Long-acting risperidone vs. placebo in the treatment of hospital inpatients with schizophrenia

Maintenance treatment regimens for patients with schizophrenia are often suboptimal. Partial adherence and outright noncompliance are associated with symptom recurrence and increased likelihood of rehospitalization. Long-acting conventional neuroleptics have limited efficacy and are associated with treatment-limiting adverse events, while oral atypical antipsychotics have not improved adherence substantially. A long-acting formulation of risperidone, an atypical antipsychotic with proven efficacy, has been developed. Introduction of long-acting injectable treatment may be appropriate during inpatient hospitalization, when consequences of relapse are most evident. To support this intervention, a subanalysis of patients who were inpatients at study initiation was conducted from a 12-week, double-blind, placebo-controlled long-acting risperidone study (N = 214). Long-acting risperidone was associated with a significant reduction in total Positive and Negative Syndrome Scale (PANSS) score (mean change +/- standard error [S.E.] at endpoint: long-acting risperidone, -9.27 +/- 1.44, n = 133; placebo, 0.72 +/- 2.59, n = 41; P < 0.001), and a significantly higher rate of treatment response, defined as > or = 20% reduction in total PANSS score (50% vs. 27%, P < 0.05). Significantly more long-acting risperidone patients had endpoint Clinical Global Impressions (CGI) assessments of not ill, very mild or mild (32% vs. 5%; P < 0.01). Long-acting risperidone was well tolerated. Long-acting risperidone initiated during inpatient treatment may be an important strategy in improving long-term outcomes among patients with schizophrenia.     

Efficacy and safety of long-acting risperidone in elderly patients with schizophrenia and schizoaffective disorder

BACKGROUND: Elderly patients are often an underserved population in terms of optimizing treatment outcomes. Long-acting risperidone, the first long-acting injectable atypical antipsychotic, can improve outcomes through continuous medication delivery. OBJECTIVE: To assess the efficacy and safety of long-acting injectable risperidone in elderly patients with psychotic disorders. METHODS: This is a subanalysis of 57 patients aged > or =65 years enrolled in an open-label study of long-acting risperidone that included 725 symptomatically stable patients with schizophrenia or schizoaffective disorder. Patients were assigned to receive 25, 50, or 75 mg of long-acting risperidone every 2 weeks for up to 50 weeks. RESULTS: Fifty-seven elderly patients (mean +/- SE age, 70.9 +/- 0.7 years) were enrolled. Mean Positive and Negative Syndrome Scale (PANSS) total scores improved significantly throughout the study and at endpoint (p < 0.001). The PANSS factor scores (positive symptoms, negative symptoms, disorganized thoughts, uncontrolled hostility/excitement, and anxiety/depression) also significantly improved (p < 0.01). Clinical improvement (> or =20% reduction in PANSS total scores) was achieved by 49% of these stable patients, and 55% improved on the Clinical Global Impressions scale. Severity of movement disorders (Extrapyramidal Symptom Rating Scale scores) was reduced significantly. Adverse events reported in >10% of patients were insomnia (14%), constipation (12%), and bronchitis (12%). CONCLUSIONS: Long-acting risperidone was associated with significant symptom improvements in stable elderly patients with schizophrenia or schizoaffective disorder. Treatment was well tolerated.     

Patients with schizophrenia previously stabilized on conventional depot antipsychotics experience significant clinical improvements following treatment with long-acting risperidone.

BACKGROUND: Conventional depot antipsychotics can provide constant pharmacologic treatment, eliminating partial compliance and reducing relapse risk. Atypical antipsychotics, have improved clinical profiles but require daily dosing, compromising their overall effectiveness. As oral risperidone provides safety and efficacy benefits over oral haloperidol, improvements may be realized by replacing conventional with atypical agents in long-acting therapy. This report examines 50-weeks of long-acting risperidone therapy in patients previously stabilized with conventional depot antipsychotics. METHODS: A multi-center, open-label study enrolled 725 patients with schizophrenia or schizoaffective disorder, judged clinically stable and maintained on stable antipsychotic doses for > or =4 weeks. Assignment by clinician judgment to receive 25-75 mg of long-acting risperidone every 2 weeks for 50 weeks followed, with performance of standard safety and efficacy assessments. Data are presented on patients receiving conventional depot antipsychotic monotherapy at study entry. RESULTS: In the 188 (25.9%) patients receiving conventional depot antipsychotic monotherapy at entry, mild-to-moderate mean (+/-S.D.) Positive and Negative Syndrome Scale (PANSS)-total scores improved significantly after receiving long-acting risperidone (64.2 +/- 18.9 to 58.2 +/- 20.3; P < 0.001). Clinical improvement of > or =20%, 40%, or 60% reduction in PANSS-total score, occurred in 52%, 34%, and 16% of patients, respectively. ESRS subjective ratings and objective physician ratings (Parkinsonism) decreased significantly (P < 0.001). CONCLUSION: Stable patients with mild, residual symptomatology treated with conventional depot antipsychotics experienced significant improvement in psychiatric and movement disorder symptomatology following 1-year of treatment with long-acting risperidone.     

