Alcohol Dependence may respond to Aripiprazole

Aripiprazole is currently approved by the US Food and Drug Administration to treat bipolar disorder as well as schizophrenia. A study of aripiprazole's potential for treating alcohol dependence has found that it significantly and dose-dependently increases the sedative effects of alcohol and, to a lesser degree, decreases the euphoric effects of alcohol.

Results are published in the April issue of Alcoholism: Clinical & Experimental Research.

"Aripiprazole is a dopamine partial agonist," explained Henry R. Kranzler, a professor in the department of psychiatry at the University of Connecticut Health Center and corresponding author for the study. "Since dopamine is involved in the rewarding effects of alcohol, we thought that aripiprazole might reduce those effects."

"Aripiprazole is an unusual drug in that it has different pharmacological effects at different doses and it might do one thing acutely and another during chronic dosing," said Raymond F. Anton, Distinguished University Professor and director of the Clinical Neurobiology Laboratory at the Medical University of South Carolina. "In general, it appears to have the potential to reduce drinking if you get the dose right for an individual patient. More work needs to be done to 'fine tune' its effectiveness, which is what this study attempts to do."

Researchers recruited 18 social drinkers from the community: nine men and nine women between the ages of 21 and 45 years of age. Each participant completed three experimental sessions in a randomized sequence; receiving on the day before the laboratory session either no medication, or 2.5 mg or 10 mg of aripiprazole. During each session, 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 (body sway), and subjective effects were measured regularly throughout the laboratory sessions.

"Findings show that aripiprazole made the drinkers sleepier and they experienced less pleasure from alcohol than they might have without it," said Kranzler.

"Aripiprazole might 'shift the balance' from alcohol being more stimulating to being more sedating," added Anton. "This has implications for both treatment and side-effect management for people taking this medication, [becoming] a balance of useful versus aversive effects. Most other dopamine-blocking drugs have too many aversive [or side] effects that make them not suitable for treatment of alcohol-use disorders. Aripiprazole might be more tolerated and have less long-term negative effects."

Kranzler concurred. "Other antipsychotic drugs - such as haloperidol and, olanzapine, which are full dopamine antagonists - reduce the pleasurable effects of alcohol, but they are associated with more adverse effects than aripiprazole is. The list of side effects associated with most medications that exert powerful enough effects to be of value in treating psychosis is long. The ones that occur substantially more commonly than with placebo are headaches, insomnia, nausea, dizziness, and vomiting."

"Aripiprazole is one of a growing list of medications that are being evaluated for the treatment of alcoholism," said Anton. "Readers should really see this as preliminary evidence and should be on the lookout for more studies to inform them of the potential treatment utility of aripiprazole by itself or in combination with other medications for alcohol-use disorders." He suggested that future research test aripiprazole on heavier drinkers and non-treatment-seeking alcoholics under longer-term dosing and natural drinking conditions, and also explore potential genetic predictors of its stimulatory versus sedation effects, with and without alcohol.

"These findings help to demonstrate that alcohol has effects on many different brain chemicals and, as such, that many different treatment approaches for alcohol dependence may be useful," said Kranzler. "That having been said, it's unclear whether aripiprazole will be very useful in this effort because its side effects may outweigh its beneficial effects."

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