Peripheral injection of risperidone,an atypical antipsychotic,alters the bodyweight gain of rats

1. Risperidone is an atypical antipsychotic drug that possesses 5-hydroxytryptamine 5-HT2 receptor antagonism combined with milder dopamine D2 receptor antagonism. 2. Excessive bodyweight gain is one of the side-effects of antipsychotics. Risperidone treatment causes a greater increase in the body mass of patients than treatment with conventional antipsychotics, such as haloperidol. Therefore, the present study was undertaken in order to address the aetiology of the risperidone-induced bodyweight change in rats by examining the expression of leptin, an appetite-regulating hormone produced in white adipose tissue (WAT), and uncoupling protein (UCP)-1, a substance promoting energy expenditure in the brown adipose tissues (BAT). 3. Eight-week-old male rats were injected subcutaneously with risperidone (0.005, 0.05 or 0.5 mg/kg) twice daily for 21 days. Both bodyweight and food intake were monitored daily. On day 21, rats were decapitated and their serum leptin and prolactin concentrations were measured. Expression levels of leptin, Ucp1 and beta3-adrenoceptor (beta3-AR) genes in WAT and BAT were quantified using real-time polymerase chain reaction amplification. 4. Injection of 0.005 mg/kg risperidone into rats increased food intake and the rate of bodyweight gain, as well as the augmentation of leptin gene expression in WAT. Injection of 0.05 mg/kg risperidone increased food intake and leptin gene expression in WAT, but the rate of bodyweight gain was not affected. Injection of 0.5 mg/kg risperidone caused a reduction in bodyweight gain, as well as enhanced Ucp1 gene expression in BAT and serum prolactin concentrations. The serum leptin concentration and beta3-AR gene expression in WAT and BAT were not affected by injection of 0.5 mg/kg risperidone. 5. Although the changes in food intake observed in risperidone-injected rats were rationalized neither by serum leptin nor prolactin concentrations, the reduction in the rate of bodyweight gain following injection of 0.5 mg/kg can be explained, in part, by increased energy expenditure, as revealed by the remarkable increase in the UCP-1 mRNA expression level in BAT. The role of leptin in risperidone-induced alterations in bodyweight gain remain to be clarified.     

Long-term effectiveness of risperidone and olanzapine in resistant or intolerant schizophrenic patients. A mirror study

OBJECTIVE: To evaluate the long-term effectiveness of the second generation antipsychotics, risperidone and olanzapine on hospitalization, clinical response, and adherence to therapy after switching from conventional antipsychotics or clozapine in a naturalistic setting of schizophrenic patients. METHOD: Data were registered for periods of identical duration before and after switching. RESULTS: Fifty-seven patients were included. Mean study period was 3.1 +/- 0.2 years. Mean number of in-patient days after switching declined by 78% of the level before switching (P=0.0002). There was no significant differences in ratio responders/non-responders between the subgroups. The number of patients with extrapyramidal symptoms (EPS) was significantly reduced after switching. However, intolerable weight gain led to a lack of adherence to therapy in 18% of the olanzapine-treated patients. CONCLUSION: Long-term treatment with the second generation antipsychotics, risperidone and olanzapine significantly improved the clinical outcome. However, weight gain may be a significant reason for discontinuation of treatment and reducing the long-term adherence to therapy.     

A case of brief psychosis associated with an arachnoid cyst

Little is known about the arachnoid cyst and there have been few reports of it accompanying psychiatric disturbances. A 57-year-old patient was admitted due to sudden headache, auditory hallucination, and delusion of persecution. An arachnoid cyst was found in the anteromedial aspect of middle cranial fossa on his magnetic resonance image. This was his first psychotic episode and he was also negative to other clinical evaluations including endocrine system. His psychotic symptoms were suspected to be induced by the arachnoid cyst and it was well controlled by low-dose risperidone administration. He left hospital free from psychotic symptoms on 14th hospital day.     

A pilot, randomized, open-label trial assessing safety and pharmakokinetic parameters of co-administration of rivastigmine with risperidone in dementia patients with behavioral disturbances

BACKGROUND: The majority of patients with Alzheimer's disease (AD) or vascular dementia display, in addition to cognitive impairment, various degrees of behavioral disturbances. As the use of cholinesterase inhibitors for the treatment of cognitive impairment in dementia becomes widespread, many of these patients will be treated concomitantly with cholinesterase inhibitors and with anti-psychotic drugs to ameliorate behavioral disturbances. Despite the widespread use of this combination in clinical practice, the safety and tolerability of such combination therapy has not been evaluated in controlled clinical trials. This pilot study examined the effects of addition of risperidone 0.5-2 mg/day to patients on rivastigmine 3-12 mg/day, and vice versa. METHODS: 65 patients suffering from AD, 10 from vascular dementia, and 15 from both were randomized to open label rivastigmine and risperidone, alone or in combination, for 20 weeks. Adverse events caused by co-administration were assessed. RESULTS: No clinically relevant adverse interactions were observed. CONCLUSIONS: These preliminary results indicate that rivastigmine and risperidone can be safely co-administered. Confirmation of these results in large clinical trials studies is warranted.     

