostility, and subjective and objective measures of withdrawal at index, 3, and 5 days of detoxification. Subjective and objective ratings of abstinence symptoms and subjective mood disturbance decreased significantly in intensity in both groups over 5 days, but there were no significant treatment differences nor treatment by time interactions. Hostility scores did not differ overall, but a group by time effect was observed (F = 5.42, df = [1,13], P < 0.05), with phenobarbital subjects reporting less hostility/aggression than those in the valproate group. There were no withdrawal-related seizures or other acute sequelae. This study offers pilot confirmation that sodium valproate is as effective as phenobarbital in the management of acute alcohol withdrawal, but it is unclear whether valproate offers a clinical advantage with respect to stabilizing changes in mood and interpersonal hostility during detoxification. Oxcarbazepine (OXC), a derivative of Carbamazepine (CBZ), may represent a solution to metabolic and side effects of CBZ treatment due to the fact that renal excretion is its major route of elimination. The goal of the study is to compare the efficacy and tolerability of OXC/Tiaprid (TIA) combination therapy to the well established Clomethiazole (CLO) therapy in an inpatient setting.
                To investigate the efficacy of OXC/TIA in terms of lower alcohol withdrawal symptoms and better tolerability, 56 alcohol-dependent patients participated in a randomized open-label trial, where OXC/TIA and CLO treatments were compared.
                Following admission, we observed that severity of alcohol withdrawal syndrome was comparable between OXC/TIA and CLO-patients. Overall tolerability was good. However, significantly more patients in the OXC/TIA-group (48.1%) displayed no AE compared to the CLO-group (24.1%). We found no significant differences between groups regarding total number of recorded adverse events (AEs).
                OXC/TIA inpatient therapy proved to be as effective and participants demonstrated the same tolerance as with CLO. In medication-based alcohol withdrawal, OXC/TIA could have the potential to become a promising alternative for alcohol dependent patients unable to undergo inpatient withdrawal therapy with CLO. Our findings further indicate that it could be worthwhile testing OXC/TIA in alcohol withdrawal in daily care units and outpatient settings. This is an important question for national health care services, since outpatient therapy is more and more asked for as alternative to inpatient settings.
                Georg Thieme Verlag KG Stuttgart - New York. Twenty male alcoholics with alcohol withdrawal syndrome were randomized to receive either oral clonidine (3-600 micrograms, six hourly) or oral chlormethiazole (500-1000 mg, six hourly) for 4 days. All subjects were also given oral carbamazepine (200 mg, 12 hourly) throughout the study. Nine subjects given clonidine and eight given chlormethiazole completed the study. Clonidine was as effective as chlormethiazole in suppressing the symptoms and signs of alcohol withdrawal. However, plasma catecholamines, blood pressure, and pulse rate fell more rapidly and to a greater extent during clonidine than following chlormethiazole, findings which could have therapeutic implications. It is suggested that activation of brain noradrenergic neurons constitutes a common denominator in the pathophysiology of several withdrawal syndromes. The present study represents an open-label clinical trial comparing treatment with a benzodiazepine (lorazepam) to divalproex in 11 inpatients with uncomplicated alcohol withdrawal syndrome. The trial used the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scale. There were no significant differences in demographics or substance use parameters between the divalproex group (n = 6) or the lorazepam group (n = 5). A significant Group x CIWA-Ar score interaction [F(8,72) = 2.57, p < or = .01] was confirmed and further substantiated by a quadratic trend component for the interaction [F(1,9) = 24.9, p < or = .001]. This preliminary study supports further investigation of divalproex in the treatment of alcohol withdrawal. This study was carried out to compare the efficacy of chlormethiazole and chlordiazepoxide in the treatment of acute alcohol withdrawal syndrome in 40 patients. Repeated biochemical, clinical, and psychophysiological measurements were obtained in a randomized, double-blind design in which one group of patients received chlormethiazole and a second group received chlordiazepoxide over a period of 7 days. Analysis indicated both drugs to be of equivalent potency and were equally well tolerated by patients. The more severe aspects of withdrawal were brought under control within the first 4 days of treatment. However, even at 7 days, there still persisted some symptoms attributable to the withdrawal from alcohol. Benzodiazepines are the standard pharmacotherapies for ethanol detoxification, but concerns about their abuse potential and negative effects upon the transition to alcohol abstinence drive the search for new treatments. Glutamatergic activation and glutamate receptor up-regulation contribute to ethanol dependence and withdrawal. This study compared 3 antiglutamatergic strategies for ethanol detoxification with placebo and to the benzodiazepine, diazepam: the glutamate release inhibitor, lamotrigine; the N-methyl-D-aspartate glutamate receptor antagonist, memantine; and the AMPA/kainite receptor inhibitor, topiramate.
