Lithium Carbonate and Mood Disorder in Recently Detoxified Alcoholics: A Double-Blind, Placebo-Controlled Pilot Study

The effects of lithium carbonate were assessed in a double-blind, placebo-controlled study of a small group of recently detoxified alcoholics. The patients were treated during their 2nd and 3rd week of abstinence. A previous study demonstrated the existence in these patients of a syndrome of mildly elevated psychomotor rate, including irritability, grandiosity, an increased need for social contact, loquaciousness, and sexual preoccupation. The intensity of this syndrome was significantly decreased by treatment with low dose lithium carbonate, with no effect of placebo treatment.     

A Double-Blind, Placebo-Controlled Pilot Study of Carbamazepine for the Treatment of Alcohol Dependence

Carbamazepine, chemically related to the tricyclic antidepressants, has multiple clinical actions. It is a potent anticonvulsant, mild sedative, and mood stabilizer. It is nonaddictive and has little toxicity when clinical and laboratory monitoring is performed. It has proven efficacy in the treatment of acute alcohol withdrawal. Kindling and protracted withdrawal are the theoretical rationale for the mechanism of its action in the treatment of alcohol dependence. This 12-month double-blind placebo-controlled pilot study of 29 subjects evaluated the efficacy of carbamarepine for the treatment of alcohol dependence. Subjects were randomly assigned to either placebo or carbamazepine. A baseline assessment and bimonthly follow-up for 12 months assessed demographic variables, mood and functioning, treatment compliance, drinking behaviors, biological markers of drinking, and medication toxicity. Despite the small sample size, compliance difficulties after 4 months and a sizable drop-out rate, there were treatment effects favoring carbamazepine. Univariate analyses showed a decrease in drinks per drinking day and maximum number of heavy drinking days in a row at 2 and 4 months of follow-up. Survival analysis revealed a significant delay in time to first episode of heavy drinking, and close to a trend level of significance for time to first drink. There were significant time, but not time by treatment group, effects on multiple measures of mood. These pilot results are encouraging and support carbamazepine as a possible pharmacologic tool in the treatment of alcohol dependence.     

A Double‐Blind,Placebo‐Controlled Study With Quetiapine as Adjunct Therapy With Lithium or Divalproex in Bipolar I Patients With Coexisting Alcohol Dependence

Background: This study evaluated the efficacy of quetiapine versus placebo as an adjunct to lithium or divalproex in reducing alcohol consumption in patients with bipolar I disorder and coexisting alcohol dependence. Methods: Male and female outpatients (21 to 60 years) with a history of bipolar I disorder and alcohol dependence were included in this 12‐week, placebo‐controlled study. Patients treated with lithium or divalproex (ongoing or assigned at screening) were randomized to receive quetiapine (dosed up to 400 mg/d over 7 days, followed by 300 to 800 mg/d flexible dosing until study end) or placebo. The primary outcome measure was the change in the proportion of heavy drinking days from baseline to Week 12 (as derived from the Timeline Followback method). Secondary outcome measures included time to the first consecutive 2 weeks of abstinence, changes from baseline to Week 12 in the proportion of nondrinking days, mean number of standardized drinks per day, and Clinical Global Impressions‐Severity of Illness score. Results: Of 362 enrolled patients (mean 38.6 years), 176 were randomized to receive quetiapine and 186 to placebo. The mean proportion of heavy drinking days at baseline was 0.66 in the quetiapine group and 0.67 in the placebo group. At Week 12, the mean change in the proportion of heavy drinking days was ?0.36 with quetiapine and ?0.36 with placebo (p = 0.93). No statistically significant differences in any of the secondary outcome measures were noted between the quetiapine and placebo groups. The incidence of adverse events was consistent with the previously known tolerability profile of quetiapine. Conclusions: The efficacy of quetiapine in the treatment of bipolar disorder is already well established. In this study, however, quetiapine added to lithium or divalproex did not result in significantly greater improvement compared with placebo in measures of alcohol use and dependence in patients with bipolar I disorder and alcohol dependence.     

