Pregnenolone as an adjunct to risperidone for treatment of women with schizophrenia: A randomized double-blind placebo-controlled clinical trial

There have been few studies of pregnenolone therapy in schizophrenia and those that exist have been subject to several critical limitations, thus yielding inconsistent results. We attempted to assess the therapeutic effect of pregnenolone in a patient sample as homogeneous as possible. In this randomized double-blind clinical trial, 82 female inpatients with chronic schizophrenia, who had discontinued their antipsychotic medications for at least one week in case of any oral antipsychotic medication or a month for any depot antipsychotic medication, received risperidone plus either pregnenolone (50 mg/day) or placebo for 8 weeks. Inclusion criteria were acute illness with a baseline Positive and Negative Syndrome Scale (PANSS) negative subscale score of ≥20. Exclusion criteria were the presence of severe depression or other concomitant psychiatric disorders. Primary outcome was defined as the difference in the PANSS total score change from baseline to week 8 in the pregnenolone group compared to the placebo group. No significant difference was found in the PANSS total score changes between the two arms (mean difference (CI 95%) = −9.41 (−20.24 to 1.41); p = 0.087). Significant differences were initially found for PANSS negative change scores (mean difference (CI 95%) = −2.61 (−5.03 to −0.19); p = 0.035) and general psychopathology change scores (mean difference (CI 95%) = −5.93 (−11.37 to −0.48); p = 0.033). However, these findings did not survive Bonferroni correction for multiple testing. While this trial may suggest a potential effect of pregnenolone on schizophrenia symptoms, further studies are warranted.     

A double-blind, placebo-controlled trial of extract of Ginkgo biloba added to haloperidol in treatment-resistant patients with schizophrenia.

BACKGROUND: Many studies have indicated that excess free radical formation may be involved in the pathogenesis of patients with schizophrenia. Some investigators suggested that the use of free radical scavengers might provide improvement in schizophrenia. The aim of this study was to determine the effectiveness and to evaluate the side effects of extract of Ginkgo biloba (EGb) plus haloperidol in chronic, treatment-resistant inpatients with schizophrenia. METHOD: One hundred nine patients meeting DSM-III-R criteria for schizophrenia completed a double-blind, placebo-controlled, parallel-group study of EGb plus haloperidol. Fifty-six of the patients were randomly assigned to receive a fixed dose of 360 mg/day of EGb plus a stable dose of haloperidol, 0.25 mg/kg/day, and 53 were assigned to receive placebo plus the same dose of haloperidol for 12 weeks. Patients were assessed using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), and the Scale for the Assessment of Positive Symptoms (SAPS) at baseline, week 6, and week 12 and the Treatment Emergent Symptom Scale (TESS) for side effects at week 12. RESULTS: There was a significant reduction in both groups in BPRS total score after 12 weeks of treatment (p < .05). However, a significant reduction in total SAPS and SANS scores was noted in the EGb group (p < .05), but not in the placebo group. There was a lower SAPS total score in the EGb group than in the placebo group at the end of 12 weeks of treatment (p < .05). Of those treated with EGb plus haloperidol, 57.1% were rated as responders as compared with only 37.7% of those receiving placebo plus haloperidol when assessed by the SAPS (chi2 = 4. 111, p = .043). After 12 weeks of treatment, TESS subscore 1 (behavioral toxicity) and subscore 3 (symptoms of nerve system) were significantly decreased in the EGb group compared with the placebo group (p < .05). CONCLUSION: EGb treatment may enhance the effectiveness of antipsychotic drugs and reduce their extrapyramidal side effects.     

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.     