                This placebo-controlled randomized single-blinded psychopharmacology trial studied male alcohol-dependent inpatients (n=127) with clinically significant alcohol withdrawal symptoms. Subjects were assigned to 1 of 5 treatments for 7 days: placebo, diazepam 10 mg TID, lamotrigine 25 mg QID, memantine 10 mg TID, or topiramate 25 mg QID. Additional diazepam was administered when the assigned medication failed to suppress withdrawal symptoms adequately.
                All active medications significantly reduced observer-rated and self-rated withdrawal severity, dysphoric mood, and supplementary diazepam administration compared with placebo. The active medications did not differ from diazepam.
                This study provides the first systematic clinical evidence supporting the efficacy of a number of antiglutamatergic approaches for treating alcohol withdrawal symptoms. These data support the hypothesis that glutamatergic activation contributes to human alcohol withdrawal. Definitive studies of each of these medications are now needed to further evaluate their effectiveness in treating alcohol withdrawal. Forty patients with primary chronic alcoholism took part in a randomized, double-blind, comparative group study of clobazam and chlordiazepoxide in the treatment of acute alcohol withdrawal. Assessments were carried out during an initial in-patient week followed by a week of out-patient assessments. Both benzodiazepines were shown to be highly effective when compared with baseline measurements. However, the Hamilton Anxiety Rating Scale showed clobazam to be more effective than chlordiazepoxide at both 7 days (p = 0.03) and 14 days (p less than 0.05). The clobazam group showed significant improvements compared with baseline for all four factors of the Leeds Sleep Evaluation Questionnaire, whereas the chlordiazepoxide group showed a significant improvement in only one factor. At the end of the in-patient week, clobazam showed a significant improvement (p less than 0.01) compared to chlordiazepoxide for the Linear Analogue Rating Scale of anxiety/tension. The 1,5 benzodiazepine clobazam has been shown to be a valuable addition to currently available regimens when used alone in the treatment of acute alcohol withdrawal, especially during the initial period where anxiety and insomnia related symptoms are at their peak. To examine the effect of bolus vs. continuous infusion adjustment on severity and duration of alcohol withdrawal syndrome (AWS), the medication requirements for AWS treatment, and the effect on ICU stay in surgical intensive care unit (ICU) patients.
                Prospective randomized, double-blind controlled trial in a surgical ICU.
                44 patients who developed AWS after admission to the ICU.
                Patients were randomized to either (a). a continuous infusion course of intravenous flunitrazepam (agitation), intravenous clonidine (sympathetic hyperactivity), and intravenous haloperidol (productive psychotic symptoms) if needed (infusion-titrated group), or (b). the same medication (flunitrazepam, clonidine, or haloperidol) bolus adjusted in response to the development of the signs and symptoms of AWS (bolus-titrated group).
                The administration of "as-needed" medication was determined using a validated measure of the severity of AWS (Clinical Institute of Withdrawal Assessment). Although the severity of AWS did not differ between groups initially, it significantly worsened over time in the infusion-titrated group. This required a higher amount of flunitrazepam, clonidine, and haloperidol. ICU treatment was significantly shorter in the bolus-titrated group (median difference 6 days) due to a lower incidence of pneumonia (26% vs. 43%).
                We conclude that symptom-orientated bolus-titrated therapy decreases the severity and duration of AWS and of medication requirements, with clinically relevant benefits such as fewer days of ventilation, lower incidence of pneumonia, and shorter ICU stay. 1. Efficacy and safety of tetrabamate and chlordiazepoxide in the treatment of the acute or Primary Alcohol Withdrawal Syndrome (PAWS) were assessed during a randomized double blind clinical trial, carried out on sixty male alcoholic in-patients. 2. The two drugs were administered four times a day in double dummy conditions, according to a fixed-flexible decreasing dosage schedule (six days basic regimen). 3. Drug efficacy was measured daily throughout the study period using a battery of standard instruments for collecting quantitative clinical, behavioral, psychopathological and laboratory data. Side effects were daily recorded. 4. Tetrabamate was found to be as efficient as chlordiazepoxide in reducing the intensity of the PAWS, improving sleep and vital signs rapidly and alleviating anxiety progressively. 5. Tetrabamate was found particularly beneficial for severe tremor. Psychomotor and mood scores consistently favored tetrabamate, suggesting psychoanaleptic properties of this compound (increased diurnal vigilance). 6. Side effects were minimal with tetrabamate and generally of weak intensity with chlordiazepoxide. 7. The results of this study indicate that tetrabamate may represent a new alternative drug of choice for the therapy of the acute alcohol withdrawal syndrome. To assess the effect of three different alcohol withdrawal therapy regimens in traumatized chronic alcoholic patients with respect to the duration of mechanical ventilation and the frequency of pneumonia and cardiac disorders during their intensive care unit (ICU) stay.
