Sertindole improves both the positive and negative symptoms of schizophrenia: Results of a phase III trial

OBJECTS: This large multicentre, double-blind, randomized study was designed to evaluate four doses of sertindole and haloperidol 10 mg in the treatment of patients with DSM-III-R schizophrenia. METHOD: 617 patients were randomized, of whom 595 were included in an intention-to-treat analysis. 375 patients completed the study. Patients were randomized to receive sertindole 8 mg/day, sertindole 16 mg/day, sertindole 20 mg/day, sertindole 24 mg/day or haloperidol 10 mg/day for 56days. Efficacy was assessed through the changes in score on the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impressions (CGI) scale. Improvement in all end-points was observed for all treatment groups. RESULTS: Sertindole 16 mg showed significantly greater efficacy against negative symptoms than haloperidol 10 mg. The optimal dose of sertindole was 16 mg/day. Sertindole 8 mg appeared to be suboptimal with respect to efficacy, and increasing the dose of sertindole above 20 mg did not appear to offer any additional benefit. Sertindole at all doses caused significantly fewer extrapyramidal symptoms than haloperidol. CONCLUSION: Sertindole is effective against positive and negative symptoms of schizophrenia within the dose range 12-24 mg daily, with an optimal starting dose of 16 mg daily. Efficacy is comparable to 10 mg of haloperidol with no difference in the time course of treatment response. The dose response relationship for efficacy with sertindole seems to plateau at about 16 mg daily with no demonstrable difference in increasing doses above this point. (Int J Psych Clin Pract 2000; 4:55-62)     

Sertindole is associated with a low level of extrapyramidal symptoms in schizophrenic patients: Results of a phase III trial

OBJECT: The objective of this double-blind, multicentre study was to evaluate four doses of sertindole and haloperidol 10 mg. METHOD: The 617 schizophrenic patients were randomized to receive sertindole 8, 16, 20 or 24 mg/day or haloperidol 10 mg/day. Patients were assessed for extrapyramidal symptoms (EPS) using the Simpson-Angus Scale (SAS) and Barnes Akathisia Scale (BAS), and for movement disorders using the Abnormal Involuntary Movement Scale (AIMS). RESULTS: Patients receiving haloperidol experienced significantly more EPS than patients receiving sertindole, supporting observations made in previous studies. The incidence of adverse events was similar for all doses of sertindole. SAS and BAS scores were significantly worse in the haloperidol group than in the sertindole groups. There were significantly greater increases in mean QT c interval in the sertindole groups than in the haloperidol group. Sertindole did not cause sedation. CONCLUSIONS: Sertindole is well tolerated and does not cause the debilitating EPS associated with traditional antipsychotic drugs. (Int J Psych Clin Pract 2000; 4:47-54)     

Sexuality and quality of life of patients with schizophrenia

Patients with schizophrenia continue to have sexual lives despite the nature of their illness. Sexuality, sexual relationships and sexual functioning are all important quality-of-life issues for these patients. Clinicians should be aware of this and not be hesitant to inquire as to the patient's experience and functioning in these areas. The importance of the patient's sexual life should be reflected in our quality of life questionnaires, and be incorporated as part of psychiatric rehabilitation programs through formal sex education. (Int J Psych Clin Pract 2000; 4:29-33)     

The efficacy of zotepine in treating acute negative symptoms of schizophrenia: The results of a meta-analysis

INTRODUCTION: Zotepine is a unique antipsychotic drug, having effects which are both antiserotonergic and antidopaminergic that may make it more effective in the treatment of negative symptoms of schizophrenia than more conventional agents. METHOD: A meta-analysis was performed on the effect of zotepine on the negative symptoms in seven double-blind studies, as measured by the SANS scale. RESULTS: Of the trials selected for this meta-analysis, one showed significant improvement in acute negative symptoms in favour of zotepine. Negative symptoms measured in the other trials showed trends in favour of zotepine, except for one study where the trend was in favour of perazine. The meta-analysis showed zotepine to be significantly better then either placebo or conventional antipsychotic comparators using the standardized treatment difference methodology, and it confirmed the results from a previous study using patients with predominantly negative symptoms. CONCLUSION: Zotepine may have a place in the treatment of this group of patients where conventional antipsychotic drugs have had little effect. ( Int J Psych Clin Pract 2000; 4: 209 - 214)     

