Pharmacoeconomic Evaluation of Perospirone in the Treatment of Schizophrenia ：A Study Based on Major Adverse Events / 中国药房

OBJECTIVE：To evaluate the economy of pe rospirone in the treatment of schizophrenia ，to provide guidance for clinically proper use of medications more cost-effectively ，and related health decision-making . METHODS ：A short-term decision tree model was constructed from the perspective of medical insurance payer to calculate the cost and health outcomes of different treatment plans considering major adverse events including extrapyramidal reaction ，weight gain ，diabetes，hyperlipidemia. The cost-utility of perospirone were compared with quetiapine ，aripiprazole and olanzapine respectively ，using QALYs as the measure of health outcomes ，3 times GDP per capita as the willingness-to-pay threshold ；probability sensitivity analysis was performed. RESULTS：The results of base-case analysis showed that the cost of perospirone （6 688.25 yuan）was lower than those of quetiapine （9 887.45 yuan），aripiprazole（13 284.65 yuan）and olanzapine （15 332.80 yuan）. The utility of perospirone （0.79 QALYs）was better than those of quetiapine （0.76 QALYs），aripiprazole（0.77 QALYs）and olanzapine （0.75 QALYs）. Compared with quetiapine ， aripiprazole and olanzapine ，peropirone had lower cost and higher health outcome ，which indicated that strong dominance favors perospirone over the other 3 drugs. The results of sensitivity analysis were consistent with those of base-case analysis. CONCLUSIONS：Perospirone has economic advantages in treating schizophrenia patients compared to other commonly used atypical antipsychotic drugs.

Perospirone versus Risperidone in the Treatment of Schizophrenia: A Systematic Review / 中国药房

OBJECTIVE:To systematically evaluate the therapeutic efficacy and safety of perospirone versus risperidone in the treatment of schizophrenia,and to provide evidence-based reference for clinical treatment.METHODS:Retrieved from Wanfang database,VIP,CJFD,CBM and PubMed,randomized controlled trials (RCTs) of perospirone(trial group) vs.risperidone (control group) in the treatment of schizophrenia were collected.After data extraction and quality evaluation of included studies according to modified Jadad evaluation criteria,Meta-analysis of response indexes was performed by using Rev Man 5.0 statistical software.RESULTS:A total of 12 RCTs were included,involving 1 050 patients.Results of Meta-analysis showed,the cure rate of 2 groups had no statistical significance [OR=0.99,95％CI(075,1.30),P=0.93].The incidences of extrapyramidal reactions [OR=0.63,95％CI(0.43,0.92),P=0.02],the incidences of prolactin levels increasing [OR=0.23,95％CI(0.14,0.38),P＜0.001] and the incidences of weight gain [OR=0.23,95％CI(0.13,0.39),P＜0.001] in control group were significantly higher than trial group,with statistical significance (P＜0.05).CONCLUSIONS:The therapeutic efficacy of perospirone and risperidone is similar in the treatment of schizophrenia,but the safety of perospirone is better than that of risperidone.

Clinical Observation of Perospirone in the Treatment of Elderly Depression / 中国药房

OBJECTIVE:To observe therapeutic efficacy and side effect of perospirone in the treatment of elderly depression. METHODS:64 elderly patients with depression were randomly divided into paroxetine combined with perospirone group (drug combination group) and paroxetine group (single drug group) with 32 patients in each group. Both groups were given paroxetine 20-40 mg/d,and drug combination group was additionally given perospirone 4-8 mg/d. HAMD and CGI-SI were adopted to evalu-ate therapeutic efficacy after 8 weeks treatment,and side effect was evaluated with TESS scale;those were compared between 2 groups. RESULTS:After 8 weeks treatment,the effective rate of drug combination group and single drug group were 75.0% and 50.0%;there was statistical significance(P0.05). CONCLUSIONS:Small-dose of perospirone can improve therapeutic efficacy of paroxetine in the treatment of elderly depression with less side effect and good safety.

Long-term Efficacy and Tolerability of Perospirone for Young Help-seeking People at Clinical High Risk: a Preliminary Open Trial

