title: Antagonist and partial agonist at the dopamine D2 receptors in drug-naïve and non-drug-naïve schizophrenia: a randomized, controlled trial.
abstract: 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.
authors.affiliation: Department of Biomedical and NeuroMotor Sciences, University of Bologna, Viale Carlo Pepoli 5, 40123, Bologna, Italy. takekity@takii.kmu.ac.jp.|Department of Neuropsychiatry, Kansai Medical University, 10-15 fumizono-cho, Moriguchi-shi, Osaka, 570-8506, Japan. takekity@takii.kmu.ac.jp.
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Takekita
authors.affiliation: Department of Biomedical and NeuroMotor Sciences, University of Bologna, Viale Carlo Pepoli 5, 40123, Bologna, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fabbri
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, 10-15 fumizono-cho, Moriguchi-shi, Osaka, 570-8506, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe-shi, Kobe, 650-8530, Japan.
authors.forename: Shinpei
authors.initials: S
authors.lastname: Nonen
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, 10-15 fumizono-cho, Moriguchi-shi, Osaka, 570-8506, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Sakai
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, 10-15 fumizono-cho, Moriguchi-shi, Osaka, 570-8506, Japan.
authors.forename: Naotaka
authors.initials: N
authors.lastname: Sunada
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, 10-15 fumizono-cho, Moriguchi-shi, Osaka, 570-8506, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Koshikawa
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, 10-15 fumizono-cho, Moriguchi-shi, Osaka, 570-8506, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Wakeno
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, 10-15 fumizono-cho, Moriguchi-shi, Osaka, 570-8506, Japan.
authors.forename: Gaku
authors.initials: G
authors.lastname: Okugawa
authors.affiliation: Department of Neuropsychiatry, Kansai Medical University, 10-15 fumizono-cho, Moriguchi-shi, Osaka, 570-8506, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kinoshita
authors.affiliation: Department of Biomedical and NeuroMotor Sciences, University of Bologna, Viale Carlo Pepoli 5, 40123, Bologna, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Serretti
mesh_terms: D000328:Adult; D000368:Aged; D017109:Akathisia, Drug-Induced / Q000209:etiology; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D000068180:Aripiprazole / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000139:chemically induced; D018491:Dopamine Agonists / Q000627:therapeutic use*; D065127:Dopamine D2 Receptor Antagonists / Q000627:therapeutic use*; D054333:Drug Partial Agonism; D005260:Female; D006801:Humans; D054833:Isoindoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017448:Receptors, Dopamine D2 / Q000819:agonists; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D013844:Thiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D065127:Dopamine D2 Receptor Antagonists; D054833:Isoindoles; D017448:Receptors, Dopamine D2; D013844:Thiazoles; D000068180:Aripiprazole; C065533:perospirone
keywords: Antipsychotic medication history; Aripiprazole; Drug naïve; Perospirone; Response; Schizophrenia