Avaliação dos desfechos clínicos e desempenho cognitivo em pacientes com diagnóstico de esquizofrenia refratária em uso de clozapina

A esquizofrenia é um transtorno crônico, grave e com alto impacto socioeconômico. Apesar dos avanços científicos, a esquizofrenia mantém-se como um dos transtornos mentais mais debilitantes. Cerca de 30% dos pacientes não respondem aos antipsicóticos usualmente prescritos, sendo considerados refratários ao tratamento. Para estes pacientes, a medicação de escolha é a clozapina que, embora mais efetiva, tem o seu uso como primeira opção restrito a este grupo de pacientes devido ao seu potencial de efeitos adversos graves. Mesmo com eficácia bem estabelecida, existem poucos estudos sobre o uso de clozapina a longo prazo. O objetivo do nosso estudo foi avaliar pacientes em tratamento com clozapina a longo prazo quanto a desfechos clínicos e desempenho cognitivo. Este estudo foi realizado em duas etapas. A primeira foi a avaliação de pacientes em uso de clozapina por uma média de 18.94 (±3.72) anos provenientes do Programa de Atenção à Esquizofrenia Refratária. Foram incluídos inicialmente 56 pacientes com diagnóstico de esquizofrenia refratária, idade entre 18-65 anos, sendo que 30 pacientes completaram o último seguimento. A segunda etapa consistiu na avaliação transversal destes pacientes em uso de clozapina comparados a pacientes em uso de outros antipsicóticos em relação ao desempenho cognitivo. No primeiro artigo, analisamos os desfechos clínicos dos pacientes em uso de clozapina a longo prazo através da Brief Psychiatric Rating Scale (BPRS), entrevista clínica e protocolo de efeitos adversos. Clozapina foi efetiva na redução de sintomas nos primeiros 6 meses de uso (BPRS média no baseline 77.9±16.1, BPRS média em 6 meses 44.4±16.4), seguida por um período de estabilidade e continuidade da melhora a longo prazo (BPRS 17.3±11.67 no último follow up, p < 0.05) e na redução do número de internações após o seu uso (média 5.5 versus 1.4). Apenas um efeito adverso grave (agranulocitose) com necessidade de interrupção do uso foi relatado (1.8% da amostra). No segundo artigo, analisamos a capacidade de aprendizado dos pacientes através da Hopkins Verbal Learning Test - Revised (HVLT-R) e encontramos uma curva de aprendizado semelhante entre os grupos (F (54,1) = 0.499, p=0.483). Os pacientes em uso de clozapina apresentavam idade de início da doença mais precoce e maiores escores de sintomas gerais (sugerindo quadros mais graves), além de iniciarem a clozapina tardiamente no curso do transtorno (9.40±6.79 anos após o diagnóstico), o que poderia estar associado à performance similar entre os grupos a despeito do uso da clozapina. Algumas limitações precisam ser consideradas, como o tamanho da amostra. Contudo, pode-se concluir que, pelo menos para o grupo seguido em média 20 anos após o uso da clozapina, esta é uma droga eficaz na redução de sintomas e diminuição do número de internações, além de apresentar segurança no tratamento a longo prazo.Schizophrenia is a chronic and severe disorder with a high social and economic impact. Despite scientific advances, it is still one of the most debilitating psychiatric disorders. About thirty percent of patients do not respond to antipsychotics usually prescribed, being considered treatment-resistant. For those, clozapine is the drug of choice, considered the most effective antipsychotic in this setting, although it tends to be used as a last resource due to its potential serious adverse effects. Even with its proved efficacy, there are few studies on long-term use of clozapine. The present study aimed to evaluate patients on clozapine treatment in the long-term for clinical outcomes and cognitive performance. This study was performed in two phases. The first phase comprised evaluation of patients from the Refractory Schizophrenia Attention Program on clozapine for a mean 18.94 (±3.72) years. Fifty-six patients with a diagnosis of treatment-resistant schizophrenia aged 18 to 65 years were included, with 30 patients completing last follow-up. The second phase was a cross-sectional study comparing cognitive performance of patients on clozapine with patients on other antipsychotics. In the first article, we analyzed clinical outcomes in patients on long-term clozapine use through the Brief Psychiatric Rating Scale (BPRS), clinical interview and an adverse event report protocol. Clozapine was effective in reducing symptoms in the first 6 months (mean baseline BPRS 77.9 ±16.1, mean 6 months BPRS 44.4 ±16.4), followed by a period of stability and then a continued improvement on the long-term (mean BPRS 17.3 ±11.67 at last follow-up, p < 0.05) and in reducing number of hospitalizations (mean 5.5 versus 1.4). Only one case of serious adverse event (agranulocytosis), requiring treatment interruption, was reported (1.8% of the sample). In the second article, we evaluated patients’ learning ability through Hopkins Verbal Learning Test - Revised (HVLT-R) and found a similar verbal learning performance between groups (F(54,1) = 0.499, p = 0.483). However, patients on clozapine had a younger age at diagnosis and higher symptoms scores (suggesting a more severe disorder), and started treatment long after they were diagnosed (9.40±6.79 years), what could explain their similar performance despite the use of this drug. A few limitations must be considered, such as the sample size. However, we may conclude that, for the individuals followed for almost 20 years using clozapine, this is an effective drug at reducing symptoms and number of hospitalizations. In addition, it was shown to be a safe treatment on the long-term