                A prospective, randomized, blinded, controlled clinical trial.
                A university hospital ICU.
                Multiple-injured alcohol-dependent patients (n=180) transferred to the ICU after admission to the emergency room and operative management. A total of 180 patients were included in the study; however, 21 patients were excluded from the study after assignment.
                Patients who developed actual alcohol withdrawal syndrome were randomized to one of the following treatment regimens: flunitrazepam/clonidine (n=54); chlormethiazole/haloperidol (n=50); or flunitrazepam/haloperidol (n=55). The need for administration of medication was determined, using a validated measure of the severity of alcohol withdrawal (Revised Clinical Institute Withdrawal Assessment for Alcohol Scale).
                The duration of mechanical ventilation and major intercurrent complications, such as pneumonia, sepsis, cardiac disorders, bleeding disorders, and death, were documented. Patients did not differ significantly between groups regarding age, Revised Trauma and Injury Severity Score and Acute Physiology and Chronic Health Evaluation II score on admission. In all except four patients in the flunitrazepam/clonidine group, who continued to hallucinate, the Revised Clinical Institute Withdrawal Assessment for Alcohol Scale decreased to <20 after initiation of therapy. ICU stay did not significantly differ between groups (p=.1669). However, mechanical ventilation was significantly prolonged in the chlormethiazole/haloperidol group (p=.0315) due to an increased frequency of pneumonia (p=.0414). Cardiac complications were significantly (p=.0047) increased in the flunitrazepam/clonidine group.
                There was some advantage in the flunitrazepam/clonidine regimen with respect to pneumonia and the necessity for mechanical ventilation. However, four (7%) patients had to be excluded from the study due to ongoing hallucinations during therapy. Also, cardiac complications were increased in this group. Thus, flunitrazepam/haloperidol should be preferred in patients with cardiac or pulmonary risk. Further studies are required to determine which therapy should be considered. Sixty in-patient alcoholics, presenting with an alcohol withdrawal syndrome after at least one week's drinking bout, were randomly allocated to fixed dose regimens of either piracetam or chlormethiazole in a one-week double-blind trial. The patients were studied in respect to physical and biochemical parameters as well as symptom reduction and side-effects. The battery of rating scales demonstrated a good symptom reduction in both drug groups. On the whole a small tendency to more symptom items being reduced on piracetam in comparison with chlormethiazole was found. But the tree items, sleep disturbances, decreased libido at the initial phase, and the staff's assessment showed statistically significant differences in favour of chlormethiazole. This study demonstrated that piracetam was just as efficient as chlormethiazole in patients not requiring sedation. The authors conducted a randomized trial of second-line anticonvulsant treatments for neonates. The response to treatment was assessed using continuous video-EEG because the clinical diagnosis of seizure in neonates is known to be unreliable. Of 27 neonates with EEG-confirmed seizures, 5 were excluded because of protocol violations, and 11 responded to phenobarbitone in a dose of 40 mg/kg as first line. Three of five neonates treated with lignocaine responded. Six neonates were treated with benzodiazepines as second line: None responded, and their neurodevelopmental outcome was poor. Eighty patients admitted to a specialized alcohol detoxification unit, who had blood alcohol levels of .15% or less and were not currently intoxicated, participated in a double-blind trial involving treatment with either halazepam or chlordiazepoxide. A flexible dosage schedule was followed for 5 days with the objective of using the largest dose on the first day, followed by daily reductions as clinically feasible. Efficacy evaluations indicated that halazepam was as effective as chlordiazepoxide in the control of symptoms in patients hospitalized for the medical management of acute alcohol withdrawal. No significant side effects were noted. The effect of gamma-hydroxybutyric acid (GHB) on ethanol withdrawal syndrome in alcoholics was investigated in a randomised double-blind study. Patients with withdrawal symptoms were treated either with GHB (orally in a syrup preparation) (11 patients) or with the syrup alone (12). GHB treatment (50 mg/kg) led to a prompt reduction in withdrawal symptoms, such as tremors, sweating, nausea, depression, anxiety, and restlessness. The only side-effect was dizziness. GHB may be useful in the management of alcohol withdrawal syndrome in man. Alcohol withdrawal treatment efficacy of tiapride/carbamazepine (A) vs clomethiazole (B) vs diazepam (C) in non-intoxicated patients and vs tiapride/carbamazepine in intoxicated patients (D; breath alcohol concentration > or = 1 g/l) was tested (n = 127) in a controlled randomized open-label study.
