Metabolic dysregulation in early onset psychiatric disorder before and after exposure to antipsychotic drugs

Antipsychotic Drugs (APDs) are being widely prescribed to treat various disorders, including schizophrenia and bipolar disorder; however, abnormal glucose metabolism and weight gain have been reported with Atypical Anti-Psychotic drugs (AAPDs) that can lead to insulin-resistance and type 2 diabetes mellitus. The study was designed to assess various biochemical parameters including insulin and blood sugar before and after exposure to APDs in order to exclude the involvement of psychiatric disorders and certain other factors in metabolic dysregulations. Fifty seven APDs-naïve patients with first episode psychosis were divided into six groups who received olanzapine, quetiapine, risperidone, aripiprazole, haloperidol or combination of olanzapine with escitalopram and haloperidol. The serum samples were taken before the intake of the first dose and then on follow-up. Decrease in the level of elevated insulin and glucose was observed post-treatment in some patients, while others were observed whose insulin and glucose levels increased post-treatment, yet some patients did not show any disturbance in the insulin and glucose levels. It is concluded that psychiatric disorders by itself, narcotics, cigarette smoking and use of oral snuff may be also be implicated in metabolic dysregulations. The effects of APDs on insulin and glucose in healthy volunteers might be different than in patients with psychiatric disorders.

Short-term oral administration of risperidone induces pancreatic damage and hyperamylasemia in Sprague-dawley rats

Risperidone is an atypical antipsychotic acting mainly as a dopamine D2 and serotonin 5-HT2 receptors antagonist prescribed in the treatment of schizophrenia and various affective disorders. Risperidone has been reported to be associated with weight gain, panreatitis and type 2 diabetes mellitus. Various mechanisms of risperidone-induced toxicities have been reported but the histology of tissues especially pancreas has never been studied. Therefore, the current study was designed to elucidate the toxic effects of chronic administration of risperidone on pancreas, liver and kidneys. Animals (rats) of either gender were divided into two groups, the risperidone and control groups. Risperidone was administered in a dose of 2.5 mg/kg/d for three weeks. The controls received acidified saline only. Both the groups received restricted diet (20 g/12 h). The body weight and level of random blood sugar (RBS) were measured on a weekly basis. The levels of lipase and amylase were determined at the conclusion of the experiment. At the end of the experiment, the tissues were dissected out for histopathological evaluation. Risperidone showed no weight gain, hyperglycemia or rise in the level of lipase (P> 0.05); however, the level of amylase was raised (***P<0.05). Histological examination under light microscope showed no hepatotoxicity, nephrotoxicity but did show damage to the pancreas. The findings of this study indicated that the incidence of adverse effects associated with risperidone could be prevented/alleviated/delayed by allowing restricted diet.

Actualización en enfermedad con cuerpos de Lewy / Update in Lewy body disease

La enfermedad con cuerpos de Lewy incluye 2 entidades que podrían ser consideradas variantes clínicas de una misma patología: la demencia con cuerpos de Lewy y la demencia en enfermedad de Parkinson. Con la finalidad de describir correctamente lo que sucede en la evolución de la enfermedad se divide el cuadro en etapa prodrómica y de demencia propiamente dicha. La primera está clínicamente representada por aquel período en el cual, si bien el paciente exhibe algunos signos y síntomas propios de la enfermedad, no reúne criterios de demencia. A pesar de ser difícil de definir y por carecerse todavía de contundentes datos clínicos y biomarcadores, se caracteriza principalmente por deterioro leve selectivo en función atencional ­ visuoespacial, trastorno del sueño REM y disautonomía‒. La segunda etapa está claramente caracterizada en los criterios de consenso del año 2005. Recientemente hemos publicado la validación de un instrumento llamado ALBA Screening Instrument, que permite diagnosticar con alta sensibilidad y especificidad la enfermedad aun en etapas tempranas y diferenciarla de otras patologías semejantes. La tomografía por emisión de positrones (PET) para transportador de dopamina es el procedimiento de referencia (gold standard) del diagnóstico. El tratamiento sintomático con anticolinesterásicos y neurolépticos atípicos favorece una buena evolución de la enfermedad y es fundamental tener en cuenta evitar medicamentos que pueden dañar gravemente a los pacientes como los anticolinérgicos y antipsicóticos típicos. Los avances en el diagnóstico y la difusión del impacto de esta enfermedad en la población contribuirán a generar mayores esfuerzos de investigación para hallar un tratamiento eficaz, preventivo o curativo o de ambas características. (AU)