维思通与氯氮平治疗以阴性症状为主的精神分裂症的疗效对照研究

目的探索维思通对以阴性症状为主的精神分裂症的疗效与副反应。方法对８０例以阴性症状为主的精神分裂症住院患者，用维思通与氯氮平随机对照，采用ＳＡＮＳ、ＢＰＲＳ和临床疗效总评进行评定。结果维思通的疗效优于氯氮平，而副反应发生率也较低。结论维思通是治疗以阴性症状为主的精神分裂症较理想的药物     

Quality of Life in 833 outpatients with major depression treated with open-label venlafaxine extended release: An observational 24-week study

BACKGROUND Quality of Life (QoL) assessments are common in medicine and, recently, in psychiatry, mostly in patients with chronic mental illness. We evaluated QoL in depressed outpatients treated with venlafaxine-XR over a period of 24 weeks. METHOD We evaluated 833 patients with DSM-IV major depression using the Hamilton Depression Rating Scale (HAM-D), the Hamilton Anxiety Rating Scale (HAM-A), the Montgomery-Åsberg Depression Rating Scale (MÅDRS), and the QoL in Depression Scale (QLDS). The patients received venlafaxine-XR and we evaluated them after 4, 8, and 24 weeks of treatment. RESULTS HAM-D scores decreased from a baseline of 24.6 &#45 6.3 to 6.0 &#45 5.5 (mean &#45 SD; P <0.0001) after 24 weeks. HAM-A scores decreased from a baseline of 32.3 &#45 7.9 to 6.8 &#45 6.8 ( P <0.0001) after 24 weeks. QLDS scores decreased from a baseline of 25.8 &#45 5.8 to 6.6 &#45 7.5 ( P <0.0001) after 24 weeks, indicating improvement in QoL. The response after 4 weeks was also significant and continued improving during the study. Venlafaxine-XR was shown to be safe and well tolerated. DISCUSSION Open-label venlafaxine-XR was safe, effective, well tolerated, and improved not only depression and anxiety symptoms, but also QoL, in outpatients with major depression. This study has the limitations of any non-randomized, non-blinded multiple-site clinical trial.     

Computerized measurement of negative symptoms in schizophrenia

Accurate measurement of negative symptoms is crucial for understanding and treating schizophrenia. However, current measurement strategies are reliant on subjective symptom rating scales, which often have psychometric and practical limitations. Computerized analysis of patients' speech offers a sophisticated and objective means of evaluating negative symptoms. The present study examined the feasibility and validity of using widely-available acoustic and lexical-analytic software to measure flat affect, alogia and anhedonia (via positive emotion). These measures were examined in their relationships to clinically-rated negative symptoms and social functioning. Natural speech samples were collected and analyzed for 14 patients with clinically-rated flat affect, 46 patients without flat affect and 19 healthy controls. The computer-based inflection and speech rate measures significantly discriminated patients with flat affect from controls, and the computer-based measure of alogia and negative emotion significantly discriminated the flat and nonflat patients. Both the computer and clinical measures of positive emotion/anhedonia corresponded to functioning impairments. The computerized method of assessing negative symptoms offered a number of advantages over the symptom scale-based approach.     

