Effects of atypical and typical antipsychotic treatments on sexual function in patients with schizophrenia: 12-month results from the Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study.

PURPOSE: Sexual dysfunction in patients with schizophrenia can reduce quality of life and treatment compliance. This report will compare the effects of selected atypical and typical antipsychotics on sexual function in a large, international population of outpatients with schizophrenia who were treated over 1 year. SUBJECTS AND METHODS: Outpatients with schizophrenia, who initiated or changed antipsychotic treatment, and entered this 3-year, prospective, observational study were classified according to the monotherapy prescribed at baseline: olanzapine (N=2638), risperidone (N=860), quetiapine (N=142) or haloperidol (N=188). RESULTS: Based on patient perception, the odds of experiencing sexual dysfunction during 1 year of therapy was significantly lower for patients treated with olanzapine and quetiapine when compared to patients who received risperidone or haloperidol (all P< or =0.001). Females on olanzapine (14%) or quetiapine (8%) experienced a lower rate of menstrual irregularities, compared to females on risperidone (23%) or haloperidol (29%). Significant discordance was evident between patient reports and psychiatrist perception of sexual dysfunction, with psychiatrists underestimating sexual dysfunction (P< or =0.001). CONCLUSION: These findings indicate clinically relevant differences exist in the sexual side effect profiles of these selected antipsychotics. These factors should be considered when selecting the most appropriate treatment for outpatients with schizophrenia.     

Depression in schizophrenia: comparison of first- and second-generation antipsychotic drugs

The aim of this study was to compare the effects of different antipsychotics on depressive symptoms in schizophrenic patients. The data were drawn from a retrospective, naturalistic, observational study in which 222 subjects diagnosed as being affected by schizophrenia during a re-exacerbation phase received 6 weeks of monotherapy with fluphenazine decanoate, haloperidol decanoate, haloperidol, clozapine, olanzapine, quetiapine, risperidone or l-sulpiride. The Brief Psychiatric Rating Scale (BPRS), Extrapyramidal Side Effects Rating Scale (EPSE) and Anticholinergic Rating Scale (ACS) were administered at baseline and six weeks after the beginning of the study; depressive symptoms were evaluated using the BPRS items "depressive mood" and "guilt feelings". All of the antipsychotic drugs led to improvements in the depressive dimension, but this was statistically significant only in the case of fluphenazine decanoate, haloperidol, olanzapine, risperidone and l-sulpiride. A clinical improvement in the depressive dimension significantly correlated with the severity of the psychotic picture and its amelioration. Female patients were significantly more likely to show an improvement in depressive symptoms. In conclusion, our findings suggest that atypical antipsychotics as a class do not seem to be more effective on the depressive dimension during the course of schizophrenia than typical ones, at least as far as the collected BPRS data are concerned. The only factor that seemed to influence the improvement in depressive symptoms during our study was gender, as females were significantly more likely to improve although there were no between-gender differences in the baseline severity of the clinical picture.     

Treatment with olanzapine, risperidone or typical antipsychotic drugs in Asian patients with schizophrenia

