Risperidone治疗精神分裂症的临床研究

本文介绍新药Ｒｉｓｐｅｒｉｄｏｎｅ治疗精神分裂症的临床研究进展

新药Risperidone治疗精神分裂症的临床研究

报告了新型非典型抗精神病药物Risperidone治疗精神分裂症的临床研究结果，通过自身对照及与氟哌啶醇、奋乃静、氯氮平对照研究发现，Risperidone对阴、阳性症状有效，尤对阴性症状效果好，而且很少有锥外系副反应，是一种很有前途的抗精神病药物。

Platelet cytochrome c-oxidase activity in patients with acute schizophrenia in the course of their treatment with risperidone

Objectives: Testing a hypothesis, that platelet cytochrome c-oxidase (COX) activities in patients with paranoid schizophrenia, acute episode, may be linked to dynamics of their clinical patterns and quality of cognitive functioning under antipsychotic treatment. Methods: Psychopatho-logical (PANSS, NSA-16) and cognitive assess-ments;platelet COX enzymatic activity determination, post-hoc nonparametric statistical analysis. Results: Psychopathological and cognitive assessments were done and blood was sampled in patients before (at baseline) and after treatment with risperidone. Following regu- larities were found after the treatment of patients: Significant elevation of COX, wherein the higher was COX at baseline, the more prominent was decrease in PANSSneg and NSA rates;significant negative correlation between COX and executive time in cognitive tests. When the patient group was divided by median of COX at baseline into two subgroups (greater or equal median, and 20% was assigned to the first subgroup;significantly larger amount of patients with PANSSneg by <20% was assigned to the second group. Conclusions: Therapy with risperidone seems to be more effective for patients with higher COX activity at baseline, but this fact requires further study.

Different effects of paliperidone and risperidone therapy on blood lipid and Hcy metabolism as well as endocrine hormones in patients with schizophrenia

Objective: To explore the different effects of paliperidone and risperidone therapy on blood lipid and Hcy metabolism as well as endocrine hormones in patients with schizophrenia. Methods: A total of 118 patients with schizophrenia who were treated in the hospital between December 2014 and February 2017 were collected as the research subjects and divided into control group and study group by random number table, each group with 59 cases. Control group received risperidone therapy, observation group received paliperidone therapy, and the differences in the levels of blood lipid indexes, Hcy metabolism indexes and endocrine hormones were compared between the two groups before and after treatment. Results:There was no statistically significant difference in the levels of blood lipid indexes, Hcy and endocrine hormones between the two groups before treatment. After treatment, lipid indexes TG and TC levels in peripheral blood of study group were lower than those of control group while HDL-C content was higher than that of control group;Hcy level in serum of study group was lower than that of control group;endocrine hormones FT3, FT4, T and E2 levels in serum of study group were higher than those of control group. Conclusion: paliperidone therapy for schizophrenia can be more effective than risperidone in regulating blood lipid metabolism, Hcy metabolism and endocrine hormones.

Correlation of hair risperidone concentration and serum level among patients with schizophrenia

Background Risperidone (RSP) has a rapid onset in vivo, low dosage and high plasma protein binding rate, therefore therapeutic drug monitoring (TDM) is needed to ensure safety in clinical treatment. However, compared with blood, hair is non-invasive, safe, non-infectious and easy to transport and store. Aims This study aims to investigate the correlations among the drug concentrations of RSP in hair and serum, which provides an experimental basis to explore hair as a novel biomaterial to meet the needs of clinical detection. Methods 34 patients with schizophrenia treated with RSP for more than 3 months were enrolled in this study. About 1 cm section of hair near the scalp was taken from the subjects, pretreated and detected by liquid chromatography-mass spectrometry. A correlation analysis was conducted among the drug concentrations in hair, the serum concentrations and the daily dosage. The data were analysed usi叩 SPSS 20.0 software. Results There was significant correlation between the hair concentration of RSP (two-tailed test, r=0.440, p=0.009) with the serum concentration of RSP, and the hair concentration of 9-hydroxyrisperidone (9-HR) with the serum concentration of 9-HR had no significant correlation (two-tailed test, r=-0.217, p=0.217);the total concentration of the RSP and 9-HR had no significant correlation between hair and serum (r=0.227, p=0.196). The dosage had no statistically significant correlation with the concentration of RSP in hair (r=0.207, p=0.241), 9-HR in hair (r=-0.194, p=0.271) and the total concentration of RSP and 9-HR in hair (r=0.188, p=0.288). There was no statistical correlation between the dosage and the concentration of RSP in serum (r=-0.059, p=0.741), but significant correlation between the dosage and 9-HR in serum (r=0.581 p<0.001) was found, and the correlation between the dosage and the total concentration of the two drugs RSP and 9-HR in serum was also significant (r=0.437, p=0.01). Conclusion The correlation analysis showed that the concentration of RSP in hair was statistically significant with the serum RSP concentration. In this study, we provided some experimental basis for hair as a new biomaterial to monitor the therapeutic drug concentration.