Health-related quality of life in patients with schizophrenia during treatment with long-acting, injectable risperidone

BACKGROUND: We investigated the impact of treatment with long-acting, injectable risperidone versus placebo on health-related quality of life (HRQoL) in patients with schizophrenia. Results are discussed in the context of HRQoL in the general U.S. population. METHOD: Patients with DSM-IV schizophrenia entered a randomized, double-blind, placebo-controlled trial. After screening, previous antipsychotics were discontinued, and oral risperidone was titrated up to a dose of 4 mg/day over 1 week. Patients were then randomly assigned to receive placebo [N = 92] or long-acting risperidone (25 [N = 93], 50 [N = 97], or 75 mg [N = 87] every 2 weeks) for 12 weeks. HRQoL was measured using the Medical Outcomes Study Short-Form 36-item questionnaire (SF-36). RESULTS: At week 12, patients receiving long-acting risperidone had improved significantly (p <.05) in 5 domains of the SF-36 (bodily pain, general health, social functioning, role-emotional, and mental health) compared with patients receiving placebo. The effect was greatest for the 25-mg group, with significant improvement versus placebo in 6 domains (p <.05). At baseline, all SF-36 domain scores except bodily pain were significantly lower (p <.05) than normal values in all groups. With placebo, scores in all 8 domains remained below normal values after 12 weeks, while patients receiving long-acting risperidone showed improvement in HRQoL toward normal levels, with clinically meaningful improvements in all mental-health domains. In the 25-mg group, scores in 7 domains were not statistically different from normal values after 12 weeks. CONCLUSIONS: Long-acting, injectable risperidone improved HRQoL toward normal levels. After 12 weeks, HRQoL of patients receiving 25 mg was not significantly different from normal.     

Treatment of schizophrenia with long-acting injectable risperidone: a 12-month open-label trial of the first long-acting second-generation antipsychotic

BACKGROUND: The long-term safety and efficacy of long-acting injectable risperidone, the first long-acting second-generation antipsychotic, were evaluated in stable patients with schizophrenia. METHOD: After a 2-week run-in period during which patients with DSM-IV schizophrenia received flexible doses of 1 to 6 mg of oral risperidone, patients received injections of 25 mg, 50 mg, or 75 mg of long-acting risperidone every 2 weeks for 12 months. Severity of extrapyramidal symptoms was assessed with the Extrapyramidal Symptom Rating Scale (ESRS), and efficacy was assessed with the Positive and Negative Syndrome Scale (PANSS). This study was conducted from March 29, 1999 to July 19, 2000. RESULTS: The subjects were 615 patients with schizophrenia who received at least 1 injection of long-acting risperidone. The 12-month trial was completed by 65% of patients. Treatment was discontinued because of adverse events in 5% of patients. Extrapyramidal symptoms as adverse events were reported by 25% of the patients. Severity of extrapyramidal symptoms (according to ESRS scores) was low at baseline and decreased in each of the groups during the 12 months. The other most common adverse events were anxiety in 24%, insomnia in 21%, psychosis in 17%, and depression in 14% of the patients. Little pain was associated with the injections. Severity of symptoms of schizophrenia was improved in each group, with significant reductions in PANSS total scores (p <.01) and positive (p <.01) and negative (p <.001) factor scores. CONCLUSION: In terms of both safety and efficacy, symptomatically stable patients with schizophrenia benefit from being switched to long-acting injectable risperidone.     

Long-acting risperidone in young adults with early schizophrenia or schizoaffective illness.

