In patients with a psychotic disorder, substance abuse is a major problem. Substance abuse is associated with changes in dopaminergic neurotransmission of dopamine D1 and D2 receptors. Differences in efficacy between antipsychotics on substance abuse could be explained by differences in D2 receptor occupancy rate, differences in dissociation rate of the dopamine D2 receptor and differences in D1/D2 receptor occupancy ratio. Since clozapine and risperidone show a maximal difference in these properties, we review the effect of these antipsychotics on substance abuse. The results suggest a superior effect of clozapine for the long-term treatment of substance abuse. This could support the hypothesis that low occupancy of the dopamine D2 receptor, a high dissociation rate and a high D1/D2 receptor ratio is related to efficacy on substance abuse. The results of this review suggest that clozapine could be considered as the medication of first choice in treating patients with substance use disorder.
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