A pilot study of the safety and efficacy of amisulpride and risperidone in elderly psychotic patients

ObjectiveThe primary objective of this randomised, active–controlled, parallel group, double-blind study was to evaluate the tolerability of treatment with either amisulpride or risperidone in elderly patients with schizophrenia aged over 65 years; evaluation of efficacy was a secondary objective.MethodsThe study included patients of either sex aged 65 years or older fulfilling DSM IV-diagnostic criteria for psychotic disorders and who presented psychotic symptoms severe enough to require antipsychotic medication. Subjects were randomly allocated to a flexible dose of either amisulpride (100–400 mg/day) or risperidone (1–4 mg/day) for six weeks following a three- to six-day placebo wash-out period. Safety assessment involved adverse event reporting, physical examination, blood pressure, heart rate and ECG monitoring, and laboratory tests. Extrapyramidal symptoms were evaluated with the Simpson–Angus Scale, Barnes Akathisia Scale and the AIMS. Efficacy parameters were changes in score on the PANSS, BPRS, CDS and MMSE scores.ResultsThirty-eight patients were randomised, 25 to amisulpride and 13 to risperidone. A total of 26 adverse events were experienced by 10 patients in the amisulpride group and five patients in the risperidone group. One patient in each group discontinued the study due to the emergence of a movement disorder. Changes in scores on the three measures of extrapyramidal symptoms were similar in the two groups. The PANSS total score decreased by 27.8% in the amisulpride group and by 29% in the risperidone group between inclusion and study end.ConclusionAmisulpride and risperidone are generally well tolerated in elderly patients with schizophrenia. Both drugs appeared to be efficacious in this study population, with no differences in efficacy being observed. However, the sample size was too low to reveal potential inter-group differences. Both these atypical antipsychotics thus appear to be suitable for the treatment of schizophrenia in the elderly.     

Adjunctive divalproex and hostility among patients with schizophrenia receiving olanzapine or risperidone

OBJECTIVE: This study compared the specific antihostility effects of atypical antipsychotic monotherapy (olanzapine or risperidone) with that of combination treatment with divalproex sodium among patients with schizophrenia experiencing an acute psychotic episode. METHODS: A total of 249 inpatients with schizophrenia were randomly assigned to receive olanzapine plus placebo, olanzapine plus divalproex, risperidone plus placebo, or risperidone plus divalproex in a double-blind, 28-day multicenter trial. The target daily dose was 15 milligrams for olanzapine, 6 milligrams for risperidone, and up to 30 milligrams per kilogram (minimum, 15 milligrams per kilogram) for divalproex. The hostility item of the Positive and Negative Syndrome Scale (PANSS) was the principal outcome measure. Covariates included the PANSS items reflecting positive symptoms of schizophrenia (delusions, suspiciousness/persecution, grandiosity, unusual thought content, conceptual disorganization, and hallucinatory behavior). RESULTS: Combination treatment with risperidone or olanzapine plus divalproex was associated with different scores on the hostility item of the PANSS compared with antipsychotic monotherapy. Combination therapy had a significantly greater antihostility effect at days 3 and 7 than monotherapy. This result was not seen beyond the first week of treatment, but there was a trend toward a difference in effect for the entire treatment period. The effect on hostility appears to be statistically independent of antipsychotic effect on other PANSS items reflecting delusional thinking, a formal thought disorder, or hallucinations. CONCLUSIONS: Divalproex sodium may be useful as an adjunctive agent in specifically reducing hostility in the first week of treatment with risperidone or olanzapine among patients with schizophrenia experiencing an acute psychotic episode.     

A randomized controlled study of the efficacy of six-month supplementation with concentrated fish oil rich in omega-3 polyunsaturated fatty acids in first episode schizophrenia

Short-term clinical trials of omega-3 polyunsaturated fatty acids (n-3 PUFA) as add-on therapy in patients with schizophrenia revealed mixed results. The majority of these studies used an 8- to 12-week intervention based on ethyl-eicosapentaenoic acid. A randomized placebo-controlled trial was designed to compare the efficacy of 26-week intervention, composed of either 2.2 g/day of n-3 PUFA, or olive oil placebo, with regard to symptom severity in first-episode schizophrenia patients. Seventy-one patients (aged 16–35) were enrolled in the study and randomly assigned to the study arms. The primary outcome measure of the clinical evaluation was schizophrenia symptom severity change measured by the Positive and Negative Syndrome Scale (PANSS). Mixed models repeated measures analysis revealed significant differences between the study arms regarding total PANSS score change favouring n-3 PUFA (p = 0.016; effect size (ES) = 0.29). A fifty-percent improvement in symptom severity was achieved significantly more frequently in the n-3 PUFA group than in the placebo group (69.4 vs 40.0%; p = 0.017). N-3 PUFA intervention was also associated with an improvement in general psychopathology, measured by means of PANSS (p = 0.009; ES = 0.32), depressive symptoms (p = 0.006; ES = 0.34), the level of functioning (p = 0.01; ES = 0.31) and clinical global impression (p = 0.046; ES = 0.29). The findings suggest that 6-month intervention with n-3 PUFA may be a valuable add-on therapy able to decrease the intensity of symptoms and improve the level of functioning in first-episode schizophrenia patients.     