Clozapine use decreases the number of hospitalizations per year in patients with treatment-resistant schizophrenia.

For years, the management of schizophrenia has represented a challenge for clinicians, with antipsychotic treatments usually resulting in relapses and new hospitalizations. Clozapine has been shown to be an effective medication for treatment-resistant schizophrenia (TRS), but is currently underused due to its potential side effects. Nevertheless, research has suggested that clozapine reduces future hospitalizations in patients with TRS. This study aims to verify the rates of hospitalizations in patients with TRS under long-term use of clozapine. We retrospectively analyzed clinical data from 52 individuals with TRS before and after the use of clozapine. The mean duration of treatment with and without clozapine was 6.6 (± 3.9) and 8.5 years (± 6.6), respectively. Patients had a median of 0.5 (0.74) hospitalizations per year before the use of clozapine and 0 (0.74) hospitalizations after it (p = 0.001). Therefore, the use of clozapine resulted in an expected reduction in the number of hospitalizations per year in individuals with TRS

Clozapine use decreases the number of hospitalizations per year in patients with treatment-resistant schizophrenia

For years, the management of schizophrenia has represented a challenge for clinicians, with antipsychotic treatments usually resulting in relapses and new hospitalizations. Clozapine has been shown to be an effective medication for treatment-resistant schizophrenia (TRS), but is currently underused due to its potential side effects. Nevertheless, research has suggested that clozapine reduces future hospitalizations in patients with TRS. This study aims to verify the rates of hospitalizations in patients with TRS under long-term use of clozapine. We retrospectively analyzed clinical data from 52 individuals with TRS before and after the use of clozapine. The mean duration of treatment with and without clozapine was 6.6 (± 3.9) and 8.5 years (± 6.6), respectively. Patients had a median of 0.5 (0.74) hospitalizations per year before the use of clozapine and 0 (0.74) hospitalizations after it (p = 0.001). Therefore, the use of clozapine resulted in an expected reduction in the number of hospitalizations per year in individuals with TRS

Long-term treatment with clozapine and verbal memory performance in schizophrenia

Clozapine is more efficacious than first-generation antipsychotics for positive and negative symptoms, although it is related with serious adverse effects. Because of this profile, it could also have an impact on cognition. Therefore, we evaluated learning ability of 31 treatment-resistant individuals with SZ using clozapine uninterruptedly for 18.23 ± 4.71 years and 26 non-treatment-resistant using other antipsychotics that never used clozapine. Long-term treatment with clozapine did not improve verbal learning ability better than other antipsychotics. Although clozapine has a unique profile for reducing clinical symptoms, it may not have an additional benefit for cognition when started later on the course of schizophrenia

Avaliação dos desfechos clínicos e desempenho cognitivo em pacientes com diagnóstico de esquizofrenia refratária em uso de clozapina