OBJECTIVE: Interest in the "at-risk mental state" (ARMS) for psychosis has increased because early intervention is expected to delay or prevent the onset of schizophrenia. However, the optimum intervention strategy remains controversial, especially with regard to antipsychotics. Although administration of antipsychotic medications is often associated with adverse effects and raises ethical considerations, recent studies have shown that some novel antipsychotics are safer and more tolerable for young people than conventional antipsychotics. We investigated whether administration of perospirone, a combined serotonin (5-HT)/dopamine antagonist and 5-HT1A receptor agonist, could alleviate prodromal symptoms and be well tolerated by clinical high risk patients. METHODS: The participants were outpatients seeking help. The Structured Interview for Prodromal Symptoms was performed in patients identified as being at clinical high risk. The Scale of Prodromal Symptoms (SOPS) was also completed and changes of subjective experience were assessed with the Subjective Well-being under Neuroleptics, short version. The incidence of akathisia was recorded by using the Barnes Akathisia Scale. Subjects were monitored for 26 weeks after starting medication. RESULTS: SOPS scores improved significantly after 26 weeks of perospirone therapy, while BAS scores did not show deterioration. No serious adverse events occurred during the study. CONCLUSION: This trial suggests that perospirone therapy provides a clinical benefit for clinical high risk subjects without causing serious adverse events. Although further placebo-controlled studies are needed for confirmation, perospirone might be one of optimum treatments for individuals at imminent risk of psychosis.

Genetic Polymorphisms in Dopamine- and Serotonin-Related Genes and Treatment Responses to Risperidone and Perospirone

We investigated the possible association between genetic polymorphisms in the dopamine receptor and serotonin transporter genes and the responses of schizophrenic patients treated with either risperidone or perospirone. The subjects comprised 27 patients with schizophrenia who were clinically evaluated both before and after treatment. The genotyping of the polymorphisms of the dopamine D2 receptor gene (DRD2) (rs1801028 and rs6277), the dopamine D4 receptor gene (DRD4) (120-bp tandem repeats and rs1800955), and serotonin transporter gene (5HTT)(variable number of tandem repeats; VNTR) were performed using the real-time polymerase chain reaction and sequencing. In DRD2 and 5HTT-VNTR, there were no significant correlations between clinical response and polymorphism in the case of risperidone, and for perospirone treatment it was impossible to analyze the clinical evaluation due to the absence of genotype information. On the other hand, in DRD4 there were significant correlations in the two-factor interaction effect on the Positive and Negative Syndrome Scale (PANSS) between the two drugs [120-bp tandem repeat, p=0.003; rs1800955, p=0.043]. Although the small sample represents a serious limitation, these results suggest that variants in DRD4 are a predictor of whether treatment will be more effective with risperidone or with perospirone in individual patients.

Survey regarding pregnant women receiving novel antipsychotic agents / 医薬品情報学

<b>Objective</b>: Novel antipsychotic agents less frequently cause extrapyramidal side effects compared to conventional antipsychotic agents, contributing to improvement in the QOL.  Recently, these agents have also been increasingly prescribed to females who may become pregnant.  In Japan, no epidemiological survey regarding the application of novel antipsychotic agents in pregnant women has been published.  In this study, we investigated the influence on fetuses in pregnant women receiving novel antipsychotic agents.<br><b>Methods</b>: In pregnant women on novel antipsychotic agents who consulted the Pregnancy and Drug Consultation Outpatient Clinic of Toranomon Hospital, the outcome of pregnancy was confirmed.<br><b>Results</b>: Twenty-nine pregnant women took novel antipsychotic agents in the organogenesis phase, in which the risk of teratogenicity is the highest.  The agents consisted of olanzapine in 8 patients, risperidone in 11, quetiapine fumarate in 7, and perospirone hydrochloride hydrate in 4.  The outcomes of pregnancy were full-term delivery in 24 patients, premature delivery in 1, spontaneous abortion in 2, and artificial abortion in 2.  Of the 29 patients, 15 (60%) had continuously taken these agents until delivery.  All 25 neonates were healthy without malformation.<br><b>Conclusion</b>: This report describes the first prospective survey in Japan regarding infants delivered by pregnant women receiving novel antipsychotic agents.  All patients delivered healthy neonates; the incidence of congenital anomalies did not exceed that in the general population.  This survey included a small number of patients; cohort studies should be conducted to evaluate the safety in fetuses.

Determination of the Dissolution of Perospirone Hydrochloride Tablets / 中国药房

OBJECTIVE:To establish a method for the determination of the dissolution of perospirone hydrochloride tablets(PHT).METHODS:The dissolution of PHT was determined in accordance with Chinese Pharmacopeia(2005 Edition) using water as solvent with the rotation speed at 50 r?min~(-1).The sample was taken at 30 minutes with its absorbability detected at a wavelength of 316 nm determinated by UV.Then the dissolution was calculated.RESULTS:The linear range of perospirone hydrochloride was 2～20?g?mL~(-1)(r=0.999 9)with an average recovery at 99.76%(RSD = 0.27%).The dissolutions of 3 batches of samples were all above 80%.CONCLUSION:The method was proved to be simple and reliable, and it can be used to determine the dissolution of PHT.