Riluzole combination therapy for moderate-to-severe major depressive disorder: A randomized,double-blind,placebo-controlled trial

Recent evidences suggest that glutamatergic dysregulation implicated in neural plasticity and cellular resilience may contribute to the pathophysiology of Major Depressive Disorder (MDD). Riluzole, which exerts its effect by targeting glutamate neurotransmission, has shown antidepressant effect in recent preclinical, observational and open label studies. This study aimed to assess the efficacy and tolerability of riluzole in patients with MDD. Sixty-four inpatients with diagnosis of moderate to severe major depressive disorder participated in a parallel, randomized, controlled trial, and sixty patients underwent 6 weeks treatment with either riluzole (50 mg/bid) plus citalopram (40 mg/day) or placebo plus citalopram (40 mg/day). All participants were inpatients for the whole duration of the study. Patients were assessed using Hamilton depression rating scale (HDRS) at baseline and weeks 2, 4 and 6. The primary outcome measure was to assess the efficacy of riluzole compared to placebo in improving the depressive symptoms. General linear model repeated measures demonstrated significant effect for time × treatment interaction on HDRS [F (1.86, 107.82) = 8.63, p < 0.001]. Significantly greater improvement was observed in HDRS scores in the riluzole group compared to the placebo group from baseline HDRS score at weeks 2, 4 and 6 (p < 0.001, p = 0.001, p = 0.002, respectively). Significantly greater response with greater speed to treatment was observed in the riluzole group than the placebo group. No serious adverse event occurred. This study showed a favorable safety and efficacy profile in patients with major depressive disorder. Larger controlled studies with longer treatment periods are needed to investigate long term safety, efficacy and optimal dosing.     

The efficacy of quetiapine vs haloperidol and placebo: a meta-analytic study of efficacy

INTRODUCTION: Atypical antipsychotics form a new class of treatment for psychotic disorders that offers advantages over conventional antipsychotics, such as haloperidol. Among these advantages is a lower risk of side effects-in particular movement disorders. The atypical antipsychotics that are currently commercially available are clozapine, risperidone, olanzapine, quetiapine, and ziprasidone. The focus of this report is on the efficacy of quetiapine. DATA SOURCES/STUDY SELECTION: A meta-analysis was performed on three placebo- and five haloperidol-controlled clinical trials of quetiapine. Efficacy was assessed using the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression (CGI), and the Scale for the Assessment of Negative Symptoms (SANS). In addition, a responder analysis was performed assessing patients who demonstrated a 40% improvement on the BPRS total score. RESULTS: The results showed that quetiapine was significantly (p<0.05) superior to placebo in improving psychotic symptoms. In addition, quetiapine was not significantly different from haloperidol on measures of efficacy measured by BPRS change score, but was superior to haloperidol in terms of response rate using observed case analysis (but not using last observation carried forward analysis). CONCLUSION: This meta-analysis supports the use of quetiapine as a front-line treatment for schizophrenia.     