Suicide and undetermined death by drowning

INTRODUCTION : To compare the efficacy and safety of olanzapine and haloperidol in partial-responder paranoid schizophrenic patients. METHOD : In this multi-centre, double-blind study, 28 patients with DSM-IV paranoid schizophrenia were randomized to receive 14 weeks treatment with either olanzapine or haloperidol at flexible doses. The pre- and post-treatment assessment included the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the CGI, the Simpson-Angus Rating Scale, and the Barnes Akathisia Rating Scale. RESULTS : The two treatment groups showed similar improvement on the BPRS positive symptoms subscale, while the improvement of BPRS negative symptoms subscale was significant only in the olanzapine group (ANOVA with repeated measures, group effect: F=5.89, P =0.023). Only the olanzapine-treated patients experienced a significant improvement of negative symptoms as rated by the SANS (ANOVA with repeated measures, group effect: F=6.81, P =0.016). No significant differences were found between the two groups on the Simpson and Angus Rating Scale scores, but a significant difference was found in the Barnes Akathisia Rating Scale scores: no patient in the olanzapine-treated group experienced akathisia, while a few patients in the haloperidol-treated group showed this side-effect, thus resulting in a significant group effect detected by the ANOVA (F=4.23, P =0.05). CONCLUSIONS : These preliminary results suggest that olanzapine is superior to haloperidol in the treatment of partial-responder paranoid schizophrenic patients, and also shows a better tolerability profile. Further investigations, including different diagnostic subgroups, are still needed to further clarify the clinical profile of olanzapine. (Int J Psych Clin Pract 2002; 6: 107-111)     

From first episode to long-term care: The need for sustained clinical commitment

There is considerable evidence to suggest that many patients experience difficulties in gaining access to treatment after the onset of significant symptoms and social disability. Delay in obtaining appropriate support and treatment can have profound effects on both the patient and their family and may also be associated with a poorer long-term outcome. As stated in the Principles of Practice, prompt and comprehensive clinical assessment, by a clinician experienced in the recognition and treatment of severe mental illness, is therefore important for achieving the best possible outcome for the patient. The primary objectives of early-stage treatment for schizophrenia are to achieve a full improvement in psychopathological symptoms and a recovery of premorbid levels of function. However, even with optimal treatment, the reality for many patients is that their symptoms and impairment continue. Many patients can therefore be regarded as only partially responsive, or even resistant, to treatment. When assessing the utility of an antipsychotic treatment regimen for such patients, clinicians should not just consider the objective manifestations of the disorder but also the subjective experience of the patient. Relapse of illness is also a common and serious problem for many patients with schizophrenia, despite continual treatment. Prevention and management of relapse are two of the main challenges in the effective treatment of schizophrenia. The optimal use of antipsychotic treatment and the adherence by patients to that treatment offer valuable protection against relapse. Symptoms of depression or low mood affect a high proportion of patients with schizophrenia at some point in their illness and are also associated with an increased risk of relapse. Treatment objectives in the early stages may need to be modified if a pattern of partial response or resistance to treatment, a cycle of relapse of the illness or the presence of depressive symptoms, develops. Clinicians should continue to offer a sustained and positive clinical commitment to all.     

精神分裂症伴强迫症状的临床研究

目的 分析伴强迫症状的精神分裂症临床特点及治疗效果,为临床诊断及治疗提供参考。方法 对伴强迫症状的精神分裂症与不伴强迫症状的精神分裂症各38例进行对照分析,使用维思通抗精神病药物治疗,采用阳性及阴性症状量表（PANSS）、强迫症状量表（Y—BOCS）、Hamilton抑郁量表（HAMD）、Hamilton焦虑量表（HAMA）评定疗效。结果 伴强迫症状的精神分裂症起痛年龄早,起病隐袭,病程迁延,以阴性症状为主,住院时间长,治疗效果差,Y—BOCS、HAMD、HAMA等量表评分明显高于不伴强迫症状的精神分裂症,有显著性差异。结论 伴强迫症状的精神分裂症,具有一定的异质性,单一使用抗精神病药物疗效差。     

Parenting a child with cancer: promotion and prevention-focused parenting

Applying regulatory focus theory (RFT), it was predicted that, among survivors of childhood cancer, quality of life (QoL) may be compromised by prevention-focused parenting (the focus on avoiding negative outcomes), rather than promotion-focused parenting (the focus on approaching positive outcomes). Interviews with mothers of survivors of Acute Lymphoblastic Leukaemia (ALL) and tumours of the Central Nervous System (CNS) were coded for reports of parenting and related to child QoL. Parents reported overall more promotion than prevention; however, mothers of children with tumours of the CNS reported more prevention-focus than mothers of children with ALL. Furthermore, prevention focus was related to child QoL, regardless of diagnosis. The study points toward the value of further development of RFT in clinical contexts.     

