Clinical efficacy and safety of amisulpride in the treatment of schizophrenia / 中国基层医药

Objective:To investigate the clinical efficacy and safety of amisulpride in the treatment of schizophrenia.Methods:Ninety patients with schizophrenia admitted to Quzhou Third Hospital from August 2020 to March 2022 were included in this study. They were randomly divided into an observation group and a control group ( n = 45/group). The control group was treated with olanzapine, and the observation group was treated with amisulpride. All patients were treated for 8 consecutive weeks. Total response rate, Positive and Negative Syndrome Scale score, Clinical Global Impression Scale-Severity of Illness score, glucose and lipid metabolism indicators, Treatment Emergent Symptom Scale score, and adverse reactions were compared between the two groups. Results:Total response rate was 88.89% (40/45) in the control group and 93.33% (42/45) in the observation group. There was no significant difference in total response rate between the two groups ( χ2 = 0.14, P > 0.05). After treatment, the PANSS score [(52.14 ± 3.99) points] and CGI-S score [(3.05 ± 0.86) points] in the observation group were significantly lower than (56.38 ± 4.05) points and (4.34 ± 0.92) points in the control group ( t = 5.00, 6.87, both P < 0.001). The levels of fasting plasma glucose [(5.25 ± 0.33) mmol/L], total cholesterol [(4.08 ± 0.67) mmol/L], triglyceride [(1.29 ± 0.35) mmol/L], and low density lipoprotein-cholesterol [(2.60 ± 0.31) mmol/L] in the observation group were significantly lower compared with the control group [(6.02 ± 0.51) mmol/L, (4.71 ± 0.59) mmol/L, (1.61 ± 0.26) mmol/L, (2.91 ± 0.34) mmol/L, t = 8.50, 3.61, 4.92, 4.52, all P < 0.001]. High density lipoprotein-cholesterol level in the observation group was significantly higher than that in the control group [(1.57 ± 0.36) mmol/L vs. (1.18 ± 0.42) mmol/L t = -4.73, P < 0.001]. Treatment Emergent Symptom Scale score in the observation group was significantly lower than that in the control group [(2.39 ± 0.58) points vs. (2.87 ± 0.62) points, t = 3.79, P < 0.05]. The incidences of drowsiness [6.67% (3/45)], constipation [8.89% (4/45)], and weight gain [2.22% (1/45)] in the observation group were significantly lower than those in the control group [73.33% (33/45), 28.89% (13/45), 17.78% (8/45), χ2 = 4.14, 4.64, 4.44, P < 0.05]. Conclusion:The efficacy of sulfapride in the treatment of schizophrenia is equivalent to that of olanzapine. Sulfapride is better than olanzapine in improving symptoms and reducing disease severity and has better safety.

Efeitos citotóxicos do aripiprazol nas linhagens celulares MKN45 e NIH3T3 e efeitos genotóxicos nos linfócitos sanguíneos periféricos humanos / Cytotoxic effects of aripiprazole on mkn45 and nih3t3 cell lines and genotoxic effects on human peripheral blood lymphocytes

ABSTRACT BACKGROUND: Gastric cancer is known as the fourth most common cancer. Current treatments for cancer have damaged the sensitive tissues of the healthy body, and in many cases, cancer will be recurrent. Therefore, need for treatments that are more effective is well felt. Researchers have recently shifted their attention towards antipsychotic dopamine antagonists to treat cancer. The anticancer activities of aripiprazole remain unknown. OBJECTIVE: This study aimed to evaluate the efficacy and safety of aripiprazole on gastric cancer and normal cell lines. METHODS: In this regard, the cytotoxicity and genotoxicity of aripiprazole were investigated in MKN45 and NIH3T3 cell lines by methyl tetrazolium assay and on peripheral blood lymphocytes by micronucleus assay. For this purpose, cells were cultured in 96 wells plate. Stock solutions of aripiprazole and cisplatin were prepared. After cell incubation with different concentrations of aripiprazole (1, 10, 25, 50, 100 and 200 μL), methyl tetrazolium solution was added. For micronucleus assay fresh blood was added to RPMI culture medium 1640 supplemented, and different concentrations of aripiprazole (50, 100 and 200 μL) were added. RESULTS: The finding of present study showed that the IC50 of aripiprazole in the cancer cell line (21.36 μg/mL) was lower than that in the normal cell line (54.17 μg/mL). Moreover, the micronucleus assay showed that the frequency of micronuclei of aripiprazole at concentrations below 200 μM was much less than cisplatin. CONCLUSION: Aripiprazole can be a good cytotoxic compound and good candidate for further studies of cancer therapy.

