利培酮合用米氮平治疗精神分裂症阴性症状的研究

目的　探讨米氮平治疗精神分裂症阴性症状的疗效和安全性。方法　将 86例以阴性症状为主的住院精神分裂症患者随机分为研究组对对照组 ,分别给予利培酮合用米氮平及单用利培酮治疗 ,疗程 12周 ,用PANSS、TESS评定疗效和安全性。结果　疗后 4周两组PANSS总分、阳性因子分、阴性因子分及 8、12周末两组PANSS总分和各因子分与疗前比较差异有显著性 (P <0 0 5或P <0 0 1)。治疗后 8、12周两组间比较PANSS总分及阴性因子分差异有显著性 (P <0 0 5或P <0 0 1)。结论　米氮平治疗精神分裂症阴性症状疗效较好 ,副作用少。     

Cognition and communication dysfunctions in early-onset schizophrenia: Effect of risperidone

Background

Cognitive impairment and formal thought disorder, also referred to as communication disturbances, are considered the core symptoms of schizophrenia, strongly affecting social functioning and long-term outcome. Several studies in adult patients suggest improvement of both functions after the treatment with atypical antipsychotic drugs. Such medications are also used as first line treatment in early-onset schizophrenia, however their efficacy in cognitive and communication domains in this population have not been systematically assessed.

Aim of the study

Evaluation of risperidone efficacy at psychopathological symptoms, cognitive impairment and formal thought disorder in adolescents with schizophrenia spectrum diagnosis.

Material and method

Psychopathological symptoms, cognitive functioning and formal thought disorder were evaluated in 32 hospitalized adolescent patients with schizophrenia spectrum diagnosis at the beginning of risperidone treatment and after clinical improvement and compared to the results of matched healthy control group.

Results

Risperidone treatment was associated with reduction of symptom severity and moderate improvement of formal thought disorder and some aspects of executive functions. Working memory and verbal fluency were not improved. There were few correlations between psychopathological symptoms and results of cognitive tests, mainly between negative symptoms and executive functions.

Discussion

In early-onset schizophrenia spectrum disorders atypical antipsychotic treatment is associated with alleviation of symptoms and only selective and moderate cognitive and communication improvement.     

More evidence on proneurocognitive effects of add-on mirtazapine in schizophrenia

Enhancement of neurocognition is essential in the treatment of schizophrenia. In our previously reported six-week Randomized Controlled Trial (RCT) mirtazapine added to conventional antipsychotics improved not only negative, but also positive symptoms and neurocognition in difficult-to-treat schizophrenia. The present study aimed to explore whether a prolonged exposure to mirtazapine could further improve neurocognition.Completers of the RCT who were able and willing to proceed to the extension phase received open label mirtazapine for an additional 6 weeks. During the extension phase, both groups (i.e., patients who previously received mirtazapine and those who received placebo) and the whole population showed improvement on a number of neurocognitive tests. Patients who shifted to open label mirtazapine from placebo achieved in the six following weeks similar results as their initially mirtazapine-treated counterparts did during their first 6 weeks of mirtazapine exposure. Middle-term mirtazapine treatment (12 weeks) demonstrated an advantage over short-term mirtazapine treatment (6 weeks) on Stroop Dots time and Trail Making Test, part B, number of mistakes (t = − 2.562, p = 0.035 and t = − 2.42, p = 0.043, correspondingly).Mirtazapine added to antipsychotics consistently shows desirable effects on neurocognition. Lengthy treatment seems worthwhile. Mirtazapine may become a safe and cost-saving neurocognitive enhancer in schizophrenia, yet more studies are needed.     

