Switching from oral risperidone to flexibly dosed oral paliperidone extended-release: core symptoms, satisfaction, and quality of life in patients with stable but symptomatic schizophrenia: the RISPALI study.

OBJECTIVE: The purpose of this prospective study was to evaluate the effects of switching from oral risperidone to flexibly dosed oral paliperidone extended-release (ER) in Brazilian adults with schizophrenia because of lack of efficacy, intolerability, or nonadherence after a minimum trial of 30 days on adequate (labeled) doses of oral risperidone, according to individual clinical judgment. RESEARCH DESIGN AND METHODS: Subjects with Positive and Negative Syndrome Scale total scores above 78, and/or intolerable adverse effects, with risperidone received open-label paliperidone ER 3 to 12 mg daily for 26 (main phase) to 52 (extension phase) weeks. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01010776. RESULTS: The intent-to-treat (efficacy) populations comprised 213 subjects in the main phase and 159 in the extension phase. Of 213 subjects with baseline and post-baseline efficacy data, 154 (72.3%) switched from risperidone to paliperidone ER because of a lack of efficacy and 59 (27.7%) because of tolerability issues, according to individual clinical judgment. Paliperidone ER significantly (p < 0.0500) improved a broad spectrum of efficacy endpoints from baseline, as early as the first post-baseline visit (Visit 2; 4 weeks) and persisting through 26 to 52 weeks. On most efficacy endpoints, function improved from baseline to the first post-baseline visit (week 4) and remained significantly improved compared to baseline at each visit for paliperidone ER treatment, at weeks 8, 13, 26, 39, 26, and 52; data are reported herein mainly for 26 and 52 weeks compared to baseline. Significant improvements from baseline were observed for the Positive and Negative Syndrome Scale total score and subscale scores (each p < 0.0001 at 26 and 52 weeks vs. baseline); and personal and social functioning (p < 0.0001 at 26 and 52 weeks). Paliperidone ER also significantly improved health-related quality of life (Short-Form 36) from baseline, particularly on the Mental Component Summary (p = 0.0011 at 26 weeks and p = 0.0019 at 52 weeks). Treatment with paliperidone ER also significantly improved (vs. baseline) sleep quality (according to decreases on the Pittsburgh Sleep Quality Index; p < 0.0001 at each visit vs. baseline) and disease severity (Clinical Global Impression-Severity; p < 0.0001 at each visit vs. baseline). Paliperidone ER was well tolerated. Adverse events occurring in at least 10% of subjects in either phase were insomnia (14.9% in the main phase and 8.8% in the extension phase); increased body weight (10.7% and 12.6%, respectively); and anxiety (10.7% and 2.5%). Most of these adverse events were: 1) rated as mild or moderate; 2) did not prompt interventions such as paliperidone ER dose adjustment or interruption; and 3) decreased in frequency from the main to the extension phase. CONCLUSIONS: Oral paliperidone ER is a rational treatment alternative for patients with schizophrenia whose antipsychotic regimens are switched because of unsuccessful treatment with oral risperidone according to individual clinical judgment. Study limitations included the open-label study design, lack of placebo, and use of subjective clinical judgment to determine lack of efficacy, intolerability, or nonadherence with oral risperidone.

Long-acting injectable risperidone in partially adherent and nonadherent patients with schizophrenia.

BACKGROUND: Long-acting injectable antipsychotics may improve medication adherence, thereby improving overall treatment effectiveness. This study aimed to evaluate the effectiveness, safety, and tolerability of risperidone long-acting injection in schizophrenic patients switched from oral antipsychotic medication. METHODS: In a 12-month, multicenter, open-label, noncomparative study, symptomatically stable patients on oral antipsychotic medication with poor treatment adherence during the previous 12 months received intramuscular injections of risperidone long-acting injection (25 mg starting dose) every 2 weeks. The primary endpoint was the change in Positive and Negative Syndrome Scale (PANSS) total score. RESULTS: Of the 60 patients who were screened, 53 received at least one injection (safety population), and 51 provided at least one postbaseline assessment. Mean PANSS total scores improved significantly throughout the study and at endpoint. Significant improvements were also observed in Clinical Global Impression of Severity, Personal and Social Performance, and Drug Attitude Inventory scales. Risperidone long-acting injection was safe and well-tolerated. Severity of movement disorders on the Extrapyramidal Symptom Rating Scale was reduced significantly. The most frequently reported adverse events were insomnia (22.6%), increased prolactin (17.0%), and weight gain (13.2%). CONCLUSION: Risperidone long-acting injection was associated with significant symptomatic improvements in stable patients with schizophrenia following a switch from previous antipsychotic medications.

Estudos multicêntricos da ziprasidona oral no tratamento de pacientes com esquizofrenia ou transtorno esquizoafetivo / Multicenter studies of oral ziprazidone for the treatment of patients with schizophrenia and schizoaffective disorder

Introdução: Através de dois estudos seqüenciais a eficácia, segurança e a tolerabilidade da ziprasidona oral foram avaliadas em pacientes brasileiros portadores de transtorno esquizofrênico ou esquizoafetivo. Métodos: Estudos prospectivos e abertos. No primeiro estudo os pacientes receberam entre 80 e 160 mg/dia de ziprasidona durante seis semanas e foram avaliados através da Positive and Negative Symptom Scale (PANSS), Impressão Clinica Global para Gravidade da doença (CGI-S), Questionário de Intensidade de Cuidados (ICQ) e Preferência do Paciente (PPS). A segurança e tolerabilidade foram avaliadas por análises clínica, eletrocardiográfica e laboratoriais, escala de Avaliação dos Sintomas Extrapiramidais (ESRS) e Avaliação de Acatisia de Barnes (BAS). Os pacientes com resposta ao tratamento poderiam ser incluídos no segundo estudo, com duração de até 12 meses. Resultados: No primeiro estudo 162 pacientes foram avaliados quanto à eficácia e 164 quanto à segurança e tolerabilidade. O tratamento reduziu o escore na escala PANSS a partir do início de 94,3 para 76,2 (P<0,0001). Também houve reduções significativas dos escores nas escalas CGI-S e ICQ. Através da PPS 64,8 dos pacientes preferiram a ziprasidona ao medicamento anterior. Não houve sintomas extrapiramidais significativos avaliados pela ESRS e BAS nem alterações eletrocardiográficas. Dos 106 pacientes incluídos no segundo estudo, 86 foram analisados quanto à eficácia. A duração mediana do tratamento foi de 5,6 meses e o escore médio na escala PANSS foi mantido. O perfil de eventos adversos ao longo dos dois estudos foi semelhante. Conclusão: A ziprasidona oral é eficaz e segura no tratamento crônico de pacientes portadores de esquizofrenia e distúrbio esquizoafetivo.