Risperidone Long-acting Injection Treatment Research Articles

Bipolar patients treated with long-acting injectable risperidone in Taiwan: A 1-year mirror-image study using a national claims database

ObjectiveBipolar disorder (BD) is burdensome for patients and healthcare systems. This study evaluated changes in concomitant medication patterns, healthcare utilization, and costs after the initiation of risperidone long-acting injection (RLAI) treatment among BD patients. Method287 BD patients receiving regular RLAI treatment for 1 year were identified from the Taiwan National Health Insurance Research database during 2007–2012. The bootstrapping procedure was performed to create 1000 samples to generate normally distributed data. The paired t-tests with a correction for multiple comparisons using Bonferroni correction were used to compare the proportion of patients of concomitant psychiatric medication and resource use and costs between pre- and post-RLAI periods. Rapid and non-rapid cycling stratification was performed based on the number of change-in-mood episodes within 1 year prior to the index date. ResultsThe mean annual dose of RLAI was 638.41mg, which was equal to an average dose of 24.6mg every 2 weeks. The prevalence of concomitant use of conventional antipsychotics, atypical antipsychotics, lithium, and antidepressants decreased from the pre-RLAI period to the post-RLAI period by 23.75%, 31.91%, 1.29%, and 7.08%, respectively. RLAI use decreased emergency room (ER) visits, hospital admissions, length of hospital stay, and non-medication costs (all P<0.0001). The cost savings with RLAI were attributed to lower hospitalization costs in spite of higher medication costs. Moreover, rapid cycling patients (n=36) demonstrated greater reduction in ER and inpatient services with RLAI than non-rapid cycling patients (n=251). LimitationsOf the patients who initiated RLAI, 15% of them who had regular treatment were included. Furthermore, data on measures of symptom severity, side effects, and hyperprolactinemia were not available. ConclusionBD patients had lower inpatient and ER utilization, and non-medication costs after using RLAI. In addition, RLAI use decreased the number of change-in-mood episodes in rapid cycling patients; which provides additional insights into the treatment of rapid cycling BD patients.

Risperidone long-acting injectable in the treatment of treatment-resistant schizophrenia with dopamine supersensitivity psychosis: Results of a 2-year prospective study, including an additional 1-year follow-up.

Dopamine supersensitivity psychosis (DSP) resulting from antipsychotic treatment is related to treatment-resistant schizophrenia (TRS), and its treatment has not been established to date. Maintaining thoroughly stable occupancy of the dopamine D2 receptor by risperidone long-acting injectable (RLAI) is one strategy for treatment. In this study, RLAI was given as an adjunctive medication to oral antipsychotic(s), which were switched partially and gradually to RLAI in 108 treatment-resistant patients for an additional 1-year follow-up in a 2-year study, and to compare the effects in 72 patients with a DSP history (DSP group) and 36 patients without this history (NonDSP group). Although both groups showed significant improvements in the total Brief Psychotic Rating Scale (BPRS) score during the follow-up period, greater improvement was observed for the DSP group than the NonDSP group. High doses (> 850 mg chlorpromazine-dose combined of oral antipsychotics and RLAI) did not significantly change in both groups throughout the study period; however, extrapyramidal symptoms, including tardive dyskinesia, were significantly improved only in the patients with DSP. This study strongly suggested that the RLAI treatment, even with only partial switching, provides relief from refractory symptoms, particularly for patients with a history of DSP. http://www.umin.ac.jp/:UMIN000008487.

A prospective, open-label study to evaluate symptomatic remission in schizophrenia with risperidone long-acting injectable in Korea