Efficacy of flupentixol and risperidone in chronic schizophrenia with predominantly negative symptoms

The study investigated the non-inferiority of flupentixol compared to risperidone in the treatment of negative symptoms. In addition, the effects of flupentixol on mood and cognitive symptoms were explored. In a randomized, double-blind multicenter study, 144 non-acute schizophrenia patients with predominant negative symptoms were treated with a flexible dose of either flupentixol (4-12 mg/d) or risperidone (2-6 mg/d) for up to 25 weeks. In addition to a non-inferiority analysis, a principal component analysis (PCA) of the PANSS was performed post hoc. Regarding negative symptoms, flupentixol proved to be non-inferior to risperidone. Both drugs improved depressed mood with effect sizes favoring flupentixol. PCA suggested a five-factor structure. Effect sizes for the cognitive factor were up to 0.74 for flupentixol and up to 0.80 for risperidone. EPS scores were rather low and Parkinsonism improved in both groups, but anticholinergic drugs were prescribed significantly more frequently in the flupentixol group, which generally showed significantly more adverse events. Results indicate that the 1st generation antipsychotic flupentixol improves negative, affective and cognitive symptoms in chronic schizophrenia comparable to risperidone. Further studies should confirm the latter using neuropsychological performance tests and should investigate whether tolerability improves with a markedly lower dose range.     

A double-blind, placebo-controlled study of traditional Chinese medicine sarsasapogenin added to risperidone in patients with negative symptoms dominated schizophrenia

Objective

To identify whether sarsasapogenin, a sapogenin from the Chinese medicinal herb Anemarrhena Asphodeloides Bunge, would augment the efficacy of risperidone and significantly improve cognitive functions in patients with negative symptoms dominated schizophrenia.

Methods

The trial was a double-blind, placebo-controlled, parallel-group design. The eligible patients were randomized into 2 treatment groups: sarsasapogenin group (sarsasapogenin plus risperidone for 8 weeks, n = 41) and placebo group (risperidone only for 8 weeks, n = 39). At the baseline, as well as at weeks 2, 4 and 8 of treatment, the therapeutic response was measured by using scales including Positive and Negative Symptoms Scale (PANSS), Wechsler Memory Scale (WMS), modified Chinese Wechsler Adult Intelligence Scale (mWAIS), Clinical Global Impression (CGI) and Brief Psychiatry Rating Scale (BPRS). The study period for each subject was 8 weeks and duration of overall trial was 2 years.

Results

Patients treated with sarsasapogenin plus risperidone demonstrated no statistically significant differences in changes in PANSS, WMS or mWAIS score at the end-point of the trial compared with patients treated with placebo plus risperidone. The incidence of treatment-emergent adverse events in patients treated with sarsasapogenin was not different from that observed in placebo group.

Conclusion

Sarsasapogenin did not augment the efficacy of risperidone in treating negative symptoms dominated schizophrenia. Sarsasapogenin at a dosage of 200 mg per day added to a flexible dosage of risperidone at 2–4 mg per day is safe and well tolerated by patients with negative symptoms dominated schizophrenia.     

Verbal learning contributes to cognitive insight in schizophrenia independently of affective and psychotic symptoms

Objective

Patients with schizophrenia exhibit distorted beliefs and experiences, and their own evaluation of this is labeled cognitive insight. We examined the relationship between cognitive insight and neurocognition, as well as the contribution of neurocognition in explaining cognitive insight.

Method

Clinically characterized patients with schizophrenia (n = 102) were assessed with a measure of cognitive insight, Beck Cognitive Insight Scale (BCIS) and a neuropsychological test battery. The contribution of neurocognition to the explained variance in BCIS components self-reflectiveness (i.e. objectivity and reflectiveness) and self-certainty (i.e. overconfidence in own beliefs) was examined controlling for current affective and psychotic symptoms.

Results

A significant negative correlation was found between self-certainty and verbal learning, whereas no associations were found between self-reflectiveness and any of the neuropsychological tests. Verbal learning was added significantly to the explained variance in self-certainty after controlling for potential confounders.

Conclusion

High self-certainty was associated with poor verbal learning. This suggests that overconfidence in own beliefs is associated with cognitive dysfunction in schizophrenia.     

Effects of tapering of long-term benzodiazepines on cognitive function in patients with schizophrenia receiving a second-generation antipsychotic

Background

The high use of long-term benzodiazepines (BZDs) with second-generation antipsychotics (SGAs) has been identified as an important issue in the treatment of schizophrenia in Japan. The aim of this study was to evaluate the effects of gradual reduction or discontinuation of daytime BZD use on cognitive function and quality of life (QOL) in patients with chronic schizophrenia receiving an SGA.

