Pharmacokinetic drug interaction potential of risperidone with cytochrome p450 isozymes as assessed by the dextromethorphan, the caffeine, and the mephenytoin test.

Two published case reports showed that addition of risperidone (1 and 2 mg/d) to a clozapine treatment resulted in a strong increase of clozapine plasma levels. As clozapine is metabolized by cytochrome P450 isozymes, a study was initiated to assess the in vivo interaction potential of risperidone on various cytochrome P450 isozymes. Eight patients were phenotyped with dextromethorphan (CYP2D6), mephenytoin (CYP2C19), and caffeine (CYP1A2) before and after the introduction of risperidone. Before risperidone, all eight patients were phenotyped as being extensive metabolizers of CYP2D6 and CYP2C19. Risperidone at dosages between 2 and 6 mg/d does not appear to significantly inhibit CYP1A2 and CYP2C19 in vivo (median plasma paraxanthine/caffeine ratios before and after risperidone: 0.65, 0.69; p = 0.89; median urinary (S)/(R) mephenytoin ratios before and after risperidone:0.11, 0.12; p = 0.75). Although dextromethorphan metabolic ratio is significantly increased by risperidone (median urinary dextromethorphan/dextrorphan ratios before and after risperidone: 0.010, 0.018; p = 0.042), risperidone can be considered a weak in vivo CYP2D6 inhibitor, as this increase is modest and none of the eight patients was changed from an extensive to a poor metabolizer. The reported increase of clozapine concentrations by risperidone can therefore not be explained by an inhibition of CYP1A2, CYP2D6, CYP2C19 or by any combination of the three

Fatores associados ao abandono de tratamento em saúde mental em uma unidade de nível secundário do Sistema Municipal de Saúde Factors associated to treatment dropout in mental health

A ocorrência de abandono de tratamento psiquiátrico de nível secundário é uma relevante questão clínica e econômica. Taxas de abandono em psiquiatria são mais altas que em outras especialidades médicas. Estudos publicados nos últimos 15 anos têm identificado diversos fatores estatisticamente associados ao não-comparecimento às consultas e/ou ao abandono de tratamento em saúde mental. OBJETIVO: Avaliar variáveis demográficas, psicopatológicas, de diagnóstico e tratamento enquanto possíveis preditores de abandono de tratamento em serviço especializado de saúde mental. MÉTODO: Estudo observacional, avaliando 896 pacientes encaminhados, no período de abril de 2004 a março de 2006, por Unidades Básicas de Saúde da área de abrangência do serviço especializado. RESULTADOS: Pacientes solteiros, com idade abaixo da média do grupo (39,2 anos) e desempregados abandonaram significantemente mais o tratamento. Duas variáveis relativas ao exame psicopatológico se associaram significantemente com abandono de tratamento (memória quanto ao passado recente e relação do humor com fatos reais, atuais). Pacientes adultos que receberam diagnóstico psiquiátrico de oligofrenia abandonaram significantemente menos e pacientes com diagnóstico relativo aos transtornos da infância e adolescência (F80-F98 da CID-10) também abandonaram significantemente mais o tratamento. O registro de comorbidade psiquiátrica e tratamento exclusivamente farmacológico se associaram a não abandono do tratamento. CONCLUSÃO: Os resultados confirmam achados de diferentes autores da evidência de características associadas a abandono ao tratamento. Tais achados sugerem que determinados subgrupos de pacientes necessitem de abordagens customizadas, a fim de influenciar positivamente sua adesão final ao tratamento indicado.<br>Psychiatric out-treatment drop-out is a relevant clinical and economical issue. Drop-out rates in psychiatry are higher than in any other medical specialties. Articles published in the last 15 years have identified several factors statistically associated to no-compliance and treatment dropping-out. OBJETIVE: The objective of this paper is to evaluate demographical, psychopathological, diagnose and treatment variables as possible predictors of attrition from a mental health out-service. METHOD: Natural experiment, evaluating 896 patients referred by primary care units from April 2004 till March 2006. RESULTS: Single patients, unemployed people, and those whose age was below group-average (39.2 years) dropped-out significantly more than others. Two variables related to psychopathological examination were associated to treatment drop-out (recent memory and relation of affective disposition to current circumstances). Adult patients that received a diagnosis of Mental Retardation and those with a diagnosis related to groups F80-F98 (CID-10) also dropped-out significantly more. The identification of a psychiatric comorbidity and exclusively pharmacological treatment were associated to adherence. CONCLUSION: Results support the findings of different researchers as to the evidence of characteristics associated to treatment dropping-out. These findings suggest that certain group of patients need a more customized care, in order to positively influence their final adherence to their treatment