帕利哌酮合用艾司西酞普兰对精神分裂症患者BDNF及阴性症状的影响

目的探讨帕利哌酮舍用艾司西酞普兰对精神分裂症患者血清脑源性神经营养因子（BDNF）浓度及阴性症状的影响。方法将84例以阴性症状为主的精神分裂症患者随机分为研究组（帕利哌酮合用艾司西酞普兰）与对照组（单用帕利哌酮）,治疗12周。于治疗第0、4、8、12周监测血清BDNF浓度,同时采用阳性与阴性症状量表（PANSS）和副反应量表（TESS）评定疗效和不良反应。结果①两组有效率分别为85．7％和64．3％,经比较差异有统计学意义（χ^2=4．29;P〈O．05）;②疗后8、12周,两组BDNF浓度较治疗前升高,但研究组BDNF浓度升高较对照组明显（t=2．0814,2．4719;P〈0．05）;③两组PANSS总分和各阴性因子均较治疗前减少（P均〈0．05）,但研究组PANSS总分及各阴性因子分差异较对照组差异有统计学意义（t=2．059,2．014,P〈0．05）;④两组药物不良反应比较无显著差异。结论帕利哌酮合用艾司西酞普兰可明显提高BDNF浓度,改善精神分裂症的阴性症状。     

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。     

Cognitive and clinical predictors of success in vocational rehabilitation in schizophrenia

Cognitive impairments in schizophrenia appear to be associated with social problem solving, social and vocational functioning, and psychosocial skill acquisition. The present study examined the relationship of cognitive functioning, as well as clinical symptoms, to vocational outcomes among individuals with schizophrenia. One hundred and twelve participants with DSM-IV schizophrenia spectrum diagnoses underwent a comprehensive neuropsychiatric evaluation after enrolling in one of several employment programs. The neuropsychological evaluation examined verbal learning and memory, attention, speed of information processing, and executive functioning. Clinical symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS). Vocational outcomes were assessed 4 months after baseline assessment and included both measures of employment outcome (e.g., earnings) and of work performance as assessed by the Work Behavior Inventory (WBI). Negative symptoms, learning and memory performance, processing speed, and executive functioning were related to hours, weeks, and wages earned on the job. Stepwise multiple regression analyses found that among baseline clinical and cognitive predictors, only verbal learning and memory and cognitive disorganization symptoms were significant predictors of work behaviors 4 months later. Learning and memory were the only significant predictors of integrated employment at 4 months. These results suggest specific aspects of cognition may be modestly predictive of vocational outcomes.     

Electrophysiological basis for the ability of olanzapine to improve verbal memory and functional outcome in patients with schizophrenia: a LORETA analysis of P300

Abnormality of P300 waveforms of event-related potentials (ERPs) has been suggested to represent an aspect of the pathophysiology of schizophrenia. Previous work points to the contribution of altered neural function in discrete brain regions in the left hemisphere to psychotic symptoms and cognitive deficits of schizophrenia. In this study, we sought to determine: 1) if patients with schizophrenia elicit a decreased P300 current source density in brain areas, such as the superior temporal gyrus (STG); 2) if decreased P300 generator density in the left STG is recovered by treatment with the most widely-used antipsychotic drug olanzapine; and 3) if the recovery of P300 source density is associated with improvements of cognitive and functional status. P300 in response to an auditory oddball task, as well as verbal learning memory, psychopathology, and quality of life were evaluated in 16 right-handed patients with schizophrenia before and after treatment with olanzapine for 6 months. ERP data were also obtained from 16 right-handed age and gender-matched normal volunteers. Low resolution electromagnetic tomography (LORETA) analysis was used to obtain current density images of P300. Patients with schizophrenia showed significantly smaller LORETA values in several brain regions in the left side, particularly STG, middle frontal gyrus, and precentral gyrus, compared with control subjects. Six-month treatment with olanzapine significantly increased P300 source density only in the left STG. Positive symptoms, negative symptoms, verbal learning memory, and quality of life were also improved during treatment. Significant correlations were found between the increase in LORETA values of left STG vs. improvements of negative symptoms, as measured by Scale for the Assessment of the Negative Symptoms, and verbal learning memory, as measured by the Japanese Verbal Learning Test. Improvement of quality of life, as evaluated by the Quality of Life Scale, were significantly associated with an increase in LORETA values of middle frontal gyrus, and tended to correlate with that of precentral gyrus. The results of this study suggest that changes in cortical activity, as measured by ERPs, are responsible for the ability of some antipsychotic drugs to improve cognition and functional outcome in patients with schizophrenia.     