利培酮合并碳酸锂治疗青少年期躁狂症的临床对照研究

目的 比较利培酮和氯丙嗪分别合并碳酸锂治疗青少年期有精神病性症状的躁狂症的疗效及安全性。方法 将符合CCMD—3诊断标准的青少年期有精神病性症状的躁狂症患者70例，随机分为两组，在使用碳酸锂的同时，分别合并利培酮或氯丙嗪进行为期8周的治疗。结果 利培酮组在治疗第8周周末显效率为77．14％，有效率为94．28％，与氯丙嗪组相近，但副反应少于氯丙嗪组，且有显著差异(P＜0．05)。结论 利培酮合并碳酸锂治疗青少年期有精神病性躁狂症的疗效好、安全性高。     

Characteristics of responders and non-responders to risperidone monotherapy or placebo in co-occurring bipolar disorder and anxiety disorder

Clinical characteristics predicting response and remission to psychopharmacological treatment of bipolar disorder (BD) and co-occurring anxiety disorders have been understudied. We hypothesized that non-response to risperidone or placebo in individuals with co-occurring BD and anxiety symptoms would be associated with a more severe clinical course of BD, and certain demographic variables. This study was a secondary analysis of a randomized, double-blind, parallel, 8-week study comparing risperidone monotherapy and placebo in individuals with BD plus current panic disorder, current generalized anxiety disorder (GAD), or lifetime panic disorder (n = 111) [31]. We compared clinical characteristics of responders (50% improvement on the Hamilton Anxiety Scale [HAM-A]) and non-responders as well as remitters (HAM-A < 7) and non-remitters in risperidone treatment (n = 54) and placebo (n = 57) groups. For non-responders in the risperidone group, co-occurring lifetime panic disorder was significantly more common than for non-responders in the placebo group. Apart from this, no significant differences in course of illness or demographics were found either between or across groups for patients with BD and co-occurring anxiety symptoms receiving risperidone or placebo in this acute phase study.     

Pilot clinical investigation of risperidone in the treatment of psychotic patients.

Sixty-one adult psychotic patients were treated for four weeks in an open dose-finding study with the new combined serotonin-dopamine antagonist risperidone (R 64 766). Risperidone had a rapid onset of action; a highly significant decrease in the total score on the Brief Psychiatric Rating Scale (BPRS) was already noticed after the first week of treatment. There was also a significant decrease in score for individual BPRS items related to positive, negative, and affective symptoms. In spite of the withdrawal of antiparkinson medication at selection, a significant decrease in extra-pyramidal symptoms (EPS) was observed, as assessed on the Simpson and Angus Scale. The Clinical Global Impression of therapeutic effect was consistent with the BPRS scores, showing a constant improvement throughout the study. The mean daily dose of risperidone at the end of the study was 3.7 mg. Tolerance was excellent and only mild side-effects were reported. Vital signs, ECG-parameters, and laboratory values remained within normal limits. This study demonstrates that risperidone has great potential as an effective and well-tolerated alternative for the treatment of chronically psychotic patients. It has potent antipsychotic effects, a low EPS-inducing profile, and, at the same time, it improves the negative and affective symptoms of schizophrenia.     

Switching to risperidone after unsuccessful treatment of olanzapine in the first-episode schizophrenia: an open trial

The purpose of this study was to assess the effect of switching to risperidone in the treatment of first-episode schizophrenia who had failed to respond to an initial-prescribed antipsychotic, olanzapine. Fifty-one patients with first-episode schizophrenia after unsuccessful treatment of olanzapine (the mean (S.D.) dosage: 16.4 (4.4) mg/day) were included in this switching study. Of the 51 patients, 43 (84.3%) completed the full 12-week trial and 8 (15.7%) dropped out. The mean dosage of risperidone at the endpoint (last observation) was 3.1 (2.0) mg/day. The total scores of Brief Psychiatric Rating Scales (BPRS) were significantly reduced from baseline to endpoint, especially in the positive and excitement factors (p<0.001). Responder rate (at least 20% decrease in BPRS total score plus final Clinical Global Impression score of 3 or less) was 35.3%. These findings indicate that the switching to risperidone could be one of the useful treatment options in this population.     

