Efficacy of olanzapine and risperidone in schizophrenia: a randomized double-blind crossover design

This article compares the efficacy of olanzapine and risperidone for positive and negative symptoms using an 18-week, randomized, double-blind, crossover design. The hypotheses were that olanzapine would be more efficacious for treating negative symptoms, and that risperidone would be superior in treating positive symptoms. Positive and negative symptoms scores improved throughout treatment, regardless of medication type. Differences between the medications were found for negative and general psychopathology rating scales. Overall, olanzapine led to greater improvements in negative symptoms than did risperidone. When each scale was analyzed individually, greater improvements were found for olanzapine on Positive and Negative Symptoms Scale (PANSS) General,PANSS total, and Scale for the Assessment of Negative Symptoms (SANS)attention. A nearly significant trend favoring olanzapine was found for the Calgary Depression Scale. Several negative symptom subscales followed a nonsignificant trend toward olanzapine being more efficacious than risperidone.Thus, there was a very consistent pattern of greater efficacy for olanzapine, particularly for negative symptoms. Despite the small number of subjects, this study shows the potential of a within-subject design to elucidate differences in efficacy.     

Efficacy and tolerability of ziprasidone versus risperidone as augmentation in patients partially responsive to clozapine: a randomised controlled clinical trial

Patients suffering from schizophrenic psychoses sometimes insufficiently respond to antipsychotic monotherapy and then combination approaches are preferred. We aimed in validating the add-on of ziprasidone and risperidone to clozapine, and we performed a randomised head-to-head trial. Patients with partial response to clozapine were randomly attributed to augmentation with ziprasidone (n = 12) or risperidone (n = 12). Efficacy assessments included the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS), the Hamilton Depression Scale (HAMD), the Clinical Global Impression (CGI) and the Global Assessment of Functioning (GAF). Furthermore, several safety and tolerability measures were obtained. After six weeks, both groups showed significant reductions of positive and negative symptoms. In addition, affective state, psychosocial functioning and clozapine side effects improved without significant differences between the groups. Both approaches were well tolerated. However, the ziprasidone group experienced a small elongation of the QTc interval and a reduction of extrapyramidal symptoms. Patients under clozapine-risperidone therapy developed a rise of serum prolactin levels. The clozapine augmentation with ziprasidone or risperidone resulted in significant psychopathological improvements. The side effects differed between the treatment groups. Further head-to-head comparisons of atypical antipsychotics as add-on to clozapine are necessary.     

Effect of olanzapine or risperidone treatment on some cognitive functions in a one-year follow-up of schizophrenia outpatients with prominent negative symptoms.

AIMS: To compare olanzapine and risperidone outcome on some neurocognitive dimensions in chronic schizophrenia patients with prominent negative symptoms. METHOD: We randomised and followed for 1 year 235 chronic schizophrenia outpatients with a SANS global score > or =10 to open-label flexible-dose treatment with olanzapine or risperidone. Clinical, functional and cognitive assessments [including the COGLAB battery reaction time, vigilance-span of apprehension (VSA) and a card-sorting task] were done periodically. RESULTS: There were no significant differences between olanzapine (n=120) and risperidone (n=115) treatments in the neurocognitive dimensions tested. Mean+/-SD doses were 12.2+/-5.8 mg/day of olanzapine and 4.9+/-2.0 mg/day of risperidone. Patients in the olanzapine group showed a significant improvement in the VSA total score, but the within-group change was modest (effect size of 0.26); the difference with the risperidone group was not significant (p=0.207). Patients in both groups showed a significant improvement in a composite measure of executive efficiency based on the card-sorting task, with within-group effect size of 0.21 (risperidone) and 0.35 (olanzapine); the between-group difference was not significant (p=0.164). At baseline, better functional status correlated with VSA. Patients scoring lower on VSA or executive efficiency at baseline improved more on these respective measures. CONCLUSION: Modest pro-cognitive effects can also be found in chronic schizophrenia outpatients with prominent negative symptoms when treated with olanzapine or risperidone.     