RESUMO CONTEXTO: O câncer gástrico é conhecido como o quarto câncer mais comum. Os tratamentos atuais para o câncer danificaram os tecidos sensíveis do corpo saudável e, em muitos casos, o cancro será recorrente. Portanto, a necessidade de tratamentos que são mais eficazes é desejada. Recentemente, os pesquisadores mudaram sua atenção para os antagonistas antipsicóticos da dopamina para tratar o câncer. As atividades anticâncer de aripiprazol permanecem desconhecidas. OBJETIVO: Este estudo objetivou avaliar a eficácia e a segurança do aripiprazol no câncer gástrico e nas linhagens celulares normais. MÉTODOS: A este respeito, a citotoxicidade e a genotoxicidade do aripiprazol foram investigadas em linhas celulares MKN45 e NIH3T3 por ensaio de metil tetrazólio e em linfócitos periféricos de sangue por ensaio de micronúcleos. Para este efeito, as células foram cultivadas em 96 placas. As soluções de estoque de aripiprazol e cisplatina foram preparadas. Após incubação celular com diferentes concentrações de aripiprazol (1, 10, 25, 50, 100 e 200 μL), a solução de metil tetrazólio foi adicionada. Para o ensaio do micronúcleo o sangue fresco foi adicionado ao meio de cultura RPMI 1640 suplementado, e as concentrações diferentes de aripiprazole (50, 100 e 200 μL) foram adicionadas. RESULTADOS: O presente estudo mostrou que o IC50 de aripiprazol na linhagem celular cancerosa (21,36 μg/mL) foi menor do que na linha celular normal (54,17 μg/ mL). Além disso, o ensaio de micronúcleos demonstrou que a frequência de micronúcleos de aripiprazol em concentrações inferiores a 200 μM foi muito inferior à cisplatina. CONCLUSÃO: O aripiprazol pode ser um bom composto citotóxico e bom candidato para estudos adicionais da terapia do câncer.

Effects of bromopride on abdominal wall healing with induced peritoneal sepsis after segmental colectomy and colonic anastomosis in rats / Efeitos da bromoprida na cicatrização da parede abdominal com sepse peritoneal induzida e submetidos à ressecção segmentar e anastomose do cólon esquerdo em ratos

PURPOSE: Evaluate the effects of bromopride on abdominal wall healing of rats with induced peritoneal sepsis after segmental colectomy and colonic anastomosis. METHODS: Forty rats underwent sectioning of the left colon and end-to-end anastomosis and were divided into two groups of 20 animals for the administration of bromopride (bromopride group - B) or saline solution (control group - C). Each group was divided into subgroups of 10 animals each to be killed on the third (GB3 and GC3) or seventh postoperative day (GB7 and GC7). It was analyzed the following characteristics: breaking strength of the abdominal wall's wound; surgical and histopathological features of the abdominal wall; and clinical features of the rats. RESULTS: There was no difference between the groups in relation to the weight of the rats and the breaking strength of the abdominal wall's wound. The GB7 group presented less edema and less quantity of fibrin during histopathological evaluation compared to the GC7 group. CONCLUSION: Bromopride did not have harmful effects on the healing of abdominal wall in rats.

OBJETIVO: Avaliar o efeito da bromoprida, na cicatrização da ferida operatória da parede abdominal de ratos com sepse peritoneal experimentalmente induzida e submetidos a ressecção segmentar e anastomose de cólon esquerdo. MÉTODOS: 40 ratos distribuídos em dois grupos contendo 20 animais, para administração de bromoprida (grupo bromoprida- B) ou solução de NaCl 0,9 por cento (grupo controle - C). Cada grupo foi dividido em subgrupos contendo 10 animais, para eutanásia no terceiro (GB3 e GC3) ou sétimo dia (GB7 e GE7) de pós-operatório. Os ratos foram submetidos à secção do cólon esquerdo e anastomose término-terminal. No dia da eutanásia foram avaliadas as características cirúrgicas da cavidade abdominal e clínicas dos ratos. Foram coletados segmentos da parede para a avaliação histopatológica e de resistência tênsil da ferida operatória. RESULTADOS: Não houve diferenças entre os pesos dos ratos e resistência tênsil da ferida operatória nos dois grupos. Em relação a análise histopatológica, o grupo GB7 apresentou menos edema e menos fibrina que o grupo GC7. Não houve outras diferenças. CONCLUSÃO: A utilização de bromoprida não resultou em distúrbios ou retardo da cicatrização no grupo de ratos submetidos à laparotomia e anastomose término-terminal em condições de sepse peritoneal.