Lewy body disease includes 2 entities that could be considered clinical variants of the same pathology: Dementia with Lewy bodies and Parkinson's disease Dementia. Two stages of the disease are described in this review, a prodromal stage and one of explicit dementia. The first one is clinically represented by that period in which, the patient exhibits some typical features of the disease, but not dementia criteria. Despite being difficult to define the prodromal stage and that strong clinical data and biomarkers are still lacking, there is evidence to characterize it mainly by mild selective impairment in attention and visuo-spatial function, REM sleep disorder and dysautonomia. The second stage is clearly characterized in the known consensus criteria of 2005. We have recently published the validation of an instrument called ALBA Screening Instrument which showed a high sensitivity and specificity for diagnosis of the disease even in the early stages. It´s useful to differentiate the disease from other similar pathologies. Positron Emission Tomography for dopamine transporter is the gold standard of diagnosis in life. Symptomatic treatment with anticholinesterases and atypical neuroleptics help patients in their evolution of the disease. Anticholinergics and typical antipsychotics are agents to avoid in the treatmen of the disease because can severely damage patients. Future advances in the diagnosis and dissemination of the knowledge of the disease will contribute to generate greater research efforts to find an effective preventive and / or curative treatment. (AU)

Meta-analysis on the efficacy and tolerability of the augmentation of antidepressants with atypical antipsychotics in patients with major depressive disorder

We assessed the efficacy and tolerability of the augmentation of antidepressants (ATDs) with atypical antipsychotics (AAPs) to treat patients with major depressive disorder. A retrograde study to identify relevant patient data included databases of PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Database of Abstracts of Reviews of Effects. Data from 17 trials, involving 3807 participants, were identified. The remission rate (RR) and overall response rate (ORR) of adjunctive treatment with AAPs were significantly higher than placebo treatment: RR=1.90 (95%CI=1.61-2.23, z=7.74, P<0.00001) and ORR=1.68 (95%CI=1.45-1.94, z=7.07, P<0.00001). We found that the short-term (4 weeks) treatment [ORR=1.70 (95%CI=0.98-2.95, Z=1.89, P=0.06)] was significantly different from the long-term (6-12 weeks) treatment [ORR=1.68 (95%CI=1.45-1.94, z=7.07, P<0.00001)]. No significant difference in ORR was observed between groups with or without sedative drugs. The discontinuation rate due to adverse effects was higher for adjunctive treatment with AAPs: ORR=3.32 (95%CI=2.35-4.70, z=6.78, P<0.00001). These results demonstrate that the augmentation of ATDs with AAPs (olanzapine, quetiapine, aripiprazole, and risperidone) was more effective than a placebo in improving response and remission rates, although associated with a higher discontinuation rate due to adverse effects.

Palmitato de paliperidona para o tratamento de esquizofrenia / Paliperidone palmitate for the treatment of schizophrenia

