Quetiapine versus olanzapine for the treatment of negative symptoms in patients with schizophrenia

Negative symptoms are considered the most debilitating and refractory aspect of schizophrenia, being associated with poor social, occupational and global outcomes. Conventional antipsychotics have limited efficacy against these symptoms and poor tolerability profiles. Atypical antipsychotics are an alternative treatment, and this 12-week, randomised, flexibly dosed study compared the efficacy, safety and tolerability of quetiapine and olanzapine in this regard. Of the 40 patients who entered the study (32 male; 8 female), 19 were randomised to quetiapine (mean dose 637 mg/day, mean treatment duration 80 days) and 21 to olanzapine (mean dose 16 mg/day, mean treatment duration 78 days). Quetiapine and olanzapine were similarly effective: in each treatment group significant improvements at Week 12 were observed for negative symptom scores on the SANS and the PANSS, and for subscale scores of affective flattening and alogia on the SANS. Both treatments were well tolerated in this patient population, with no worsening of extrapyramidal symptoms in either case. Anxiety and insomnia were the most common adverse events (> or =7% of patients in each group), but were not drug-related. Although this is a small study with limited power, the results support the effectiveness of quetiapine and olanzapine in treating the negative symptoms of schizophrenia.     

The pharmacology and safety of paliperidone extended-release in the treatment of schizophrenia

Paliperidone extended-release (ER) is a newly commercialised antipsychotic formulated using the principal active metabolite of risperidone, 9-hydroxyrisperidone. It has been developed as an osmotic controlled-release oral delivery system that minimizes peak-trough fluctuations in plasma concentrations, allowing once-daily administration and theoretically leading to a decreased incidence of adverse effects. Available data from preregistration, multicenter, short-term, double-blind, placebo-controlled studies indicate that paliperidone ER, at dosages of 3 – 15 mg/day, is relatively safe and well tolerated in adult patients with schizophrenia. As with risperidone, paliperidone may cause extrapyramidal symptoms and hyperprolactinemia in a dose-dependent manner. Preliminary long-term studies (up to 52 weeks) appear to confirm the findings from short-term trials indicating a low liability for paliperidone ER to cause metabolic effects (i.e., weight gain, hyperglycaemia and lipid dysregulation). Safety data from elderly patients appear to be promising. Due to negligible hepatic biotransformation, paliperidone ER is unlikely to be involved in clinically significant metabolic drug–drug interactions.     

抗抑郁药文拉法辛对精神分裂症阴性症状、社会功能恢复的临床疗效研究

目的:探讨抗抑郁药文拉法辛对精神分裂症患者的治疗效果。方法:回顾性分析2013年11月-2015年1月收治的64例精神分裂症患者的临床资料,其中,对照组采用利培酮治疗,而观察组采取文拉法辛联合利培酮治疗,比较2组患者的阴性症状、社会功能恢复情况以及不良事件发生情况。结果:治疗后,观察组与对照组患者的PANSS阴性症状、PSP评分均较治疗前出现明显改善,且在12周时,观察组患者的以上指标改善效果均优于对照组,组间差异具有统计学意义(P<0.05);2组不良反应发生率最高的主要为锥体外系副反应但组间各项相比,差异均无统计学意义(P>0.05)。结论:抗抑郁药文拉法辛可有效改善精神分裂症患者的阴性症状,提高患者的认知能力,从而较大程度改善患者的社会功能,促进患者的预后,其疗效显著且安全可靠,值得临床应用。     

Efficacy of amisulpride in treating primary negative symptoms in first-episode psychosis: a pilot study

OBJECTIVE: Negative symptoms are debilitating and associated with poor role functioning and reduced quality of life. There is a paucity of research on antipsychotic efficacy against the primary negative symptoms, particularly in first-episode psychosis (FEP). We undertook a prospective, open-label pilot trial to investigate the use of amisulpride in the treatment of young people with FEP characterised by primary negative symptoms. METHOD: Twelve male and two female first-episode patients with primary negative symptoms (aged 16-26) were commenced on low-dose amisulpride (mean 250 mg/day) and followed-up over a 6-month period. Primary outcome measures were the Scale for the Assessment of Negative Symptoms (SANS), the Quality of Life Survey (QLS) and their respective subscales. RESULTS: For the 12 completers there was a statistically significant improvement in SANS summary score (p = 0.036), Affective Flattening subscale global score (p = 0.046), QLS total score (p = 0.021), QLS subscales of Instrumental Role (p = 0.018) and Intra-psychic Foundations (p = 0.009) from baseline to week 24. CONCLUSIONS: Amisulpride appears to be associated with less severe negative symptoms and improved quality of life. Generalisabilty of the findings is limited by the small sample size and open-label design of our study, however the positive findings suggest that further controlled trials are warranted.     

