A randomized, double-blind comparison of lorazepam and chlordiazepoxide in patients with uncomplicated alcohol withdrawal. A double blind study of chlordiazepoxide and hydroxyzine HC1 therapy in acute alcohol withdrawal utilizing chronic electromyography for tremor assessment. Treatment of the acute alcohol withdrawal state: a comparison of four drugs. Comparative efficacy of propranolol and chlordiazepoxide in alcohol withdrawal. Is daily single dosage of diazepam as effective as chlordiazepoxide in divided doses in alcohol withdrawal--a pilot study. [Gamma-hydroxybutyrate for treatment of alcohol withdrawal syndrome in intensive care patients. A comparison between with two symptom-oriented therapeutic concepts]. Residual effects of ethanol and chlordiazepoxide treatments for alcohol withdrawal. Clinical conditions and central dopamine metabolism in alcoholics during acute withdrawal under treatment with different pharmacological agents. Comparison of chlormethiazole (Heminevrin) and chlordiazepoxide (Librium) in the treatment of acute alcohol withdrawal. Halazepam in the management of acute alcohol withdrawal syndrome. Effects of beta-blocking drugs in alcohol withdrawal: a double-blind comparative study with propranolol and diazepam. Double-blind study of cyamemazine and diazepam in the alcohol withdrawal syndrome. Therapy of alcohol withdrawal syndrome in intensive care unit patients following trauma: results of a prospective, randomized trial. A double-blind comparison of the efficacy and safety of lorazepam and diazepam in the treatment of the acute alcohol withdrawal syndrome. Thioridazine HC1 Vs. chlordiazepoxide HC1 in controlling symptoms attributable to alcohol withdrawal. Comparison of two benzodiazepines in the treatment of alcohol withdrawal: effects on symptoms and cognitive recovery. MMPI and drug treatment in alcohol withdrawal. Alprazolam versus chlormethiazole in acute alcohol withdrawal. Delirium tremens: a comparison of intravenous treatment with diazepam and chlordiazepoxide. Drug treatment of anxiety and depression in detoxified alcoholic patients. Double-blind study of alprazolam, diazepam, clonidine, and placebo in the alcohol withdrawal syndrome: preliminary findings. Antiglutamatergic strategies for ethanol detoxification: comparison with placebo and diazepam. Control of acute alcoholic withdrawal symptoms: a comparative study of haloperidol and chlordiazepoxide. Gamma-hydroxybutyric acid (GHB) in the treatment of alcohol withdrawal syndrome: a randomized comparative study versus benzodiazepine. Gamma-hydroxybutyrate reduces both withdrawal syndrome and hypercortisolism in severe abstinent alcoholics: an open study vs. diazepam. A controlled trial of chlormethiazole and chlordiazepoxide in the treatment of the acute withdrawal phase of alcoholism. A comparison of the efficacy and tolerability of clobazam and chlordiazepoxide in the treatment of acute withdrawal from alcohol in patients with primary alcoholism. Tiapride and chlordiazepoxide in acute alcohol withdrawal. A controlled clinical trial. Alcohol withdrawal treatment in intoxicated vs non-intoxicated patients: a controlled open-label study with tiapride/carbamazepine, clomethiazole and diazepam. Treatment of delirium tremens. A comparative evaluation of four drugs. Benzoctamine and oxazepam in the management of alcohol withdrawal states. Comparison by double-blind trial. Nonpharmacologic intervention in acute alcohol withdrawal. Double-blind controlled trial of bromocriptine, chlordiazepoxide and chlormethiazole for alcohol withdrawal symptoms. Double-blind comparison of lorazepam and chlordiazepoxide in the treatment of the acute alcohol abstinence syndrome. Double blind study on the efficacy and safety of tetrabamate and chlordiazepoxide in the treatment of the acute alcohol withdrawal syndrome. Enlarged double-blind randomised trial of benzodiazepines against psychotropic analgesic nitrous oxide for alcohol withdrawal. Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial. Carbamazepine versus oxazepam in the treatment of alcohol withdrawal: a double-blind study. Transdermal clonidine versus chlordiazepoxide in alcohol withdrawal: a randomized, controlled clinical trial. Divalproex sodium (Depakote) for alcohol withdrawal and relapse prevention. Delirium tremens: a double-blind comparison of diazepam and barbital treatment. Clonidine vs chlordiazepoxide in the management of acute alcohol withdrawal syndrome. Comparative evaluation of treatments of alcohol withdrawal syndromes. Clorazepate dipotassium (Tranxene): a controlled evaluation in alcoholic patients after withdrawal. Double-blind trial of alprazolam and chlordiazepoxide in the management of the acute ethanol withdrawal syndrome. The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial. Double-blind controlled trial comparing carbamazepine to oxazepam treatment of alcohol withdrawal. Self-reported sleep, sleepiness, and repeated alcohol withdrawals: a randomized, double blind, controlled comparison of lorazepam vs gabapentin. Alcohol withdrawal severity is decreased by symptom-orientated adjusted bolus therapy in the ICU. Propranolol versus diazepam in the management of the alcohol withdrawal syndrome: double-blind controlled trial. Double-blind comparison of alprazolam and diazepam for subchronic withdrawal from alcohol. A double-blind comparison of abecarnil and diazepam in the treatment of uncomplicated alcohol withdrawal. [Comparative study of chlordiazepoxide and hypertonic MgSO4 in the alcohol withdrawal syndrome]. Clinical symptomatology and computer analyzed EEG before, during and after anxiolytic therapy of alcohol withdrawal patients. Diazepam loading: simplified treatment of alcohol withdrawal.
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. nan nan Propranolol alone was more effective than either chlordiazepoxide or a combination of chlordiazepoxide and propranolol in alleviating the symptoms of the alcohol withdrawal syndrome. nan 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. Eighteen male alcoholics were randomly assigned to one of two alcohol detoxification treatments. One group received a low dose ethanol treatment while the other group received a chlordiazepoxide treatment. This study compares recovery of sleep EEG and clinical symptomatology following these two detoxification treatments. Sleep EEG and clinical measures were obtained for the final medication day and during a 6-day postmedication "recovery" period. The chlordiazepoxide treatment produced suppression of rapid eye movement (REM) sleep lasting for about 4 days and virtually eliminated delta sleep (stages III and IV) during the recovery period. The low dose ethanol treatment regimen produced less disruption of REM and delta sleep during the recovery period. These findings suggest that under some circumstances an ethanol treatment regimen may prove more beneficial to the healthy alcoholic patient than current regimens which employ other psychoactive medication. In particular, the long lasting suppression of delta sleep during the recovery period in subjects treated with chlordiazepoxide suggests a vulnerability of the slow wave sleep mechanisms during early alcohol abstinence and raises the possibility that this regimen prolongs functional tolerance to alcohol effects. Continued clinical evaluation of low dose ethanol detoxification treatment is suggested. A group of 45 male alcoholics were studied during acute withdrawal. Patients were kept in hospital and treated with amobarbital (15 patients), oxazepam (15 patients), and melperone (15 patients) respectively in a double-blind design. Clinical symptoms were rated with a modified version of the Comprehensive Psychopathological Rating Scale after 1, 4 and 7 days. Blood pressure, body temperature and pulse rate were also recorded. Lumbar cerebrospinal fluid was collected after 1 and 7 days. A group of healthy males served as controls. The three treatment groups showed only small differences with regard to the investigated clinical items, except for a higher incidence of epileptic fits being evidenced in the melperone group. Levels of HVA in the cerebrospinal fluid did not differ between the treatment groups and the controls and did not change during treatment. Statistically significant correlations were noted between levels of HVA and auditory and visual hallucinations as well as concentration difficulties. Assuming that HVA levels reflect the activity of the central nervous dopamine system, the findings indicate a connection between central dopamine metabolism, psychotic symptoms and possibly other symptoms during acute alcohol withdrawal in man. 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. 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. 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. Cyamemazine is an original phenothiazine derivative which showed similar efficacy and tolerability to lorazepam during ethanol withdrawal in mice. This study investigated cyamemazine for its efficacy and tolerability in alcohol-dependent patients electing an alcohol withdrawal procedure, in comparison with diazepam.