This study was designed to investigate long-term clinical outcomes of risperidone long-acting injectable (RLAI) in patients with schizophrenia or schizoaffective disorder. An open-label, 48-week, prospective study of RLAI treatment was carried out at 63 centers in South Korea. Initial and maintenance dosage of RLAI were adjusted according to clinical judgment. Efficacy was measured by the remission rate, continuation rate, and changes in the clinical measurements such as eight items of the Positive and Negative Symptom Scale (PANSS), the Clinical Global Impression - Severity, and the Schizophrenia Quality of Life Scale. In terms of the safety, Simpson-Angus rating Scale, adverse events (AEs), and BMI were investigated. Of the 522 patients who were enrolled, 472 patients who had been assessed on the eight items of PANSS at baseline and at least once during RLAI treatment were included in the intention-to-treat (ITT) population. The per-protocol (PP) population included 184 patients (39.0%), who completed all assessments during 48 weeks of the follow-up period. Total scores of eight items of PANSS, Clinical Global Impression - Severity, and Schizophrenia Quality of Life Scale were reduced significantly from baseline to endpoint in both ITT and PP populations. The mean dose (SD) of RLAI was 33.2 (7.6) mg. In the PP population, the number of patients who scored 1-3 on eight items of PANSS were 47 (25.5%) at baseline and 144 (78.3%) at 48 weeks. According to the remission defining as scores 1-3 on eight items of PANSS sustaining of at least 6 months' duration by Andreasen, the numbers of patients who achieved remission were 45 (24.5%) at 24 weeks and 120 (65.2%) at 48 weeks. A significant decrease in the mean score of Simpson-Angus rating Scale and a significant increase in BMI over time in last observation carried forward were observed, and patients who fulfilled the remission criteria during the study showed more weight gain than those who did not. During the study period, a total of 645 AEs were noted in 233 patients (49.3%) who were included in the ITT population. Sixty-nine serious AEs in 51 patients were reported, but all of them were not directly attributable to administration of RLAI. This prospective, open-label study showed improvements in symptom and AEs and a significant increase in BMI during 48 weeks of biweekly RLAI treatment. The rate of study completion was 39.0% and the remission rate among those who completed the study was 65.2%. None of the serious AEs were directly related to the administration of RLAI.

DI-094 The use of long-acting injectable formulations in subjects with schizophrenia: paliperidone palmitate versus others atypical antipsychotic drugs

BackgroundSchizophrenia is a serious mental health condition that causes disordered ideas, beliefs and experiences. The primary treatment is medicines. Non-compliance is one of the major problems of drop out. An...

EPA-1552 - Flexibly dosed paliperidone palmitate in non-acute but symptomatic patients with schizophrenia previously unsuccessfully treated with long-acting injectable risperidone

To explore tolerability, safety and treatment response of flexibly dosed paliperidone palmitate (PP) in adult non-acute but symptomatic patients with schizophrenia previously unsuccessfully treated with risperidone long-acting injectable treatment (RLAT). International, prospective 6-month open-label study. Major outcomes were clinical response (percentage of patients with ≥20% improvement in Positive and Negative Syndrome Scale (PANSS) total score at endpoint), functioning (Personal and Social Performance scale (PSP)), Extrapyramidal Symptom Rating Scale (ESRS), sleep quality, daytime drowsiness and treatment-emergent adverse events (TEAEs). The intent-to-treat population comprised 56 patients (64.3% male, mean age 39.9±11.0 years, 71.4% paranoid schizophrenia). 71.4% of patients completed the 6-month study. Withdrawal of consent (8.9%) and adverse events (10.7%) were the most frequent reasons for early discontinuation. Mean PANSS baseline total score was 67.5±20.7 and decreased by -9.2 points at endpoint (95% confidence interval -15.0;-3.5, p<0.0001). At endpoint, 61.1% of patients had improved by ≥20% in PANSS total score. Patient functioning in PSP increased by 5.2±15.3 points (p=0.0163). Sleep quality and daytime drowsiness improved significantly (both p<0.0292). Extrapyramidal symptoms in ESRS significantly improved from 3.7±7.2 at baseline to 2.4±6.4 at endpoint (p=0.0011). TEAEs reported in ≥5% were psychotic disorder (10.7%), injection site pain, headache, schizophrenia, anxiety (7.1% each), constipation and somnolence (5.4% each). Mean body weight decreased by 0.9±4.5 kg from baseline to endpoint. These data suggest that paliperidone palmitate is associated with a meaningful clinical response and functional improvement and is well tolerated with less EPS in non-acute, symptomatic schizophrenia patients previously unsuccessfully treated with RLAT.