Esquizofrenia é uma síndrome caracterizada por uma variedade de problemas comportamentais, emocionais e cognitivos. Os sintomas da esquizofrenia são classificados em positivos e negativos. Os sintomas positivos são relacionados a distorções das funções sensoriais, incluindo alucinações (geralmente auditivas), ilusões, fala desorganizada ou desordem do pensamento e comportamento desorganizado, bizarro ou catatônico. Os sintomas negativos são relacionados à inibição das funções afetivas e psicomotoras e incluem: apatia emocional, isolamento social, comportamento anormalmente desinteressado, falta de motivação e perda do prazer. O controle da esquizofrenia envolve vários cuidados com o objetivo de suprir todas as necessidades clínicas, emocionais e sociais do indivíduo. O tratamento farmacológico da esquizofrenia é realizado com drogas antipsicóticas. Os antipsicóticos convencionais, ou típicos, atualmente disponíveis no SUS são o haloperidol (oral e injetável de longa ação), clorpromazina e tioridazina. A melhora clínica é definida como uma diminuição de pelo menos 30% nos escores da escala BPRS-A. Entretanto, todos os medicamentos antipsicóticos são associados a eventos adversos que variam de acordo com o indivíduo e com o tipo de medicamento. Esses eventos incluem sintomas extrapiramidais (como parkinsonismo, distonia aguda, acatisia e discinesia tardia), efeitos autônomos (como visão borrada, aumento da pressão intra-ocular, olhos e boca secos, constipação e retenção urinária), aumento dos níveis de prolactina, convulsões, sedação, disfunção sexual e ganho de peso. Diante das limitações aos antipsicóticos convencionais, ou típicos, foram desenvolvidos os novos antipsicóticos ou antipsicóticos atípicos, que focam em produzir alívio de ambos os sintomas positivos e negativos através de efeitos simultâneos nos níveis de dopamina e serotonina no Sistema Nervoso Central. Estes medicamentos apresentam menor probabilidade do que os típicos em induzir sintomas extrapiramidais agudos. De acordo com o Protocolo Clínico e Diretrizes Terapêuticas do Ministério da Saúde para o tratamento da Esquizofrenia Refratária atualmente vigentes antipsicóticos atípicos são a segunda linha de tratamento, sendo indicados quando os medicamentos de primeira linha (antipsicóticos típicos), não fazem mais efeito ou são intolerados. Dentre os antipsicóticos atípicos disponíveis no SUS estão clozapina em comprimidos de 25 e 100 mg; olanzapina em comprimidos de 5 e 10 mg; quetiapina em comprimidos de 25, 100 e 200 mg; risperidona em comprimidos de 1 e 2 mg; e ziprasidona em cápsulas de 40 e 80 mg. No entanto, este protocolo está sendo atualizado. Nele, todos os antipsicóticos foram considerados semelhantes em termos de eficácia, por isso, não há ordem de preferência para a escolha do antipsicótico a ser utilizado (haloperidol, clorpromazina, risperidona, quetiapina, ziprasidona ou olanzapina), com exceção à clozapina, que deve ser utilizada após refratariedade a pelo menos 2 medicamentos. O uso do decanoato de haloperidol (injetável de deposição) é indicado em pacientes com impossibilidade de adequada adesão ao uso oral de qualquer um dos medicamentos acima. O palmitato de paliperidona, metabólito ativo da risperidona, é um novo antipsicótico atípico injetável de liberação prolongada, como tratamento da esquizofrenia e prevenção da recorrência dos sintomas da esquizofrenia. A evidência disponível até o momento mostra benefício do palmitato de paliperidona (PP) em comparação ao placebo quando aplicado ao tratamento da esquizofrenia. Os resultados de eficácia foram avaliados por meio de redução na escala PANSS. Foi encontrado um único estudo que avaliou a taxa de recaída, e que também mostrou benefício do PP em relação ao placebo. Os estudos de não-inferioridade demonstram que o PP é não inferior à risperidona injetável de longa ação, em relação à descontinuação do tratamento, melhora clínica (redução do PANSS) e taxas de recaída. O que não traz novidades uma vez que o PP é o principal metabólito ativo da risperidona. Estes estudos, no entanto, tiveram algumas limitações importantes, tais como a comparação com placebo, a curta duração e as perdas significativas de seguimento. Os eventos adversos observados nos estudos mostram que o uso do PP é seguro, no entanto, em se tratando de medicamento novo e de uso crônico, os estudos foram demasiadamente curtos para fazer tal afirmativa. Embora nos estudos econômicos elaborados pelo demandante o palmitato de paliperidona tenha se mostrado custo-efetivo, deve-se ressaltar que os dados de efetividade utilizados no modelo foram obtidos de estudos da risperidona injetável de longa ação e não da paliperidona. Como a proposta da paliperidona injetavel é oferecer alternativa de tratamento antipsicotico para pacientes com baixa adesão ao tratamento oral, o decanoato de haloperidol, já disponível no elenco do SUS para esta condição clínica, deveria ter sido o comparador escolhido para a análise. Considerou-se que o arsenal medicamentoso atualmente disponibilizado no SUS é suficiente para atender às necessidades dos portadores da doença, devendo os esforços do sistema se concentrar na oferta de práticas que garantam o atendimento integral em saúde mental, promovam o melhor conhecimento e aceitação da doença entre pacientes e familiares e favoreçam a adesão aos tratamentos e a maximização dos resultados. Diante do exposto, os membros da CONITEC, presentes na 10ª Reunião Ordinária do plenário, realizada no dia 08/11/2012, recomendaram a não incorporação do medicamento palmitato de paliperidona para o tratamento da esquizofrenia. Os membros da CONITEC presentes na 3ª reunião extraordinária do plenário do dia 20/12/2012, por unanimidade, ratificaram a deliberação de não recomendar a incorporação do medicamento Palmitato de Paliperidona para o tratamento da Esquizofrenia. O Conselho Nacional de Saúde se absteve de votar conforme posição acordada pelo Plenário do CNS. A Portaria SCTIE-MS N.º 15, de 2 de abril de 2013 - Torna pública a decisão de não incorporar o medicamento palmitato de paliperidona para o tratamento de esquizofrenia no Sistema Único de Saúde (SUS).