BACKGROUND: Treatment with long-acting injectable risperidone was evaluated in young adults likely to be in the early stages of schizophrenia or schizoaffective disorder. METHOD: An open-label 50-week trial included young adults (men aged 18-25 years and women aged 18-30 years). RESULTS: Sixty-six young adults received at least 1 injection of long-acting risperidone (25 or 50 mg) every two weeks; 64% of the patients completed the 50-week trial. A mode dose of 25 mg/14 days was received by 23 patients and 50 mg/14 days by 43 patients. Mean PANSS scores improved significantly from baseline at each time point, with 64% of the patients showing clinical improvement (>or=20% reduction in PANSS total scores) at endpoint. Patient-rated quality of life (SF-36 scores) improved and patients' attitudes toward the medication were positive (DAI scores). Severity of movement disorders (ESRS) and injection-site pain ratings were low throughout the trial. Results were similar in the population of other (older) patients. CONCLUSIONS: Long-acting risperidone was associated with clinical benefits in stable young adults with early schizophrenia or schizoaffective illness.     

Practical application of pharmacotherapy with long-acting risperidone for patients with schizophrenia

OBJECTIVE: It is now generally accepted that the use of second-generation, or atypical, antipsychotics for schizophrenia represents an advance over conventional antipsychotic agents. However, adherence continues to be a problem, as with other medications for chronic disorders. Long-acting formulations of conventional antipsychotics partly address adherence problems, but their use is limited by tolerability issues. This article provides practical advice to physicians on the characteristics of patients who would benefit from treatment with long-acting atypical antipsychotic agents and offers suggestions on how to initiate treatment. METHODS: A literature search for studies published between 1980 and 2003 that evaluated the treatment of patients with schizophrenia with long-acting atypical agents was conducted by using MEDLINE and EMBASE. The primary search parameters were "schizophrenia," "atypical," "antipsychotic," and "long-acting." As expected, long-acting risperidone was the only long-acting atypical agent identified; thus this article focuses on practical advice and suggestions on how to initiate therapy with long-acting risperidone. RESULTS AND DISCUSSION: From the results of the literature search and the discussion of a panel of experts at a meeting held in Dublin in 2003 and supported by Johnson & Johnson, it is possible to conclude that long-acting risperidone has demonstrated efficacy and tolerability, even among patients who are considered clinically stable on other antipsychotics. Most patients can switch safely and effectively to long-acting risperidone if appropriate strategies are applied. Long-acting risperidone provides a new and promising therapeutic option for the treatment of schizophrenia.     

Effectiveness and tolerability of long-acting risperidone: A 9-month open-label extension of a 12-week switching study from oral antipsychotics

Objectives. The aim of this non-randomized, single-arm, multi-center, 9-month extension study was to evaluate the maintained efficacy and tolerability of long-acting risperidone injection when we switched to it from previous oral antipsychotics in symptomatically stable patients with schizophrenia or other psychotic disorders. Methods. A total of 98 patients who had completed a previous 12-week acute phase study were included. Efficacy and tolerability were assessed with the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI), Global Assessment of Functioning (GAF), and Extrapyramidal Symptom Rating Scale (ESRS). Results. The remission rate of 77.6% (76/98) at baseline and 57.1% (56/98) at the end of the study. Of patients who were in remission at baseline, 65.8% (50/76) maintained their remission state until the end. The symptom worsening rate was relatively low (11.1%), and there was no aggravation in mean PANSS total and subscale scores. Spontaneous treatment-emergent adverse events (TEAE) were reported by 21 (21.4%) patients, and most commonly reported adverse events were extrapyramidal symptoms (N=6, 6.1%) and insomnia (N=4, 4.1%). Extrapyramidal symptoms were significantly improved. Conclusions. Switching to long-acting risperidone injection from oral antipsychotics was a safe and well-tolerated strategy for maintaining clinical stability in symptomatically stable patients with schizophrenia.     