Effect of genetic polymorphisms on the interplay of P-glycoprotein transporter and cytochrome P450 enzymes: Pharmacokinetics of risperidone

Inter-individual variability in oral drug efficacy and toxicity is commonly observed in all therapeutic areas.Importantly,interindividual variability in drug uptake and metabolism can result in poor drug response,adverse drug reactions,or unfavorable drug–drug interaction.One of the common causes of individual variations in drug response is genetic variation of drug transporters and metabolizing enzymes[1,2].We focus on the interplay between efflux transporter(ATP-binding cassette,subfamily B(MDR/TAP),member 1/ABCB1)and cytochrome P450s according to genetic polymorphism[3].The objective of this lecture is to investigate the combined influence of genetic polymorphisms in ABCB1 and CYP2D6 genes on risperidone pharmacokinetics[4].

Optimal needle insertion length for intramuscular injection of risperidone long-acting injectable (RLAI)

Risperidone long-acting injectable (RLAI) is approved for the treatment of schizophrenia in many countries. The suggested site is the gluteal muscle with a needle length of two inches (50 mm) in Japan, which is longer than the ordinarily used needle for intramuscular injections. The aim of this study was to determine the optimal needle insertion length for accurate delivery of RLAI procedure among subjects who have normal body mass index (BMI: 18 to 25) and high BMI (>25). Thirty-seven patients with schizophrenia were administered RLAI intramuscularly into the dorsogluteal muscle. The standard procedure required inserting 80% of the two inch needle. By using data collected by ultrasonography, the findings confirmed that the median needle insertion lengths for subjects with normal and high BMI were 39.0 and 45.5 mm, respectively. To deliver RLAI effectively and safely, the authors strongly recommend that a specialized needle be used that is “marked” at the 40 mm point from the tip of the needle to the base. In this way regardless of subcutaneous fat content, the RLAI can be safely delivered into the muscle without causing untoward or side effects.

A meta-analysis of phlegm-resolving Chinese medicine combined with risperidone for treatment of schizophrenia

Objective:The efficacy and occurrence of adverse reactions of prescriptions containing phlegm-resolving Chinese medicine combined with risperidone in the treatment of schizophrenia were retrospectively studied by means of meta-analysis.Methods:A variety of different Chinese and English databases were searched from January 1,2000 to May 1,2020.Review Manager 5.3 software was used to evaluate the methodological quality of the included studies.The positive and negative symptom scale(PANSS)was used as the evaluation standard to analyze the total scores,positive scores,negative scores and general psychopathological scores,clinical efficacy and safety of prescriptions containing phlegmresolving Chinese medicine combined with risperidone of schizophrenia.The heterogeneity test and sensitivity analysis were also carried out by Review Manager 5.3,and the potential publication bias was analyzed by"funnel plot".Results:A total of 1515 patients were included in 15 studies.Compared with control group of risperidone alone,the total PANSS scale score,positive symptom score,negative symptom score and general psychopathological score of the treatment group of phlegm-resolving Chinese medicine combined with risperidone were all lower than those of the control group(P=0.01,MD=-6.35,95%CI[-11.29,-1.40]),(P=0.04,MD=-1.42,95%CI[-2.74,-0.09]),(P<0.01,MD=-2.16,95%CI[-3.41,-0.91]),and(P<0.01,MD=-3.80,95%CI[-6.37,-1.24]),the clinical efficacy of phlegm-resolving Chinese medicine combined with risperidone treatment group on schizophrenia was better than that of the control group[P<0.01,RR=1.09,95%CI(1.05-1.13)].The incidence of adverse reactions was reduced(P=0.02,RR=0.56,95%CI[0.34-0.93]).Conclusion:The combination of prescriptions containing phlegm-resolving Chinese medicine and risperidone can effectively improve the efficacy of patients with schizophrenia and reduce the occurrence of adverse drug reactions compared with risperidone alone.