Priapismo secundario a antipsicóticos: a propósito de un caso asociado a risperidona / Priapism associated with risperidone use: Report of one case

Background: The use of drugs with α-adrenergic antagonistic effect is one of the most prominent etiologies of priapism. We report a 32-year-old schizophrenic male in treatment with risperidone who consulted in the emergency room for a painful priapism. A low flow priapism was diagnosed. Medical treatment was unsuccessful and the patient was subjected to a proximal corporo-spongiosal shunt (Quackels technique), with good results. The patient was discharged in good conditions.

Antipsychotic treatment and weight gain: does risperidone behave differently in Pakistani psychiatric patients?

Studies from the Western world have shown that antipsychotic medications in psychiatric patients result in weight gain and other metabolic diseases. This study was undertaken to investigate whether any one of the five most commonly prescribed antipsychotics, [risperidone, olanzepine, trifluoperazine, quetiapine and haloperidol] could behave differently in terms of causing weight gain among patients attending the psychiatric outpatient clinics in a tertiary care hospital in Karachi, Pakistan. For this retrospective cohort study, data were collected from outpatient records of the Aga Khan University Hospital, from 2003 to 2007. Demographic and clinical data were analysed. Repeated measures ANOVA, using a linear mixed model approach was used to assess weight gain over time due to the use of antipsychotic medications. A total of 124 subject records [68 males and 56 females] were evaluated. One-way ANOVA revealed that the groups being prescribed with antipsychotics were comparable with respect to age, duration of treatment and weight measurements. Frequencies were calculated which showed that weight increases significantly over time with respect to the prescribed antipsychotic medications, except for risperidone. Repeated measures ANOVA using the linear mixed model approach showed that the serial weight measurements were significantly different across the follow up times [p<0.05]. Four of the commonly prescribed antipsychotic drugs do result in an increase in weight; however risperidone has no such effect, making it an option in treating psychiatric disorders without worrying for any gain in weight. In view of the increased prevalence of obesity and other metabolic diseases, measures should be taken towards careful prescription of antipsychotic medications

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.