Switching to long-acting injectable risperidone is beneficial with regard to clinical outcomes, regardless of previous conventional medication in patients with schizophrenia

INTRODUCTION: Using an atypical long-acting antipsychotic may improve patient outcome by offering the good efficacy and tolerability of an atypical antipsychotic with improved compliance through depot administration. METHODS: This subanalysis of an international, 6-month, open-label trial of risperidone long-acting injectable (RLAI) focused on non-acute schizophrenic adult patients switching from oral or depot conventional antipsychotic. Efficacy assessments included Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF), quality of life, treatment satisfaction, hospitalization rates, and treatment-emergent adverse events (TEAEs). RESULTS: Over 70% of patients switching from oral (n=100) or depot (n=565) conventional medication completed treatment. Improvements were observed for PANSS total and subscale scores, GAF, quality of life, treatment satisfaction and hospitalization. Overall RLAI was well tolerated. TEAEs occurring in >5% were: anxiety (11.0%), insomnia (9.0%), weight increase (6.0%) for patients switching from oral, and weight increase (6.0%) and disease exacerbation (5.3%) for patients switching from depot medication. CONCLUSION: Patients with schizophrenia, unsatisfactorily treated with oral or depot conventional antipsychotics, showed improvement in symptom control, tolerability, and patient satisfaction after switching to RLAI.     

Effectiveness of switching to ziprasidone for stable but symptomatic outpatients with schizophrenia

BACKGROUND: Many outpatients with schizophrenia experience persistent symptoms or side effects on their current antipsychotic regimen. Few studies have prospectively examined the effects of the prior medication or switching method on the safety and efficacy of a newly available antipsychotic. Efficacy and tolerability of ziprasidone were evaluated in patients with DSM-IV schizophrenia or schizoaffective disorder who were switched from conventional or atypical antipsychotics in three 6-week, multicenter, randomized, open-label, parallel-group trials. METHOD: Stable outpatients with persistent symptoms or troublesome side effects on (1) conventional antipsychotic (N = 108), (2) olanzapine (N = 104), or (3) risperidone (N = 58) therapy were switched to an open-label, 6-week, flexible-dose trial of ziprasidone (40-160 mg/day). Patients were randomly assigned at baseline to 1 of 3 switching schedules during the first week of ziprasidone therapy. Baseline and outcome assessments included Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impressions of Severity (CGI-S) ratings. RESULTS: All 3 switching strategies were well tolerated for all 3 patient groups. After 6 weeks on ziprasidone therapy, significant (p <.05) improvements were observed on all major symptom measures and almost all subscales for all switched subgroups. CONCLUSION: Switching stable but symptomatic outpatients from their previous antipsychotic to ziprasidone was generally well tolerated and was associated with symptom improvements 6 weeks later. Improvements occurred in patients recently on other first-line atypical antipsychotic, as well as in those on conventional antipsychotic, treatment. While limitations of switching study designs do not permit interpretation of comparative efficacy, these studies suggest that outpatients who partially respond to conventional antipsychotics, risperidone, or olanzapine may experience improved control of psychotic symptoms following a switch to ziprasidone.     

Symptom control,functioning, and hospitalization status in French patients changed from oral atypical antipsychotics to risperidone long-acting injectable

Objective. To investigate efficacy and tolerability of risperidone long-acting injectable (RLAI) in French patients with schizophrenia or other psychotic disorders, who were all switching from previous treatment with oral atypical antipsychotics. The impact of treatment with RLAI on the hospitalization status of these patients was also examined. Methods. Clinically stable patients requiring a treatment change received 25 mg RLAI (increased to 37.5 or 50 mg if required) every 2 weeks for 6 months. Results. Of 130 patients (68.5% male, mean age 36.2 years), most (83.8%) had DSM-IV schizophrenia (mainly paranoid). Previous treatments were risperidone (80.8%), olanzapine (10.0%) and amisulpride (10.0%). Out of 66 patients hospitalized at baseline, 51 were outpatients at endpoint. Mean total PANSS, CGI-S and GAF scores were significantly reduced from baseline to treatment endpoint (p<0.001). Of those patients reported as moderate to severely ill at the beginning of the trial (81.3%), fewer had the same classification at endpoint (50.8%). Mean scores for total ESRS and Parkinsonism subscales were significantly reduced after only 1 month of treatment (p<0.001). Conclusion. Treatment with RLAI significantly improved disease symptoms, functioning, hospitalization status, and reduced movement disorders, in psychotic patients considered clinically stable on oral atypical antipsychotics.     