OBJECTIVE: To examine clinical outcomes in Asian patients with schizophrenia receiving monotherapy with olanzapine, risperidone or typical antipsychotics in naturalistic settings. METHOD: In this report, data from the first 12 months of the prospective, observational, 3-year Intercontinental Schizophrenia Outpatient Health Outcomes study are presented for patients from participating Asian countries (Korea, Taiwan and Malaysia) who were started on, or switched to, monotherapy with olanzapine (n = 484), risperidone (n = 287) or a typical antipsychotic drug (n = 127) at baseline. RESULTS: At 12 months, overall reduction in the score of Clinical Global Impressions-Severity of Illness rating scale was greatest with olanzapine (p < 0.001 vs typical agents), followed by risperidone (p = 0.007 vs typical agents) treatment. Olanzapine treatment was found to have significantly better effects than typical agents on negative and depressive symptom scores, and significantly greater improvements than risperidone on negative and cognitive symptoms. The occurrence of extrapyramidal symptoms was least likely with olanzapine (p < 0.001 vs typical agents, and p = 0.012 vs risperidone), while the estimated odds of tardive dyskinesia were greatest in the typical treatment group (p = 0.046 vs olanzapine, and p = 0.082 vs risperidone). Mean weight increase was greater for olanzapine-treated patients compared with the other agents (p = 0.030 vs typical agents and p < 0.001 vs risperidone). The risk of menstrual disturbance was relatively high with risperidone when compared with olanzapine treatment (p < 0.001). CONCLUSIONS: The results of this observational study indicate that, in Asian patients with schizophrenia, olanzapine may offer benefits when compared with typical agents or risperidone. However, the significantly greater odds of weight gain should be considered in the clinical management of olanzapine-treated patients.     

Effectiveness of clozapine, olanzapine, quetiapine, risperidone, and haloperidol monotherapy in reducing hostile and aggressive behavior in outpatients treated for schizophrenia: a prospective naturalistic study (IC-SOHO).

OBJECTIVE: Antipsychotic medications may reduce hostile and aggressive behavior in schizophrenia. This study compared the effectiveness of antipsychotics in the treatment of aggression. METHOD: The Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study compares the effectiveness of antipsychotic treatments in practice setting. Schizophrenia outpatients who initiated or changed to a new antipsychotic are followed in this non-interventional, prospective observational study for up to 3 years, with 6-months data now available on the entire cohort (N=7655). The presence or absence of verbal or physical hostility/aggression was assessed retrospectively for the period of 6 months before enrollment, and prospectively in the period of 6 months after enrollment (the study treatment period). At baseline, patients in five monotherapy treatment groups (combined N=3135) were prescribed one of the treatments: clozapine, olanzapine, quetiapine, risperidone, or haloperidol, and had complete data. RESULTS: Hostile/aggressive behavior was reduced during the treatment period. Olanzapine and risperidone were significantly superior to haloperidol and to clozapine in this respect. These results remained essentially unchanged when adjusting for baseline imbalances in age, gender, age of onset, and substance abuse. CONCLUSIONS: As monotherapy, both olanzapine and risperidone were superior to haloperidol and clozapine in reducing aggression. The relative lack of effectiveness of clozapine may be specific to this study population.     

Effects of atypical antipsychotics on the syndromal profile in treatment-resistant schizophrenia

BACKGROUND: There has been considerable support for the observation that atypical antipsychotics have a broader range of therapeutic effects than traditional antipsychotics. We are exploring whether this expanded clinical efficacy can also be seen in patients with treatment-resistant schizophrenia. METHOD: The subjects were 157 treatment-resistant inpatients diagnosed with DSM-IV schizophrenia or schizoaffective disorder. They were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol in a 14-week double-blind trial and rated with a standard measure of clinical antipsychotic efficacy (Positive and Negative Syndrome Scale [PANSS]). Factor analysis at baseline and endpoint together with changes in 5 PANSS-derived factors were examined. Data were gathered from June 1996 to December 1999. RESULTS: The underlying PANSS factor structure, as indicated by the factor loadings, was essentially identical at baseline and endpoint. At baseline, the excitement factor was followed by the positive, negative, cognitive, and depression/anxiety factors, explaining 49.4% of the total variance. At endpoint, the positive factor was followed by the negative, excitement, cognitive, and depression/anxiety factors, explaining 55.5% of the total variance. The endpoint data indicated statistically significant (p <.05) improvements over time on the positive factor for all 3 atypicals, but not for haloperidol. The negative factor showed significant improvement for clozapine and olanzapine, with significant worsening for haloperidol. Clozapine, olanzapine, and risperidone were superior to haloperidol on the negative factor, while clozapine was also superior to risperidone. The cognitive factor showed significant improvement for all atypicals, as did the depression/anxiety factor. Only clozapine showed improvement on the excitement factor and was superior to both haloperidol and risperidone. CONCLUSIONS: Treatment with atypical antipsychotics did not substantially change the underlying PANSS 5-factor structure. However, antipsychotic treatment with all 3 atypical medications was associated with significant improvements on 3 of 5 syndromal domains (positive, cognitive, and depression/anxiety) of schizophrenia. Clozapine and olanzapine also showed improvement on the negative factor. Only clozapine was associated with improvement on the excitement domain. This finding confirms that atypicals are associated with improvement of an expanded spectrum of symptoms in treatment-resistant patients.     

Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder

OBJECTIVE: The authors compared the efficacy and safety of three atypical antipsychotics (clozapine, olanzapine, and risperidone) with one another and with haloperidol in the treatment of patients with chronic schizophrenia or schizoaffective disorder. METHOD: In a double-blind trial, 157 inpatients with a history of suboptimal treatment response were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol for 14 weeks (an 8-week escalation and fixed-dose period followed by a 6-week variable-dose period). RESULTS: Clozapine, risperidone, and olanzapine (but not haloperidol) resulted in statistically significant improvements in total score on the Positive and Negative Syndrome Scale. Improvements seen in total and negative symptom scores with clozapine and olanzapine were superior to haloperidol. The atypical drugs, particularly olanzapine and clozapine, were associated with weight gain. CONCLUSIONS: The effects of atypical antipsychotics in this population were statistically significant but clinically modest. The overall pattern of results suggests that clozapine and olanzapine have similar general antipsychotic efficacy and that risperidone may be somewhat less effective. Clozapine was the most effective treatment for negative symptoms. However, the differences among treatments were small.     

Ethnicity and prescription patterns for haloperidol, risperidone, and olanzapine

OBJECTIVE: Patients with schizophrenia may respond better to second-generation antipsychotics than to older antipsychotics because of their superior efficacy and safety profiles. However, the reduced likelihood among ethnic minority groups of receiving newer antipsychotics may be associated with reduced medication adherence and health service use, potentially contributing to poor response rates. This study examined whether ethnicity helped predict whether patients with schizophrenia were given a first- or a second-generation antipsychotic, haloperidol versus risperidone or olanzapine, and what type of second-generation antipsychotic was prescribed, risperidone or olanzapine, when other factors were controlled for. METHODS: Texas Medicaid claims were analyzed for persons aged 21 to 65 years with a diagnosis of schizophrenia or schizoaffective disorder who started treatment with olanzapine (N=1875), risperidone (N=982), or haloperidol (N= 726) between January 1, 1997 and August 31, 1998. The association between antipsychotic prescribing patterns among African Americans, Mexican Americans, and whites was assessed by using logistic regression analysis. Covariates included other patient demographic characteristics, region, comorbid mental health conditions, and medication and health care resource use in the 12 months before antipsychotic initiation. RESULTS: The results of the first- versus second-generation antipsychotic analysis indicated that African Americans were significantly less likely than whites to receive risperidone or olanzapine. Although not statistically significant, the odds ratio indicated that Mexican Americans were also less likely to receive risperidone or olanzapine. Ethnicity was not associated with significant differences in the prescribing patterns of risperidone versus olanzapine. CONCLUSIONS: When other factors were controlled for, African Americans were significantly less likely to receive the newer antipsychotics. Among those who received the newer antipsychotics, ethnicity did not affect medication choice.     

Effectiveness and tolerability of schizophrenia treatment in Central and Eastern Europe: results after 1 year from a prospective,observational study (IC-SOHO)

Objective. The Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study is intended to complement smaller, shorter-term observational studies and randomised controlled clinical trials in providing information on the treatment of schizophrenia in various geographies that have not been well studied previously.

Methods. Interim results after 12 months are presented for a subset of patients from eight Central and Eastern European (CEE) countries initiating or switching to olanzapine, risperidone, or typical antipsychotic monotherapy at Baseline (n=1387).