Randomized, double-blind 6-month comparison of olanzapine and quetiapine in patients with schizophrenia or schizoaffective disorder with prominent negative symptoms and poor functioning

This study compared the effects of olanzapine (OLZ) with those of quetiapine (QUE) for improving negative symptoms in patients diagnosed with schizophrenia or schizoaffective disorder who had prominent negative symptoms and marked deficits in social or occupational functioning. In this 6-month, multicenter, double-blind clinical trial, patients were randomized to treatment with OLZ (n = 171, 10-20 mg/d) or QUE (n = 175, 300-700 mg/d). Patients were treated at community mental health centers and assigned case managers who developed individualized psychosocial treatment plans. The primary efficacy measure was the reduction in negative symptoms using the Scale for the Assessment of Negative Symptoms. Secondary measures assessed changes in functioning, psychopathology, and treatment tolerability. Treatment with OLZ or QUE led to a significant reduction in negative symptoms, with no between-group difference (P = 0.09). Both treatment groups also showed significant improvement on most efficacy measures. Olanzapine-treated patients showed significantly greater improvement on positive symptoms and on several measures of functioning including Global Assessment of Functioning Scale, Quality of Life Instrumental Role domain, and level of effort in psychosocial or occupational rehabilitation programs. Significantly more OLZ-treated patients completed the study (52.6% OLZ, 37.7% QUE, P = 0.007). Treatment differences in safety were relatively small and not thought to be clinically relevant. Patients with schizophrenia who manifest prominent negative symptoms and marked functional deficits demonstrated significant improvement in negative symptoms after treatment with OLZ or QUE. Greater improvement in positive symptoms and a greater study completion rate may hold relevance to enhanced functional outcomes observed after OLZ therapy.     

Symptom response and side-effects of olanzapine and risperidone in young adults with recent onset schizophrenia

The symptom response and side-effects of olanzapine and risperidone were compared in patients with recent onset schizophrenia. Actively symptomatic patients (n=44) randomly received olanzapine 15 mg (median dose) or risperidone 4 mg (median dose). Symptom response and side-effects were measured during a 6-10-week treatment study. No major differences were observed between the two treatment groups. Symptoms improved significantly on the Positive and Negative Syndrome Scale total score, positive subscale and general psychopathology subscale for both treatment groups. Using five symptom dimensions, both drugs were effective in treating positive symptoms and agitation/excitement symptoms, and neither olanzapine or risperidone influenced disorganization and depression symptoms. Results on the negative symptoms subscale and symptom dimension were inconclusive. No major differences were found in the frequency of the reported side-effects akathisia, parkinsonism and weight gain. These data indicate that the differences between olanzapine and risperidone in symptom response are small. In spite of the relatively low power of the study, we could exclude the presence of substantially different treatment effects between olanzapine and risperidone.     

The effect of augmentation with moclobemide on symptoms of schizophrenia.

The effectiveness of adding moclobemide to antipsychotic treatment in schizophrenic patients with prominent negative symptoms was examined. Eleven chronic schizophrenic patients had their regular antipsychotic treatment augmented by the addition of moclobemide 450 mg/day for 8 weeks. A significant improvement was seen on the Positive and Negative Syndrome Scale (PANSS) negative factor and for the Scale for the Assessment of Negative Symptoms (SANS) scores, PANSS total score, PANSS general factor score and Hamilton Depression Scale scores. Positive symptoms were not altered. Moclobemide augmentation may ameliorate negative, depressive and general symptoms in schizophrenia.     

利培酮口服液与奥氮平治疗脑器质性精神障碍疗效与安全性分析

目的:比较利培酮口服液与奥氮平在治疗脑器质性精神障碍疗效与安全性的差异.方法:分析2007年5月至2011年5月在本院住院4周以上,符合CCMD-3中脑器质性精神障碍诊断标准的患者共133例,其中利培酮口服液组62例,奥氮平组71例.比较两组患者入院时与治疗4周末在简明精神病评定量表、阳性症状量表、阴性症状量表、副反应量表总分以及实验室检查上的差异.结果:两组在治疗4周末简明精神病评定量表、阳性症状量表、阴性症状量表分值上无统计学差异(P＞0.05).在锥体外系副反应,催乳素水平升高上利培酮口服液组要大于奥氮平组(P＜0.05),而在体重增加和镇静、嗜睡上要少于奥氮平组(P＜0.05);在其余副反应项目的比较上则未见统计学差异(P＞0.05).结论:利培酮口服液与奥氮平对脑器质性精神障碍的治疗效果是相当的,对脑炎所致精神障碍的有效率在80％左右,两者在副反应上有所差别,在临床治疗时需根据患者具体情况制定个体化治疗方案.     

Lack of a pharmacokinetic interaction between mirtazapine and the newer antipsychotics clozapine, risperidone and olanzapine in patients with chronic schizophrenia.