Efficacy of risperidone versus olanzapine in patients with schizophrenia previously on chronic conventional antipsychotic therapy: a switch study

The objective of the study was to examine whether patients with schizophrenia who were judged to be stable on long-term treatment with conventional antipsychotic medications would further benefit from a switch to an atypical antipsychotic drug. Thirty-six subjects with schizophrenia spectrum disorder, on conventional antipsychotic medication therapy for at least 2 years, were randomized in double-blind fashion to risperidone versus olanzapine. Patients were titrated up to 6 mg risperidone or 15 mg olanzapine as tolerated, followed by tapering and discontinuation of conventional antipsychotic medication. Atypical antipsychotic agents were then administered alone (monotherapy) for 12 weeks. Efficacy and tolerability were assessed using the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale, and Simpson Angus Scale. Body weight was measured at each visit. Both treatment groups exhibited marked and similar improvement in the total PANSS score from baseline to study endpoint (22 weeks) [risperidone: baseline=59.3 (SE 3.1), 22 weeks=44.3 (SE 2.3) (p<0.001); olanzapine: baseline=55.9 (SE 3.3), 22 weeks=46.9 (SE 3.2) (p<0.001). Both groups also exhibited significant reductions in PANSS factor scores for positive and negative symptoms and disorganized thoughts. Only risperidone-treated patients exhibited significant decreases in uncontrolled hostility/excitement and anxiety and depression. Of note, while positive factor scores exhibited the majority of change within the first 10 weeks, negative factor scores continued to decline significantly in both treatment groups throughout the study. Tolerability assessments did not differ between groups. The results indicate that both atypical antipsychotic medications provided significant additional improvement in symptom severity in patients with schizophrenia previously on conventional antipsychotic agents.     

Symptom control,functioning and satisfaction among Swiss patients treated with risperidone long-acting injectable

Objective: To investigate antipsychotic efficacy and tolerability of risperidone long-acting injectable (RLAI) in Swiss patients with schizophrenia or other psychotic disorders, changed directly from their previous antipsychotic medication. Methods: Patients symptomatically stable for ≥1 month on their previous medication and considered to require a treatment change, received 25 mg RLAI (increased to 37.5 or 50 mg, if required) every 2 weeks for 6 months. Results: Of 60 patients enrolled (68.3% male, average age 40.4 years), most (81.7%) had DSM-IV schizophrenia (mainly paranoid). Previous treatments were with atypical antipsychotics (58.3% of patients), depot (38.3%) and conventional oral (13.3%) neuroleptics. Mean total PANSS scores were significantly reduced from baseline to treatment endpoint (76.1 vs. 64.4, P<0.001), as were all PANSS subscale and symptom factor scores. The CGI, GAF, and patient satisfaction with treatment were also significantly improved at endpoint (P<0.001). At endpoint, 37.0% of patients rated their satisfaction as “very good” compared with only 4.3% at baseline. Mean scores for total ESRS and Parkinsonism subscales were significantly reduced at endpoint (P<0.001). Conclusion: Treatment with RLAI significantly improved disease symptoms, functioning, patient satisfaction, and reduced movement disorders. It provides an important option for long-term treatment of patients with psychotic disorders.     

A comparative efficacy and safety study of long-acting risperidone injection and risperidone oral tablets among hospitalized patients: 12-week randomized, single-blind study

OBJECTIVE: The superiority of risperidone long-acting injection (RLAI) over oral typical and atypical antipsychotics demonstrated in previous studies may be related to the improved drug compliance. The aim of the 12-week randomized, single-blind study was to test whether the superiority of RLAI remained among hospitalized patients that drug compliance could be optimally controlled. METHODS: Fifty hospitalized stable schizophrenic patients, who had maintained on oral risperidone for more than 3 months, were randomized to the RLAI and oral risperidone group. Finally 49 patients (98 %) completed the study, and no dose change of oral risperidone, or RLAI was noted among all patients. RESULTS: The RLAI group showed significantly increased positive score of Positive and Negative Syndrome Scale (PANSS) than the risperidone group (0.72 +/- 3.52 vs. -1.24 +/- 3.81, p = 0.022), but without significance difference for the PANSS total, negative and general psychopathology scores. The RLAI group also showed a significantly improved Udvalg for Kliniske Undersogelser (UKU) Scale (p = 0.037), social life domains of Short-Form Health Survey (SF-36) (p = 0.011), and reduced prolactin level (p = 0.001). CONCLUSION: The results indicated that with optimal controlling of drug compliance among hospitalized patients, RLAI showed no benefit of efficacy over oral risperidone, but with advantages of improved side-effect profiles, social life ratings, and reduced prolactin levels.     