Retrospective comparison of weight gain between olanzapine- and risperidone- treated patients

Weight gain as a side effect of the second generation antipsychotics have been increasingly noted during therapy; however no studies addressed such a valid clinical concern in Iraq till now. The objective of this study was to determine the weight changes among patients treated with either Olanzapine or Risperidone. A retrospective study was performed by reviewing the charts of 80 patients who have been treated with Olanzapine monotherapy [60 patients] or Risperidone monotherapy [20 patients] through the period of April 2008 to April 2009, comparing the baseline weight in kilograms with after one month of therapy weight. Among the 60 patients treated with Olanzapine, 42 [70%] gained weight, 70.37% of males and 69.69% of females treated with Olanzapine gained weight. Among the 20 patients treated with Risperidone, 12 [60%] gained weight, 50% of males and 75% of females treated with Risperidone gained weight. Those treated with Olanzapine, gained 3.96 kg after 30 days of treatment, while the amount of gain was 2.25 kg among those treated with Risperidone after the same period. Olanzapine treated group gained about 6.21% of their baseline weight which was significantly higher than that of Risperidone-treated group who gained about 2.89% of their baseline weight [P value of 0.03]. Females gained more amount of weight than males in both group. Both second generation antipsychotics, Olanzapine and Risperidone, are associated with weight gain. However, Olanzapine appears to have a greater potential in inducing weight gain. Both genders affected nearly equally, though females were victims of more amount of weight gain

Toxicological profile of typical and atypical anti-psychotic drugs in psychotic disorders

To evaluate the safety of antipsychotic drugs in psychotic patients. Randomized, comparative and categorical study. This study was conducted in the Department of Pharmacology, Faculty of Pharmacy, University of Karachi collaboration with Sir Cows Jee Jehangir Institute of Psychiatry Hyderabad and duration of study 1[st] Nov. 2007 to 3[rd] Jan. 2008. Patients were selected from OPD, Male and Female wards of Sir Cows Jee Jehangir Institute of Psychiatry Hyderabad. Total two hundreds patients were enrolled in the study out of them 192 patients continue through out study and eight lost follow up the study. The side effects were noticed according to UKU side effect scale. Same criteria was followed for both drugs in the study, assessments was done on the 07, 14, 28 and 42 days. Adverse effect of two drugs presented rigidity and tremors were the most common adverse effect in halopenridol 14.6% and 12.5% and in Risperidone 4.2% and 4.2% respectively. Overall Risperidone in our study proved efficacious and economical drug in psychotic patients. On the other hand haloperidol was also effective and cost effective but produced more side effects. Overall Risperidone in our study proved less toxic and cost effective drug in psychotic patients, on other hand halopendol was also effective and economical drug but should be more side effects

Comparación del efecto de la terapia prolongada con antipsicóticos atípicos o convencionales en la incidencia de diabetes mellitus 2: Revisión sistemática y metaanálisis / Risk of type 2 diabetes mellitus among users of atypical antipsychotic drugs or conventional treatment: Systematic review

Atypical antipsychotic drugs have less extra pyramidal side effects and are more effective to control the clinical manifestations of schizophrenia. However, their use may be associated to a higher incidence of weight gain, dyslipidemia, metabolic syndrome, glucose intolerance and type 2 diabetes mellitus. We performed a systematic literature search to evaluate the risk of type 2 diabetes mellitus incidence associated to the use of atypical antipsychotic drugs, compared to conventional treatment. If users of all types of atypical antipsychotic drugs are compared with users of conventional treatment, no significant differences in the incidence of type 2 diabetes mellitus were observed. If individual drugs are evaluated, clozapine and risperidone are associated with a higher risk of diabetes than haloperidol. Quetiapine is associated with a lower risk of diabetes than conventional treatment. The quality of the evidence found was low; therefore, new studies should been performed.

