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A substantial body of evidence supports a role for serotonin in modulating alcohol intake, which suggests that this neurotransmitter represents a promising target for pharmacotherapy development for alcohol use disorders. Dexfenfluramine. a serotonin releaser and reuptake inhibitor, decreases alcohol self-administration by rats. Its greater potency and several mechanisms of action suggest it should be more effective in treating alcohol dependence than drugs that only inhibit serotonin reuptake.We conducted an 11 week, randomized, double-blind trial that compared oral placebo and dexfenfluramine 7.5, 15, 22.5, and 30 mg bid in 136 alcohol-dependent patients. A brief behavioral intervention was offered concurrently.The majority of subjects were male (72%), and the age of the group was 44 +/- 1 years (mean +/- SD). Both placebo- and drug-treated groups significantly reduced alcohol consumption compared with baseline (a 55% decrease in mean drinks per day; p0.01), but there were no significant differences between drug and placebo groups or dose effects for most outcome measures.Our results with dexfenfluramine are further evidence that serotonergic medications on their own do not significantly reduce alcohol consumption in alcohol-dependent individuals. Combination pharmacotherapy with agents that act on different receptors or neurotransmitter systems (e.g., naltrexone plus dexfenfluramine) may be one way to enhance serotonergic effects on drinking behavior and should be considered in future medication development clinical trials.

The incidence of nonmedical use of alprazolam is very low relative to its widespread legitimate medical use; in fact, given the millions of patients who have received this medication, the incidence is remarkably small. In particular, among patients with anxiety disorders, dependence does not appear to be a clinically important problem. Alprazolam abuse and dependence represent only a small fraction of the large and serious nonmedical use problem in the United States, and when they occur, are among individuals who abuse other drugs. For example, a serious problem of alprazolam abuse may exist among patients in methadone maintenance treatment. A similar problem exists with diazepam. Alcohol abusers and alcohol-dependent individuals are another group among whom concern about benzodiazepine and alprazolam abuse exists. However, more and better information about the extent and nature of this use is needed. Many patients with alcohol or drug abuse also have anxiety disorders for whom effective pharmacotherapy may be needed. In the interim, caution but not prohibition to use should prevail in prescribing alprazolam to such patients. To the extent that nonmedical alprazolam use exists, evidence suggests that the vast majority of such use is the consequence of the inappropriate prescribing of the medication by a small number of physicians. One way to reduce the inappropriate use of benzodiazepines in methadone programs is to drug test the methadone-maintenance patients and to link positive urine tests to contingency-management strategies. The available data provide some support to the idea that alprazolam and diazepam have more abuse liability than other benzodiazepines.

The pharmacologic effects of lorazepam (2 mg), buspirone (20 mg, 10 mg), secobarbital (100 mg), and placebo were compared in 15 male, experienced, intermittent nontherapeutic drug users. All drugs produced a "drug effect," however, buspirone 20 mg was significantly less liked than were lorazepam, secobarbital, or buspirone 10 mg (p less than .05) but not placebo. Lorazepam was liked better than were other drugs only at 1 hour and only compared with buspirone 20 and placebo. Compared with other drugs, lorazepam drug effects were greater and resulted in more prolonged impairment of a motor tracking task, standing steadiness, and memory. Buspirone 20 mg significantly impaired memory at 1 hour compared with placebo. Subjects were more likely to identify buspirone as unfamiliar. Because buspirone 20 mg was less liked than were other drugs, dose escalation as part of drug abuse is not likely to occur. Lorazepam also was not particularly liked and was not different from placebo on most subjective abuse-relevant measures.