                A multicenter, randomized, double-blind study in 89 alcohol-dependent patients (CIWA-Ar score between 10 and 30), electing an alcohol withdrawal procedure, was used to find effective doses of cyamemazine and to compare it with diazepam for efficacy and tolerability. On day 1 (D(1)), cyamemazine or diazepam (50 mg and 10 mg capsule, respectively) were administered at hourly intervals to reduce CIWA-Ar = 5, up to a maximum of eight administrations. Starting from D(2), the compounds were given twice a day in progressively decreasing doses during a maximum period of 13 days (D(end)).
                At h(8) (8 h after the first treatment of D(1)), therapeutic success (CIWA-Ar score </= 5) was achieved in 32 out of 43 ITT patients treated with cyamemazine (74.4%), a value very similar to that of diazepam (32/44; 72.7%). Most such patients (29/32) were controlled with 2-6 capsules of cyamemazine (100-300 mg). In the PP population, cyamemazine (n = 28) was significantly non-inferior to diazepam (n = 33), with a threshold of 10% for non-inferiority bound and 2.5% for one-sided type I error rate. Such therapeutic similarity was confirmed by the analysis of other efficacy criteria. Safety analysis did not show substantial differences between the two treatments.
                Cyamemazine showed similar efficacy and tolerability to diazepam for the treatment of alcohol withdrawal symptoms at therapeutic doses in the range 100-300 mg.
                Copyright (c) 2005 John Wiley & Sons, Ltd. 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. 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. nan 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. Thirty-four inpatients in a mild phase of alcohol withdrawal, exhibiting anxious and depressive symptoms, were administered an MMPI before and immediately after a 4-week drug treatment period. A double-blind design was used; 17 patients were treated with chlordiazepoxide and 17, with thioridazine. The pretreatment MMPI profile was typical of alcoholic patients; namely, peaks on scales 4 and 2. After the fourth week, the MMPI indicated that thioridazine was significantly more effective than chlordizaepoxide. Decreases in 7 of the 10 clinical scales averaged 7.29 T-score points, whereas only scale 6 was significantly decreased for the patients treated with chlordiazepoxide. nan nan nan 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. 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. nan 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. 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. nan 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. 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. 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. nan nan The importance of nonpharmacologic and pharmacologic interventions in the treatment of alcohol withdrawal is not known. A randomized, double-blind, placebo-controlled trial was conducted with 41 patients in alcohol withdrawal in an emergency department. The patients received either supportive care (10 min of standardized assessments, reassurance, reality orientation, and nursing care an hour) with three doses of sublingual lorazepam 2 mg every 2 hr (21 patients, drug group) or supportive care with three doses of sublingual placebo every 2 hr (20 patients, no-drug group). Immediately before each drug dose, the clinical course of alcohol withdrawal was assessed hourly by the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-A). Interraters reliability in using CIWA-A was high. After each assessment, supportive care was given for 10 min before each dose. After completion of a 7-hr initial phase, patients were discharged and reassessed daily for 5 days. Thirty-seven patients (90.2%) improved in the initial phase. Treatment failures (CIWA-A greater than 10) were more common in the patients treated without drug (3/20, 15%) than in those treated with drug (1/21, 4.8%). Overall variations in intergroup CIWA-A scores during the initial phase were not significant. The rate of improvement of CIWA-A scores over the first 2 hr after drug was slightly faster in patients receiving lorazepam than in the control group. CIWA-A scores were the same during follow-up. These results indicate that most outpatients in mild to moderate alcohol withdrawal without medical complications improve without drug therapy in the emergency department setting. Seventy-one patients undergoing withdrawal from alcohol were randomly assigned to treatment with oral bromocriptine, chlormethiazole or chlordiazepoxide. Forty-one percent had alcoholic hepatitis and/or cirrhosis. Patients were stratified into two groups: major and minor withdrawal symptoms. The latter group included a placebo tratment. Bromocriptine was ineffective in treating withdrawal symptoms, whilst chlormethiazole and chlordiazepoxide were equally effective. These findings do not support the evidence from animal and clinical studies suggesting that the disturbances in the dopaminergic system found in alcohol dependence and withdrawal can be reversed by dopamine agonists. 