Use Of Risperidone Long-acting Injection Research Articles

Registro Electrónico de Adherencia al Tratamiento de Esquizofrenia en Latinoamérica (e-STAR): Resultados clínicos del uso de risperidona inyectable de liberación prolongada a dos años de seguimiento

La esquizofrenia genera elevados costos al sistema de salud. La falta de adherencia al tratamiento es una de las principales causas de recaídas y hospitalizaciones en la esquizofrenia. Lo anterior conduce a un pobre pronóstico y deterioro funcional de los pacientes. La risperidona inyectable de liberación prolongada (RILP) ha demostrado su eficacia en el tratamiento de la esquizofrenia, ofreciendo la posibilidad de que los pacientes tengan una mayor adherencia terapéutica. Objetivo: Determinar la eficacia y efecto sobre la funcionalidad y el uso de recursos hospitalarios de la RILP en una muestra de pacientes con esquizofrenia de América Latina a dos años de seguimiento. Método: El Registro Electrónico de Adherencia al Tratamiento de Esquizofrenia en Latinoamérica (e-STAR) es un estudio observacional del uso de la RILP en la esquizofrenia. Se reclutaron pacientes de México, Colombia y Brasil. Se registró la información clínica del paciente un año previo al inicio del tratamiento con la RILP y de forma prospectiva cada tres meses hasta cumplir los 24 meses de seguimiento. Se registraron las hospitalizaciones y el esquema de tratamiento con la RILP. La escala de Impresión Clínica Global-Gravedad (CGI-S) se utilizó como indicador de eficacia mientras que la Escala Global de Funcionamiento (GAF) y la Escala de Desempeño Personal y Social (PSP) se utilizaron para evaluar el funcionamiento. Resultados: Setenta y tres pacientes completaron los dos años de seguimiento. La proporción de pacientes hospitalizados disminuyó del 16.4 al 4.1% después de dos años de tratamiento con la RILP. El 2.7% descontinuó el tratamiento debido a falta de eficacia. Se observó una mejoría significativa en cuanto a la gravedad del padecimiento y el funcionamiento global. Discusión: En la práctica clínica cotidiana, la RILP resulta ser un tratamiento a largo plazo efectivo para la esquizofrenia con el beneficio adicional de una menor utilización de recursos del sistema de salud.

Risperidone Long-Acting Injection in the Treatment of First Episode Schizophrenia

Pharmacological treatments of first episode schizophrenia are of particular relevance because most clinical and psychosocial deterioration with cognitive decline and changes in brain volume occurs in the first five years of disease onset. Although the efficacy of antipsychotic maintenance treatment has been demonstrated to reduce risk of relapse, nonadherence is common even in first episode schizophrenia patients. Antipsychotic long-acting injections (LAIs) could be an option in early treatment although international guidelines recommend their use in patients who have already experienced significant non-adherence and who have repeated relapse. At the present time there is some concern about the acceptability of LAIs in first episode schizophrenia: some studies suggest that LAI treatment is feasible in these patients because of distinct advantages in terms of better treatment adherence. In the present review, we analyze the few currently studies published on the use of risperidone long-acting injection (RLAI) to improve adherence in first episode schizophrenia. Further research is needed to support the routine use of LAIs and of the other second generation antipsychotic LAIs (olanzapine long-acting and paliperidone palmitato) in this population of patients to improve adherence. Keywords: Adherence, antipsychotics, atypical antipsychotics, compliance, depot formulation, efficacy, first episode schizophrenia, long-acting injection, medication discontinuation, patients attitude, psychiatric attitude, relapse, remission, schizophrenia, tolerability

