A 12-week randomized, open-label study of perospirone versus aripiprazole in the treatment of Japanese schizophrenia patients

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Abstract

Object

To evaluate the efficacy and safety of aripiprazole and perospirone in Japanese patients with schizophrenia.

Methods

In this 12-week, randomized, flexible-dose, open-label study, patients diagnosed with schizophrenia were randomized to receive aripiprazole (3–30 mg/day, n = 49) or perospirone (8–48 mg/day, n = 51). Efficacy and safety were evaluated using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression-Severity Scale (CGI-S), the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) and the Barnes Akathisia Rating Scale (BAS) before treatment and every 4 weeks after the initiation of treatment.

Results

Fifty-eight patients completed this study (aripiprazole, n = 31; perospirone, n = 27). No significant differences in gender, episode, age, schizophrenia type, weight, previous treatment and PANSS score were observed between the two groups at baseline. Both groups showed significant improvements during the study, with reductions in the total PANSS scores (Repeated measure analysis of variance, both p < 0.0001). There were no significant differences in the PANSS change scores, CGI-S change scores, DIEPSS total score, BAS total score or over time between groups. The most common adverse event was insomnia in both groups.

Conclusions

In Japanese schizophrenia patients, aripiprazole and perospirone showed equal efficacy, tolerability and patient compliance. Both drugs showed good efficacy for treating schizophrenia. This paper is the first randomized study to evaluate the comparative efficacy and safety of aripiprazole and perospirone in the treatment of patients with schizophrenia.

Highlights

► Perospirone and aripiprazole showed good efficacy for the treatment of schizophrenia. ► No significant difference was found in efficacy and tolerability between two drugs. ► Perospirone may improve anxiety and depression earlier than aripiprazole.

Introduction

Launched in the 1980s, second-generation antipsychotics (SGAs) have greatly influenced drug therapies for schizophrenia. Currently, international guidelines for schizophrenia recommend SGAs as a first-choice treatment (Falkai et al., 2005, Lehman et al., 2004, Moore et al., 2007). Clinically, SGAs are distinguished from first-generation antipsychotics by few extrapyramidal symptoms (EPS) and their effectiveness for negative symptoms. However, SGAs as a group are pharmacologically diverse and include serotonin dopamine antagonists, dopamine D2 partial agonists, dopamine D2 antagonists with rapid dissociation and serotonin partial agonists at 5HT1A receptors.

One of the most frequently prescribed SGAs in Japan since 2001 is perospirone, which has a unique pharmacological character in that it is a high-affinity antagonist for D2 receptors and 5HT2A receptors while also acting as a partial agonist for 5HT1A receptors (Sekine et al., 2006, Shiwa et al., 2003). With these pharmacological properties, perospirone is expected to affect not only positive but also negative symptoms.

Aripiprazole, well known as a partial agonist at the D2 receptors, is similar to perospirone in serotonergic action, i.e. both agents act as a partial agonist at the 5HT1A receptors and as an antagonist at the 5HT2A receptors (Hirose et al., 2004, Jordan et al., 2002, Kikuchi et al., 1995, Potkin et al., 2003).

These two drugs are antipsychotics that are frequently used in Japan. Both drugs have been reported to sufficiently improve positive and negative symptoms with low incidence of sedation. Accordingly, to choose between 2 agents with similar effects, hypotheses should be proposed on the basis of data from clinical studies with high evidence levels such as randomized controlled trial. But only one randomized clinical trial using perospirone has been performed thus far (Okugawa et al., 2009), and none have directly compared aripiprazole and perospirone in schizophrenia patients. Therefore, we performed a randomized controlled trial comparing perospirone and aripiprazole for the clinical treatment of schizophrenia. The main object of this study was to evaluate the effects of perospirone vs. aripiprazole for the treatment of schizophrenia over a 12-week period.

Section snippets

Study design

This randomized, flexible-dose, open-label, 12-week clinical study was performed at Kansai Medical University Takii Hospital from October 2006 to July 2011, in accordance with the Declaration of Helsinki. Institutional review board approval was obtained from Kansai Medical University. All participants provided their written informed consent.

Patients

Subjects were inpatients (36%) and outpatients (64%), > 15 years age, meeting the diagnostic criteria for schizophrenia established by the DSM-IV-TR.

Patients and treatment

In total, 100 patients were randomly assigned to either aripiprazole (n = 49) or perospirone (n = 51). All patients were included in the final analysis (Fig. 1). Baseline demographic and clinical characteristics were similar for both groups (Table 1). Eight patients (15.6%) in the aripiprazole and 6 (11.8%) in the perospirone group discontinued their treatment because of adverse events. Overall, the proportions completing assigned treatments were similar for aripiprazole (63.3%) and perospirone

Discussion

This research is the first open-label randomized controlled study to compare the efficacy, tolerability, and safety of aripiprazole and perospirone in schizophrenia patients. The primary efficacy scores of the two drugs showed significant improvements from the baseline values (aripiprazole =  13.9, perospirone =  15.6, all p < 0.0001). Moreover, for both drugs, there were no significant differences between the baseline values and the endpoints in the measures evaluating efficacy and tolerability,

Conclusion

This study is the first randomized controlled trial comparing aripiprazole and perospirone in schizophrenia patients. Our results revealed both aripiprazole and perospirone to be useful and to have equal efficacy and tolerability profiles for treating schizophrenia. Marginal differences were seen in the early effects on anxiety and depression, which favored perospirone. Further investigation of these differences is warranted.

Role of funding source

This work was supported by a grant from the Promotion and Mutual Aid Corporation for Private Schools of Japan and Grant-in-Aid for Scientific Research (no.23791357). Two study sponsors had roles in the study design, the data collection, the data analysis, the data interpretation, the report writing, and the decision to submit for publication.

Contributors

Yoshiteru Takekita, Masaki Kato, Masataka Wakeno, and Gaku Okugawa designed the study. Yoshiteru Takekita obtained funding and supervised the study. Yoshiteru Takekita, Masaki Kato, Shiho Sakai, Azusa Suwa, Keiichiro Nishida, Gaku Okugawa, and Toshihiko Kinoshita interpreted the data and drafted the report. All of the authors contributed to and have approved of the final manuscript.

Acknowledgments

The authors thank Drs. Satoshi Irisawa, Masafumi Yoshimura, Katunori Takase, Aran Tajika, Keizo Yamada, Hiroshi Mii, Yuichi Kitaura, Takeshi Kitamoto, Yoko Unoda, Yoshiko Fujiyama, Aki Yoneyama, Nao Abe, Tomoyasu Murata, Ayumi Suzuki, Satoshi Kono, Yoshimi Sasaoka, Risa Hama, and Takahiro Unoda, for data collection.

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