ALDH2 polymorphism,associated with attenuating negative symptoms in patients with schizophrenia treated with add-on dextromethorphan

ObjectiveIncreasing the evidence of inflammation's contribution to schizophrenia; using anti-inflammatory or neurotrophic therapeutic agents to see whether they improve schizophrenia treatment. Dextromethorphan (DM), a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, might protect monoamine neurons. Whether treating schizophrenia with risperidone plus add-on DM is more effective than risperidone (RISP) alone, and the association between the ALDH2 polymorphism and treatment response were investigated.MethodsA double-blind study in which patients with schizophrenia were randomly assigned to the RISP + DM (60 mg/day; n = 74) or the RISP + Placebo (n = 75) group. The Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS) scores were used to evaluate clinical response during weeks 0, 1, 2, 4, 6, 8, and 11. The genotypes of the ALDH2 polymorphism were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. A generalized estimating equation was used to analyze the effects of ALDH2 polymorphism on the clinical performance of DM.ResultsPANSS and SANS scores were significantly lower in both groups after 11 weeks of treatment. SANS total scores were significantly lower in the RISP + DM group in patients with the ALDH2*2*2 genotype.ConclusionsRISP plus add-on DM treatment reduced negative schizophrenia symptoms in patients with the ALDH2 polymorphism.     

Efficacy and safety of anti-inflammatory agents in treatment of psychotic disorders – A comprehensive systematic review and meta-analysis

ObjectiveAntipsychotic effects of immunomodulating drugs have been suggested; however, a thorough, comprehensive meta-analysis on the effect and safety of anti-inflammatory add-on treatment on psychotic disorders is lacking.MethodMultiple databases were searched up until February 2020. Only double-blinded, randomized, placebo-controlled clinical trials (RCTs) were included. Primary outcomes were change in total psychopathology and adverse events. Secondary outcomes included, amongst others, positive and negative symptoms, general psychopathology and cognitive domains. We performed random-effects meta-analyses estimating mean differences (MD) and standardized mean differences (SMD) for effect sizes.ResultsSeventy RCTs (N = 4104) were included, investigating either primarily anti-inflammatory drugs, i.e. drugs developed for immunomodulation, such as NSAIDs, minocycline and monoclonal antibodies (k = 15), or drugs with potential anti-inflammatory properties (k = 55), e.g. neurosteroids, N-acetyl cysteine, estrogens, fatty acids, statins, and glitazones. Antipsychotics plus anti-inflammatory treatment, compared to antipsychotics plus placebo, was associated with a PANSS scale MD improvement of -4.57 (95%CI = -5.93 to -3.20) points, corresponding to a SMD effect size of -0.29 (95%CI = -0.40 to -0.19). Trials on schizophrenia (MD = -6.80; 95%CI, -9.08 to -4.52) showed greater improvement (p < 0.01) than trials also including other psychotic disorders. However, primarily anti-inflammatory drugs (MD = 4.00; 95%CI = -7.19 to -0.80) were not superior (p = 0.69) to potential anti-inflammatory drugs (MD = 4.71; 95%CI = -6.26 to -3.17). Furthermore, meta-regression found that smaller studies showed significantly larger effect sizes than the larger studies (p = 0.0085), and only 2 studies had low risk of bias on all domains. Small but significant effects were found on negative symptoms (MD = -1.29), positive symptoms (MD = -0.53), general psychopathology (MD = -1.50) and working memory (SMD = 0.21). No differences were found regarding adverse events, but only 26 studies reported hereon.ConclusionsAnti-inflammatory add-on treatment to antipsychotics showed improvement of psychotic disorders; however, no superiority was found in primarily anti-inflammatory drugs, raising the question of the mechanism behind the effect, and treatment effect might be overestimated due to the large number of small studies.     

Risperidone in treatment-refractory schizophrenia.