Defining and measuring negative symptoms of schizophrenia in clinical trials

Recent attention has focused on negative symptoms as a target for new therapeutic approaches including pharmacological agents, medical devices, and psychosocial treatments. Each of these approaches requires an instrument for measuring the severity of negative symptoms as well as changes in severity over time. The instrument selected should provide coverage for the domains of negative symptoms; it should be sensitive to change; it should be reliable and relatively brief; and it should be useful for large international trials. These criteria were used to evaluate a number of older instruments including the Schedule for the Assessment of Negative Symptoms (SANS), the Positive and Negative Symptoms Scale (PANSS), and the Negative Symptom Assessment Scale (NSA). Two newer scales, the Brief Negative Symptom Scale (BNSS) and the Clinical Assessment Interview for Negative Symptoms (CAINS) were developed following a National Institute of Mental Health consensus meeting and addressed some of the shortcomings of earlier instruments.     

奥氮平与喹硫平治疗以阴性症状为主精神分裂症的对照研究

目的评价国产奥氮平治疗以阴性症状为主的精神分裂症的疗效和安全性。方法将80例符合DSM-Ⅳ精神分裂症患者随机分为2组,分别给予奥氮平和喹硫平治疗,疗程共8周,用阳性症状与阴性症状量表(PANSS)、临床疗效总评量表(CGI)评定疗效,药物副反应量表(TESS)评定不良反应。结果奥氮平组显效率87.2%、喹硫平组显效率为81.1%,两药对阴性症状的疗效无显著性差异(P>0.05)。2组在治疗过程中出现较多的不良反应是嗜睡、体质量增加,但两者之间无显著性差异(P>0.05)。结论奥氮平对以阴性症状为主的精神分裂症有较好的疗效,与喹硫平的疗效和不良反应相当。     

An assessment of iloperidone for the treatment of schizophrenia

Iloperidone (Novartis’ Zomaril?) is an atypical antipsychotic agent for the treatment of schizophrenia. Current trends in the treatment of schizophrenia indicate that some atypical antipsychotics are being recommended as first-line therapy. Atypical antipsychotics, in addition to being dopamine (D) receptor antagonists, are all relatively potent serotonin (5-HT) receptor antagonists and are less likely than conventional dopamine antagonists to induce movement disorders. However, all of these agents differ in their receptor profiles and clinical profiles. Iloperidone, a benzisoxazole, is a mixed 5-HT_2A/D₂ antagonist. Iloperidone was found to be more potent than its analogues when compared with haloperidol in antagonising climbing behaviour in mice. Iloperidone is extensively metabolised and the main circulating metabolite is reduced iloperidone. In patients treated with iloperidone, a low incidence of extrapyramidal symptoms and weight gain has been shown. Data from Phase II trials demonstrated efficacy in patients at doses of 8 mg/day and tolerability was good up to 32 mg/day. Phase III prospective, double-blind, randomised trials with iloperidone are in progress under the ZEUS (Zomaril? Efficacy Utility and Safety) programme involving 3300 patients. Iloperidone, with a balance of activity at the dopaminergic and serotonergic receptors, has obvious advantages over clozapine and olanzapine, both of which have a similar receptor profile as they favour serotonergic over dopamine receptors. Iloperidone is likely to reach the market in 2001 and has favourable prospects in the atypical antipsychotic market for schizophrenia, which is expanding from US$ 1.5 billion in 2000 to US$ 3 billion in 2005.     

The negative symptoms of schizophrenia and the monoamine oxidase inhibitors

Thirty chronic ambulatory schizophrenic patients whose main psychopathology was characterized by the persistence of negative symptoms, such as emotional withdrawal, depressed mood, motor retardation and blunted affect were included in this project in order to evaluate the therapeutic efficacy of tranylcypromine plus chlorpromazine therapy. The results show that tranylcypromine when added to the usual dose of chlorpromazine, in many instances, induces a definite improvement in these patients' clinical condition, that such treatment is safe and it may be also useful in preventing the occurrence of extra-pyramidal symptoms.     