The effect of mirtazapine on steady-state plasma concentrations of the newer atypical antipsychotics clozapine, risperidone and olanzapine was investigated in 24 patients with chronic schizophrenia. In order to treat residual negative symptoms, additional mirtazapine (30 mg per day) was administered for six consecutive weeks to nine patients stabilized on clozapine therapy (200-650 mg per day), eight on risperidone (3-8 mg per day) and seven on olanzapine (10-20mg per day). There were only minimal and statistically insignificant changes in mean plasma concentrations of clozapine and its metabolite norclozapine, risperidone and its metabolite 9-hydroxyrisperidone, and olanzapine during the study period. Mirtazapine co-administration with either clozapine, risperidone or olanzapine was well tolerated. In the overall sample, a slight improvement in negative symptomatology, as assessed by the Scale for Assessment of Negative Symptoms, was observed at final evaluation (P<0.01) and six patients (two in each treatment group) were classified as responders. While double-blind, controlled studies are needed to evaluate the potential clinical benefits of mirtazapine in chronic schizophrenia, our findings indicate that mirtazapine has a negligible effect on the metabolism of clozapine, risperidone and olanzapine and can be added safely to an existing treatment with these antipsychotics.     

No negative symptoms in healthy volunteers after single doses of amisulpride, aripiprazole, and haloperidol: a double-blind placebo-controlled trial

Noncompliance and poor outcome in patients with schizophrenia are closely related to the negative symptoms secondary to antipsychotics. No controlled study has evaluated whether amisulpride and aripiprazole induce negative symptoms. The aim of this study was to assess the effects of single doses of amisulpride, aripiprazole, haloperidol, and risperidone in healthy volunteers. Seventy-eight young volunteers took part in this double-blind, randomized, placebo-controlled, parallel study of four antipsychotics: 400 mg amisulpride, 10 mg aripiprazole, 3 mg haloperidol, and 2 mg risperidone. Assessments of negative symptoms were done 4 h after administration using both subjective rating scales (Neuroleptic Induced Deficit Syndrome Scale and Subjective Deficit Syndrome Scale) and an objective rating scale (Scale for the Assessment of Negative Symptoms). Risperidone only produced significant increases on the avolition score of the Neuroleptic Induced Deficit Syndrome Scale and blunted affect and alogia scores of the Scale for the Assessment of Negative Symptoms compared with placebo. The effect on blunted affect persisted after controlling for mental sedation. Amisulpride, aripiprazole, and haloperidol did not induce negative symptoms. Aripiprazole and risperidone induced mild extrapyramidal symptoms. The most common adverse events were somnolence and cognitive slowing. These data indicate that a single risperidone dose induces negative symptoms in normal volunteers, whereas amisulpride, aripiprazole, and haloperidol do not. These characteristics of antipsychotics should be considered when choosing optimal drugs for patients with psychosis.     

左旋千金藤啶碱与奋乃静治疗精神分裂症双盲比较

目的 :研究左旋千金藤啶碱 (SPD)特有的D1受体激动 D2 受体阻滞双重作用对精神分裂症的治疗效果。方法 :住院病人 61例随机分为SPD组和奋乃静组的双盲对照研究。SPD组 (n =31)服用SPD 2 2 5～ 62 5mg·d- 1,奋乃静组 (n =30 )服用奋乃静 16～ 4 4mg·d- 1,分别为 8wk。结果 :SPD组完全缓解率为 71% (2 2 /31) ,奋乃静组为 5 0 %(15 /30 ) ;显著进步分别为 10 % (3/31) ,2 3%(7/30 )。SPD组的有效率为 80 % ,奋乃静组为73%。SPD组的简明精神病量表 (BPRS)疗效在 2 ,4wk时显著强于奋乃静组 (P <0 .0 5 )。SPD组的阴性症状评定量表 (SANS)和阳性症状评定量表(SAPS)疗效显著强于奋乃静组 (P <0 .0 5 )。SPD组的治疗作用显效快。SPD组无锥体外系不良反应 ,SPD组的TESS总分低于奋乃静组 (P <0 .0 5 )。结论 :SPD对精神分裂症有疗效 ,出现快 ,对阳性和阴性症状疗效优于奋乃静 ,无锥体外系不良反应     

Olanzapine augmentation in treatment-resistant panic disorder: a 12-week, fixed-dose, open-label trial