利培酮对分裂症患者血清胆碱酯酶活力的影响及疗效研究

目的：探讨利培酮对分裂症患者血清胆碱酯酶活力的影响及疗效。方法：采用自身对照的方法，分别于治疗前，治疗后1、2、3、4周测血清胆碱酯酶活力，并测BPRS和TESS。结果：治疗前与治疗后1、2,3、4周血清胆碱酯酶活力的比较差异无统计学意义（p〉0．05）。治疗前与治疗后第2、4周BPRS比较差异均有显著性，t值分别为t=2．40，P〈0．02；t=5．24，P〈0．01。结论：利培酮对分裂症患者血清胆碱酯酶活力无明显影响，有显著疗效。     

维思通辅助治疗难治性抑郁症的效果

①目的 观察抗抑郁药合并维思通治疗难治性抑郁症的效果。②方法 36例难治性抑郁症病人．在原用抗抑郁剂不变的情况下，加维思通治疗，疗程4周．在治疗前及治疗后分别以汉密顿抑郁量表(HAMD)、汉密顿焦虑量表(HAMA)评定疗效，并用副反应量表(TEES)观察不良反应。③结果 加用维思通对难治性抑郁症有较好的疗效和加强作用。④结论 对于抗抑郁药治疗反应不佳的难治性抑郁症加维思通辅助治疗可提高疗效。     

Atypical antipsychotic drugs: Part 1

This column on atypical antipsychotics is the first of two parts. Part I consists of a review of foundational information and a discussion on clozapine and risperidone. Part II will address olanzapine, quetiapine, and ziprasidone.     

维思通与舒必利治疗精神分裂症阴性症状的对照研究

目的 探讨维思通治疗精神分裂症阴性症状的疗效及不良反应.方法 采用随机对照研究方法,用维思通和舒必利分别治疗以阴性症状为主的精神分裂症.疗程12周,以简明精神病评定量表(BPRS)、阴性症状评定量表(SANS)评定疗效,以治疗中需处理的不良反应症状量表(TESS)评定药物不良反应.结果 两药对精神分裂症阴性症状疗效近似,维思通对意志缺乏、兴趣缺乏及社交缺乏改善明显,不良反应少且轻微.结论 维思通对精神分裂症阴性症状有一定疗效.     

Antipsychotics and dopamine transporter gene polymorphisms in delirium patients

The main objective of the present study was to determine the relationship between treatment responses of delirium and genetic polymorphisms in the dopamine transporter. The optimal dosages of haloperidol and risperidone in the treatment of delirium were also investigated. Either haloperidol or risperidone was administered to delirium patients, and delirium symptoms were measured daily until remission. Variable number of tandem repeat (VNTR) polymorphisms of the dopamine transporter were determined using the polymerase chain reaction. Among 42 subjects, symptoms of delirium appeared a mean of 9.68 days after hospitalization. A majority of the subjects (83.3%) had the type 10/10 polymorphism. Dosages of haloperidol and risperidone at the day of recovery were 1.67 mg/day (SD = 1.32; range 0.5-2.5 mg/day) and 1.19 mg/day (SD = 1.14; range 0.5-5.0 mg/day), respectively. The mean drug response time was 8.5 days in the haloperidol group and 4.8 days in the risperidone group (no significant difference). The response rates at the 3rd and 7th days after medication did not differ with either the drug group or the dopamine transporter polymorphism. Relatively low doses of risperidone and haloperidol exhibited similar efficacies, and dopamine transporter polymorphisms do not appear to play a major role in the action of antipsychotics on delirium.     

Psychotropic drug use in older people with mental illness with particular reference to antipsychotics: a systematic study of tolerability and use in different diagnostic groups

OBJECTIVE: The objective of the study was to provide observational clinical data on psychotropic drugs used in older people with mental illness. METHODS: This was an observational, single-centre, one-week prevalence study of psychiatric symptoms, disorders and psychotropic drug use in older with mental illness cared for by the South West people Yorkshire Mental Health NHS Trust (Wakefield Locality), UK. The clinical assessment included completion of the Psychosis Evaluation Tool for Common use by Caregivers. RESULTS: A total of 593/660 older patients with mental illness (mean +/- SD age, 76 +/- 8.1 years were assessed. 44.5% had dementia (excluding vascular dementia) and 33.7% had a mood disorder. Of the total, 20.4% did not receive CNS active medication. Of those receiving CNS active medication approximately half (51.3%) took antipsychotics and 46.2% antidepressants. Of 304 patients taking antipsychotics, 87% took only one medication. However, patients with schizophrenia and related disorders were significantly more likely to be prescribed two or more antipsychotics (p < 0.001). Risperidone was the most frequently prescribed antipsychotic (n = 136, 44.7%). Risperidone doses were significantly lower for patients with dementia and mood disorders than with schizophrenia (p < 0.002). Side-effects from antipsychotics were significantly greater in patients with schizophrenia, suggesting a dose-related effect. Risperidone appeared to be well tolerated in all patients with no evidence of cerebrovascular side-effects in patients taking it. CONCLUSIONS: Psychotropic drugs were commonly used by older people in contact with mental health services. The doses of antipsychotics used in dementia and affective disorders were significantly lower than in schizophrenia. Risperidone was the most commonly used drug in all diagnostic groups including dementia. Despite a relatively large numbers of patients receiving risperidone in this naturalistic study, no serious side-effects were reported or identified. In this paper we focus our findings on antipsychotics in the light of recent advice from the Committee on Safety of Medicines (UK).