Effectiveness of long-acting injectable risperidone versus oral antipsychotics in the treatment of recent-onset schizophrenia

Long-acting injectable antipsychotics may offer a relevant improvement in treatment adherence in recent-onset psychosis, leading to a decreased rate of hospital readmission, a better rate of clinical remission and improved psychosocial adjustment. The aim of the study was to compare the clinical remission rates, number of hospital readmissions and personal and social functioning after 2 years between patients with recent-onset schizophrenia (<2 years) in treatment with risperidone long-acting injectable (RLAI) and patients with recent-onset schizophrenia receiving oral antipsychotics. This is a case-control study comparing patients with recent-onset schizophrenia who initiated RLAI treatment between 2004 and 2008 (n=26) with a control group matched for age and sex, diagnosed with recent-onset schizophrenia and treated with oral antipsychotics (n=26). Study assessments included sociodemographic variables, the Positive and Negative Syndrome Scale, the Personal and Social Functioning Scale, the number of hospital readmissions and the Andreasen remission criteria. To assess the effect of treatment on each dependent variable, separate generalized estimating equations models were constructed. After 2 years of treatment, and adjusting for educational level, the RLAI group showed a greater reduction in the Positive and Negative Syndrome Scale total scale [mean (SD)=47.7 (12.0) vs. 66.2 (18.5); mean difference =-17.56; 95% confidence interval (CI)=-27.11 to -8.00; P<0.001], as well as in the negative [mean (SD) 14.3 (6.1) vs. 19.4 (6.4); mean difference=-5.02; 95% CI=-8.28 to -1.77; P=0.002] and general psychopathology [mean (SD)=23.4 (6.3) vs. 32.7 (8.1); mean difference=-9.16; 95% CI=-13.3 to -5.03; P<0.001] subscales compared with the oral antipsychotic group. Personal and Social Functioning Scale scores were also higher in the RLAI group [mean (SD)=72.4 (14.8) vs. 59.7 (13.5); mean difference=13.41; 95% CI=5.65-21.18; P<0.001]. Although not statistically significant, there were fewer readmissions (adjusted odds ratio 0.28; 95% CI=0.06-1.35; P=0.114) and more illness remissions (adjusted odds ratio 3.24; 95% CI=0.20-11.93; P=0.077) in the RLAI group. Treatment with RLAI instead of oral antipsychotics in recent-onset schizophrenia might improve clinical symptoms and social functioning. The efficacy of RLAI treatment on remission and readmission rates should be researched further.

A cost-consequence analysis of long-acting injectable risperidone in schizophrenia: A one-year mirror-image study with national claim-based database in Taiwan

ObjectiveThe development of long-acting atypical antipsychotics has provided a new paradigm for schizophrenia treatment. The economic effectiveness of risperidone long-acting injection (RLAI) on service costs has, however, never been studied in the real world with national claim-based database. MethodTo assess the change of service utilization and costs for schizophrenia before and after RLAI treatment, we conducted this 1-year mirror-image study with Taiwanese national claimed-data. Comparison was made for service sectors (the number of visits, acute admissions and relapse events) and cost components (outpatient, inpatient, emergency, medication and non-medication costs). ResultsService uses reduced in the post-RLAI period, along with a reduction of 34% and 32% on total inpatient services costs and inpatient non-medication costs, respectively (p < 0.005). However, overall psychiatric service costs went up by 26%, with an increase of 190% on total outpatient service costs and 177% on overall medication costs (p < 0.0001). ConclusionsThis 1-year mirror-image analysis showed that RLAI treatment was associated with reductions of service uses; however, overall psychiatric service costs were compromised by costs incurred from increased utilization of outpatient service and RLAI medication costs under the context of healthcare in Taiwan.

Descriptive analyses of the aripiprazole arm in the risperidone long-acting injectable versus quetiapine relapse prevention trial (ConstaTRE)