A esquizofrenia é um transtorno crônico, grave e com alto impacto socioeconômico. Apesar dos avanços científicos, a esquizofrenia mantém-se como um dos transtornos mentais mais debilitantes. Cerca de 30% dos pacientes não respondem aos antipsicóticos usualmente prescritos, sendo considerados refratários ao tratamento. Para estes pacientes, a medicação de escolha é a clozapina que, embora mais efetiva, tem o seu uso como primeira opção restrito a este grupo de pacientes devido ao seu potencial de efeitos adversos graves. Mesmo com eficácia bem estabelecida, existem poucos estudos sobre o uso de clozapina a longo prazo. O objetivo do nosso estudo foi avaliar pacientes em tratamento com clozapina a longo prazo quanto a desfechos clínicos e desempenho cognitivo. Este estudo foi realizado em duas etapas. A primeira foi a avaliação de pacientes em uso de clozapina por uma média de 18.94 (±3.72) anos provenientes do Programa de Atenção à Esquizofrenia Refratária. Foram incluídos inicialmente 56 pacientes com diagnóstico de esquizofrenia refratária, idade entre 18-65 anos, sendo que 30 pacientes completaram o último seguimento. A segunda etapa consistiu na avaliação transversal destes pacientes em uso de clozapina comparados a pacientes em uso de outros antipsicóticos em relação ao desempenho cognitivo. No primeiro artigo, analisamos os desfechos clínicos dos pacientes em uso de clozapina a longo prazo através da Brief Psychiatric Rating Scale (BPRS), entrevista clínica e protocolo de efeitos adversos. Clozapina foi efetiva na redução de sintomas nos primeiros 6 meses de uso (BPRS média no baseline 77.9±16.1, BPRS média em 6 meses 44.4±16.4), seguida por um período de estabilidade e continuidade da melhora a longo prazo (BPRS 17.3±11.67 no último follow up, p < 0.05) e na redução do número de internações após o seu uso (média 5.5 versus 1.4). Apenas um efeito adverso grave (agranulocitose) com necessidade de interrupção do uso foi relatado (1.8% da amostra). No segundo artigo, analisamos a capacidade de aprendizado dos pacientes através da Hopkins Verbal Learning Test - Revised (HVLT-R) e encontramos uma curva de aprendizado semelhante entre os grupos (F (54,1) = 0.499, p=0.483). Os pacientes em uso de clozapina apresentavam idade de início da doença mais precoce e maiores escores de sintomas gerais (sugerindo quadros mais graves), além de iniciarem a clozapina tardiamente no curso do transtorno (9.40±6.79 anos após o diagnóstico), o que poderia estar associado à performance similar entre os grupos a despeito do uso da clozapina. Algumas limitações precisam ser consideradas, como o tamanho da amostra. Contudo, pode-se concluir que, pelo menos para o grupo seguido em média 20 anos após o uso da clozapina, esta é uma droga eficaz na redução de sintomas e diminuição do número de internações, além de apresentar segurança no tratamento a longo prazo.Schizophrenia is a chronic and severe disorder with a high social and economic impact. Despite scientific advances, it is still one of the most debilitating psychiatric disorders. About thirty percent of patients do not respond to antipsychotics usually prescribed, being considered treatment-resistant. For those, clozapine is the drug of choice, considered the most effective antipsychotic in this setting, although it tends to be used as a last resource due to its potential serious adverse effects. Even with its proved efficacy, there are few studies on long-term use of clozapine. The present study aimed to evaluate patients on clozapine treatment in the long-term for clinical outcomes and cognitive performance. This study was performed in two phases. The first phase comprised evaluation of patients from the Refractory Schizophrenia Attention Program on clozapine for a mean 18.94 (±3.72) years. Fifty-six patients with a diagnosis of treatment-resistant schizophrenia aged 18 to 65 years were included, with 30 patients completing last follow-up. The second phase was a cross-sectional study comparing cognitive performance of patients on clozapine with patients on other antipsychotics. In the first article, we analyzed clinical outcomes in patients on long-term clozapine use through the Brief Psychiatric Rating Scale (BPRS), clinical interview and an adverse event report protocol. Clozapine was effective in reducing symptoms in the first 6 months (mean baseline BPRS 77.9 ±16.1, mean 6 months BPRS 44.4 ±16.4), followed by a period of stability and then a continued improvement on the long-term (mean BPRS 17.3 ±11.67 at last follow-up, p < 0.05) and in reducing number of hospitalizations (mean 5.5 versus 1.4). Only one case of serious adverse event (agranulocytosis), requiring treatment interruption, was reported (1.8% of the sample). In the second article, we evaluated patients’ learning ability through Hopkins Verbal Learning Test - Revised (HVLT-R) and found a similar verbal learning performance between groups (F(54,1) = 0.499, p = 0.483). However, patients on clozapine had a younger age at diagnosis and higher symptoms scores (suggesting a more severe disorder), and started treatment long after they were diagnosed (9.40±6.79 years), what could explain their similar performance despite the use of this drug. A few limitations must be considered, such as the sample size. However, we may conclude that, for the individuals followed for almost 20 years using clozapine, this is an effective drug at reducing symptoms and number of hospitalizations. In addition, it was shown to be a safe treatment on the long-term