OBJECTIVE: The purpose of this study was to evaluate the clinical safety and efficacy of risperidone compared to haloperidol in patients with treatment-refractory schizophrenia. METHOD: Sixty-seven medication-unresponsive subjects were randomly assigned to treatment with risperidone (N = 34) or haloperidol (N = 33). After a 3-7 day-placebo washout period, there was a 4-week, double-blind, fixed-dose comparison trial that was followed by a 4-week, flexible-dose phase. Measures of clinical change were quantified by standard psychopathologic and neuromotor instruments. RESULTS: Risperidone demonstrated clinical efficacy superior to that of haloperidol on the total Brief Psychiatric Rating Scale (BPRS) after the first 4 weeks of treatment. Risperidone did not show any advantage over haloperidol after an additional 4 weeks. Overall improvement on the BPRS at 4 weeks was significantly better for the risperidone group (24%) than for the haloperidol group (11%). Risperidone-treated subjects were significantly less likely than haloperidol-treated subjects to require concomitant anticholinergic medication after 4 weeks (20% versus 63%); they also had significantly les observable akathisia (24% versus 53%) and significantly less severe tardive dyskinesia. Baseline characteristics that correlated significantly with risperidone response were positive symptoms, conceptual disorganization, akathisia, and tardive dyskinesia. CONCLUSIONS: Risperidone was better tolerated and more effective in a subset of patients with treatment-refractory schizophrenia. Positive psychotic symptoms and extrapyramidal side effects at baseline appear to be powerful predictors of subsequent response to risperidone.     

The efficacy of a rapid-acting intramuscular formulation of olanzapine for positive symptoms

Rapid tranquilization of acutely psychotic patients with schizophrenia is usually carried out using typical antipsychotic agents. The objective of such treatment is to control agitation, not to treat psychosis, which usually responds only after a few weeks of treatment. An intramuscular formulation of the atypical antipsychotic olanzapine was developed for treatment of agitation in acutely psychotic patients. Studies conducted to assess control of agitation in schizophrenia also investigated the positive symptom efficacy of olanzapine when used to provide rapid tranquilization. This article summarizes the results of 3 clinical trials with intramuscular olanzapine with regard to positive symptom efficacy as measured by the Brief Psychiatric Rating Scale (BPRS; 0-6 scale) positive subscale. In 2 open-label trials, patients treated with intramuscular olanzapine experienced a mean decrease from baseline in BPRS positive subscale score. In 1 double-blind clinical trial of intramuscular olanzapine versus intramuscular haloperidol and intramuscular placebo, the mean decrease from baseline in BPRS positive subscale score for patients treated with intramuscular olanzapine was statistically significant (p < .05). In all 3 studies, positive symptom improvement continued following transition to oral olanzapine. These results suggest that intramuscular olanzapine has positive symptom efficacy early in the course of treatment and may provide a smooth transition to maintenance therapy with oral olanzapine.     

Clozapine augmented with risperidone in the treatment of schizophrenia: a randomized, double-blind, placebo-controlled trial

OBJECTIVE: The authors evaluated the efficacy and safety of augmenting clozapine with risperidone in patients with treatment-resistant schizophrenia. METHOD: In a randomized, double-blind, placebo-controlled 12-week trial, 40 patients unresponsive or partially responsive to clozapine monotherapy received a steady dose of clozapine combined with either placebo (N=20) or up to 6 mg/day of risperidone (N=20). Patient psychopathology was assessed at 2-week intervals with the Brief Psychiatric Rating Scale (BPRS) and the Scale for the Assessment of Negative Symptoms (SANS), among other measures. Movement disorders were assessed with the Simpson-Angus Rating Scale. RESULTS: From baseline to week 6 and week 12, mean BPRS total and positive symptom subscale scores were reduced significantly in both groups, but the reductions were significantly greater with clozapine/risperidone treatment. Reductions in SANS scores were also significantly greater with clozapine/risperidone treatment than with clozapine/placebo. The adverse event profile for clozapine/risperidone treatment was similar to that for clozapine/placebo. Simpson-Angus Rating Scale scores were lower with clozapine/risperidone treatment throughout the trial but increased to approach those of clozapine/placebo treatment at week 12. Clozapine/risperidone treatment did not induce additional weight gain, agranulocytosis, or seizures compared with clozapine/placebo treatment. CONCLUSIONS: In patients with a suboptimal response to clozapine, the addition of risperidone improved overall symptoms and positive and negative symptoms of schizophrenia. The combination appears to be safe and well tolerated. Augmentation of clozapine with risperidone may provide additional clinical benefit for patients who are nonresponsive or only partially responsive to clozapine alone.     