Methods

Thirty schizophrenic patients who had received an SGA with concomitant BZDs for at least 3 months were enrolled. Before and 4 weeks after tapering of daytime BZDs, the Brief Assessment of Cognition in Schizophrenia Japanese-language version (BACS-J) and the Schizophrenia Quality of Life Scale Japanese-language version (SQLS-J) were administered. Clinical evaluation also included the Positive and Negative Syndrome Scale (PANSS). To compare for practice effects on the BACS-J, 10 patients with chronic schizophrenia were assessed without tapering BZDs.

Results

BZDs were reduced or discontinued safely in most patients, and no emergent withdrawal symptoms were observed. Significant improvements were shown in verbal memory, working memory, and composite score, as measured by the BACS-J without practice effects. In addition, the motivation/energy score on the SQLS-J, the negative symptoms and total scores on the PANSS significantly improved after tapering BZDs.

Conclusion

Reduction or discontinuation of long-term daytime use of BZDs may be warranted in patients with schizophrenia treated with SGAs, as it may improve cognitive function, subjective QOL, and psychiatric symptoms with no significant adverse effects.     

A placebo controlled study of the propentofylline added to risperidone in chronic schizophrenia

Impaired activity of the purinergic system is a plausible common factor that could be responsible for many aspects of schizophrenia. Based on purinegic hypothesis of schizophrenia, pharmacological treatments enhancing adenosine activity could be effective treatment in schizophrenia. Propentofylline is a novel xantine derivative which is being developed for treatment of degenerative and vascular dementia. It enhances extracellular adenosine level via inhibition of adenosine uptake. The purpose of the present investigation was to assess the efficacy of propentofylline as an adjuvant agent in the treatment of chronic schizophrenia in an 8-week double blind and placebo controlled trial. Eligible participants in this study were 50 patients with chronic schizophrenia. All patients were inpatients and were in the active phase of the illness, and met DSM-IV-TR criteria for schizophrenia. Patients were allocated in a random fashion, 25 to risperidone 6 mg/day plus propentofylline 900 mg/day (300 mg TDS) and 25 to risperidone 6 mg/day plus placebo. The principal measure of the outcome was Positive and Negative Syndrome Scale (PANSS). Although both protocols significantly decreased the score of the positive, negative and general psychopathological symptoms over the trial period, the combination of risperidone and propentofylline showed a significant superiority over risperidone alone in the treatment of positive symptoms, general psychopathology symptoms as well as PANSS total scores. The means Extrapyramidal Symptoms Rating Scale for the placebo group were higher than in the propentofylline group over the trial. However, the differences were not significant. The present study indicates propentofylline as a potential adjunctive treatment strategy for chronic schizophrenia. Nevertheless, results of larger controlled trials are needed, before recommendation for a broad clinical application can be made.     

精神分裂症症状与认知功能损害的关系

目的：探讨精神分裂症症状与认知功能损害的关系。方法：对１８例阴性精神分裂症和１５例阳性精神分裂症采用氯氮平治疗;对１１例阴性精神分裂症和１３例阳性精神分裂症采用利培酮治疗。并分别评估其治疗前和治疗８周后的阳性症状,阳性症状记忆,注意及执行功能。结果：精神分裂症的记忆损害与阴性症状和阳性症状都呈显著性相关,注意及执行功能损害与阴性症状显著相关,与阳性症状无明显相关;记忆随思维贫乏的改善而改善,注意和执行功能损害的改善与症状的改善无明显相关。结论：精神分裂症认知功能损害主要与阴性症状相关,但精神分裂症的大部分认知功能并不随阴性症状改善而改善。     

Risperidone,negative symptoms and cognitive deficit in schizophrenia: an open study