The purpose of our study was to evaluate the efficacy and tolerability of low-dose olanzapine augmentation in selective serotonin reuptake inhibitor (SSRI)-resistant panic disorder (PD) with or without agoraphobia. In this 12-week, open-label study, 31 adult outpatients with treatment-resistant PD who had previously failed to respond to SSRI treatment were treated with fixed dose of olanzapine (5 mg/d) in addition to SSRI. Efficacy was assessed using the Panic Attack and Anticipatory Anxiety Scale (PAAAS), the Agoraphobic Cognitions Questionnaire (ACQ), the Hamilton Rating Scale for Anxiety (HAM-A), the Hamilton Rating Scale for Depression (HAM-D), the Global Assessment of Functioning Scale (GAF), and the Clinical Global Impression of Improvement (CGI-I). Twenty-six patients completed the trial period with a dropout rate of 16.1%. At week 12, 21 patients were responders (81.8%), and an overall improvement on all rating scales was observed in all patients both with or without agoraphobia. Fifteen patients (57.7%) achieved remission. Olanzapine was well tolerated and the most frequent adverse effects were mild-to-moderate weight gain and drowsiness. No extrapyramidal symptoms were reported. Olanzapine appears to be effective as augmentation strategy in the treatment of SSRI-resistant PD, but study limitations must be considered and placebo-controlled studies are needed.     

5-HT2A receptor promoter polymorphism, -1438G/A and negative symptom response to olanzapine in schizophrenia

The 5-HT2A receptor promoter -1438G/A polymorphism, which is in complete linkage disequilibrium with the 5-HT2A 102T/C polymorphism, may be related to antipsychotic response. The aim of this paper is to determine relationships between the -1438G/A polymorphism and olanzapine negative symptom response. DNA from 41 subjects with schizophrenia (as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) was analyzed for the -1438G/A polymorphism. Olanzapine (7.5-20 mg/day) was given for 6 weeks and response was assessed using the Scale for Assessment of Negative Symptoms (SANS). A linear regression used a dependent variable of percent change in SANS. Independent variables included 5-HT2A polymorphisms and interactions. The -1438G/A polymorphism and percent change in SANS showed a significant trend (P=.0542). The A/A genotype group had a 45% reduction in SANS compared with 19% in the other groups. We conclude that the A/A genotype may be associated with olanzapine negative symptom response, seen as a 2-fold greater percent reduction in SANS, and may be clinically relevant.     

A double-blind, controlled study of sertindole versus risperidone in the treatment of moderate-to-severe schizophrenia

Sertindole is a non-sedating atypical antipsychotic effective in the management of schizophrenia and is associated with placebo-level incidence of extrapyramidal symptoms (EPS). In this randomized, double-blind, parallel-group, flexible-dose, multi-centre study, the efficacy and tolerability of sertindole was directly compared with another atypical antipsychotic in patients with schizophrenia. A total of 187 patients were randomly assigned to treatment with sertindole (12-24 mg/day, n=98) or risperidone (4-10 mg/day, n=89) for 12 weeks. Although early termination reduced the power of the study, some significant between-group differences were evident. Sertindole reduced the mean Positive and Negative Syndrome Scale total scores to a greater extent than risperidone, and the difference reached statistical significance at endpoint for the Observed Cases (OC) dataset. Moreover, sertindole was superior for the treatment of negative symptoms compared to risperidone (P<0.05, Last Observation Carried Forward and OC). Both treatment groups were similarly effective in improving Clinical Global Impression (Severity and Improvement), the Drug Attitude Inventory and Global Assessment of Functioning scores. Sertindole and risperidone were both well tolerated. Numerically, fewer patients in the sertindole group (19%) reported EPS-related adverse events than in the risperidone group (28%), although significantly more sertindole-treated patients reported QT prolongation and abnormal ejaculation volume (P<0.05). In conclusion, sertindole was well tolerated and demonstrated clinically relevant efficacy advantages over risperidone.     

The association of weight gain and olanzapine plasma concentrations

Atypical antipsychotics, including olanzapine, have been associated with clinically significant weight gain in some patients. The purpose of this study was to determine if weight gain was associated with increasing plasma concentrations during olanzapine treatment in subjects with schizophrenia. This study included 39 acutely ill subjects with schizophrenia, schizoaffective disorder, or schizophreniform disorder (DSM-III-R or DSM-IV). Assessments included the Brief Psychiatric Rating Scale (BPRS), the Scale for Assessment of Negative Symptoms (SANS), and weight measurements. Olanzapine was titrated to a dose of 5 to 20 mg/d for 2 to 6 weeks. A 24-hour plasma concentration was obtained after 6 weeks of treatment. Analysis using a receiver operator characteristic curve identified a threshold dose-weighted plasma concentration of 20.6 ng/mL being associated with an increased likelihood of clinically significant weight gain (> or =7% baseline weight) during olanzapine treatment. The associations remained significant after adjusting for age, gender, baseline body mass index, baseline symptom severity, and symptom improvement (OR = 10.1; 95% CI, 1.3-75.0; P = 0.024). Similar analysis determined that a threshold olanzapine dose of 13.3 mg/d was associated with > or =7% weight gain. However, after adjusting for potential confounders, the results did not remain significant. The association of weight gain with plasma concentrations during treatment with olanzapine may support the utilization of plasma drug concentration as a marker for antipsychotic-induced weight gain in the treatment of schizophrenia.     