Results. Patients initially prescribed olanzapine and risperidone experienced significantly greater improvements in a broad range of schizophrenia symptom domains compared with patients prescribed typicals. Furthermore, patients in the olanzapine group showed significantly greater improvements in overall and negative symptom domains compared with the risperidone group (all P≤0.05). While patients in the olanzapine group gained more weight than the other two groups, they had significantly lower odds of developing extrapyramidal symptoms, loss of libido, and sexual dysfunction. Patients initially prescribed olanzapine were also significantly less likely to have changed or added antipsychotics during 12 months of treatment compared with the risperidone and typicals groups.

Conclusion. In this CEE sample, schizophrenia treatment outcomes after 12 months varied between patients initially prescribed different antipsychotics.     

Cognitive function and social abilities in patients with schizophrenia: relationship with atypical antipsychotics

Although atypical antipsychotics have been associated with improvements in cognitive function in schizophrenia, the neurochemical basis for such effects is not well understood. Candidate neurotransmitter systems primarily involve dopamine and serotonin. The current study explored this issue by examining the cognitive abilities, social function and quality of life in patients with schizophrenia who were medicated with atypical antipsychotics. Comparisons were done for matched schizophrenia patients who were on antipsychotics with (i) an affinity for multiple receptors (olanzapine, clozapine, quetiapine) versus those that have preferential affinity for dopamine receptors (risperidone, amisulpride); and patients on medication with (ii) a high affinity for serotonin (5HT-2A) receptors (risperidone, olanzapine, clozapine) versus those with a low (or no) affinity for 5HT-2A receptors (quetiapine, amisulpride). No differences emerged between groups on any cognitive or social variable when the groups were compared for the dopaminergic properties of antipsychotic medication. By contrast, differences did emerge when patients were compared on the 5HT-2A affinity of their antipsychotic medications. Patients on low 5HT-2A-affinity antipsychotics exhibited a better performance on a measure of selective attention and adjustment to living. These findings accord with the notion that serotonergic mechanisms are important determinants of both the cognitive and the social effects of the atypical antipsychotics.     

Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic

BACKGROUND: In the treatment of schizophrenia, changing antipsychotics is common when one treatment is suboptimally effective, but the relative effectiveness of drugs used in this strategy is unknown. This randomized, double-blind study compared olanzapine, quetiapine, risperidone, and ziprasidone in patients who had just discontinued a different atypical antipsychotic. METHOD: Subjects with schizophrenia (N=444) who had discontinued the atypical antipsychotic randomly assigned during phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) investigation were randomly reassigned to double-blind treatment with a different antipsychotic (olanzapine, 7.5-30 mg/day [N=66]; quetiapine, 200-800 mg/day [N=63]; risperidone, 1.5-6.0 mg/day [N=69]; or ziprasidone, 40-160 mg/day [N=135]). The primary aim was to determine if there were differences between these four treatments in effectiveness measured by time until discontinuation for any reason. RESULTS: The time to treatment discontinuation was longer for patients treated with risperidone (median: 7.0 months) and olanzapine (6.3 months) than with quetiapine (4.0 months) and ziprasidone (2.8 months). Among patients who discontinued their previous antipsychotic because of inefficacy (N=184), olanzapine was more effective than quetiapine and ziprasidone, and risperidone was more effective than quetiapine. There were no significant differences between antipsychotics among those who discontinued their previous treatment because of intolerability (N=168). CONCLUSIONS: Among this group of patients with chronic schizophrenia who had just discontinued treatment with an atypical antipsychotic, risperidone and olanzapine were more effective than quetiapine and ziprasidone as reflected by longer time until discontinuation for any reason.     