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.     

Effects of Risperidone and Olanzapine Dose Reduction on Cognitive Function in Stable Patients With Schizophrenia: An Open-Label,Randomized, Controlled,Pilot Study

Impact of dose reduction of atypical antipsychotics on cognitive function has not been investigated in stable patients with schizophrenia. In this open-label, 28-week, randomized controlled trial, stable patients with schizophrenia treated with risperidone or olanzapine were randomly assigned to the reduction group (dose reduced by 50% in 4 weeks and then maintained) or maintenance group (dose kept constant). Assessments at baseline and week 28 included the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Positive and Negative Syndrome Scale (PANSS), and Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). Sixty-one patients were enrolled; 2 of 31 (6.5%) and 5 of 30 (16.7%) patients prematurely withdrew from the study in the reduction and maintenance groups, respectively. While no significant differences in change in the PANSS total score were observed between the 2 groups, the reduction group showed significantly greater improvements in the RBANS and DIEPSS total scores compared with the maintenance group (mean ± SD, +7.0±7.1 vs −0.1±8.0, P < .001; −0.9±1.7 vs +0.1±1.2, P = .010, respectively). This 6-month pilot study suggests that risperidone or olanzapine dose reduction of 50% can improve cognitive function for stable patients with schizophrenia. Due to the open-label design, small sample size, and short study duration, however, there is a need to confirm the finding through double-blind, larger scale trials with longer follow-up periods. Moreover, potential risks of relapse following antipsychotic dose reduction should be thoroughly investigated in longer term studies.Key words: antipsychotics, cognitive function, dose reduction, olanzapine, risperidone, schizophrenia     

A 12-week, double-blind, placebo-controlled trial of donepezil adjunctive treatment to risperidone in chronic and stable schizophrenia

There is considerable incentive to develop new treatment strategies that effectively target cognitive deficits in schizophrenia. One of the theoretically promising novel treatment candidates is acetylcholinesterase inhibitors that increase the synaptic levels of cholinergic, nicotinic, and muscarinic receptor activity. The purpose of this study was to assess the efficacy of donepezil as an adjuvant agent in the treatment of chronic schizophrenia in particular for cognitive impairments. This investigation was a 12-week, double-blind study of parallel groups of patients with stable chronic schizophrenia. Thirty patients were recruited from inpatient and outpatient departments, age ranging from 22 to 44 years. All participants met DSM-IV-TR. diagnostic criteria for schizophrenia. To be eligible, patients were required to have been treated with a stable dose of risperidone as their primary antipsychotic treatment for a minimum period of 8 weeks. The subjects were randomized to receive donepezil (10 mg/day) or placebo, in addition to risperidone (4–6 mg/day). Clinical psychopathology was assessed with Positive and Negative Syndrome Scale (PANSS). Cognition was measured by a cognitive battery. Patients were assessed by a psychiatrist at baseline and after 8, and 12 weeks after the medication started. The PANSS scores and cognitive performance were used as the outcome measures. The donepezil group had significantly greater improvement in the negative symptoms over the 12-week trial. There were no differences between the donepezil and placebo groups on any neurocognitive assessments at endpoint (week 12). The present study indicates donepezil as a potential adjunctive treatment strategy for negative symptoms of chronic schizophrenia.     

An assessment of emergent tardive dyskinesia and existing dyskinesia in patients receiving long-acting, injectable risperidone: results from a long-term study