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.     

齐拉西酮合并舍曲林治疗精神分裂症阴性症状的疗效观察

目的 观察齐拉西酮合并舍曲林治疗精神分裂症阴性症状的疗效和不良反应.方法 本研究采用单纯随机对照研究设计,把82例符合<中国精神障碍分类与诊断标准>的精神分裂症住院患者随机分为研究组和对照组,每组41例.研究组为齐拉西酮合并舍曲林治疗,对照组仅单一使用齐拉西酮治疗,治疗期为8周.两组齐拉西酮治疗最大剂量为160 mg/d.于治疗前、治疗第2、4、8周末使用阳性和阴性症状量表(PANSS)和阴性症状量表(SANS) 评定两组患者的精神症状,于治疗第2、4、8周末使用药物副反应量表(TESS) 评定两组患者的不良反应.结果 治疗第4、8周末,研究组PANSS总分和阴性因子分低于对照组;研究组SANS总分和部分因子分低于对照组;治疗后第2、4、8周末,研究组TESS评分低于对照组.结论 齐拉西酮合并舍曲林治疗精神分裂症阴性症状安全有效.     

Predictors of clinical outcome in schizophrenic patients responding to clozapine

Many of the patients who respond better to clozapine (CLZ) than to typical antipsychotics still have residual psychopathology, but CLZ drug resistance data are lacking. The aim of this study was to evaluate the possible predictive factors of a clinical response to CLZ in a group of 20 schizophrenic patients (DSM-IV: 13 males and 7 females with a mean age of 35.5 years +/- 7.1 SD) resistant to typical antipsychotics but CLZ responders as assessed by the Brief Psychiatric Rating Scale (BPRS) (>20% improvement). After a 1-week washout period, CLZ was started at a dose of 25 mg/d, which was increased by the third week up to a maximum of 600 mg/d (mean 365.00 +/- 129.88 mg/d SD) and remained unchanged until the end of the study (week 8).The patients showed a significant improvement in the mean scores of the rating scales for positive (SAPS) and negative symptoms of schizophrenia (Scale for the Assessment of Negative Symptoms, SANS) (P < 0.003, P < 0.02). All of the patients included in the study were BPRS responders; 65% were also SAPS and 75% SANS responders (>20% improvement). The improvement in the SANS score was significantly greater among the female patients (P < 0.05). The SAPS and SANS responders had a significantly higher mean metabolic ratio [MR = (NCLZ/CLZ)] than the nonresponders (P < 0.01), and the percentage of improvement significantly correlated with the increase in MR. This finding suggests that the individual pharmacogenetics indicated by metabolic capacity may be related to clinical response. All of the patients showed a reduction in white blood cell counts, but this was significantly less in the SANS responders than the SANS nonresponders (P = 0.047). The SAPS responders had significantly lower neutrophil counts than the nonresponders (P = 0.03). Our results seem to suggest the importance of pharmacodynamic, constitutional, and genetic data over strict pharmacokinetics in determining the clinical response to CLZ.     

Practical issues with amisulpride in the management of patients with schizophrenia