Incidence of newly diagnosed diabetes attributable to atypical antipsychotic medications

OBJECTIVE: The purpose of the study was to determine the proportion of patients with schizophrenia with a stable regimen of antipsychotic monotherapy who developed diabetes or were hospitalized for ketoacidosis. METHOD: Patients with schizophrenia for whom a stable regimen of antipsychotic monotherapy was consistently prescribed during any 3-month period between June 1999 and September 2000 and who had no diabetes were followed through September 2001 by using administrative data from the Department of Veterans Affairs. Cox proportional hazards models were developed to identify the characteristics associated with newly diagnosed diabetes and ketoacidosis. RESULTS: Of the 56,849 patients identified, 4,132 (7.3%) developed diabetes and 88 (0.2%) were hospitalized for ketoacidosis. Diabetes risk was highest for clozapine (hazard ratio=1.57) and olanzapine (hazard ratio=1.15); the diabetes risks for quetiapine (hazard ratio=1.20) and risperidone (hazard ratio=1.01) were not significantly different from that for conventional antipsychotics. The attributable risks of diabetes mellitus associated with atypical antipsychotics were small, ranging from 0.05% (risperidone) to 2.03% (clozapine). CONCLUSIONS: Although clozapine and olanzapine have greater diabetes risk, the attributable risk of diabetes mellitus with atypical antipsychotics is small.     

Serum leptin and triglyceride levels in patients on treatment with atypical antipsychotics

BACKGROUND: Weight gain is a common adverse effect associated with the use of most antipsychotic drugs. Leptin has been reported to be associated with antipsychotic-induced weight gain. Previous studies have demonstrated a relationship between the atypical antipsychotics clozapine and olanzapine and serum leptin levels. We planned to comparatively investigate the effects of the atypical antipsychotics quetiapine, olanzapine, risperidone, and clozapine on leptin and triglyceride levels and weight gain. METHOD: The study population comprised 56 patients with DSM-IV schizophrenia, who were divided into 4 treatment groups: quetiapine (N = 14), olanzapine (N = 14), risperidone (N = 14), or clozapine (N = 14) monotherapy, and a control group of 11 patients receiving no psychopharmacologic treatment. The patients were evaluated at baseline and at the sixth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), weight, and fasting serum leptin and triglyceride levels. Data were gathered in 2001 and 2002. RESULTS: Olanzapine and clozapine caused a marked increase in weight and serum triglyceride and leptin levels, though increases in these variables were modest in the patients receiving quetiapine and minimal in those receiving risperidone. There were positive correlations between serum leptin levels and BMI and triglyceride levels. Clinical efficacy, as indicated by decrease in total PANSS scores, was associated with leptin levels in all atypical antipsychotic groups. CONCLUSION: Our results suggest that leptin may be associated with olanzapine- and clozapine-induced weight gain and that quetiapine appears to have modest influence and risperidone appears to have minimal influence on leptin and triglyceride levels and weight gain compared with olanzapine and clozapine.     

Comparative efficacy of typical and atypical antipsychotics as add-on therapy to mood stabilizers in the treatment of acute mania.