INTRODUCTION: Treatment-emergent tardive dyskinesia (TD) can be a serious side effect of antipsychotic treatment. Atypical antipsychotics are associated with a lower risk for TD than are conventional agents. A long-acting atypical antipsychotic, with more stable blood levels and lower peak blood levels than an oral formulation, may provide differential benefit regarding side effects, including movement disorders. This analysis assessed TD by defined research criteria in patients receiving long-acting, injectable risperidone. METHODS: Clinically stable subjects with schizophrenia or schizoaffective disorder participated in a 50-week, open-label trial of long-acting, injectable risperidone. TD was studied by defined research criteria (Schooler, N.R., Kane, J.M., 1982. Research diagnosis for tardive dyskinesia. Arch. Gen. Psychiatry. 39, 486-487; Americal Psychiatric Association, 2000. Diagnostic and Statistical Manual of Mental Disorders, fourth ed. American Psychiatric Association, Washington, DC). The severity of dyskinesia and other movement disorders were rated by the Extrapyramidal Symptom Rating Scale (ESRS). RESULTS: ESRS dyskinesia data were available for 662 patients. Five of 530 subjects without dyskinesia at baseline (0.94%) met the predefined criteria for emergent persistent TD during therapy. Based on either exposure to study medication or Kaplan-Meier analysis, the 1-year rate was 1.19%. Among the 132 subjects with dyskinesia at baseline, the mean score on the ESRS physician's exam for dyskinesia improved significantly at endpoint (-2.77; P<0.0001), regardless of anticholinergic drug use. (P=0.243 for patients with versus without anticholinergic drug use.) CONCLUSIONS: In this open-label study, treatment with long-acting risperidone was associated with a low rate of emergent persistent TD. Significant improvement in existing dyskinesias was noted. The TD rate reported here is consistent with other reports of atypical antipsychotics and substantially lower than with conventional antipsychotics.     

Adverse effects of risperidone and haloperidol treatment in schizophrenia

PURPOSE: Side effects of pharmacological treatment in schizophrenia continue to be a major issue in spite of the development of new antipsychotics. The aim of this study is to explore the adverse effects of conventional and atypical antipsychotic drugs and their associated factors. METHODS: Over 3 months, 41 patients with schizophrenia were randomized to treatment with risperidone 1-12 mg (n=21) or haloperidol 2-20 mg (n=20) daily. Efficacy was assessed by improvement of psychotic symptoms, measured on the Positive and Negative Syndrome Scale (PANSS). The safety and tolerability were assessed with the Extrapyramidal Symptom Rating Scale, the UKU Side-Effect Rating Scale and clinical laboratory assessments. RESULTS: Each treatment reduced psychotic symptoms. PANSS total scores, positive scores, and general psychopathology scores declined as trial went on without significant differences between the two groups. While PANSS negative scores improved better in the risperidone group than in the haloperidol group. The tolerability of antipsychotics was statistical significantly better in the risperidone than in the haloperidol-treated patients. The most frequent adverse effects for both groups were tremor and rigidity. Antipsychotics, their doses, and hyperprolactinemia predict short-term extrapyramidal side effects. Serum prolactin levels could predict parkinsonism and dyskinesia severity. However, dyskinesia was best predicted by the doses of neuroleptics. The predictive factor of dystonia was the antipsychotic drug itself. After adjusting drug doses and concomitant medications, side effects could be markedly improved. CONCLUSIONS: This study suggested that risperidone was superior to haloperidol in improving negative symptoms and better tolerated during the 12 weeks' treatment of schizophrenia. Serum prolactin levels could predict the severity of parkinsonism and dyskinesia.     

Randomized clinical comparison of perospirone and risperidone in patients with schizophrenia: Kansai Psychiatric Multicenter Study

Aim:  Perospirone is classified as a second-generation antipsychotic agent for the treatment of schizophrenia. Perospirone binds with high affinity to serotonin 5-HT2A receptors and dopamine D2 receptors. There are no reports of clinical comparisons of perospirone and risperidone in multicenter studies. To clarify the clinical traits of perospirone in the treatment of schizophrenia, the clinical efficacies and side-effects of perospirone and risperidone were compared in a randomized clinical multicenter trial.
Methods:  Sixty-six schizophrenia patients were enrolled in the trial. The Positive and Negative Syndrome Scale (PANSS) total, positive, negative and general symptoms scores and Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) scores were investigated at 0, 4, 8 and 12 weeks.
Results:  Significant reductions in the PANSS total and subscale scores were observed in both the perospirone and risperidone groups, with no significant between-group differences at 4 and 12 weeks. Risperidone improved the total scores and overall psychopathologic symptom total scores more effectively than perospirone at week 8. There were no significant differences in the DIEPSS scores at 0, 4, 8 and 12 weeks between the perospirone and risperidone groups. The numbers of patients who dropped out did not differ between the perospirone and risperidone groups.
Conclusions:  Perospirone was as effective as risperidone against positive and negative symptoms in patients with schizophrenia. Both antipsychotic agents were equally well-tolerated.