Amisulpride is an atypical antipsychotic with a significantly greater effect size than first-generation, typical antipsychotics, and efficacy at least similar to that of olanzapine and risperidone in large-scale clinical trials in schizophrenia. Amisulpride provides greater improvement in positive and negative symptoms of schizophrenia, a better long-term outcome than typical antipsychotics, and distinct tolerability advantages over typical antipsychotics, which are reported to cause extrapyramidal symptoms (EPS) in 20-50% of patients. In addition, amisulpride is associated with significantly less weight gain than olanzapine and risperidone, does not increase body mass index, and favourably influences lipid profiles. In many patients with schizophrenia, adverse events impair adherence to treatment, and switching from typical or atypical antipsychotic therapy to amisulpride may be clinically appropriate. Observational drug-utilization studies suggest that many physicians switch to amisulpride because of fewer EPS and/or less weight gain and improved patient adherence. Cross-tapering (over 4 weeks), rather than abrupt cessation of pre-switch treatment, is preferred. Amisulpride has a low risk of drug-drug interactions, and, during cross-tapering, patients can remain on concurrent treatments (e.g. anticholinergics and antiparkinsonian agents) until the effective dosage has been reached. An appropriate amisulpride starting dose is 800 mg/day for patients with acute psychotic exacerbations, 400-800 mg/day for patients with predominantly positive symptoms, and 100-300 mg/day for predominantly negative symptoms. Amisulpride may be particularly suitable for clozapine-augmentation therapy in patients with refractory schizophrenia. Indeed, amisulpride is more effective than quetiapine as augmentation therapy in patients partially responsive to clozapine, and several prospective open-label studies and case series have reported promising results for amisulpride/clozapine combination therapy. In three prospective studies, addition of amisulpride 200-800 mg/day to clozapine significantly reduced mean scores on the Brief Psychiatric Rating Scale (BPRS) total (-33% to -35%), Clinical Global Impression (CGI)-Severity scale (-31%), Positive and Negative Syndrome Scale total (-22%), and Scale for the Assessment of Negative Symptoms (-34%). The proportion of responders (CGI score > or =3 or BPRS improvement >20%) was 71-86%. Retrospective case-series analyses have also reported improved psychopathological state, reduced adverse events, and lower clozapine dosage requirement with use of this combination. The pharmacological and clinical profiles of amisulpride suggest that this agent is a viable clinical option when a change of antipsychotic therapy is required in patients with schizophrenia because of lack of efficacy, adverse events and poor adherence to treatment, or for augmentation of clozapine in treatment-resistant illness.     

Quetiapine treatment in an open trial in combat-related post-traumatic stress disorder with psychotic features

Patients with combat-related post-traumatic stress disorder (PTSD) with psychotic features frequently fail to respond to antidepressants. Previous research has shown that these patients improve significantly after monotherapy with two atypical antipsychotics, olanzapine and risperidone. This study investigated the clinical outcome of another atypical antipsychotic, quetiapine, in war veterans with combat-related PTSD with psychotic features. Male war veterans (n=53) with DSM-IV-diagnosed PTSD with psychotic symptoms completed 8 wk of in-patient treatment with quetiapine (25-400 mg/d). The reductions in the total and subscale scores on the Clinician-Administered PTSD Scale (CAPS), and the increase in the Clinical Global Impression - Improvement Scale (CGI-I) were the primary outcome measures, and reductions in the Positive and Negative Syndrome Scale (PANSS) were the secondary outcome measures. The CGI - Severity of Illness scale (CGI-S) was used to assess the global clinical improvement. Drug-Induced Extrapyramidal Symptoms scale recorded adverse effects. Two, 6 and 8 wk treatment with quetiapine significantly reduced total and the subscales scores on the CAPS, PANSS, and CGI-S scales, in patients with psychotic PTSD. The results indicate that 8 wk of monotherapy with quetiapine reduced the majority of the psychotic and PTSD symptoms in the patients. Our present and previous data suggest that treatment-resistant psychotic PTSD patients may improve after taking atypical antipsychotics.     

Combined serotonin-5-HT2 and dopamine-D2 antagonism in schizophrenia: Clinical,extrapyramidal and neuroendocrine response in a preliminary study with risperidone (R 64 766)

Previous studies suggested a therapeutic action of the selective serotonin 5-HT₂-antagonist ritanserin on negative symptoms of schizophrenia and on neuroleptic-induced parkinsonism. In this open trial the effect of risperidone, a combined serotonin-5-HT₂-and dopamine-D₂-antagonist, was studied on a sample of 31 schizophrenic outpatients with an unsatisfactory response to conventional neuroleptic treatment, predominance of negative symptoms, together with troublesome extrapyramidal side-effects. After 28 days of oral treatment (2–6 mg daily) the patients showed a significant improvement as measured by means of the Brief Psychiatric Rating Scale and the Scale for the Assessment of Negative Symptoms. It is possible that the 5-HT₂ receptor antagonist properties of risperidone may improve negative symptoms. In addition, confirming previous studies, extrapyramidal symptoms showed a reduced incidence compared to previous neuroleptic treatment, suggesting a serotonin--dopamine interaction in the basal ganglia. No electrocardiographic, cardiovascular or laboratory abnormalities were observed.