BACKGROUND: Typical antipsychotics are commonly used in combination with mood stabilizers for acute mania. Although typical antipsychotics are effective, they have undesirable side effects such as induction of depressive symptoms and tardive dyskinesia. Atypical antipsychotics have more favorable side effect profiles, and recent evidence shows their efficacy in treating mania. Apart from a previous small study that compared risperidone with typical neuroleptics as add-on therapy to mood stabilizers, no studies to date have directly compared atypical antipsychotics with typical antipsychotics as add-on therapy to mood stabilizers in a clinically relevant, naturalistic setting. METHOD: This study is a chart review of all patients with DSM-IV-defined bipolar disorder, current episode mania (N = 204), admitted to the University of British Columbia Hospital during a 30-month period. Patients were separated into 3 groups according to the medications used: (1) mood stabilizer and typical antipsychotic, (2) mood stabilizer and atypical antipsychotic, and (3) combination: mood stabilizer plus a typical antipsychotic, then switched to mood stabilizer plus risperidone or olanzapine within I week. The atypical group was further subdivided into risperidone and olanzapine subgroups. Outcome was measured using Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) ratings generated by review of clinical information in the chart. RESULTS: Patients treated with typical antipsychotics were more severely ill at admission and at discharge than those treated with atypical antipsychotics. Patients in the atypical (p < .005) and combination (p < .05) groups showed significantly greater clinical improvement at discharge than patients treated with typical antipsychotics. This difference was also significant in the subset of patients with psychotic features (p < .03). Risperidone and olanzapine were associated with fewer extrapyramidal side effects than were typical antipsychotics (risperidone vs. typical antipsychotics, chi2 = 8.72, p < .01; olanzapine vs. typical antipsychotics, chi2 = 16.9, p < .001). CONCLUSION: Due to their superior effectiveness and side effect profile when compared with typical antipsychotics. atypical antipsychotics are an excellent choice as add-on therapy to mood stabilizers for the treatment of patients with mania.     

Antipsychotic use in the treatment of outpatients with schizophrenia in the VA from fiscal years 1999 to 2006

OBJECTIVE: This study examined changes in prescribing patterns of antipsychotic medications to treat schizophrenia. METHODS: Pharmacy records for patients with schizophrenia were obtained from Department of Veterans Affairs databases. The proportion of patients prescribed specific second-generation antipsychotics or any first-generation antipsychotic was calculated per year. RESULTS: In fiscal year (FY) 2006, 78,849 veterans with schizophrenia were prescribed antipsychotic medication. For FY 1999 to FY 2006 the percentage of patients with schizophrenia who received first-generation antipsychotics decreased from 40.8% to 15.9%, but the percentage receiving olanzapine, after peaking at 32.0% in FY 2001, decreased to 19.0%. The percentage of patients given quetiapine increased from 2.5% to 18.8%; risperidone, from 25.5% to 29.7%. However, clozapine usage remained flat, at 2.0%-3.0%. Use of then-new ziprasidone and aripiprazole rose from 5.0% to 9.0%. CONCLUSIONS: Use of each antipsychotic newly marketed over eight years increased while use of risperidone was unchanged and use of olanzapine and the first-generation antipsychotics declined.     

Effects of changing from typical to atypical antipsychotic drugs on subjective sleep quality in patients with schizophrenia in a Japanese population

OBJECTIVE: To investigate the effects of the atypical antipsychotic drugs risperidone, olanzapine, quetiapine, and perospirone on the subjective quality of sleep in patients with schizophrenia. METHOD: Subjects were 92 inpatients (mean age = 59.9 years) who had been receiving treatment with conventional antipsychotic drugs and who met the DSM-IV criteria for schizophrenia. Subjects were randomly assigned to receive 1 of 4 atypical antipsychotic drugs (olanzapine, perospirone, quetiapine, and risperidone). Subjective sleep quality and psychopathology were assessed twice: at baseline and 8 weeks after switching. Data were collected from June 2001 to December 2001. Subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI), and psychopathology was measured by the Positive and Negative Syndrome Scale (PANSS). RESULTS: Subjective sleep quality as assessed by the PSQI was significantly improved with administration of olanzapine, risperidone, or quetiapine, but not with perospirone, in comparison with conventional antipsychotic drugs. Multiple regression analysis revealed that the improvement of sleep quality with administration of atypical antipsychotic drugs was predicted by poor sleep quality at baseline. In addition, improvement of sleep quality was significantly correlated with improvement of negative symptoms as assessed by the PANSS. CONCLUSION: These results demonstrated that atypical antipsychotic drugs improved subjective quality of sleep in patients with schizophrenia compared with conventional antipsychotic drugs, suggesting that the marked potency of serotonin-2 receptor blockade in atypical antipsychotic drugs may be involved in the mechanism of this improvement. These improvements were correlated with improvement of negative symptoms.     