Effect of Risperidone and Fluoxetine on the Movement and Neurochemical Changes of Zebrafish

Brain developmental disorders in humans, including Autism Spectrum Disorders (ASD) and Down’s syndrome, have been linked to increased serotonin levels. This work was designed to study changes in serotonin levels in the early stages of development with two classes of antipsychotic drugs: Risperidone, a drug that blocks serotonin and dopamine receptors, and fluoxetine, a serotonin reuptake inhibitor. The use of antipsychotic drugs is a solid choice to study the decrease and increase of these neurotransmitters and their influence on development. The study of these parameters will give an idea of the effects of serotonin in early developmental stages. To this end, we examined the effects of risperidone and fluoxetine on the locomotor activity, heart rate and brain development of zebrafish larvae. Our results showed that in larvae exposed to fluoxetine alone, swimming was significantly increased at 9 dpf (days post-fertilization). Erratic and abnormal movements were observed suggesting a toxic effect of fluoxetine. No erratic swimming was observed in larvae treated with fluoxetine plus risperidone. Both drugs presented morphological changes in dopaminergic neurons and mononeurons. Exposure to fluoxetine plus risperidone indicated possible reversal effects. Studies in zebrafish allow obtaining new insights into the side effects of these drugs as well as into the brain control of locomotor activity. Testing several drug-induced changes in behavior and serotonin levels is one of the experimental approaches for screening a new therapeutically relevant compound, and thus, merits further research.

Co-Administration of Risperidone and Sodium Valproate Causing Bilateral Chronic Exertional Lower Leg Compartment Syndrome

We present the case of a 24-year-old man, who was a keen runner, developing chronic bilateral lower leg compartment syndrome following co-administration of Risperidone and Sodium Valproate. Having had failed medical and physical therapies, he underwent surgical decompression of his more problematic left lower leg compartments. In the interval between sequential fasciotomies, control of his psychiatric symptoms allowed the dose of his Risperidone to be reduced, resulting in a greater exercise tolerance. Ultimately he no longer required the contra-lateral lower leg compartments to be decompressed surgically. He had returned to his original level of activity with no further psychotic episodes.

Intramuscular Diffusion Status of Risperidone and Aripiprazole Long Acting Injectable (LAI) by Ultrasonography

The aim of this study was to consider the characteristics of intramuscular diffusion status of risperidone and aripiprazole long acting injectable (LAI) by ultrasonography. Subjects were 40 adult subjects diagnosed with schizophrenia and treated with LAI [32 patients were risperidone LAI (RLAI) and 8 patients were aripiprazole LAI (ALAI)]. However, in this paper, only three cases (one RLAI case and 2 ALAI cases) were selected to illustrate the diffusion effects of both LAI. Dorsogluteal intramuscular (IM) injection sites were measured at prone position using the “double cross” method. Before LAI injection, the distance from the epidermis to the under-fascia (DEUF), and distance from the epidermis to the iliac bone (DEI) at the IM injection site were assessed by using ultrasonography: 1) the injection needle was inserted to the gluteus medius, and 2) observed the diffusion status within the muscle injected RLAI and ALAI were confirmed using the B-mode ultrasonography. Both RLAI and ALAI were depicted as high echogenicity with acoustic shadowing. It was considered that the diffusion states of LAIs by ultrasonography were important time course evaluations providing objective evidence.

Effect of berberine combined with risperidone therapy on endocrine hormones and oxidative stress in patients with schizophrenia

Objective:To study the effect of berberine combined with risperidone therapy on endocrine hormones and oxidative stress in patients with schizophrenia.Methods: A total of 90 patients with schizophrenia who were treated in our hospital between May 2014 and May 2016 were collected, reviewed and then divided into the control group (n=47) who received risperidone therapy and the observation group (n=47) who received berberine combined with risperidone therapy. Serum insulin resistance index levels, thyroid hormone and prolactin contents as well as oxidative stress index contents before and after treatment were compared between two groups of patients.Results: Before treatment, differences in serum insulin resistance index levels, thyroid hormone and prolactin contents as well as oxidative stress index contents were not statistically significant between two groups of patients. After treatment, serum FINS and HOMA-IR levels in observation group were lower than those in control group;serum T3 content was higher than that in control group while PRL content was lower than that in control group;serum MDA content was lower than that in control group while SOD, GSH-Px and CAT contents were higher than those in control group.Conclusion: Berberine combined with risperidone therapy for patients with schizophrenia won't cause severe endocrine hormone level disorder, and helps to reduce the systemic oxidative stress response.