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. 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. 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. 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. 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. In a prospective, double-blind comparison, we assessed the efficacy of transdermal clonidine with that of chlordiazepoxide in the treatment of moderately severe acute alcohol withdrawal syndrome. While having significant withdrawal symptoms, 50 hospitalized men were randomly assigned to receive either transdermal clonidine or chlordiazepoxide over a 4-day study period. Outcome was evaluated daily, medically and psychiatrically, using both objective and subjective measurements for dependent variables. No patient in either study group had seizures or progression to delirium tremens. The group receiving transdermal clonidine had a more significant response globally for the signs and symptoms of alcohol withdrawal, as measured by the Alcohol Withdrawal Assessment Scale. Also, clonidine more effectively lowered elevated systolic and diastolic blood pressure and heart rate. The core target symptom, anxiety, decreased significantly more in the patients receiving transdermal clonidine when measured by the Hamilton Anxiety Rating Scale and its subscale for somatic anxiety. Cognitive function responded equally in both study populations. Clonidine-treated patients reported less diarrhea, dizziness, headache and fatigue, and the chlordiazepoxide-treated patients reported less nausea and vomiting. We conclude that transdermal clonidine is effective treatment for the acute alcohol withdrawal syndrome. 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. The effect of diazepam and barbital in the treatment of delirium tremens and other acute conditions related to alcohol abuse was evaluated in a double-blind trial. 91 patients participated in the study, 44 in the diazepam group, 47 in the barbital group. The choice of diazepam rather than chlordiazepoxide was motivated by its major anticonvulsive properties. Barbital was given by the oral route, diazepam as intramuscular injections. Different ways of drug administration to patients with delirium tremens are discussed. It is concluded that the two different ways used in the study probably did not have a noteworthy influence on the results. All patients were excluded who had taken psychoactive drugs before admission. Nevertheless a considerable part of the patients had diazepam, but not barbital, in the blood before treatment was initiated. This may give support to the use of barbital as a "special purpose drug" in the treatment of these conditions. The patients were divided into three diagnostic categories, according to the severity of the clinical condition. No difference between the two drugs tested was found in the milder conditions, but barbital was found superior to diazepam in the treatment of fully developed delirium tremens. 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. nan nan A sequential sample of 101 patients hospitalized for ethanol withdrawal and requiring sedation for evolving withdrawal syndromes was assigned randomly according to a double-blind protocol to treatment with either alprazolam or chlordiazepoxide administered orally. The data from one patient were unevaluable due to acute bleeding, leaving a sample of 100 (50 in each condition). At discharge, three independent ratings of diaphoresis, tremor, hallucinations, nausea/vomiting, and overall severity of withdrawal were obtained, and the occurrence of delirium tremens and grand mal seizures was noted. Patients also completed the Beck Depression Inventory, and their disposition following discharge was recorded. There were no statistically significant differences between the two treatment groups on any of the dependent variables studied. It was concluded that the choice between alprazolam and chlordiazepoxide for managing ethanol withdrawal should be based on criteria other than efficacy of control. Potential antidepressant effects and drug kinetics were suggested as the basis for rational decision-making. 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. 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. 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. 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. Thirty-seven male alcoholics admitted electively for detoxification were randomized to treatment with either diazepam or propranolol. Subjects were comparable both in age and in duration and quantity of alcohol consumed. Admission laboratory parameters did not distinguish between the groups. Eleven subjects required no medication to control withdrawal signs/symptoms. Both groups showed improvement in blood pressure, pulse, and withdrawal tremor. None of the subjects randomized to diazepam manifested withdrawal seizures or hallucinations. By contrast, one subject in the propranolol group had a single withdrawal seizure. Another subject manifested increasing withdrawal that required parenteral paraldehyde treatment. Thus, this study confirms