Importance of Gender in the Treatment of Schizophrenia

To compare male and female patients participating in e-STAR (electronic Schizophrenia Treatment Adherence Registry), an international, prospective, observational study assessing use of risperidone long-acting injection in patients with schizophrenia or schizoaffective disorder in both the Czech and Slovak Republics. The demographic, clinical, and treatment-related data were collected at baseline and then prospectively for 24 months. We focused on gender differences in demographic and clinical data (hospitalizations, concomitant medication, and clinical improvement using Clinical Global Impressions-severity of illness [CGI-S], Global Assessment of Functioning [GAF], and Personal and Social Performance [PSP] scales). All psychiatric diagnoses were made according to International Classification of Diseases, Tenth Revision criteria. Data were collected from September 2006 through September 2009. A total of 868 patients (488 men and 380 women) were included in the assessment. At baseline, the women were significantly older than the men (42.1 ± 12.8 vs 34.8 ± 11.1 years, respectively; P < .0001). The women were also significantly more frequently diagnosed with schizoaffective disorder (P = .0048). There was no difference between men and women in the proportion of patients hospitalized in the retrospective and prospective period (including length of stay). At 24 months, the men were taking fewer antidepressants and benzodiazepines than the women (controlled for baseline values). In men and women, a significant decrease in the CGI-S score (P < .001) and a significant increase in the GAF and PSP scores (P < .001) from baseline were observed. The improvements in CGI-S and PSP scores were similar in both groups (no significant difference between male and female patients). The improvement (increase) in the mean GAF score was significantly higher in women than in men (P = .0317). The treatment with risperidone long-acting injection was associated with clinically significant improvement in both male and female patients with schizophrenia with comparable severity of illness. There were no significant differences in most outcome measures. Gender differences, especially concerning treatment response to individual antipsychotics and their different forms, should be more intensively studied.

Atypical Presentation of Tardive Dyskinesia Associated with Risperidone Long-Acting Injection as Maintenance Treatment in Bipolar Affective Disorder: A Case Report

Second-generation antipsychotics have been growingly implicated in the acute and maintenance treatment for bipolar affective disorder (BAD). Risperidone long-acting injection (LAI) has been the first second-generation depot indicated for its maintenance treatment. However, its long-term motor side-effects, especially tardive dyskinesia (TD), has not been commonly reported or studied. The case reported here a bipolar patient with atypical presentation of TD involving only the crico-hyoid region of the neck associated with the use of risperidone LAI in adjunct to lithium and sodium valproate as maintenance therapy.

Risperidone long-acting injection as monotherapy and adjunctive therapy in the maintenance treatment of bipolar I disorder

Importance of the field: It is very rare for patients with bipolar disorder to have a single episode of mania or depression over a lifetime and the vast majority of these individuals need long-term prophylactic/maintenance treatment. However, treatment nonadherence is a major issue for close to half of subjects with bipolar disorder who are prescribed medications. Risperidone long-acting injection (LAI) has proven efficacious for the maintenance phase of bipolar disorder and may mitigate the problem of nonadherence in the substantial group of patients for whom this is a significant concern.Areas covered in this review: This paper comprises a review and commentary regarding the use of risperidone LAI in bipolar disorder.What the reader will gain: The reader will gain an understanding regarding the risks and benefits of risperidone LAI in bipolar disorder. We review the available evidence and discuss the strengths and weaknesses of published studies, providing an opinion about the clinical usefulness of risperidone LAI as well as suggestions for future research.Take home message: The use of risperidone LAI, through improved adherence, has the potential to ameliorate the course of bipolar disorder.

The combined use of risperidone long-acting injection and clozapine in patients with schizophrenia non-adherent to clozapine: a case series

Poor adherence to clozapine treatment represents an important problem in clinical practice because additional useful treatment options are unavailable. Although switching to risperidone long-acting injection (RLAI) has been recommended for those with compliance problems, this medication has been found to be less suitable for patients who previously received clozapine. Based on the suggested beneficial effects of RLAI, such as higher rates of treatment continuation and patient satisfaction, and the possible effectiveness of oral risperidone augmentation, it seems worthwhile to try RLAI augmentation for clozapine non-adherence. In this article, we present the cases of four patients with schizophrenia undergoing combined treatment with RLAI and clozapine for more than one year after multiple relapses related to clozapine non-adherence. Durations and frequencies of hospitalizations markedly declined after RLAI augmentation. Indeed, three patients receiving RLAI and clozapine for 1.2-3.5 years were never hospitalized during this period. The lengths of hospitalizations before and after augmenting with RLAI were 54.7 +/- 33.1 and 4.2 +/- 4.2 days/year, respectively. Participants also showed great improvements in social skills. These findings suggest the possible beneficial effects of RLAI augmentation in cases of clozapine nonadherence. However, controlled clinical trials are necessary to confirm whether RLAI augmentation represents a useful treatment option for patients who have not adhered to clozapine treatment.