Long-Term Clinical Outcome of Patients Using Risperidone Long-Acting Injectable: The Romanian e-STAR Database

The objectives of e-STAR Romania (NCT00283517) were to collect clinical outcome data of Romania schizophrenia or schizo-affective disorder patients;prospectively to assess the reasons of treatment initiation, medication usage patterns;to document (long-term) clinical efficacy;and to collect safety data, as well as recording 2-year corresponding retrospective data. In total, 378 eligible subjects were enrolled who were initiated either on risperidone long-acting injectable (RLAI) (290) or on an oral antipsychotic (OA) (88) at baseline as required by the local Summary of the Product Characteristics. Data were collected from per patient both retrospectively and prospectively over a 24-month period at 3-month intervals after starting treatment. The results indicated that subjects suffering from schizophrenia or schizo-affective disorder initiated on RLAI were less likely to be hospitalized within the first 24 months after the initiation of treatment. Moreover, subjects treated with RLAI experienced significant improvements in their illness severity and functioning. Discontinuation rates for RLAI were low and doses were stable throughout the 24 months following the initiation of treatment. In addition, the necessity for supplementary concomitant medication was reduced. Adverse events were reported in 20.3% (RLAI) and 11.4% (OA) of the subjects. In general, patients initiated on RLAI and OA at baseline both clinically improved on all assessed parameters but a larger improvement was observed for patients on RLAI. Incidences of reported AEs during the use of RLAI in a naturalistic setting are comparable with those described in clinical studies;however, the incidence of extrapyramidal signs and weight gain was lower than expected.

Relationship between plasma risperidone concentrations and clinical features in chronic schizophrenic patients in China

BACKGROUND Prior studies have noted great variability in the plasma levels of risperidone(RIS).Plasma concentrations of RIS and its active moiety are highly variable and depend on absorption,metabolism,and other predictors of metabolic dysregulation;however,these factors are poorly understood and the association between metabolic change and change in psychopathology is uncertain.AIM To ascertain the characteristics of chronic schizophrenic patients treated with RIS,and to assess their relationship with plasma RIS levels.METHODS This was a descriptive cross-sectional study of 50 patients with a diagnosis of schizophrenic psychosis treated with RIS in a psychiatric service.The plasma concentrations of RIS and its metabolite 9-hydroxyrisperidone were determined by high performance liquid chromatography.The patients’demographic and clinical characteristics,and psychopathologies were assessed,and the associations between clinical variables and plasma levels of RIS were explored.RESULTS Male patients received higher doses of RIS than female ones,but plasma concentrations of RIS and risperidone+9-hydroxyrisperidone(active moiety)were higher in female patients.Age and the mean scores of the general psychopathology subscale of the Positive and Negative Syndrome Scale(PANSS)were significantly positively correlated with plasma concentrations of risperidone+9-hydroxyrisperidone adjusted for weight and dose in all 50 subjects.In male subjects,we found a statistically significant positive correlation between the concentrations of risperidone+9-hydroxyrisperidone in plasma/(dose×kg)and age,mean PANSS negative subscale scores,mean PANSS general psychopathology subscale scores,and mean PANSS total scores.CONCLUSION Long-term use of RIS should be closely monitored in older patients and females to minimize the risk of high concentrations which could induce side effects.

A Study on the Effect of Risperidone on PPI and P50 Deficit in FirstEpisode and Chronic Patients with Schizophrenia

Objective To investigate the effect of atypical antipsychotics risperidone on prepulse inhibition of the startle reflex(PPI) and P50 deficit in first-episode and chronic patients with schizophrenia. Methods PPI and P50 were tested and compared in 81 first-episode acute schizophrenia patients and 92 chronic schizophrenia patients before and after the risperidone. Results There was no significant difference in PPI and P50 indices between the two groups before treatment(P>0. 05); 2) there was no significant correlation between PPI & P50 inhibition indices and PANSS score, onset frequency and disease course(P>0.05); 3) Except the significant group main effect for S2 amplitude in P50(P=0. 02), there was no significant change for main effect and interaction of the other P50 and PPI inhibition ratio indices after treatment(P>0. 05). The effect of risperidone on PPI and P50 measurement index had nothing to do with the curative effect. Conclusion There exists a deficit in sensory gating inhibition in both first-episode schizophrenia and chronic schizophrenia, which is relatively independent from disease course. The risperidone is not effective in improving PPI and P50 inhibition deficit.

