A double-blind, placebo-controlled trial of magnesium sulfate in the ethanol withdrawal syndrome. Magnesium treatment in alcoholics: a randomized clinical trial. Oral magnesium supplementation improves metabolic variables and muscle strength in alcoholics. Gamma-hydroxybutyric acid for treatment of alcohol withdrawal syndrome. Efficacy and safety of oral magnesium supplementation in the treatment of depression in the elderly with type 2 diabetes: a randomized, equivalent trial. Magnesium sulfate for neuroprotection after traumatic brain injury: a randomised controlled trial. Gamma-hydroxybutyric acid versus clomethiazole for the treatment of alcohol withdrawal syndrome in a medical intensive care unit: an open, single-center randomized study. Gamma-hydroxybutyric acid (GHB) in the treatment of alcohol withdrawal syndrome: a randomized comparative study versus benzodiazepine. Ability of calcium bis acetyl homotaurine, a GABA agonist, to prevent relapse in weaned alcoholics.
One hundred alcoholics treated for ethanol withdrawal were assigned randomly according to a double-blind protocol to receive four intramuscular injections of 2 g of magnesium sulfate at 6-hr intervals or an equivalent amount of normal saline. All patients were treated for signs of withdrawal according to a standardized protocol using orally-administered chlordiazepoxide for sedation. Three observers rated each patient for signs of withdrawal. There was no statistically significant difference between magnesium sulfate and placebo groups on any of the variables measured. The groups required equivalent amounts of chlordiazepoxide for control of withdrawal. The authors concluded that the routine administration of magnesium sulfate is not indicated for the management of alcohol withdrawal unless accompanied by cardiac arrhythmias. Magnesium (Mg) deficiency is common among alcoholics. Earlier research suggests that Mg treatment may help to normalize elevated enzyme activities and some other clinically relevant parameters among alcoholics but the evidence is weak.
                The effect of Mg was studied in a randomized, parallel group, double-blind trial. The patients were first treated for alcohol withdrawal symptoms and then received for 8 weeks either 500 mg of Mg divided into two tablets or matching placebo. Measurements were made at the beginning and in the end of the Mg treatment period. The primary outcome was serum gamma-glutamyltransferase (S-GGT) activity; secondary outcomes included aspartate-aminotransferase (S-AST) and alanine-aminotransferase (S-ALT) activity.
                The number of randomized patients (completers) was 64 (27) in the treatment and 54 (31) in the control group. In intention-to-treat-analyses and in most analyses of study completers, there were no significant differences between the Mg-treated and placebo groups in the outcome variables. When baseline serum Mg level, coffee intake, and the number of unused Mg tablets were controlled for in a multivariate regression model, after-treatment serum Mg levels were found to be higher among the Mg-treated group than in the placebo group (t-test 3.334, df = 53, p = 0.002). After controlling for age, body weight, baseline alcohol intake, subsequent change in alcohol intake and baseline S-AST, the after-treatment S-AST levels were found to be lower among the Mg-treated group than in the placebo group (t-test 2.061, df = 49, p = 0.045).
                Mg treatment may speed up the S-AST decrease in compliant patients. This might decrease the risk of death from alcoholic liver disease.
                ClinicalTrials.gov ID NCT00325299. Magnesium deficiency is common among chronic alcoholics, but the knowledge of oral magnesium supplementation to this group is limited. We, therefore, randomized 49 chronic alcoholics, moderate to heavy drinkers for at least 10 years to receive oral magnesium or placebo treatment for 6 weeks according to a double-blind protocol. Effects on metabolic variables and muscle strength were analyzed. Significant reduction of aspartate-aminotransferase (ASAT), alanine-aminotransferase (ALAT) and gamma-glutamyl-transpeptidase (GGT) were seen after magnesium, whereas no change was observed with placebo. Bilirubin decreased in both groups. Serum Na, Ca, and P increased significantly during magnesium therapy compared with no statistically significant change in the placebo group. Serum K and Mg increased slightly after magnesium supplementation and decreased in the placebo group, resulting in a significant difference between the two groups at the end of the study. Muscle strength increased significantly during magnesium treatment, contrasting to no change with placebo. Blood pressure, heart rate, hematological variables, serum lipids (cholesterol, HDL, TG), glucose tolerance, and creatinine were unchanged in the two groups after treatment. Alcohol consumption was similar before and during the trial and does not explain the differences between the two groups The results shows that short-term oral magnesium therapy may improve liver cell function, electrolyte status, and muscle strength in chronic alcoholics. 