that a significant number of subjects admitted electively for alcohol withdrawal can be managed without medication. Minor tranquilizers still remain the "gold standard" for management of the withdrawal syndrome. The efficacy and safety of a new triazolobenzodiazepine, alprazolam, was compared to diazepam in 46 alcoholics in a double-blind study. The drugs were administered for 21 days starting on the fifth day after the last drink. The mean optimal daily oral dose of alprazolam was 2.2 mg and of diazepam 20.2 mg given in a t.i.d. fashion. Alprazolam was as effective as diazepam in the relief of anxiety as measured by the Hamilton Anxiety Rating Scale, Physician's Global Impressions, Patient's Global Impressions, Hopkins Symptom Checklist and Target Symptoms Record. At the end of the trial 95% of patients in both groups experienced moderate to marked therapeutic effect and felt much or very much better as compared to the start of the study. The number of side effects was similar in both groups and they were mostly described by patients as "mild". 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. nan In a double-blind study the clinical symptomatology and quantitatively analyzed EEG of 42 hospitalized chronic alcoholics (ICD 303) undergoing alcohol withdrawal were investigated before, during and after 3 weeks' treatment with 2 pharmacokinetically different benzodiazepines: the short-acting lopirazepam (a new pyridodiazepine) and the long-acting prazepam. At the end of weeks 1 and 3 the titrated optimal daily doses were 24 and 23 mg lopirazepam and 35 and 32 prazepam, respectively, thus confirming our earlier pharmaco-EEG predictions that on a mg to mg basis the former drug is slightly more CNS potent than the latter. Thereafter, the patient population was divided into 6 subgroups: 2 groups continuing on active medication, 2 groups receiving placebo, and 2 groups with no pharmacotherapy for 1 week. Clinical assessments included the CGI, the Hamilton Anxiety Score, the Zung Self-Rating Scale for Anxiety and Depression, the Zerssen Befindlichkeitsskala and the questionnaire for somatic findings and side effect and were carried out on days 0, 7, 21 and 28 as was a radioreceptor assay for benzodiazepines in plasma. Quantitative EEG investigations were carried out on days 0, 21 and 28 and included recordings before and 2 h after one single dose of 10 mg. Statistical analysis demonstrated a marked and highly significant decrease in psychopathology as well as good drug tolerance at the end of the first week of therapy and thereafter a slight continuation in improvement until the end of the 3rd week. There were, however, no statistically significant differences between the 2 active compounds, nor were there any statistically significant differences between the 6 subgroups in the 4th week. On the other hand, blood level investigations demonstrated that even after a 3-week treatment period, blood levels dropped down to a morning minimum 12 h after the last evening medication of the short-acting lopirazepam, while plasma levels of the long-acting prazepam remained high. This was also reflected in the spectral analyzed EEG, which showed, after one single dosage of both drugs, a typical anxiolytic profile which was more pronounced after lopirazepam than prazepam, while after the chronic administration (12 h after the evening medication) only prazepam showed an anxiolytic profile. The lopirazepam-treated patients exhibited on the one hand a lack of benzodiazepine-specific alterations, but showed on the other hand EEG changes possibly reflecting clinical improvement. The relevance of the findings will be discussed. Alcohol withdrawal therapy can be simplified with a loading dose of diazepam, taking advantage of the kinetic tapering afforded by the drug's long t 1/2s and its metabolites, and of the effectiveness of nonpharmacologic maneuvers. In a double-blind trial, 50 inpatients in moderate to severe alcohol withdrawal received 20 mg oral diazepam and supportive care (n = 25) or placebo and supportive care (n = 25) every 2 hr until they were asymptomatic. Fifty-six percent of patients responded to placebo within 5 +/- 2.9 hr (mean +/- SD), whereas 72% responded to initial diazepam within 6.3 +/- 3.9 hr. Patients treated with diazepam had more rapid and greater improvement than those treated with placebo. Patients who did not respond to six doses of diazepam received further (unblinded) diazepam, 20 mg, every 1 to 2 hr. All patients who did not initially respond (n = 18) improved after more diazepam. Thus all patients who received diazepam (n = 36), during the experimental phase or subsequently, were effectively treated. There were no adverse effects. The median number of 20-mg diazepam doses to treat alcohol withdrawal were three, given over a period of 7.6 hr (range = 1 to 12 and 0.33 to 45 hr). Complications occurred only in those who received placebo during the experimental phase, indicating that delay in therapy may be responsible for the appearance of complications in alcohol withdrawal.
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.