Efficacy and safety of atypical antipsychotic drugs (quetiapine, risperidone, aripiprazole and paliperidone) compared with placebo or typical antipsychotic drugs for treating refractory schizophrenia: overview of systematic reviews / Eficácia e segurança dos antipsicóticos atípicos (quetiapina, risperidona, aripiprazol, paliperidona) em comparação com um placebo ou medicamentos antipsicóticos típicos no tratamento da esquizofrenia refratária: overview de revisão sistemática

CONTEXT AND OBJECTIVE: According to some cohort studies, the prevalence of refractory schizophrenia (RS) is 20-40 percent. Our aim was to evaluate the effectiveness and safety of aripiprazole, paliperidone, quetiapine and risperidone for treating RS. METHODS: This was a critical appraisal of Cochrane reviews published in the Cochrane Library, supplemented with reference to more recent randomized controlled trials (RCTs) on RS. The following databases were searched: Medical Literature Analysis and Retrieval System Online (Medline) (1966-2009), Controlled Trials of the Cochrane Collaboration (2009, Issue 2), Embase (Excerpta Medica) (1980-2009), Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs) (1982-2009). There was no language restriction. Randomized controlled trials, systematic reviews and meta-analyses evaluating atypical antipsychotics for treating RS were included. RESULTS: Seven Cochrane systematic reviews and 10 additional RCTs were included in this review. The data generally showed minor differences between the atypical antipsychotics evaluated and typical antipsychotics, regarding improvement in disease symptoms, despite better adherence to treatment with atypical antipsychotics. Risperidone was specifically evaluated in patients with RS in one of the systematic reviews included, with favorable outcomes, but without definitive superiority compared with other drugs of proven efficacy, like amisulpride, clozapine and olanzapine. CONCLUSIONS: The findings underscore the difficulty in treating these patients, with high dropout rates and treatment patterns of modest improvement in assessments of effectiveness. Atypical antipsychotics have advantages over typical antipsychotics mainly through their better safety profile, which leads to better adherence to treatment. A combination of antipsychotics may also be an option for some refractory patients.

CONTEXTO E OBJETIVO: De acordo com alguns estudos de coorte, a prevalência da esquizofrenia refratária (ER) está entre 20-40 por cento. Nosso objetivo foi avaliar a efetividade e segurança de aripiprazol, paliperidona, quetiapina e risperidona no tratamento da esquizofrenia refratária. MÉTODOS: Avaliação crítica das revisões Cochrane publicadas na Biblioteca Cochrane e complementação com referências de ensaios clínicos randomizados (ECRs) mais atualizados sobre ER. As seguintes bases de dados foram pesquisadas: Medline (Medical Literature Analysis and Retrieval System Online) (1966-2009), Ensaios Controlados da Colaboração Cochrane (2009, edição 2), Embase (Excerpta Database) (1980-2009), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) (1982-2009). Não houve restrição a idiomas. Ensaios clínicos randomizados, revisões sistemáticas e metanálises que avaliaram antipsicóticos atípicos no tratamento da esquizofrenia refratária foram incluídos. RESULTADOS: Sete revisões sistemáticas Cochrane e 10 ECRs complementares foram incluídos nessa revisão. No geral os dados demonstram pequenas diferenças entre os antipsicóticos atípicos avaliados e os típicos na melhora dos sintomas da doença, apesar da melhor adesão ao tratamento com os atípicos. A risperidona foi avaliada especificamente em pacientes com esquizofrenia refratária em uma das revisões sistemáticas incluídas, a qual demonstrou desfechos favoráveis, porém não definitivos quando comparada a drogas também com eficácia comprovada como amisulprida, clozapina e olanzapina. CONCLUSÕES: Os dados reforçam a dificuldade de tratar esses pacientes, com elevadas taxas de desistência do tratamento e padrões de melhora modestos nas avaliações de eficácia. Os antipsicóticos atípicos têm vantagens sobre os típicos principalmente pelo melhor perfil de segurança, o que leva a melhor adesão ao tratamento. A associação de antipsicóticos também pode ser uma opção em alguns pacientes refratários ao tratamento.

