Antagonist and partial agonist at the dopamine D2 receptors in drug-naïve and non-drug-naïve schizophrenia: a randomized, controlled trial.

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Few data are available on the efficacy and safety of antipsychotics with different dopamine D2 receptor (D2-R)-binding properties in drug-naïve and non-drug-naïve schizophrenia. Thus, we aimed to assess whether antipsychotic medication history influences efficacy and tolerability in schizophrenia, based on a randomized controlled study of antipsychotics with mechanisms involving either full antagonism or partial agonism of D2-R. Patients with schizophrenia were recruited and given perospirone or aripiprazole in a 12-week, flexible-dose, open-label, randomized controlled study. Data were analyzed after dividing the patients into antipsychotic-naïve and antipsychotic-treated group according to antipsychotic medication histories. Efficacy and safety were evaluated using the Positive and Negative Syndrome Scale (PANSS), the Drug-Induced Extrapyramidal Symptoms Scale, and the Barnes Akathisia Rating Scale. In patients receiving perospirone, the antipsychotic-naïve group (n = 22) showed greater symptom improvement than that shown by the antipsychotic-treated group (n = 29), as assessed by efficacy evaluation scales such as the PANSS total, positive, and excited component score (p = .006, p < .001, p = .003, respectively). In patients receiving aripiprazole, however, there was no significant difference in efficacy between the antipsychotic-naïve (n = 18) and antipsychotic-treated (n = 31) groups. No significant intra-group or inter-group difference was noted with respect to any of the tolerability-related parameters assessed. The present study data support the hypothesis that antipsychotic medication history may influence efficacy in patients who receive a D2-R full antagonist but not a D2-R partial agonist.