O uso de antipsicóticos em pacientes com diagnóstico de demência / The use of antipsychotics in patients with dementia

OBJETIVO: Revisar sistematicamente as evidências que sustentam o uso de antipsicóticos no tratamento dos sintomas comportamentais e psicológicos em pacientes com demência, assim como rever as controvérsias e desvantagens dessa prescrição, tendo em vista, por um lado, a elevada prevalência destas manifestações no curso clínico das demências e, por outro, a maior susceptibilidade do idoso aos eventos adversos desses medicamentos. MÉTODO: Revisão sistemática da literatura sobre o uso de antipsicóticos típicos e atípicos em pacientes portadores de síndromes demenciais. As bases de dados usadas para este fim foram o PubMed/Medline, Embase e SciELO. A busca por trabalhos se limitou aos anos de 1986 a 2007, selecionando-se ensaios clínicos randomizados e metanálises da literatura. RESULTADOS: Há evidências a partir de ensaios randomizados, duplamente encobertos, controlados por placebo, de que os antipsicóticos típicos e atípicos são eficazes no tratamento dos sintomas comportamentais que ocorrem nas síndromes demenciais, especialmente os quadros psicóticos e alterações do comportamento motor. Entretanto, o uso destas medicações está associado a eventos adversos importantes. Embora os antipsicóticos atípicos estejam menos associados aos efeitos colaterais extrapiramidais, comuns entre os neurolépticos de primeira geração, podem aumentar a incidência de eventos cerebrovasculares e do risco de morte, sobretudo em pacientes vulneráveis. CONCLUSÃO: Os antipsicóticos devem ser usados com cautela nos pacientes com demência, buscando otimizar o regime de dosagem e duração do tratamento, e avaliando-se individualmente a relação risco-benefício.

OBJECTIVE: The objective of the present study is to systematically review the supporting evidence for the use of antipsychotics in the treatment of behavioral and psychological symptoms in patients with dementia, as well as the controversies and limitations of this prescription. We discuss the available evidence in the light of the high prevalence of behavioral and psychological symptoms of dementia in this population, along with the greater susceptibility of elderly patients to adverse events. METHOD: Systematic literature review of the use of typical and atypical antipsychotics in patients with dementia was carried out in the databases PubMed/Medline, Embase and SciELO. The search was limited to clinical trials and meta-analysis of the literature published from 1986 to 2007. RESULTS: Evidence drawn from randomized, double-blind, placebo controlled trials support the use of both typical and atypical antipsychotics in the treatment of behavioral symptoms of dementia, especially psychotic symptoms and abnormal psychomotor activity. Nevertheless, the use of these drugs in demented patients is not devoid of important adverse events. Although the induction of extrapiramidal symptoms is not as frequent or severe with atypical antipsychotics as it is with first-generation neuroleptics, the former drugs may particularly increase the risk of cerebrovascular events and death. CONCLUSION: Although effective, antipsychotic drugs must be prescribed cautiously in patients with dementia. Dose regimens, duration of treatment and a cautious assessment of risk-benefit must be established for each patient.

Hiperprolactinemia y disfunción sexual en el primer episodio psicótico tratado con risperidona / Hiperprolactinaemia and sexual disfunction in first psychotic episode treated with risperidone

Hyperprolactinemia and Sexual dysfunction are frequent, yet seldom studied, complications of the use of risperidone Objectives: To determine the prevalence and clinical correlates of sexual dysfunctions and hyperprolactinemia in a sample of young people with schizophrenia treated with risperidone. Methods: 40 outpatients (19 females; mean age: 27 years) with schizophrenia treated with risperidone, participated in the study Sexual dysfunction and quality of life were assessed with the Massachusetts General Hospital Sexual Functioning Questionnaire (MGH-SFQ) and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), respectively All patients were evaluated with the Positive and Negative Syndrome Scale and the UKU side effect rating scale. Blood samples were analyzed for prolactine. Results: Hyperprolactinemia was found in 90 percent of patients, with levels significantly higher in women. Sexual dysfunctions occurred in 25 (62.5 percent) patients. Patients with and without sexual dysfunction, did not significantly differ in gender, age or years of treatment. Although no association was found with prolactinemia or the dose of risperidone, patients with sexual dysfunction reported more psychic and neurologic side effects, and had higher scores in the negative symptoms and general psychopatology subscales of the PANSS and lower scores in the physical health and mood items of the Q-LES-Q. Conclusions: Results confirm the high prevalence of hyperprolactinemia and sexual dysfunctions in people with schizophrenia. Further study is warranted in order to clarify the association between sexual dysfunction and risperidone treatment in clinical practice and its impact in the quality of life of the patients.