The use of risperidone long-acting injection (RLAI) does not reduce the number of days spent in hospital

The use of risperidone long-acting injection (RLAI) does not reduce the number of days spent in hospital

Risperidone long‐acting injection: a 6‐year mirror‐image study of healthcare resource use

To evaluate naturalistic use of risperidone long-acting injection (RLAI) and its effect on healthcare resource use. Mirror-image comparison of healthcare resource use for 3 years before RLAI initiation and 3 years after. In total, 211 of 277 patients consecutively prescribed RLAI were evaluable over the full 6-year study period. Median days in hospital/patient increased significantly in the 3 years after RLAI initiation [87 days (inter-quartile range 25-236) before vs. 192 days (47-426) after; P < 0.001]. Those 34 patients who continued RLAI for 3 years showed no change in median bed days [64 days (6.5-182) before vs. 64 days (12-180) after] and median number of admissions was decreased [1.5 (1-2.25) before vs. 1.00 (0-1.25) after; P = 0.001]. Healthcare costs more than doubled for the whole cohort (P < 0.001) and discontinuers (P < 0.001) and increased significantly for continuers (P = 0.010). RLAI did not decrease either time spent in hospital or overall healthcare costs in this patient cohort.

Use of Risperidone Long-Acting Injection to Support Treatment Adherence and Mood Stabilization in Pediatric Bipolar Patients

Article AbstractSir: Recent studies have suggested that depot formulations of second-generation antipsychotics may be considered for controlling mood episodes in bipolar disorder (BD) patients who have relapsed due to medication nonadherence or failed to respond to standard therapies. The safety and effectiveness of risperidone long-acting injection (RLAI) have been demonstrated through clinical trials in stable BD adults, and the applicability of RLAI in frequently relapsing patients has also been shown. Although the U.S. Food and Drug Administration approved oral risperidone in 2007 for use in early-onset BD patients, no study has reported the utility of RLAI in youth.

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.

Prescribing practice of risperidone long-acting injection

Background:Risperidone the first atypical antipsychotic available in a long-acting injection formulation. In the United Kingdom is licensed to use in psychosis in patients tolerant of oral Risperidone and the Summary of Product Characteristics clearly defines the methods of initiation and titration.Methods:We performed a naturalistic observation of 25 patients belonging to 3 different community mental health teams and one in-patient facility that have been prescribed Risperidone long-acting injection (RLAI) and collected data about immediate prior use of antipsychotic medication, patient preference, compliance with treatment, documentation of effectiveness and tolerance of Risperidone oral, supplementation with Risperidone oral during the first three weeks, initial dose, intervals between dose changes, monitoring of benefits and side-effects, and reasons for discontinuation.Results:Only 7/25 patients have been prescribed oral Risperidone prior to the injectable formulation and none had received clozapine. 13/25 received oral supplementation during initiation, 3/25 dose was changed in less than 4 weeks intervals. 14/25 non-compliance was suspected and only 2/25 patients stated a preference for an injectable formulation. 17/25 continued to receive RLAI and those discontinued in 3/25 due to patient refusal, 1/25 not tolerated, 1/25 patient did not attend treatment, 1/25 not effective, 1/25 patient deceased, 1/25 no reason was specified.Conclusions:prescribing of RLAI did not follow the recommendation from the manufacturers mainly during initiation. Non-compliance with previous medication was the main reason for use of an injectable formulation but use of RLAI seems to be associated with low discontinuation rates.