The aim of this study was to evaluate the effects of a new antipsychotic compound on negative symptoms and cognitive deficit in schizophrenia. Psychiatric symptoms and cognition were assessed in 25 patients with schizophrenia, at baseline and after they had taken risperidone for 4 weeks. The Positive and Negative Symptoms Scale (PANSS), the Wisconsin Card Sorting Test (WCST) and two WAIS sub-tests were used to assess the patients. After the study period, both negative and positive symptoms and also measures of cognitive performance improved significantly. The WCST results correlated with negative symptom scores before and after treatment. This suggests that negative symptoms and cognitive deficit have a common underlying substrate which is the target of the risperidone treatment. Our data show that risperidone may have a substantial effect on complex cognitive functions in schizophrenia, and they suggest that certain cognitive deficits are relatively dependent on the negative symptoms of this disorder.     

奎硫平与利培酮治疗精神分裂症对照研究

目的：评价奎硫平与利培酮治疗精神分裂症阴性症状的临床疗效与安全性。方法：对64例首次住院的以阴性症状为主的精神分裂症患者，随机分为两组，分别选用奎硫平或利培酮进行8周治疗，采用阳性症状与阴性症状量表(PANSS)评定疗效，用副反应量表(TESS)评定不良反应。结果：两药对精神分裂症阴性症状疗效相当，不良反应发生率及严重程度均相仿。结论：奎硫平与利培酮对精神分裂症阴性症状均有肯定的疗效，且安全性较高。     

Effects of discontinuation of long-term biperiden use on cognitive function and quality of life in schizophrenia

Background

The high use of long-term antiparkinsonian anticholinergic drugs with antipsychotics has been identified as an important issue in the treatment of schizophrenia in Japan. The aim of this study was to evaluate the effects of gradual discontinuation of biperiden, an anticholinergic drug, on cognitive function and quality of life (QOL) in schizophrenia.

Methods

Thirty-four schizophrenic patients who had received a second-generation antipsychotic (SGA) with concomitant biperiden for at least 3 months were enrolled. Before and 4 weeks after discontinuation of biperiden, the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS-J) and the Schizophrenia Quality of Life Scale (SQLS-J) were administered. Clinical evaluation also included the Positive and Negative Syndrome Scale (PANSS). To compare the practice effect on BACS-J, 10 chronic patients with schizophrenia were assessed without tapering biperiden.

Results

Biperiden was discontinued safely in most patients, and no emergent extrapyramidal symptoms were observed. Significant improvements were shown in attention, processing speed, and composite score, as measured by the BACS-J without practice effect. In addition, the psychosocial condition score on the SQLS-J and the general psychopathology score on the PANSS significantly improved after biperiden discontinuation.

Conclusion

Discontinuation of long-term biperiden use may be warranted in patients with schizophrenia treated with SGAs, as it may improve cognitive function, subjective QOL, and psychiatric symptoms with no significant adverse effects.     

利培酮合并舍曲林治疗精神分裂症阴性症状的研究

目的探讨舍曲林合并利培酮治疗精神分裂症阴性症状的疗效及安全性。方法将86例以阴性症状为主的住院精神分裂症患者随机分为研究组(舍曲林 利培酮)和对照组(利培酮 安慰剂)。在治疗前及治疗后4、8、12周,用阳性与阴性症状量表(PANSS)、不良反应量表(TESS)评定疗效和安全性。结果治疗后8、12周,两组PANSS总分、阴性因子分比较差异有统计学意义(P<0.05)。研究组阴性因子各项症状评分低于对照组,差异有统计学意义(P<0.05或P<0.01)。而两组TESS评定无统计学意义(P>0.05)。结论舍曲林合并利培酮治疗精神分裂症阴性症状安全有效,副作用少。     

Mirtazapine in the treatment of essential tremor: an open-label, observer-blind study

Introduction

Essential tremor (ET) is the most common movement disorder in the adult population. At present ET treatment shows limited efficacy, particularly in patients with severe and disabling symptoms. This study evaluates the clinical efficacy of mirtazapine in an untreated ET patient population.

Materials and methods

30 ET patients (female/male = 19/11; average age = 71.4 ± 8.3 years) were examined by clinical criteria, electromyographic (EMG), and apomorphine tests to study the cortical silent period. The patients were all treated with mirtazapine 30 mg daily.