A recent randomized, open-label, relapse prevention trial (ConstaTRE) compared outcomes with risperidone long-acting injectable (RLAI) versus the oral atypical antipsychotic quetiapine. This study also included a small descriptive arm in which patients could also be randomized to aripiprazole. Results of this exploratory analysis are described here. Clinically stable adults with schizophrenia or schizoaffective disorder previously treated with oral risperidone, olanzapine, or an oral conventional antipsychotic were randomized to RLAI or aripiprazole. Efficacy and tolerability were monitored for up to 24 months. A total of 45 patients were treated with aripiprazole (10-30 mg/day) and 329 patients with RLAI (25-50 mg i.m. every 2 weeks). Relapse occurred in 27.3% (95% CI: 15.0-42.8%) of aripiprazole-treated and 16.5% (95% CI: 12.7-21.0%) of RLAI-treated patients. Kaplan-Meier estimates of mean (standard error) relapse-free period were 313.7 (20.4) days for aripiprazole and 607.1 (11.4) days for RLAI patients. Remission was achieved by 34.1% (95% CI: 20.5-49.9%) of aripiprazole and 51.1% (95% CI: 45.5-56.6%) of RLAI patients. Clinical global impression-change was improved ("minimally improved" to "very much improved") in 26.4% with RLAI and 15.9% with aripiprazole patients. Tolerability was generally good for both treatment groups. Weight gain (7.0% with RLAI vs. 4.4% with aripiprazole), extrapyramidal adverse events (AEs) (10.3% vs. 4.4%), and potentially prolactin-related AEs (4.6% vs. 0%) were more common with RLAI treatment, and gastrointestinal disorders were more common in aripiprazole-treated patients (22.2% vs. 6.1%). Time-to-relapse in stable patients with schizophrenia or schizoaffective disorder was numerically longer in RLAI-treated patients than in aripiprazole-treated patients although not statistically significant. Both treatments were generally well tolerated.

P03-119 - Improving use of resources-health care in patients with psychiatric pathology after introduction of risperidone long-acting injection (RLAI)

Enhance adherence to treatment is one of the main objectives in psychiatric clinical practice. The aim of this study is to evaluate changes in the use of oral antipsychotic medication, the use of rehabilitation resources and the number and duration of income in Psychiatric Inpatient Unit, comparing one year before and one year after RLAI's introduction, in patients with different psychiatric disorders, followed up by Mental Health Center and have maintained adherence to treatment for a defined period. We performed an observational, retrospective study by reviewing medical records of patients in ambulatory monitoring. The sample consisted of all patients (112) who had maintained RLAI treatment for a year, excluding those who did not fulfill the guideline correctly (14), remaining n = 98. We included patients of various pathologies, establishing groups as qualitative variables (F.20 = 56; F.25 = 12; F.22–28 = 20; F.60 = 10); of both sexes (V = 71; M = 27) and all ages. The preliminary results obtained showed a greater use of rehabilitation resources and decreased use of oral antipsychotics.

A Pilot, 15-month, randomised effectiveness trial of Risperidone long-acting injection (RLAI) versus oral atypical antipsychotic agents (AAP) in persons with bipolar disorder.

Chengappa KNR, Turkin SR, Schlicht PJ, Murphy SL, Brar JS, Fagiolini A, Houck PR, Garbutt RG, Fredrick N. A Pilot, 15-month, randomised effectiveness trial of Risperidone long acting injection (RLAI) versus oral atypical antipsychotic agents (AAP) in persons with bipolar disorder. Long-acting injectible antipsychotic agents are rarely considered in the treatment of bipolar patients [bipolar disorder (BPD)]. We posited that BPD patients receiving risperidone long-acting injections [Risperidone long-acting injections (RLAIs)] would experience fewer negative clinical events than those receiving oral atypical antipsychotic agents (AAP). Adult BPD patients in a hypomanic, manic or mixed episode were randomised to either oral risperdone followed by RLAI (n = 23) or an AAP (n = 25) for 15 months. Any mood stabilizers were continued. An independent clinician board declared any clinical events that occurred but the treatment assignment was concealed. Nine of the 48 patients who participated in this study did not improve, leaving 39 patients in 1-year extension. RLAI patients received the following bi-weekly dosages: 25 mg (n = 9), 37.5 mg (n = 8), and 50 mg (n = 6). The AAP group included aripiprazole (n = 11, 15-30 mg/day), quetiapine (n = 8, 300-700 mg/day), olanzapine (n = 5, 15-25 mg/day), and ziprasidone, (n = 1, 160 mg/day). In total, 47 clinical events were declared. The RLAI-treated group experienced significantly fewer clinical events (mean: 0.86 ± 0.73) compared with the AAP group (1.61 ± 1.29), t = 2.29, d.f. = 37, p = 0.028 (95% CI = 0.087-1.421). Of all, 50% of the AAP subjects gained ≥ 7% of their baseline body weight as did 38% of the RLAI-treated patients. RLAI-treated patients experienced significantly fewer negative clinical events. Further exploration should focus on which subtypes of BPD patients might benefit from RLAI treatment. Weight gain in BPD subjects requires clinical attention. Limitations include an open design, small sample size and the inability to conclude on whether this strategy is useful for depressive episodes.