Thirty‐five months experience of risperidone long‐acting injection in a UK psychiatric service including a mirror‐image analysis of in‐patient care

To report the use of risperidone long-acting injection (RLAI) in a UK psychiatric service. Retrospective case note review of all patients prescribed RLAI over a 35-month period. In the mirror-image analysis patients initiated on RLAI as in-patients had the index admission attributed to previous treatment. Patients prescribed RLAI had significantly higher baseline rates of drug misuse, alcohol misuse, unemployment and forensic markers than control patients prescribed oral antipsychotics. Most patients started RLAI because of poor compliance with oral antipsychotics. Inefficacy accounted for more discontinuations than intolerability. Fifty-eight percent (39/67) of patients were continuing RLAI 12 months after initiation. Mirror-image analysis (n = 74) showed that RLAI was associated with a reduction in the number of admissions (65 vs. 33, P < 0.005) and in total in-patient days (4550 vs. 2188 days, P < 0.005). The mean reduction in in-patient care was 29 days per patient-year of treatment, equivalent to a net financial saving over the acquisition and administration costs of RLAI of pound1172. Risperidone long-acting injection was associated with reduced in-patient care and was cost-effective.

The use of risperidone long-acting injection (RLAI) in a high secure hospital

The use of risperidone long-acting injection (RLAI) in a high secure hospital

Risperidone long-acting injection in practice - more questions than answers?

Two papers in this issue report on the clinical use of risperidone long-acting injection (RLAI). A UK study of 250 patients prescribed RLAI and followed-up for 1 year (1) shows rather disappointing outcome with respect to time spent in hospital. A Norwegian analysis of in-practice risperidone serum concentrations (2) identifies clear differences in serum levels produced by oral and injectable forms. Each of these findings is perplexing in its own way but the results of one may provide at least a partial explanation for the results of the other. In the UK study all subjects began RLAI treatment on 25 mg/2 weeks, a dose which, according to the second study, provides apparently sub-therapeutic plasma levels of risperidone and its major metabolite, 9-hydroxyrisperidone. In providing an explanation there also arises a question: what is an effective dose of RLAI in practice? Risperidone appears to exert its effect through the pharmacological activities of both the parent compound and its major metabolite 9-hydroxyrisperidone. These compounds are said to have similar activity at dopamine, D2 and serotonin, 5HT2 receptors (3) and are usually assumed to have equal antipsychotic activity. Serum levels of each are summed to provide an active moiety concentration. Oral risperidone is optimally efficacious at a dose of around 4 mg a day (4, 5), at least in patients suitable for inclusion in randomized, controlled trials. Oral doses of this magnitude have been said to give rise to plasma levels of around 40 ng/ml (97.4 nmol/l) (risperidone + 9-hydroxyrisperidone) (6). However, a human receptor occupancy study suggested sufficient dopamine D2 occupancy for clinical effect was provided by a dose of 3 mg a day and active moiety plasma levels averaging 18 ng/ml (43.8 nmol/l) (7). A readily apparent difficulty here is the variation in plasma level afforded by the same dose in different individuals – one study estimated concentration to dose ratios of between 1.8 and 36.8 (nmol/l)/mg/day (8). More predictable is the ratio of risperidone to 9-hydroxyrisperidone: 90–95% of activity seems to be provided by the metabolite (8, 9). The optimal dose of RLAI is perhaps less well established than that of oral risperidone. Fixed dose studies show no important differences in clinical outcome for doses ranging from 25 mg/2 weeks to 75 mg/2 weeks and nor was any trend for better response at higher doses identified (10, 11). However, it is possible that these studies were not designed or sufficiently powered to reveal anything but substantial advantages for higher doses. At least one naturalistic study has identified doses of >25 mg/week as being associated with improved clinical response (12). This is the same cohort of patients who did so poorly with respect to bed stay when initiated on 25 mg/2 weeks (1). The observation that the lowest licensed dose of RLAI gives rise to mean active moiety plasma levels of only 13.5 ng/ml (32.9 nmol/l) (albeit with proportionately more parent compound) (2) serves further to question to efficacy of 25 mg/2 weeks. Other studies have reported similar findings with respect to blood levels. A small naturalistic study found median active moiety plasma levels of 15.6 ng/ml (38 nmol/l) in subjects receiving 25 mg/2 weeks (13), another found levels ranged from 4.4 to 8.8 ng/ml (10.7–21.4 nmol/l) (14). Unsurprisingly, brain D2 receptor occupancy appears to be very low at these levels, ranging from 25% to 48% (14). The highest level reported for RLAI 25 mg/2 weeks is 22.7 ng/ml (55.3 nmol/l) and was significantly lower than that seen with risperidone 2 mg a day (32.9 ng/ml; 80.2 nmol/l) in the same study (15). Of course, 2 mg a day oral risperidone is known to be a sub-optimal dose, at least in relapsed schizophrenia (4). So, is a dose of 25 mg/2 weeks RLAI sufficient? It is difficult to see how it can be when this dose provides such low plasma levels and apparently sub-therapeutic in vivo D2 occupancies. Its sub-optimal effectiveness is certainly suggested by at least one naturalistic study (1, 12). Larger randomized, controlled trials of fixed doses are clearly needed but are unlikely to take place at this postmarketing stage of the preparation's life-span. Perhaps then, in clinical practice, it would be wise first to establish the effective dose of oral risperidone in an individual before starting RLAI and then to prescribe of dose of RLAI broadly equivalent to the oral dose (2 mg oral equating to 25 mg/2 weeks, and so forth) – a technique successfully used in a large, year long trial (11) and supported by in the product's official labelling.