Distonia aguda relacionada ao uso de bromoprida em pacientes pediátricos / Acute dystonia after use of bromopride in pediatric patients

OBJETIVO: Descrever dois casos de distonia aguda após uso de bromoprida em crianças e realizar revisão da literatura em relação aos mecanismos fisiopatológicos de indução de liberação extrapiramidal, sua sintomatologia e tratamento. DESCRIÇÃO DO CASO: Caso 1: adolescente de 13 anos com quadro de dor e hipertonia cervical associados a febre, náuseas e vômitos, com hipótese inicial de meningite. A investigação subsequente revelou que o quadro iniciou-se após ingestão de uma única dose de bromoprida. O paciente apresentou boa resposta ao tratamento com difenidramina, sem necessidade de coleta de líquor. Caso 2: Lactente de seis meses que desenvolveu sintomas graves de liberação extrapiramidal relacionados à superdosagem de bromoprida, com reversão rápida dos sintomas após administração de biperideno. COMETÁRIOS: Este é o primeiro relato de distonia aguda após uso de bromoprida em crianças. Embora muito utilizada no Brasil como agente pró-cinético e antiemético, nenhum estudo clínico até o momento demonstrou melhor perfil de segurança da bromoprida em relação aos demais antieméticos antagonistas da dopamina. Até que tais estudos sejam realizados, sugere-se cautela na prescrição de bromoprida. Medidas não-farmacológicas devem ser recomendadas no tratamento de vômitos e da doença do refluxo gastresofágico. Quando o tratamento farmacológico for indispensável, deve-se dar preferência a drogas com perfil de segurança mais bem estabelecido.

OBJECTIVE: To report the case of two patients with acute dystonia induced by bromopride in children, followed by a review of the mechanisms of induction of movement disorders by antidopaminergic anti-emetic drugs, its clinical symptoms and treatment. CASE DESCRIPTION: Case 1: a 13 years old teenager who developed acute hypertonia and neck pain associated to fever and vomiting, suggestive of meningitis. Further investigation revealed that symptoms were associated with the ingestion of a single dose of bromopride. The symptoms stopped after administration of diphenidramine, preventing a spinal tap. Case 2: six months old infant who developed extrapyramidal movement disorder related to bromopride overdose, with prompt resolution of symptoms after treatment with biperiden. COMMENTS: This seems to be the first report of acute dystonia after the use of bromopride in children. Although frequently used in Brazil as an anti-emetic and prokynetic agent, no clinical study has showed that bromopride has a better safety profile than other antidopaminergic anti-emetic drugs. While such studies are not available, caution is needed in the context of pediatric prescription of bromopride. Non pharmacological measures should be adopted in the management of vomiting and gastroesophageal reflux. If medical treatment cannot be avoided, one would rather use medications with a better established safety profile.

Polymorphisms and Serotonin Dopamine Antagonist-Induced Weight Gain in Patients with Schizophrenia / 대한정신약물학회지

OBJECTIVE: Several lines of pharmacological evidences including the data of animal studies indicate that serotonin 2C receptor (5HT2C) is involved in the pharmacodynamic process of serotonin dopamine antagonists (SDA)-induced weight gain. Controversial data have been reported on the association between the polymorphisms of 5HT2C receptor gene and antipsychotics-induced weight gain. This study aims at investigating the association between the polymorphisms of 5HT2C receptor gene and SDA-induced weight gain in korean schizophrenic patients. METHODS: Seventy-seven schizophrenia patients in their first episode or patients who did not take any antipsychotics for the previous two months were recruited. All the patients were administered with one of the SDAs (risperidone, olanzapine, quetiapine, clozapine) for 8weeks. Body mass index (BMI) were measured weekly during the 8weeks. The subjects were genotyped for the -759 C/T and -697 G/C polymorphism of the 5HT2C receptor gene. RESULTS: The degree of linkage disequilibrium between the two polymorphic loci genotyped are almost 100%. Significant association was not observed between polymorphisms of the 5HT2C receptor gene (-759 C/T and -697 G/C) and SDA-induced weight gain after 8 weeks of treatment. CONCLUSION: Our data do not support the involvement of the polymorphisms of 5HT2C receptor gene (-759 C/T and -697 G/C) in SDA- induced weight gain. Further studies with sufficient sample size are warranted to follow up on the trend of high weight gain in the male patients having -759 T (-697 C) allele.

Spasmodic torticollis: medical and botulinum A toxin treatment

The exact pathophysiologic mechanisms of spasmodic torticollis and other idiopathic torsion dystonias remain largely unknown. Thus, a variety of drugs have been used alone or in combination on an empirical basis to treat these disorders, but to date none have efficacy that is proven and consistent. The drugs in use include anticholinergics, benzodiazepines, dopaminergics and dopamine antagonists with variable degrees of clinical improvement. Botulinum toxin A injection treatment for spasmodic torticollis is safe and efficacious with minimal adverse effect. However, it is expensive and beneficial effects are short-lasting. Only when a spasmodic torticollis patient's symptoms are refractory to combined treatment, using various drugs and Botulinum toxin injections, should the patient be considered a candidate for neurosurgical procedures.