Switching stable patients with schizophrenia from depot and oral antipsychotics to long‐acting injectable risperidone: efficacy, quality of life and functional outcome

This international, non-randomised study evaluated maintained efficacy and safety of Risperidone Long-Acting Injectable (RLAI) compared to previous medications. To investigate the possible effect of differences in national health care systems across Europe, the UK subset efficacy, health-related quality of life (HRQoL) and functioning data are reported here. Patients with schizophrenia or other psychotic disorders, symptomatically stable on antipsychotic medication, received intramuscular injections of RLAI 25 mg (to a maximum of 50 mg) every 2 weeks for 6 months. Of 182 UK patients recruited; 79% had schizophrenia (87% paranoid), 21% other psychotic disorders; 96% had been hospitalised at sometime. Improvement in mean Positive and Negative Syndrome Scale (PANSS) total score was significant at 1 month through to endpoint (p = 0.0001). There were significant improvements in PANSS subscales (p <or= 0.001), PANSS-Marder subscores (p <or= 0.0391), and in Clinical Global Impression-Severity (p = 0.0001) at endpoint. Patients reported improvements in: HRQoL (p < 0.05), Global Assessment of Functioning (p = 0.0001) and patient satisfaction (p = 0.0001) at endpoint. The proportion of patients rating RLAI treatment as 'very good' increased from 10% to 40%. 55% (22/40) of patients hospitalised at baseline were discharged by endpoint. Sustained, significant improvement in symptom control, HRQoL and functioning was seen in stable patients treated with RLAI over 6 months following a switch from previous antipsychotic medications.

Long-term observation of patients successfully switched to risperidone long-acting injectable: A retrospective, naturalistic 18-month mirror-image study of hospitalization rates and therapy costs

Objective. The aim of the present 18-month retrospective study was to assess the association between a continuous long-term treatment with risperidone long-acting injectable (RLAI) of at least 12 months and in-patient care of patients suffering of schizophrenia or schizoaffective disorder. Furthermore we wanted to assess the cost-effectiveness of a long-term treatment with RLAI. Methods. In a mirror-image design, data of 119 patients with schizophrenia and schizoaffective disorder who were switched to RLAI treatment were analyzed retrospectively. Hospitalization rates, the duration of inpatient treatment and the overall treatment costs were assessed 12 and 18 months after switching to RLAI and compared to the equivalent time preceding the switch. Results. After 12 and 18 months of RLAI treatment, the mean reduction of inpatient care was 27.4 and 38.4 days per patient, respectively, compared to the equivalent time period prior to switching to RLAI (Wilcoxon P < 0.001). The overall savings in drug and institutional-care costs were 21.1 and 21.9%, respectively. Conclusions. Patients receiving RLAI for at least 12 months showed a reduction in inpatient days and lower overall treatment costs.

Relapse and Long-Acting Injectable Risperidone: A 1-Year Mirror Image Study with a National Claims Database in Taiwan

The development of long-acting, injectable atypical antipsychotics has provided a new paradigm for schizophrenia treatment. The study was designed to assess whether a risperidone long-acting injection (RLAI) is associated with reduced relapses and service utilization in the real world. The Psychiatric Inpatients Medical Claims dataset was used for the analysis. It is a longitudinal dataset that includes the National Health Insurance claims of service uses by a cohort of mentally ill patients. The inclusion criteria for this analysis were patients who: 1) had available information for at least 12 months after the first dose of RLAI; 2) had a primary diagnosis of schizophrenia; and 3) were regularly treated with RLAI for at least 1 year. Patients who accumulatively received at least 75-mg RLAI per 3-month period were considered to be undergoing regular treatment. Wilcoxon signed rank tests were performed to compare differences in numbers of acute admissions, hospital days, emergency room visits, and relapses between the pre- and post-RLAI periods in this 1-year mirror-image study. In total, 108 patients were eligible for analysis. Significant reductions in the total annual numbers of acute hospital admissions by 55% (80 vs. 36, P = 0.0003), hospital days by 48% (4106 vs. 2126, P = 0.0021), and relapses by 54% (115 vs. 53, P = 0.0005) were observed. A reduction of emergency room visits was also observed, but did not reach statistical significance (55 vs. 25, P = 0.1255). This 1-year mirror-image analysis with claims-based data demonstrated that RLAI treatment was associated with reductions in relapses and hospital service utilization.