Cost-Effectiveness Model Of Long-Acting Risperidone in Schizophrenia in the US

Schizophrenia is a devastating and costly illness that affects 1% of the population in the US. Effective pharmacological therapies are available but suboptimal patient adherence to either acute or long-term therapeutic regimens reduces their effectiveness. The availability of a long-acting injection (LAI) formulation of risperidone may increase adherence and improve clinical and economic outcomes for people with schizophrenia. To assess the cost effectiveness of risperidone LAI compared with oral risperidone, oral olanzapine and haloperidol decanoate LAI over a 1-year time period in outpatients with schizophrenia who had previously suffered a relapse requiring hospitalisation. US healthcare system. Published medical literature, unpublished data from clinical trials and a consumer health database, and a clinical expert panel were used to populate a decision-analysis model comparing the four treatment alternatives. The model captured: rates of patient compliance; rates, frequency and duration of relapse; incidence of adverse events (bodyweight gain and extrapyramidal effects); and healthcare resource utilisation and associated costs. Primary outcomes were: the proportion of patients with relapse; the frequency of relapse per patient; the number of relapse days per patient; and total direct medical cost per patient per year. Costs are in year 2002 US dollars. Based on model projections, the proportions of patients experiencing a relapse requiring hospitalisation after 1 year of treatment were 66% for haloperidol decanoate LAI, 41% for oral risperidone and oral olanzapine and 26% for risperidone LAI, while the proportion of patients with a relapse not requiring hospitalisation were 60%, 37%, 37% and 24%, respectively. The mean number of days of relapse requiring hospitalisation per patient per year was 28 for haloperidol decanoate LAI, 18 for oral risperidone and oral olanzapine and 11 for risperidone LAI, while the mean number of days of relapse not requiring hospitalisation was 8, 5, 5 and 3, respectively. This would translate into direct medical cost savings with risperidone LAI compared with oral risperidone, oral olanzapine and haloperidol decanoate LAI of USD 397, USD 1742, and USD 8328, respectively. These findings were supported by sensitivity analyses. The use of risperidone LAI for treatment of outpatients with schizophrenia is predicted in this model to result in better clinical outcomes and lower total healthcare costs over 1 year than its comparators, oral risperidone, oral olanzapine and haloperidol decanoate LAI. Risperidone LAI may therefore be a cost saving therapeutic option for outpatients with schizophrenia in the US healthcare setting.