Improvement in cognition associated with novel antipsychotic drugs: a direct drug effect or reduction of EPS?

BACKGROUND: Administration of novel, versus classic, antipsychotic agents to patients suffering from psychosis is associated both with moderately better scores on cognitive tests, and with fewer extrapyramidal symptoms (EPS). Because improved motor functioning may enable better performance on some components of cognitive test batteries, and because the advantages of the novel antipsychotics on cognitive performance are not very large, it is sometimes difficult to discern if improvement in a given cognitive task is due to a direct effect of the novel antipsychotic drug, or is secondary to the novel drug's decreased propensity to induce EPS. In an attempt to distinguish between these two possibilities, the present study examined the ability of patients suffering from schizophrenia receiving classic, versus novel antipsychotics, to perform a computerized visuo-motor test (VMT). VMT assesses planning capabilities, attention and executive functions known to be impaired in schizophrenia, which are suggested to be affected by novel antipsychotics. METHODS: Seventy-six patients suffering from schizophrenia or schizophreniform disorder, receiving haloperidol (23 patients, mean dose 10.01+/-6.1mg/day), olanzapine (26 patients, mean dose 10.56 +/- 4.9 mg/day) or risperidone (27 patients, mean dose 4.35 +/- 1.7 mg/day) were assessed for EPS using the parkinsonian subscale of the Extrapyramidal Symptom Rating Subscale (ESRS), and with the VMT. RESULTS: Cognitive functioning as measured by the VMT was better for patients receiving risperidone or olanzapine, compared with those receiving haloperidol (F=6.636, df=2,67, P=0. 002), while the patients receiving haloperidol or risperidone suffered from more severe EPS compared with the patients receiving olanzapine (F=3.996, df=2,71, P=0.023). DISCUSSION: Although the patients receiving risperidone suffered from EPS similar in severity to the EPS of the patients receiving haloperidol, their performance on a task involving visuo-motor and attentional skills was similar to that of the patients receiving olanzapine. This finding implies that there is a dissociation between the antipsychotic drug's ability to affect cognitive functioning, and EPS. This dissociation indirectly suggests that the advantages offered by novel antipsychotics on cognitive performance are a direct effect, rather than being entirely mediated by improved movement abilities.     

Safety and efficacy of long-acting risperidone in schizophrenia: a 12-week, multicenter, open-label study in stable patients switched from typical and atypical oral antipsychotics

BACKGROUND: The safety and efficacy of the first long-acting injectable atypical antipsychotic, risperidone, were assessed in stable patients with schizophrenia switched from oral antipsychotic medications. METHOD: Data were collected between July 1, 2001, and October 25, 2002. The study population included patients from clinics, hospitals, and physicians' offices. After a 4-week run-in period, symptomatically stable patients with schizophrenia (DSM-IV) who had been taking haloperidol (N = 46), quetiapine (N = 45), or olanzapine (N = 50) received 25 mg of long-acting risperidone. The oral antipsychotics were continued for 3 weeks after the first injection of long-acting risperidone. Injections were administered every 2 weeks at 25 mg up to a maximum dose of 50 mg for 12 weeks in this multicenter, open-label study. RESULTS: Long-acting risperidone was well tolerated. Of the 141 patients who participated in the study, the most frequently reported adverse events were insomnia (16%), headache (15%), psychosis (11%), and agitation (11%). The mean increase in body weight was 0.4 kg. No other clinically relevant laboratory abnormalities or significant electrocardiogram changes were observed during the 12-week treatment. Extrapyramidal Symptom Rating Scale total scores were reduced during treatment with long-acting risperidone. Improvements in symptoms of schizophrenia were observed with long-acting risperidone at week 4 and continued through the 12-week treatment with significant reductions in total Positive and Negative Syndrome Scale (PANSS) scores at week 8 (-2.5, p <.01) and week 12 (-3.9, p <.001). At endpoint, 37% (50/135) of these stable patients were rated as clinically improved (> or = 20% decrease in PANSS total scores). CONCLUSIONS: Switching treatment from oral antipsychotics to long-acting risperidone without an intervening period of oral risperidone was safe and well tolerated. Long-acting risperidone also significantly reduced the severity of symptoms in these stable patients with schizophrenia.     