Experience with injectable long-acting risperidone in long-term therapy after an acute episode of schizophrenia: the SPHERE Study

Background: Risperidone long-acting injectable (RLAI) is the first long-acting formulation of an atypical antipsychotic introduced into clinical practice. RLAI combines the benefits of atypical antipsychotic agents with an extended duration of activity and is intended for long-term management of schizophrenia. This study evaluated the use of RLAI as part of a long-term management strategy in patients with an acute episode of schizophrenia. Objectives: The primary objective was to determine clinicians’ approaches to the use of RLAI in patients with an acute exacerbation of schizophrenia by examining the prescribing patterns of antipsychotic and other psychotropic medications. Other objectives were to evaluate the overall safety of switching patients to RLAI from previous antipsychotic therapy and to determine patients’, caregivers’ and relatives’ attitudes towards RLAI treatment. Methods: The Safety and Profile of Handling and Employing of Risperdal® Consta® in Emergency/Acute Care Settings (SPHERE) study was an observational, non-interventional, multicenter, retrospective study involving a large cohort of patients with acute psychotic exacerbation who attended Spanish emergency/acute care facilities (between August and December 2003) and were treated with RLAI during hospitalization. Results: A total of 1232 patients (70% men; mean age 37 years; median of 8 months since most recent admission) were included in the analyses; 79% had been receiving antipsychotic therapy prior to admission. All patients received RLAI post-stabilization. The main reasons for initiating RLAI were the need for long-term treatment (76%) and a low adherence to previous treatment (71%). RLAI doses administered during hospitalization were: 25 (26%), 37.5 (29%), 50 (42%) and 75–100 mg (3%). The mean number of injections per patient (2 ± 1) and mean hospitalization time (25 ± 16 days) indicated that RLAI was administered every 2 weeks as per the manufacturer’s recommendations. All patients were discharged on RLAI treatment; 62% were prescribed concomitant therapy, mainly oral risperidone (39%), anxiolytics (25%), antiparkinsonians (15%), hypnotics (11%) and anticonvulsants (11%). Only 5.7% of patients reported adverse events, most commonly extrapyramidal symptoms (1.1%) and somnolence (0.9%). Conclusions: As part of a long-term management strategy aimed at improving treatment adherence in schizophrenic patients, RLAI was prescribed to a wide spectrum of patients with an acute episode of schizophrenia during hospitalization and at the time of discharge from emergency/acute care facilities. RLAI was well tolerated in the study population and the overall impression of patients, primary caregivers and relatives to RLAI therapy was positive.

Remission in schizophrenia: one‐year Italian prospective study of risperidone long‐acting injectable (RLAI) in patients with schizophrenia or schizoaffective disorder

To evaluate the maintenance of efficacy of risperidone long-acting injectable (RLAI) in stable patients with schizophrenia or schizoaffective disorders. The prevalence of patients who met standardized remission criteria will be also evaluated as well as the predictors factors of remission according to psychopathological, psychosocial and subjective correlates. 52-week, open-label prospective trial in 347 stable patients switching directly to RLAI from any previous antipsychotic treatment. One year of treatment was completed by 70% of patients. Positive and Negative Syndrome Scale (PANSS) total and subscale, Global Assessment of Functioning (GAF) and Clinical Global Impression (CGI) scores improved from baseline at each assessment visit (p < 0.001, p < 0.001 and p < 0.05, respectively). Drug Attitude Inventory 30 (DAI30) scores improved significantly from month 3 onwards. 32% of patients met sustained remission at week 52. In a logistic regression model less severe positive and negative PANSS scores at baseline predicted remission (p < 0.001). RLAI treatment was well tolerated: one-third of patients reported mild to moderate adverse events (AEs). Eleven patients (3.2%) discontinued treatment due to an AE. No significant weight gain (p = 0.093) was reported. RLAI treatment up to one year improved symptoms and global functioning versus baseline, indicating that an established and accepted antipsychotic therapy can enable patients with schizophrenia to achieve and maintain remission.

