Flupenthixol as a potential pharmacotreatment of alcohol and cocaine abuse/dependence

Preclinical and clinical studies suggest that the mesolimbic dopamine system plays a major role in mediating the reinforcing effects of drugs of abuse, including alcohol and psychostimulants, and that pharmacological blockade of dopamine D1 and/or D2 receptors may reduce intake of these drugs, as well as relapse rates. The neuroleptic flupenthixol, which has dopamine D1 and D2 receptor antagonist properties and which may be given intramuscularly in order to improve compliance, has been studied as a possible anti-craving drug in substance abuse disorders. Flupenthixol has been shown to attenuate the discriminative stimulus effects of psychostimulants, as well as their intake in animal models of drug abuse. In addition, the compound was found to reduce alcohol intake in a rat model of alcoholism, but the 'anti-alcohol' effect appeared to be only weakly selective and nonspecific. Clinically, the drug has been studied in alcoholics, cocaine addicts and in patients with comorbid psychiatric disorders. Although the data base is still limited and a number of recent trials have not been completely analyzed, these studies suggest that flupenthixol may be useful in decreasing cocaine consumption. Recent studies in alcoholism, however, have shown disappointing results. A number of pilot studies suggest that probably the most promising area may be the treatment of substance abuse/dependence in patients with comorbid psychiatric disorders. Future studies should focus on dosing issues, the differentiation between short- and long-term effects and the identification of subgroups of patients with particular psychopathology.