Effects of risperidone and quetiapine on cognition in patients with schizophrenia and predominantly negative symptoms

Evidence suggests that neurocognitive impairment is a key factor in the pathology of schizophrenia and is linked with the negative symptoms of the disease. In this study the effects of the atypical antipsychotics quetiapine and risperidone on cognitive function in patients with schizophrenia and with predominantly negative symptoms were compared. Patients were randomly assigned to double-blind treatment with quetiapine or risperidone for 12 weeks. Cognitive function was assessed at baseline, Week 6 and Week 12. Efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS) at baseline, Week 6 and Week 12. Extrapyramidal side-effects were assessed each week using the Simpson-Angus Scale (SAS), adverse events were recorded as additional indicators of tolerability throughout the trial. In total, 44 patients were enrolled in the study. Data from the 34 patients who completed cognitive assessments at two or more time points out of three (baseline, Week 6 and Week 12) are analysed here. Quetiapine improved significantly global cognitive index z-scores at both Week 6 (p < 0.001 vs. baseline) and Week 12 (p < 0.01 vs. baseline), whereas risperidone improved significantly global cognitive index z-scores at Week 12 (p < 0.05). Between-group comparisons at Week 6 showed significantly greater improvements in working memory and verbal memory with quetiapine than risperidone (p < 0.05) and a significantly greater improvement in reaction quality/attention with quetiapine than risperidone at Week 12 (p<0.05). Quetiapine and risperidone produced significant improvements from baseline in PANSS total (p<0.001) and subscale scores at Week 12. Significant improvements in SANS total score were also seen in both the quetiapine (p < 0.001) and risperidone (p < 0.01) groups at Week 12 compared with baseline. SAS scores, measuring the incidence of extrapyramidal side-effects, were higher in patients receiving risperidone compared with those receiving quetiapine, and significant differences were seen at Weeks 3, 4, 5 and 7. Both quetiapine and risperidone improved cognition according to changes in cognitive index scores from baseline to Week 12. These results suggest that quetiapine and risperidone provide valuable treatment options for patients with schizophrenia with predominantly negative symptoms. Also, the improvements in cognition following treatment with quetiapine and risperidone may enhance long-term outcomes for these patients.     

A comparative review of new antipsychotics.

OBJECTIVE: To review the preclinical and clinical properties of various established and putative antipsychotic medications, namely clozapine, risperidone, amisulpride, olanzapine, quetiapine, sertindole, and ziprasidone. METHODS: This paper proposes a decision algorithm for comparing drugs used for psychotic disorders, based on biochemical profile, experimental pharmacology, postiron emission tomography (PET) scan results, and clinical efficacy on positive, negative, anxious, depressive, and cognitive symptoms. This "quotient" aims to compare the different available drugs, regardless of their development and registration status. RESULTS: Antipsychotic drugs have been classified in many ways, mainly according to their chemical structure, clinical effects, receptor affinity, or side effects. Preclinical data have indicated that these drugs might be effective antipsychotic agents, causing fewer extrapyramidal side effects than most of the previously marketed drugs. However, the biological basis for the putative superiority of these drugs in treating psychosis has yet to be ascertained. CONCLUSIONS: Although most antipsychotics have been shown to be at least equivalent to haloperidol on positive symptoms, they must be studied further to establish their absolute and relative efficacy on positive symptoms, negative and primary negative symptoms, cognition, psychotic anxiety, psychotic depression, suicidality, and quality of life. These drugs should be valuable in treating schizophrenia, but their merit in the long-term management of patients with schizophrenia still needs to be confirmed.