                Efficacy and safety were not different between groups (total group: delirium, 3.9%; seizure, 0.8%), except for a lack of efficacy in 18% of intoxicated tiapride/carbamazepine patients. A change of medication in this group was necessary only when primarily intoxicated patients had reached the non-intoxicated range.
                Treatment with tiapride/carbamazepine in alcohol-intoxicated patients proved to be safe. Seventy-two hospitalized patients with alcohol withdrawal symptoms were treated with either carbamazepine (Tegretol) or barbital ( Diemal ) in a randomized, double-blind trial. The dose of trial medication as well as the duration of treatment was individual, corresponding to the conventional treatment schedule. During the trial period daily records were kept of target withdrawal symptoms, global evaluation, the patient's subjective feeling and unwanted effects. Sixty patients completed the treatment successfully. The two treatment groups were homogeneous as regards patient characteristics, pre-treatment disease severity and drop-out rate. No statistically significant differences were found in efficacy between the two treatments, and both drugs were well tolerated. It is concluded that carbamazepine is a valuable alternative drug in the treatment of mild and moderate alcohol withdrawal symptoms. For important reasons, lorazepam (Ativan) and chlordiazepoxide (Librium) are both popular treatments for alcohol-withdrawal syndrome. Nevertheless, there is little literature directly comparing the two drugs. A formal comparison is desirable because of pharmacokinetic and other differences that could affect safety and efficacy considerations relevant to practice in developing countries.
                One hundred consecutive consenting male inpatients in a state of moderately severe, uncomplicated alcohol withdrawal at screening were randomized to receive either lorazepam (8 mg/day) or chlordiazepoxide (80 mg/day) with dosing down-titrated to zero in a fixed-dose schedule across 8 treatment days. Double-blind assessments of withdrawal-symptom severity and impairing adverse events were obtained during treatment and for 4 days afterward.
                One chlordiazepoxide patient developed withdrawal delirium. Lorazepam and chlordiazepoxide showed similar efficacy in reducing symptoms of alcohol withdrawal as assessed using the revised Clinical Institute Withdrawal Assessment for Alcohol scale. During withdrawal, irritability and dizziness were more common with lorazepam, and palpitations were more common with chlordiazepoxide. No difficulties in drug discontinuation or differences in impairing adverse events were observed with either drug.
                With the treatment schedule used in this study, lorazepam is as effective as the more traditional drug chlordiazepoxide in attenuating uncomplicated alcohol withdrawal. Lorazepam, therefore, could be used with confidence when liver disease or the inability to determine liver function status renders chlordiazepoxide therapy problematic. The absence of clinically significant withdrawal complications with lorazepam in this large study contrasts with findings from previously published studies and suggests that higher doses of lorazepam than those formerly used may be necessary during alcohol withdrawal. The safety and efficacy of lorazepam and diazepam were compared in the treatment of the acute alcohol withdrawal syndrome during a five-day double-blind trial in alcoholic patients. The daily doses of lorazepam and diazepam were tapered from 6 or 8 mg to 2 mg and from 30 or 40 mg to 10 mg, respectively, during the first four days; no medication was given on day 5. Drug efficacy was measured by Total Severity Assessment Scores (TSAS), the three TSAS factor scores, and by the physician's global evaluation. Of the 55 inpatients enrolled, 47 completed the study. There were no statistically significant differences between the treatment groups in any of the efficacy assessment measures. The physical conditions of the majority of the patients treated with lorazepam (57%) and diazepam (59%) improved during therapy. There were no clinically significant differences between the treatment groups in vital signs or laboratory values. The results of this study indicate that lorazepam is as effective as diazepam in reducing the symptoms of acute alcohol withdrawal. When lorazepam and diazepam are compared in terms of their pharmacokinetics, lorazepam may have therapeutic advantages for the management of the acute alcohol withdrawal syndrome. Vigabatrin is a newly licensed drug for use in patients with epilepsy. We investigated whether this drug was comparable to standard first-line monotherapy in efficacy and incidence of adverse events.
