麻豆传媒

FARMINGTON, Conn., April 3 -- The atypical antipsychotic aripiprazole (Abilify), modified the behavioral and physiological effects of alcohol, according to a preliminary study.

Aripiprazole significantly increased the sedative and, to a lesser degree, decreased the euphoric effects of a moderate dose of alcohol in a group of healthy social drinkers, Henry R. Kranzler, M.D., of the University of Connecticut here, and colleagues, reported in the April issue of Alcoholism: Clinical & Experimental Medicine.

Aripiprazole, approved for bipolar disorder and schizophrenia, is a dopamine partial agonist with partial activity at D₂, and 5-HT _1A receptors. Since dopamine is involved in the rewarding effects of alcohol, the researchers considered that the drug might reduce these effects.

To test that theory, they recruited 18 healthy social drinkers (nine men, mean age 27.6) for a within-subject design study, in which each participant served as his or her own control. The participants were well educated and drinking was moderate during the 90 days before study enrollment.

The moderate drinkers reported at least three drinks a week and at least three drinks on one occasion in the previous month.

Each participant completed three experimental sessions in a randomized sequence. On the day before the laboratory session they received no medication, aripiparzole 2.5 mg, or aripiprazole 10 mg.

During each session, the participants consumed three standard drinks for a total of 0.8 g/kg of alcohol for the men, and 0.7 g/kg for the women.

Breath alcohol concentrations, heart rate, blood pressure, static ataxia, and subjective effects were measured regularly throughout the lab sessions.

Alcohol consumption produced expected physiological and subjective responses.

Pre-treatment with aripiprazole was generally well tolerated, with tiredness the most commonly reported adverse event (reported by 14 individuals at the 10 mg dose and seven at the 2.5 mg dose).

Nausea also varied as a function of dosage. Other adverse effects included sleepiness and difficulty sleeping. Neither tiredness nor nausea was reported for the no-medication session.

The drug was associated with modest physiological effects. Specifically, the dosage directly increased heart rate, particularly among men and non-white individuals.

Effects were also noted for blood pressure, with the medication increasing systolic pressure among women and diastolic pressure among whites. However, the drug had no effect on static ataxia.

With respect to subjective effects, as hypothesized, the higher drug dosage decreased some of the reinforcing effects of alcohol, while increasing its dose-dependent sedative effects. For example, for each mg increase in the drug, the sedative effects increased by approximately 1.04 units (SE=0.42).

To a lesser degree, the drug reduced alcohol's euphoric effects. The 10 mg dose decreased the euphoric effects of alcohol relative to no-medication and the 2.5 mg dosage.

Specifically, for each mg increase in drug dose, the euphoria score decreased by 0.40 units (SE=0.16).

Although the findings failed to reach statistical significance, the drug at 10 mg also decreased scores on the stimulation subscale, and as anticipated, given the drug's sedative effects, the 10 mg dose increased sedation scores on the various scales.

Given these findings, the researchers said, the medication could be of use for treating heavy drinkers.

The profile effects shown in this study suggest that the medication may be useful in reducing drinking by reducing alcohol's positive effects and increasing its negative effects, Dr. Kranzler said.

Other antipsychotic drugs, he said, such as haloperidol (Haldol) and olanzapine (Zyprexa), which are full dopamine antagonists, reduce the pleasurable effects of alcohol, but are associated with more adverse affects than those of aripiprazole.

The results must be considered in the context of the study's limitations, the researchers acknowledged. These included the lack of placebo control, the small size of the study, use of only an acute dose of aripiprazole, and inclusion of healthy social drinkers, rather than heavy drinkers. Also, the study lacked a measure for craving.

Future placebo-controlled research should test the drug on heavier drinkers and non-treatment-seeking alcoholics under longer-dosing and natural drinking conditions, the researchers said.

The study was supported by an unrestricted grant from Bristol-Myers Squibb and by grants from the National Institutes of Health and the University of Connecticut General Clinical Research Center. No financial conflicts were reported.

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