Eight-year follow-up of olanzapine therapy in a previous treatment-refractory schizophrenic patient: a case report

The introduction of atypical antipsychotic drugs during the 1990s represented a great step forward in the treatment of schizophrenia and other psychoses. These drugs might more effectively prevent relapse because of their effectiveness against a wider range of schizophrenic symptoms, as well as their improved tolerability, which leads to improved medication compliance. Olanzapine, a thienobenzodiazapine, is an antipsychotic drug with high affinity for the serotonergic receptors 5-HT 2 and 5-HT 6 and high affinity for dopaminergic receptors, mainly D2, D3 and D4, and with a lower propensity to cause extrapyramidal symptoms or increasing prolactin levels. The long-term efficacy and safety of olanzapine for treating treatment-refractory schizophrenia is still being investigated. The authors present a case of a 43-year-old man suffering from chronic treatment-resistant schizophrenia with both positive and negative symptoms, who was successfully treated with olanzapine for 8 years. (Int J Psych Clin Pract 2002; 6: 211-214 )     

氟西汀合并氯氮平治疗精神分裂症临床观察

目的：观察氟西汀合并氯氮平治疗精神分裂症阴性阴性症状的疗效和副反应。方法：将40例男性慢性精神分裂症病人平分为研究组（氟西汀加的氯氮平）和对照组（安慰剂加氯氮平），分别评定疗效及副反应。并同步测定氯氮平与N-去甲基氯氮平的血浓度。结果：治疗8周后研究组PANSS总分、阴性因子分比治疗前明显降低，且阴性因子分值显著低于对照组，同期氯氮平及N-去甲苦氯氮平血浓度明显升高。结论：氟西汀合并氯氮平能明显改善精神分裂症病人的阴性症状，并少有副反应。     

Improved quality of life over one year is associated with improved adherence in patients with schizophrenia

AimQuality of life (QoL) is increasingly considered an important outcome in health research. We wished to explore the determinants of change in QoL in patients with schizophrenia over the course of a one-year RCT.MethodsPredictors of change in observer-rated QoL (Quality of Life Scale: QLS) were assessed in 363 patients with schizophrenia during the CUtLASS clinical trial.ResultsChange in QLS score over the course of a year correlated with change in psychotic and depressive symptoms and treatment adherence. Linear regression showed that improvement in QoL was predicted by reduction in negative and depressive symptoms and improvement in adherence rating. These three change scores together explained 38% of the variance in QLS change. Exploration of the direction of any possible causal effect, using TETRAD, indicated that improved adherence leads to improved QoL, and that change in depression also leads to QoL change. The relationship between QoL and negative symptoms suggests that greater social activity (reflected as better QoL scores) improves negative symptoms. Such a direct relationship between treatment adherence and QoL has not been reported before.ConclusionImproving adherence to medication would appear to be a key approach to improving measured quality of life in people with schizophrenia.     

Amisulpride: efficacy in the management of chronic patients with predominant negative symptoms of schizophrenia

Amisulpride is a dopamine D2/D3-selective antipsychotic drug with potent antipsychotic efficacy in acute exacerbations of schizophrenia. It also possesses substantial efficacy in chronic schizophrenic patients with enduring predominant negative symptoms. This unique property has been demonstrated in a series of short (6 weeks) and medium-/long-term (6–12 months) double-blind placebo-controlled studies. The patients in these studies were carefully selected and assessed to avoid confounding results with non-specific changes in other symptom domains. The results not only show effects on negative symptoms at the optimal dose of 100 mg/day, but also significant improvement in global functioning. The effect observed in short-term studies was maintained over longer treatment periods (6–12 months). Amisulpride was well tolerated with a safety profile similar to placebo. These results open a new therapeutic approach for negative symptoms, one of the most disabling aspects of schizophrenia. Received: 25 July 2000 / Accepted: 26 July 2001