                We enrolled 459 patients with newly diagnosed, previously untreated partial epileptic seizures from 44 European centres and randomly assigned them carbamazepine 600 mg daily (n=230) or vigabatrin 2 g daily (n=229). After initial maintenance doses were reached, doses were adjusted downwards (in the case of adverse events) or upwards (in the case of seizures) by the clinician. The primary outcome was time to withdrawal because of lack of efficacy or adverse events. Secondary outcomes included efficacy (time to 6-month remission of seizures, time to first seizure after initial dose stabilisation), and adverse events (incidence and severity). Analysis was by intention to treat.
                Time to withdrawal for lack of efficacy or adverse events did not differ between groups (p=0.318). Vigabatrin was better tolerated than carbamazepine with fewer withdrawals, but was more frequently associated with psychiatric symptoms (58 [25%] vs 34 [15%]) and weight gain (25 [11%] vs 12 [5%]). Carbamazepine was associated with rash (22 [10%] vs seven [3%]). All efficacy outcomes favoured carbamazepine and failed to show equivalence between the two drugs. No significant difference was found for time to achieve 6 months of remission from seizures (p=0.058), but the most powerful outcome, time to first seizure after the first 6 weeks from randomisation, showed carbamazepine to be significantly more effective than vigabatrin (p=0.0001).
                Vigabatrin seems less effective but better tolerated than carbamazepine, which is the first-choice drug for the treatment of partial epilepsies. Vigabatrin cannot therefore be recommended as a first-line drug for monotherapy in this group of patients. Insomnia is a central symptom of alcohol withdrawal and increases relapse potential. The primary objective of this study was to compare the efficacy of gabapentin to lorazepam in alleviating sleep disturbances and daytime sleepiness during an episode of alcohol withdrawal. The secondary objective of this study was to determine if drug treatment efficacy differed by the patient history of previous treatments for alcohol withdrawal.
                Outpatients in treatment for alcohol withdrawal received a 4-day fixed-dose taper of gabapentin or lorazepam in a double-blind, randomized, controlled trial with an 8-day follow-up. Daily across a 5 day outpatient treatment and Days 7 and 12 post-treatment, patients self-reported daytime sleepiness using the Epworth Sleepiness Scale. Self-reports of depression (Beck Depression Inventory) were completed at Days 1, 5, 7 and 12. Staff assessed daily alcohol withdrawal using the Clinical Institute Withdrawal Assessment for Alcohol. From these instruments, self-reported sleep and sleepiness were extracted and assessed in the context of limited (0-1) or multiple (2 or more) previously treated alcohol withdrawal episodes.
                Patients with limited previous withdrawals reported similar treatment effects on self-reports of sleep and sleepiness for gabapentin and lorazepam. In contrast, patients with multiple previous alcohol withdrawals receiving gabapentin reported reduced sleep disturbances and sleepiness in comparison to those receiving lorazepam.
                During treatment for alcohol withdrawal, gabapentin as compared to standard therapy with lorazepam, was superior on multiple sleep measures, in patients who had previous withdrawals. Lorazepam subjects experienced rebound symptoms. Early drinking was related to persisting insomnia with both drugs. A double-blind, randomized trial is described which was designed to compare the clinical effect of 600 mg daily of carbamazepine (Tegretol) and of tiapride (Sereprile) in hospitalized patients with pre-delirium tremens. Physicians' assessment of patients' progress was made following 2, 4 and 7 days of treatment. Of the sixty patients admitted to the study, five dropped out for various reasons, leaving fifty-five patients who completed the study. Both drugs were effective in the treatment of alcohol withdrawal symptoms; no significant difference was found between the two treatments with respect to total symptoms, score and visual analogue scale assessment. Carbamazepine gave faster relief of symptoms and demonstrated a preferential action on symptoms like fear and hallucinations. No case of delirium tremens was observed in those patients who completed the trial. Gabapentin was compared with phenobarbital for the treatment of alcohol withdrawal in a randomized, open-label, controlled trial in 27 inpatients. There were no significant differences in the proportion of treatment completers between treatment groups or the proportion of patients in each group requiring rescue medication for breakthrough signs and symptoms of alcohol withdrawal. There were no significant treatment differences in withdrawal symptoms or psychological distress, nor were there serious adverse events. These findings suggest that gabapentin may be as effective as phenobarbital in the treatment of alcohol withdrawal. Given gabapentin's favorable pharmacokinetic profile, further study of its effectiveness in treating alcohol withdrawal is warranted. 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.
Results of this review do not provide sufficient evidence in favour of anticonvulsants for the treatment of AWS. There are some suggestions that carbamazepine may actually be more effective in treating some aspects of alcohol withdrawal when compared to benzodiazepines, the current first-line regimen for alcohol withdrawal syndrome. Anticonvulsants seem to have limited side effects, although adverse effects are not rigorously reported in the analysed trials.