利培酮口服液合用氯硝西泮与氟哌啶醇针剂肌内注射治疗精神分裂症急性激越症状疗效和安全性的研究

目的 比较利培酮口服液合用氯硝西泮与氟哌啶醇针剂肌内注射(以下简称肌注)对精神分裂症急性激越症状的疗效和安全性,以及由氟哌啶醇肌注换利培酮口服(以下简称换药组)对急性期疗效的影响.方法 205例伴有急性激越症状的精神分裂症患者按随机数字表方法分为利培酮口服液组(104例)和氟哌啶醇肌注组(101例).研究分为急性激越症状疗效评价(治疗前5 d)和换药后急性期疗效评估(治疗6周)2个阶段.以阳性和阴性症状量表兴奋因子(PANSS-EC)及阳性和阴性症状量表(PANSS)总分作为主要疗效评价指标.安全性评估采用锥体外系副反应量表(Simpson-Angus Rating Scale,SAS)和静坐不能评定量表(Barnes Akathisia Scale,BAS)评定锥体外系症状、记录不良事件和实验室检查.结果 治疗前5 d利培酮口服液组和氟哌啶醇肌注组的急性激越症状都有明显改善(P＜0.01),2组间疗效差异无统计学意义(P＞0.05);利培酮口服液组合作程度好于氟哌啶醇肌注组(P＜0.05),锥体外系不良反应低于氟哌啶醇肌注组(P＜0.05).由氟哌啶醇肌注换利培酮口服后,治疗6周末口服组和换药组疗效及总体不良事件发生率比较差异均无统计学意义(P均＞0.05),但锥体外系不良反应换药组高于口服组,差异有统计学意义(P＜0.05).结论 利培酮口服液合用氯硝西泮口服治疗精神分裂症急性激越症状与氟哌啶醇肌注疗效相当,但利培酮口服液合作程度好,锥体外系不良反应发生率低.由氟哌啶醇肌注换利培酮口服对急性期疗效无明显影响.     

Double-blind randomized controlled study showing symptomatic and cognitive superiority of bifrontal over bitemporal electrode placement during electroconvulsive therapy for schizophrenia

BackgroundSeveral studies show that bifrontal electrode placement produces relatively fewer cognitive adverse effects than bitemporal placement during electroconvulsive therapy (ECT) in depression. There are no reports comparing these electrode placements in schizophrenia.ObjectivesThis study compared the clinical and cognitive effects of bifrontal and bitemporal electrode placements in schizophrenia patients referred for electroconvulsive therapy (ECT).Methods122 schizophrenia patients who were prescribed ECT were randomized to receive ECT with either bifrontal (BFECT; n = 62) or bitemporal (BTECT; n = 60) placement. Their concomitant anti-psychotic medications and the number of ECT sessions were not controlled. Psychopathology was assessed using the Brief Psychiatric Rating Scale (BPRS), Bush-Francis Catatonia Rating Scale (BFCRS), and the Nurse Observation Scale for Inpatient Evaluation (NOSIE). Cognitive functions were assessed 24-h after the final ECT using a battery of tests. Clinical improvement was compared using chi-square test, repeated measures ANOVA and analysis of covariance (ANCOVA). Cognitive adverse effects were compared using t-test.ResultsAt the end of 2 weeks (after 6 ECT sessions) 63% and 13.2% of BFECT and BTECT patients respectively had met the response criterion for BPRS (40% reduction in total score; OR = 20.8; 95% CI = 3.61–34.33). BFECT patients showed significantly faster clinical response on BPRS (Time × Group interaction effect: P = 0.001), BFCRS (P < 0.001) and the NOSIE total assets score (P = 0.003). ANCOVA using baseline scores as covariates and treatment-resistance status as between-subject factor showed that BFECT patients had significantly greater improvement in all measures. BFECT patients had significantly higher PGI-memory-scale total score than BTECT patients (t = 5.16; P < 0.001). They also showed superior performance in other cognitive measures.ConclusionsBFECT results in superior clinical and cognitive outcomes than BTECT in schizophrenia patients referred for ECT.