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. To evaluate the efficacy and safety of oral magnesium supplementation, with magnesium chloride (MgCl2), in the treatment of newly diagnosed depression in the elderly with type 2 diabetes and hypomagnesemia. Twenty-three elderly patients with type 2 diabetes and hypomagnesemia were enrolled and randomly allocated to receive either 50 mL of MgCl2 5% solution equivalent to 450 mg of elemental magnesium or Imipramine 50 mg daily during 12 weeks. Widowhood or divorce in the last six months, alcoholism, degenerative illnesses of the nervous central system, recent diagnosis of diabetes, previous or current treatment with antidepressants, chronic diarrhea, use of diuretics, and reduced renal function were exclusion criteria. Hypomagnesemia was defined by serum magnesium levels < 1.8 mg/dL and depression by Yasavage and Brink score > or = 11 points. The primary trial end point was the improvement of depression symptoms. At baseline, there were no differences by age (69 +/- 5.9 and 66.4 +/- 6.1 years, p = 0.39), duration of diabetes (11.8 +/- 7.9 and 8.6 +/- 5.7 years, p = 0.33), serum magnesium levels (1.3 +/- 0.04 and 1.4 +/- 0.04 mg/dL, p = 0.09), and Yasavage and Brink Score (17.9 +/- 3.9 and 16.1 +/- 4.5 point, p = 0.34) in the groups with MgCl2 and imipramine, respectively. At end of follow-up, there were no significant differences in the Yasavage and Brink score (11.4 +/- 3.8 and 10.9 +/- 4.3, p = 0.27) between the groups in study; whereas serum magnesium levels were significantly higher in the group with MgCl2 (2.1 +/- 0.08 mg/dL) than in the subjects with imipramine (1.5 +/- 0.07 mg/dL), p < 0.0005. In conclusion, MgCl2 is as effective in the treatment of depressed elderly type 2 diabetics with hypomagnesemia as imipramine 50 mg daily. Traumatic brain injuries represent an important and costly health problem. Supplemental magnesium positively affects many of the processes involved in secondary injury after traumatic brain injury and consistently improves outcome in animal models. We aimed to test whether treatment with magnesium favourably affects outcome in head-injured patients.
                In a double-blind trial, 499 patients aged 14 years or older admitted to a level 1 regional trauma centre between August, 1998, and October, 2004, with moderate or severe traumatic brain injury were randomly assigned one of two doses of magnesium or placebo within 8 h of injury and continuing for 5 days. Magnesium doses were targeted to achieve serum magnesium ranges of 1.0-1.85 mmol/L or 1.25-2.5 mmol/L. The primary outcome was a composite of mortality, seizures, functional measures, and neuropsychological tests assessed up to 6 months after injury. Analyses were done according to the intention-to-treat principle. This trial is registered with , number .
                Magnesium showed no significant positive effect on the composite primary outcome measure at the higher dose (mean=55 average percentile ranking on magnesium vs 52 on placebo, 95% CI for difference -7 to 14; p=0.70). Those randomly assigned magnesium at the lower dose did significantly worse than those assigned placebo (48 vs 54, 95% CI -10.5 to -2; p=0.007). Furthermore, there was higher mortality with the higher magnesium dose than with placebo. Other major medical complications were similar between groups, except for a slight excess of pulmonary oedema and respiratory failure in the lower magnesium target group. No subgroups were identified in which magnesium had a significantly positive effect.
                Continuous infusions of magnesium for 5 days given to patients within 8 h of moderate or severe traumatic brain injury were not neuroprotective and might even have a negative effect in the treatment of significant head injury. 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. 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. After they had been weaned off alcohol in hospital 85 severe alcoholics (above 200 g alcohol/day) were included in a double-blind study of calcium bis acetyl homotaurine (Ca AOTA, 25 mg/kg/day), a new gamma-aminobutyric acid agonist, versus placebo. Patients were treated as outpatients during the 3-month study. The only other treatment that patients received was meprobamate, 800 to 1200 mg/day, in the first month. The criterion for success was abstinence at 3 months (with normal gamma-glutamyl transpeptidase being one of the criteria). Of the 70 patients who completed the study, 33 received Ca AOTA and 37 placebo. 20 patients on Ca AOTA did not relapse, compared with 12 on placebo (p less than 0.02 by X2 test). Side-effects were noted by 7 patients on Ca AOTA and 2 on placebo. The results suggest that Ca AOTA may be useful in helping severe alcoholics who have been weaned off alcohol not to relapse.
There is insufficient evidence to determine whether magnesium is beneficial or harmful for the treatment or prevention of alcohol withdrawal syndrome.