Treating Alcohol Dependence

The opioid antagonist naltrexone is approved for the treatment of alcohol dependence at an oral dosage of 50 mg daily. However, an alternative to daily use is for patients to take naltrexone when they anticipate a high-risk drinking situation. This targeted use of naltrexone seems to be particularly effective in men, according to a study by Kranzler and associates.¹

Their study included 163 heavy drinkers whose goal was to reduce their drinking to safe limits. The participants were instructed to use naltrexone (50 mg) or placebo either daily or targeted to situations they considered to be high risk for heavy drinking. The participants also received brief biweekly counseling. An interactive voice-response system was used to obtain daily reports of naltrexone use and drinking.

After 12 weeks, the primary outcome measure-mean drinks per day-was significantly lower in men in the targeted naltrexone group than in participants in the other groups. Those in the naltrexone group had fewer drinks per drinking day than those in the placebo group.

In a separate study, Anton and associates² assessed the efficacy of combining flumazenil (a benzodiazepine receptor antagonist) and gabapentin (a stabilizer of the γ-aminobutyric acid and glutamate systems) in the treatment of alcohol dependence. Their study included 60 alcohol-dependent persons, 16 of whom had significant pretreatment alcohol withdrawal symptoms. The participants were randomly assigned to receive intravenous flumazenil and oral gabapentin or placebo. Alcohol withdrawal was assessed for 2 days, and drinking, sleeping parameters, and adverse events were monitored weekly. The participants also had weekly behavioral counseling sessions.

There was no main effect of flumazenil and gabapentin on the primary outcomes measures-percent of days abstinent and time to first heavy drinking day. However, the medication resulted in significant improvement in both outcomes among the participants who had pretreatment alcohol withdrawal symptoms. This pattern was maintained for up to 8 weeks after treatment.

References
1. Kranzler HR, Tennen H, Armeli S, et al. Targeted naltrexone for problem drinkers. J Clin Psychopharmacol. 2009;29:350-357.
2. Anton RF, Myrick H, Baros AM, et al. Efficacy of a combination of flumazenil and gabapentin in the treatment of alcohol dependence: relationship to alcohol withdrawal symptoms. J Clin Psychopharmacol. 2009;29:334-342.

Mortality Risks in Patients With Schizophrenia
An increased mortality risk in schizophrenic patients has been well documented, but the effect of long-term antipsychotic therapy on mortality risk is unknown. After reviewing 12 studies, Weinmann and coworkers¹ concluded that there is some evidence that long-term use of antipsychotics increases mortality risk, although the results of studies comparing first-generation and second-generation agents have been inconsistent. In contrast, the results of a study in Finland suggest that long-term treatment with antipsychotic drugs is associated with decreased mortality risk.²

Tiihonen and colleagues² compared mortality data from 66,881 schizophrenic patients with data from the total population between 1996 and 2006. The proportional use of second-generation antipsychotics increased from 13% to 64% between 1996 and 2006, but the gap in life expectancy between patients with schizophrenia and the general population did not widen. In 1996, 20-year-olds with schizophrenia had a life expectancy of 32.5 years, compared with 57 years for the general population. In 2006, the life expectancies were 37.4 years and 59.9 years, respectively.

Compared with the current use of the typical antipsychotic perphenazine, the lowest risk of overall mortality was associated with clozapine, while the highest risk was associated with quetiapine. Long-term cumulative exposure to any antipsychotic agent was associated with decreased mortality risk, compared with no drug use.

It is clear that many factors-cancer, cardiovascular disease, and suicide, just to name a few-contribute to the increased risk of death in patients with schizophrenia. Improving their ability to manage their health care needs, access appropriate medical care, and adhere to prescribed therapy should translate into reduced morbidity and mortality. In fact, Copeland and associates³ recently reported that increased use of primary care was significantly associated with improved survival in patients with schizophrenia.

References
1. Weinmann S, Read J, Aderhold V. Influence of antipsychotics on mortality in schizophrenia: systematic review. Schizophr Res. 2009;113:1-11.
2. Tiihonen J, Lnnqvist K, Wahlbeck K, et al. 11-Year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet. 2009;374:620-627.
3. Copeland LA, Zeber JE, Wang CP, et al. Patterns of primary care and mortality among patients with schizophrenia or diabetes: a cluster analysis approach to the retrospective study of healthcare utilization. BMC Health Serv Res. 2009;9:127.