P03-23 Descriptive analyses of the aripiprazole arm in the risperidone long-acting injectable versus quetiapine relapse prevention trial (ConstaTRE)

Objective:A recent randomized, open-label, relapse prevention trial (ConstaTRE) of risperidone long-acting injectable (RLAI) versus quetiapine and the oral atypical antipsychotic aripiprazole was carried out. Here we report the descriptive analysis of the aripiprazole arm.Methods:Clinically stable adults with schizophrenia or schizoaffective disorder previously treated with oral risperidone, olanzapine, or oral conventional antipsychotic were randomized to treatment with RLAI, quetiapine, or aripiprazole (in some countries). Efficacy and tolerability were monitored for up to 24 months of treatment.Results:A total of 45 patients were treated with aripiprazole (10-30 mg/day) and 329 patients with RLAI. Relapse occurred in 27.3% aripiprazole and 16.5% RLAI-treated patients. Kaplan-Meier estimates of mean relapse-free period were 314 versus 607 days for aripiprazole and RLAI patients, respectively. Full-remission, as defined by Andreasen et al, (2005), was achieved by 34% aripiprazole and 51% RLAI patients and was maintained until the end of the trial by 30% aripiprazole and 44% RLAI patients. According to Clinical Global Impression-Severity, there were 61% aripiprazole and 62% RLAI patients moderately ill or worse at baseline, and 59% aripiprazole and 45% RLAI at endpoint, respectively. Tolerability was generally similar between aripiprazole and RLAI treatment groups. However, weight gain, extrapyramidal adverse events (AEs), and possibly prolactin-related AEs were more common with RLAI treatment. Gastrointestinal disorders were more common in aripiprazole-treated patients.Conclusions:Time-to-relapse in stable patients with schizophrenia or schizoaffective disorder tended to be longer in RLAI-treated patients when compared with aripiprazole-treated patients. both RLAI and aripiprazole treatments were generally well tolerated.

P03-21 Relapse prevention in schizophrenia and schizoaffective disorder with risperidone long-acting injectable versus quetiapine: Randomized, long-term, open-label, clinical trial results (ConstaTRE)

Objective:The ConstaTRE study was designed to compare long-term relapse in stable patients treated with risperidone long-acting injectable (RLAI) or the oral atypical antipsychotic quetiapine.Methods:This was a randomized, open-label, prospective, active-controlled, multicenter, 2-year trial in symptomatically stable patients with schizophrenia or related disorder who were switched from stable treatment with oral risperidone, olanzapine, or oral conventional antipsychotic to RLAI or quetiapine. Primary efficacy measure was time-to-relapse. Positive and Negative Syndrome Scale (PANSS) scores and safety (adverse events [AEs] and Extrapyramidal Symptom Rating Scale [ESRS]) evaluations were reported.Results:710 patients were randomized (n=355 per group), with 666 patients (n=329 RLAI and n=337 quetiapine) being evaluable. Mean doses were 32.8±8.0 mg every-two-weeks for RLAI and 396.8±141.9 mg/day for quetiapine. Kaplan-Meier analysis indicated a significantly longer relapse-free period with RLAI treatment (log rank: p&lt; 0.0001). Relapse occurred in 16.5% of RLAI and 31.3% of quetiapine patients. Mean duration of treatment was 483.8±277.8 and 400.7±290.6 days for RLAI and quetiapine, respectively. Total PANSS scores improved significantly from baseline to endpoint for the RLAI-treated group (p&lt; 0.001). the endpoint difference favors RLAI over quetiapine (p&lt; 0.001). Treatment-emergent AEs were similar between groups. ESRS total scores decreased for both groups. Possibly prolactin-related AEs occurred more often with RLAI than quetiapine (4.6% versus 1.5%, respectively). Somnolence was reported less often with RLAI than quetiapine (1.8% versus 11.3%, respectively).Conclusions:Time-to-relapse was significantly longer and relapse rates were significantly lower for RLAI compared with quetiapine. both treatments were well tolerated.