利培酮口服液在老年期痴呆患者中的应用

目的:探究利培酮药物在老年痴呆中的临床疗效。方法:选取200例患者,随机分组,观察组予利培酮治疗100例;对照组予氟哌啶醇治疗100例。结果:BPRS减分率分析:观察组:显效60例,良好22例,无效18例,好转率(显效+良好):88%;对照组显效54例,良好20例,无效26例,好转率:74%;CMAI减分率分析:观察组:显效55例,良好33例,无效12例,好转率(显效+良好):88%;对照组显效45例,良好31例,无效24例,好转率:76%;观察组:消化道不适、头晕、失眠14例,占14%;锥体外系症状12例,占12%。对照组:消化道不适、头晕、失眠21例,占21%;锥体外系症状33例,占33%。结论:利培酮口服液在老年期痴呆患者临床治疗起到积极作用。

Effect of clozapine on the serum total bile acid, glucose and lipid metabolism in patients with schizophrenia

Objective:To observe the effect of clozapine on the serum total bile acid (TBA), glucose and lipid metabolism in patients with schizophrenia.Methods:A total of 80 patients with first-episode schizophrenia who were admitted in our hospital from January, 2015 to January, 2016 were included in the study and randomized into the observation group and the control group with 40 cases in each group. The patients in the observation group were given clozapine, while the patients in the control group were given risperidone. The serum TBA, T-Bil, D-Bil, I-Bil, glucose and lipid metabolism before and after treatment in the two groups were compared. Results:The comparison of TBA before and after treatment between the two groups was not statistically significant (P>0.05). T-Bil, D-Bil, and I-Bil after treatment were significantly reduced when compared with before treatment (P<0.05), but the comparison between the two groups was not statistically significant (P>0.05). BMI, waistline, hipline, and waist-hip ratio after treatment in the two groups were significantly elevated when compared with before treatment (P<0.05), and BMI, waistline, hipline, and waist-hip ratio after treatment in the observation group were significantly higher than those in the control group (P<0.05). The comparison of FBS, TC, TG, HDL-C, and LDL-C levels before treatment between the two groups was not statistically significant (P>0.05). FBS, TC, TG, and LDL-C levels 12 months after treatment were significantly elevated when compared with before treatment (P<0.05), but HDL-C was significantly reduced when compared with before treatment (P<0.05). FBS, TC, TG, and LDL-C levels 12 months after treatment in the observation group were significantly higher than those in the control group (P<0.05), but HDL-C was significantly lower than that in the control group (P<0.05).Conclusions:Clozapine has no obvious effect on TBA in patients with schizophrenia. Both of the two medications can produce effects on the glucose and lipid metabolism, but the effect by clozapine is more obvious;therefore, it should be paid attention in the clinical application.

Effects of combination pharmacotherapy and social skills training for schizophrenia: A randomized controlled trial

Pharmaco-psychosocial treatment (PPST) refers to a treatment paradigm combining pharmacotherapy with psychosocial therapy. We conducted an 18-month randomized controlled tracking study to evaluate the efficacy of social skills training (SST) in 11 individuals with schizophrenia on risperidone monotherapy. They were randomized to either SST or non-SST group, and Global Assessment Functioning (GAF) and Brief Psychiatric Rating Scale (BPRS) scores in the 2 groups showed gradual improvement. In the SST group, Digit Span Distraction Test (DSDT) at 12 and 18 months showed significant improvement. The Subjective Deficit Syndrome Scale (SDSS) scores in the SST group showed significant improvement after 6 months and showed a significant difference in comparison between the groups. After the subjective feeling of health was recovered, the items of motivation were recovered as a direct effect of SST. Some items of the Life Assessment Scale for the Mentally Ill (LASMI) score showed significant improvement (or significant trend) in only the SST group after 6 months. Items of daily life, work skills, and self-recognition were continuously improved. We report 2 cases in the SST group that had DSDT improvement in parallel with change of action and communication as a change of social function. This study is only exploratory due to the small number of cases. However, we have demonstrated potential improvement in cognitive function due to learning experiences that required working memory and attention, thus providing improvement in social life.

Endoscopic Adenoidectomy Secondary to Druginduced Trismus

We present the case of a 4 year old girl whose adenoidectomy had to be performed via an endoscopictrans oral approach due to the unexpected inability to fully open the mouth during the procedure. The patient had previously been taking Risperidone for behavioral symptoms associated with her autism. The jaw tone returned to normal following the procedure and there were no complications. An interaction between the Risperidone and the anesthetics were the likely cause of the trismus.