Sulpiride in negative schizophrenia: A placebo-controlled double-blind assessment

Twenty-four chronic schizophrenic long-stay hospital patients were identified, who had not received neuroleptic drugs for 8–30 (average 8 months) and met or exceeded a minimum criterion of severity of negative symptoms. They were rendomly alocated to either sulpiride 200 mg twice daily or matching placebo, on a double-blind basis for 12 weeks. The results showed that low-dose sulpiride was significantly better than placebo in relation to improvements in negative symptoms. The changes in social behaviour were complex and not obviously related to symptom improvement; exhibited abnormal behaviour, a major factor in preventing successful return to the community, consistently improved only on the active drug.     

Negative symptoms in schizophrenia: considerations for clinical trials

There is little agreement about the methodology of clinical trials of antipsychotic drugs in patients with negative symptoms. A literature review revealed wide variation in experimental design, rating scales and study duration. This reflects differing views as to the definition and response to treatment of negative symptoms. Some degree of standardization would improve comparability of studies and aid the development of new compounds. Patients included in such studies should have displayed negative symptoms for at least 6 months. Depressive symptoms, positive schizophrenic symptoms and extrapyramidal signs may all influence or be confused with negative symptoms and may respond to treatment; they should be at a low level at baseline and should be measured during the study period. Studies should last at least 8 weeks. Several scales are available for measuring negative symptoms and are reviewed; a global impression score should be used additionally.     

非典型抗精神病药治疗精神分裂症的临床应用评价

目的:系统论述非典型抗精神病药治疗精神分裂症临床研究和应用的进展,评价其临床疗效和安全性.方法:通过互联网查阅Medline、Pubmed、Ovid、Science Direct、Proquest及国内外相关专业杂志所公开发表的研究报道进行综合评价和分析.结果与结论:非典型抗精神病药近10年来的临床应用研究进展迅速,除氯氮平外,大多数新型非典型抗精神病药如利培酮、奥氮平、喹硫平、齐拉西酮及阿立哌唑等已成为精神分裂症各种症状维度、不同病期和复发预防的一线临床选择,特别是在不良反应方面克服了经典抗精神病药和氯氮平的诸多严重缺点,同时,各种临床研究结果已被多项应用循证医学方法的系统研究所证实.     

喹硫平(35例)与氯丙嗪(34例)治疗精神分裂症的比较

目的 :比较喹硫平与氯丙嗪治疗精神分裂症的疗效及不良反应。方法 :6 9例病人分 2组。喹硫平组 35例 (男性 18例 ,女性 17例 )给予喹硫平 ;氯丙嗪组 34例 (男性 19例 ,女性 15例 )给予氯丙嗪 ,2药剂量均为 2 0 0～ 6 0 0mg·d- 1,分 2次服 ;疗程12wk ;用阳性与阴性症状量表 (PANSS)评定临床疗效 ,用不良反应量表 (TESS)评定药物不良反应。结果 :喹硫平组有效率 6 6 % ;氯丙嗪组有效率 6 5 %(P >0 .0 5 ) ,氯丙嗪组的不良反应较多。结论 :喹硫平治疗精神分裂症安全有效 ,疗效与氯丙嗪相似 ,不良反应较少。     

喹硫平治疗精神分裂症的随机、平行对照和多中心临床研究

目的 :评价喹硫平治疗精神分裂症的疗效及安全性。方法 :精神分裂症病人 12 5例 ,其中喹硫平组 6 5例 ,给喹硫平 30 0～ 6 0 0mg·d- 1治疗 ;利培酮组 6 0例 ,给利培酮 3～ 6mg·d- 1治疗。观察时间6wk。疗效评定用PANSS ,BPRS ,CGI。安全性评价用TESS等。结果 :经 6wk治疗后 ,喹硫平组总有效率为 80 % ,利培酮组为 88% ,2组相比P >0 .0 5;喹硫平组血清催乳素浓度为 399IU±s 4 50IU ,利培酮组为 1351IU± 76 3IU ,P <0 .0 1。喹硫平组不良反应有失眠 (9% )、ECG轻度异常 (8% )、兴奋或激越 (8% )等。喹硫平组静坐不能的发生率 (0 )显著低于利培酮组 (10 % )。结论 :喹硫平治疗精神分裂症疗效与利培酮相当 ,但对血清催乳素的影响小 ,锥体外系症状少     