Results

Mirtazapine proved to be a good control agent for tremor symptomatology in 23/27 patients (85%) who completed 1 month of treatment, with a marked reduction of tremor; the benefit was maintained during the 12-month follow-up. No significant variation in EMG parameters was observed aside from two prevalent and distinct frequencies of tremors (5–6 Hz and 7–8 Hz) and a group of selected patients whose cortical silent period (SP) was markedly reduced. There were no clinical differences between the two subgroups. All apomorphine-tested patients showed an SP with no significant modifications.

Conclusions

Mirtazapine proved to be an efficacious drug treatment for tremor symptoms in patients suffering from ET. It had limited side effects and excellent overall tolerability, could be used as daily monotherapy, and did not interfere with any of the many other medications being taken simultaneously by the patients.     

No association of serotonin transporter polymorphism (5-HTTVNTR and 5-HTTLPR) with characteristics and treatment response to atypical antipsychotic agents in schizophrenic patients

Background

Serotonin transporter is a candidate gene for the pathogenesis of some psychiatric disorders. The aim of this study was to examine the role of the serotonin transporter gene polymorphism in the clinical aspects of schizophrenia including symptomatology and therapeutic response.

Methods

This study comprised 141 unrelated patients who strictly met the DSM-IV criteria for schizophrenia and 115 control subjects. All subjects were of Korean ethnicity. Serotonin transporter intron 2 VNTR polymorphism (5-HTTVNTR) and serotonin transporter linked polymorphic region polymorphism (5-HTTLPR) were analyzed in schizophrenia patients and control subjects. The Positive and Negative Symptom Scale (PANSS) was used at baseline and 6 weeks after atypical antipsychotic treatment to evaluate the clinical symptoms. Body mass index (BMI), the Barnes Akathisia Rating Scale (BARS), the Simpson–Angus Rating Scale (EPS) for adverse effect and the Calgary Depression rating Scale for Schizophrenia (CDSS) were measured.

Results

There were no significant differences in the frequency of genotypes between schizophrenia patients and control subjects. There were no significant differences in PANSS scores before treatment according to the serotonin transporter genotypes. Treatment response after atypical antipsychotics did not differ among the genotypes. No difference was shown among the genotypes for the scales in adverse effects and depression (BMI, BARS, EPS, CDSS).

Conclusions

Our results suggest that the serotonin transporter polymorphism does not seem to be a susceptibility factor for schizophrenia. Similarly, the serotonin transporter polymorphism might not affect the therapeutic response and adverse effect to atypical antipsychotics in Korean patients with schizophrenia. Further studies with a larger number of subjects are required to better understand the role of the serotonin transporter polymorphism in schizophrenia.     

Insight into illness, neurocognition and quality of life in schizophrenia

Objective

The aim of this study was to assess the impact of insight into illness on self-reported quality of life (QoL) for patients with schizophrenia.

Methods

This cross-sectional study was conducted in the psychiatric department of a French public university teaching hospital. The data collected included socio-demographic information, clinical characteristics, medications, cognitive performance assessments, insight into illness, and the S-QoL 18. A multivariate analysis using multiple linear regressions was performed to determine variables potentially associated with QoL levels.

Results

One hundred and thirteen outpatients with stable schizophrenia were enrolled in our study.Significant associations were found between QoL and socio-demographic characteristics: a higher QoL was associated with marital status (in couple) and employment. Concerning insight into illness, lower QoL levels were associated with better awareness of the mental disorder, whereas higher QoL levels were associated with better awareness of positive and negative symptoms. Elementary neuropsychological measures were not statistically associated with QoL.

Conclusion

Insight into illness, marital status and employment were the most important features associated with QoL, whereas there was no evidence that elementary neurocognition directly influenced QoL. The different facets of insight into illness should be considered to guide the development of specific interventions intended to improve QoL. Moreover, this study highlights the need for clinicians to pay more attention to the personal impact of schizophrenia, especially upon family life and work.     