P03-25 Risperidone long-acting injectable in stable patients with schizophrenia or related disorders switched from oral olanzapine

Objective:To explore the efficacy of risperidone long-acting injectable (RLAI) in patients previously treated with oral olanzapine requiring therapy change.Methods:This 6-month, multicenter, prospective, open-label trial evaluated adult patients with psychotic disorders treated with a stable dose of olanzapine, who required a treatment change due to lack of efficacy and/or tolerability. Three weeks after RLAI initiation, olanzapine use was tapered over 1 or 3 weeks at the discretion of the investigator. Primary efficacy evaluation was Positive and Negative Syndrome Scale (PANSS) total score change. Secondary endpoints included PANSS subscales, Clinical Global Impression-Severity (CGI-S), and Global Assessment of Functioning (GAF). Safety was evaluated by recording treatment-emergent adverse events (TEAEs).Results:96 patients were enrolled (53 tapered olanzapine within 1-week and 43 over 3-weeks). Mean olanzapine baseline dose was 19.2±11.8 and 29.9±17.5 mg/day in 1-week tapering and 3-week tapering groups, respectively. 40.6% of patients were initiated on 25 mg RLAI every-two-weeks. Treatment was completed by 79 patients (82.3%). Treatment discontinuation was mainly due to withdrawal of consent (n=4), AE (n=3), injection refusal (n=2), or lost to follow-up (n=2). Improvements in PANSS total and subscale scores, CGI-S and GAF were significant from baseline to endpoint (p&lt; 0.0001). 74 TEAEs were reported in 42 patients (42.9%). TEAEs reported in ≥2% of patients were agitation (3.6%), insomnia (3.6%), and schizophrenia (9.1%). Serious AEs occurred in 10 patients.Conclusions:Switching treatment from oral olanzapine to RLAI led to clinically-relevant symptomatic and functional improvement in more than half of all patients. RLAI treatment was generally well-tolerated.

Risperidone long acting injection: Findings of a 2-year retrospective follow-up study

Objective. The aim of this retrospective study was to assess the clinical effectiveness of risperidone long acting injection (RLAI) at 2 years within an acute mental health setting. Method. All patients who received RLAI between July 2002 and December 2004 were identified from pharmacy records, and data collected by retrospective case note review. In order to give an indication that their condition was unresponsive to treatment, patients’ drug histories were reviewed to determine whether or not they had previously been treated with clozapine or received two or more failed trials of other antipsychotic medication. Results. Eighty-four patients were included in the study and 56 discontinued at 2 years. The most common reason for treatment discontinuation was lack of effectiveness, accounting for 32 patients, whilst eight patients discontinued due to adverse effects. Patients remaining on treatment spent 67% of the time in an outpatient setting. Conclusion. The proportion of patients remaining on RLAI at 2 years was 33%. Limitations of the naturalistic methodology used in this study hindered any precise determination of which patients were likely to continue RLAI. However, it was apparent that a history of previous treatment failure with at least two antipsychotics was associated with RLAI treatment discontinuation.

Risperidone Long-Acting Injection

To evaluate outcomes of clinical use of risperidone long-acting injection (RLAI) and determine factors predicting continuation with treatment. This prospective, 3-year follow-up of consecutive patients started on treatment with RLAI in normal clinical practice between August 2002 and September 2003 obtained demographic and clinical data from case notes, prescription charts, and hospital computer records. To determine predictors of continuation, a proportional hazards regression (Cox) model was constructed. The study included 211 evaluable patients. Over 3 years, 84% of subjects discontinued RLAI; 27.7% of these switched to oral risperidone. The Cox model showed that younger age (p = .001), longer duration of illness (p = .001), inpatient status at initiation (p = .002), and an RLAI dose of 25 mg/2 weeks (p < .001) predicted greater probability of discontinuation. A small proportion of patients initiated on treatment with RLAI continued for 3 years. Outcome is likely to be improved by targeting RLAI treatment at specific patient groups and by using a dose of more than 25 mg/2 weeks.