Measurement of antipsychotic-induced side effects: support for the validity of a self-report (LUNSERS) versus structured interview (UKU) approach to measurement

A self-report measure of antipsychotic side effects (LUNSERS) was compared with that of an established semi-structured interview (UKU side effect rating scale). The validity and the ability of the LUNSERS to determine false positives by use of an internal 'red herring' subscale were assessed. 'Red herring' items are those which do not directly relate to known antipsychotic side effects. In an open study, 29 patients with schizophrenia and schizoaffective disorder from inpatient and outpatient settings within an Australian metropolitan mental health service were assessed for antipsychotic-induced side effects using both the LUNSERS and UKU. The LUNSERS and UKU were similar in their overall assessment of antipsychotic side effects (total score correlation of 0.58) and were correlated on a wide array of individual side effect items. Correlations between total scores and individual items were higher for those patients scoring low on the LUNSERS 'red herring' items compared with both those with high 'red herring' scores and the sample as a whole. Several LUNSERS items were identified as potentially problematic, requiring further explanation or supplementation with direct questioning. The 'red herring' scale appears to enable detection of patients that may be over-reporting symptomatology. The LUNSERS is a valuable self-report measure of antipsychotic side effects, particularly in cases where red herring scores are low.     

Selective serotonin re-uptake inhibitor augmentation in the treatment of negative symptoms of schizophrenia

Negative symptoms are core features of schizophrenia that respond poorly to first-generation antipsychotics and present a major obstacle in rehabilitation. Patients may be somewhat more responsive to clozapine and second-generation antipsychotics but even then, considerable impairment remains. This paper reviews the use of selective serotonin re-uptake inhibitor (SSRI) augmentation of antipsychotics in the treatment of negative symptoms in schizophrenia. Important methodological issues particular to the study of negative symptoms are also discussed. Current evidence indicates that at least two SSRIs, fluvoxamine and fluoxetine, can ameliorate primary negative symptoms in chronic schizophrenic patients treated with first-generation antipsychotics. Onset of improvement may be detected within 2 weeks of starting treatment. The combination is well-tolerated, although as antipsychotic drug concentrations may rise, close monitoring of drug doses and possibly drug concentrations is needed. So far, evidence regarding SSRI augmentation of second-generation antipsychotics is limited and in view of the increasing use of these newer agents, controlled studies are urgently needed. SSRI augmentation may be a useful addition to the treatment of schizophrenic patients with persistent negative symptoms. The paradoxical findings that both clozapine, a serotonin antagonist, and an SSRI antidepressant added to antipsychotics, can improve negative symptoms suggests that these pharmacologically distinct treatments may share common final mechanisms. A better understanding of these mechanisms can shed light on the pathogenesis of negative symptoms and provide new targets for drug development.     

利培酮联合艾司西酞普兰治疗慢性精神分裂症阴性症状的对照研究

目的：探讨利培酮联合艾司西酞普兰治疗慢性精神分裂症阴性症状的临床疗效以及安全性。方法将80例以阴性症状为主的慢性精神分裂症患者随机分为合用组和单用组,疗程12周,采用阳性和阴性症状量表（PANSS）和治疗中出现的症状量表（TESS）评定疗效和安全性。结果合用组显效率77.5%,单用组显效率55%。治疗后两组PASS评分均较治疗前有显著性下降,差异有统计学意义（P〈0.01）。治疗后2、4、8、12周末,合用组阴性因子分较单用组明显下降,差异有统计学意义（P〈0.05）。两组不良反应差异无统计学意义（P〉0.05）。结论利培酮联合艾司西酞普兰治疗慢性精神分裂症阴性症状起效快、疗效好,不良反应少。     

Amphetamine and negative symptoms of schizophrenia

The purpose of this study was to assess further the effect of amphetamine on negative symptoms of schizophrenia. Thirty-seven schizophrenic males meeting DSM-III criteria were rated with the Brief Psychiatric Rating Scale, the Abrams and Taylor Scale, and the Abnormal Involuntary Movements Scale before and after double-blind administration of either amphetamine (n=26) or placebo (n=11). Our results indicated that amphetamine administration generally did not improve negative symptoms, even when accounting for changes in positive symptoms. However, greater baseline negative symptoms were associated with a modest diminution after amphetamine treatment. Therefore, amphetamine may modestly improve negative symptoms in those schizophrenics in whom this symptomatology is more severe.