氨磺必利治疗精神分裂症阴性症状的对照研究

目的探讨氨磺必利治疗精神分裂症阴性症状的效果。方法采用随机数字表法将符合《中国精神障碍分类与诊断标准第3版》(CCMD-3)精神分裂症诊断标准的72例精神分裂症患者分为氨磺必利组(研究组)和利培酮组(对照组)各36例,观察8周。采用阳性与阴性症状量表(PANSS)评定疗效,副反应量表(TESS)评定不良反应。结果经8周治疗,两组PANSS总分均较治疗前低(P均0.01)。氨磺必利组与利培酮组有效率分别为88.9%和86.1%,差异无统计学意义(P0.05)。但氨磺必利组阴性症状评分减分与利培酮组比较,差异有统计学意义(P0.05)。治疗结束时两组TESS评分差异无统计学意义(P0.05)。结论氨磺必利对精神分裂症阳性症状的疗效与利培酮相当,而对精神分裂症的阴性症状的疗效优于利培酮。     

精神分裂症患者认知功能损害与阴阳性症状的关系

目的：探讨精神分裂症认知功能损害与阴性、阳性症状的关系。方法:至73例入组的患者随机给予利培酮、氯氮平治疗12周,并于治疗前、后盲法评定Wisconsin卡片分类测验（WCST）,Wechsler记忆测验（WMS）,阴状症状评定量表（SANS）与阳性症状评定量表（SAPS）。结果：治疗前精神分裂症患者的阴性症状、阳性症状均与认知功能有显著相关。主要与执行功能相关;注意障碍与记忆相关。治疗后,仅SAPS中怪异行为得分与WCST的持续反应数、持续错误数显著相关。结论：精神分裂症的认知功能损害是原发性的,并不是在阳性、阴性症状基础上产生的。     

利培酮和氯氮平对精神分裂症阴性症状的疗效及不良反应比较

目的比较利培酮与氯氮平对精神分裂症阴性症状的疗效和不良反应。方法应用利培酮和氯氮平治疗精神分裂症各２０例，其阴性症状评定量表评分≥６５分者入组。用阴性症状评定量表（ＳＡＮＳ）评定疗效，用副反应量表（ＴＥＳＳ）评定药物不良反应。结果利培酮和氯氮平对精神分裂症阴性症状的疗效相当，起效时间为２周。两药的副反应不同，利培酮多见锥体外系反应，而氯氮平多见心动过速、嗜睡、流涎、便秘等。结论利培酮对精神分裂症阴性症状有效、疗效与氯氮平相当。     

A 12-week, double-blind, placebo-controlled trial of donepezil adjunctive treatment to risperidone in chronic and stable schizophrenia

There is considerable incentive to develop new treatment strategies that effectively target cognitive deficits in schizophrenia. One of the theoretically promising novel treatment candidates is acetylcholinesterase inhibitors that increase the synaptic levels of cholinergic, nicotinic, and muscarinic receptor activity. The purpose of this study was to assess the efficacy of donepezil as an adjuvant agent in the treatment of chronic schizophrenia in particular for cognitive impairments. This investigation was a 12-week, double-blind study of parallel groups of patients with stable chronic schizophrenia. Thirty patients were recruited from inpatient and outpatient departments, age ranging from 22 to 44 years. All participants met DSM-IV-TR. diagnostic criteria for schizophrenia. To be eligible, patients were required to have been treated with a stable dose of risperidone as their primary antipsychotic treatment for a minimum period of 8 weeks. The subjects were randomized to receive donepezil (10 mg/day) or placebo, in addition to risperidone (4–6 mg/day). Clinical psychopathology was assessed with Positive and Negative Syndrome Scale (PANSS). Cognition was measured by a cognitive battery. Patients were assessed by a psychiatrist at baseline and after 8, and 12 weeks after the medication started. The PANSS scores and cognitive performance were used as the outcome measures. The donepezil group had significantly greater improvement in the negative symptoms over the 12-week trial. There were no differences between the donepezil and placebo groups on any neurocognitive assessments at endpoint (week 12). The present study indicates donepezil as a potential adjunctive treatment strategy for negative symptoms of chronic schizophrenia.