A Double-Blind, Placebo-Controlled Pilot Study to Evaluate the Efficacy and Safety of Oral Nalmefene HCI for Alcohol Dependence

A dozen studies have been published showing that opiate antagonists suppress alcohol drinking in animals, and two independent placebo-controlled, double-blind clinical trials of naltrexone found this agent was associated with decreased alcohol craving and consumption in alcohol-dependent patients. Nalmefene is a newer opiate antagonist that has a number of potential advantages over naltrex-one in the treatment of alcoholism, including no dose-dependent association with liver toxicity and more effective binding to central opiate receptors. Consequently, a double-blind pilot study was conducted to gather preliminary data on the safety and efficacy of nalmefene for reducing alcohol consumption in alcohol-dependent subjects. Twenty-one alcohol-dependent subjects meeting admission criteria were randomly assigned to 12 weeks of double-blind treatment with 40 mg nalmefene, 10 mg nalmefene, or placebo, resulting in 7 patients/treatment group. Nalmefene was well tolerated, with no serious adverse drug reactions. The 40 mg group had a significantly lower rate of relapse ( p 0.05), and a greater increase in the number of abstinent days/week ( p 0.09), than the other treatment groups. A significant decrease in the number of drinks/drinking day was noted for both nalmefene groups ( p 0.04), but not for placebo. These results were supported by parallel decreases in ALT. These pilot data provide preliminary support for the hypotheses that nalmefene can be safely given to alcoholics, and that nalmefene may have a role in reducing alcohol consumption and preventing relapse, particularly at the 40 mg level. A full-scale study is underway to confirm these preliminary findings.     

A Systematic Review of Naltrexone for Attenuating Alcohol Consumption in Women with Alcohol Use Disorders

Several clinical trials have evaluated naltrexone as a treatment for alcohol use disorders (AUDs), but few have focused on women. The aim of this review was to systematically review and summarize the evidence regarding the impact of naltrexone compared to placebo for attenuating alcohol consumption in women with an AUD. A systematic review was conducted using PubMed, Cochrane, Web of Science, CINAHL, and Alcohol Studies Database to identify relevant peer‐reviewed randomized controlled trials (RCTs) published between January 1990 and August 2016. Seven published trials have evaluated the impact of naltrexone on drinking outcomes in women distinct from men; 903 alcohol‐dependent or heavy drinking women were randomized to receive once daily oral or depot (injectable) naltrexone or placebo with/without behavioral intervention. Two studies examining the quantity of drinks per day observed trends toward reduction in drinking quantity among women who received naltrexone versus placebo. The 4 studies examining the frequency of drinking had mixed results, with 1 study showing a trend that favored naltrexone, 2 showing a trend that favored placebo, and 1 that showed no difference. Two of the 3 studies examining time to relapse observed trends that tended to favor naltrexone for time to any drinking and time to heavy drinking among women who received naltrexone versus placebo. While the growing body of evidence suggests a variety of approaches to treat AUD, the impact of naltrexone to combat AUD in women is understudied. Taken together, the results suggest that naltrexone may lead to modest reductions in quantity of drinking and time to relapse, but not on the frequency of drinking in women. Future research should incorporate sophisticated study designs that examine gender differences and treatment effectiveness among those diagnosed with an AUD and present data separately for men and women.     

Bupropion-SR for Smoking Cessation in Early Recovery from Alcohol Dependence: A Placebo-Controlled,Double-Blind Pilot Study

We conducted a double-blind pilot study involving 11 alcohol- and nicotine-dependent patients randomized to receive either bupropion or placebo. Four of six patients on bupropion and one of five patients on placebo were abstinent from smoking at the end of medication phase. Those in the bupropion group reported significantly less craving (p < .02) and less exposure to cigarette smoke over time (expired carbon monoxide; p < .01). There were no serious adverse events and no main effects of medication group on either per subject or total number of adverse events. All those who completed treatment remained abstinent from alcohol.