La hiperprolactinemia y las disfunciones sexuales son complicaciones frecuentes, pero poco estudiadas del tratamiento con risperidona. Objetivos: Determinar la prevalencia de hiperprolactinemia y disfunciones sexuales en un grupo de personas jóvenes con esquizofrenia, tratadas con risperidona. Métodos: Un total de 40 pacientes (19 mujeres, edad promedio: 27 años) completaron el Cuestionario de Funcionamiento Sexual del Hospital General de Massachussets y el Cuestionario sobre Calidad de Vida: Satisfacción y Placer. Todos los pacientes fueron evaluados con las escalas PANSS y UKU y se determinó su nivel plasmático de prolactina. Resultados: El 90 por ciento de los pacientes presenta hiperprolactinemia, con valores significativamente más altos para las mujeres. El 62,5 por ciento de los pacientes, informó padecer alguna disfunción sexual, sin diferencias con la contraparte no afectada, en cuanto a género, edad ni tiempo de tratamiento. Aunque no se encontró relación con la prolactinemia, ni con la dosis de risperidona, quienes reportaron alguna disfunción sexual obtuvieron mayores puntajes de efectos adversos psíquicos y neurológicos en la escala UKU. Las disfunciones sexuales se asociaron con los síntomas negativos y generales de la PANSS y con menores puntajes en las subescalas de salud física y ánimo del Cuestionario sobre Calidad de Vida: Satisfacción y Placer. Conclusiones: Los resultados confirman la elevada frecuencia de disfunciones sexuales e hiperprolactinemia en las personas enfermas de esquizofrenia. Nuevos estudios se requieren para clarificar, en la práctica clínica habitual, la asociación entre disfunción sexual y el empleo de la risperidona, y su impacto en la calidad de vida de los pacientes.

[ case of priapism following atypical anyipsychotic drugs]

Priapism is a rare but serious side effect of psychotropic drugs with incidence of 15-26%. Approximately all of the atypical antipsychotic drugs are reported with this complication. In this report a 24-years old man with multiple delusions which was treated with risperidone [6mg], was affected by priapism after two months. After drug dose reduction and finally discontinuation, olanzapine [5mg] was started. Only one dose of this drug causes recurrence of priapism. Therefore this drug was discontinued also. After clozapine starting [150mg],priapism was induced. Therefore it is necessary for physicians whom prescribe serotonin-dopamin antagonist drugs must consider this rare but serious side effect

randomized, double-blind, placebo-controlled trial of metformin treatment for weight gain associated with initiation of risperidone in children and adolescents

To evaluate the effect of metformin treatment on the risperidone-induced body weight gain in patients. In a 12-weeks, double-blind, placebo controlled, randomized trial between October 2006 and October 2007 which was conducted in the Child and Adolescent Psychiatric Consultation Center of Isfahan University of Medical Sciences, 49 patients were entered the study with schizophrenia diagnosis. Then metformin [500 mg bid] or placebo was administrated with risperidone [6 mg] for the patients. Weight, height, and body mass index BMI were measured at the beginning, at 4 weeks, and at 12 weeks of the study. Changes in weight and BMI were evaluated by using repeated measures analysis of variance. Seventeen patients were excluded from the study. Repeated measure analysis of variances showed a significant difference between weight and BMI in both metformin [p<0.001, p<0.015] and placebo group [p<0.013, p<0.005]. Metformin treatment did not show a significant effect to control the body weight of patients after 12 weeks

Multi-drug overdose risperidone, ziprasidone, valproate, trihexyphenidyl, and clonazepam.

Risperidone and ziprasidone are commonly used as first line drugs for the treatment of psychotic disorders and overdose with these agents is increasingly being reported. Relatively few of these reports have involved co-ingestion of multiple psychotropic agents. We report a case of overdose with risperidone, ziprasidone, valproate, trihexyphenidyl and clonazepam in a 25 years female, who recovered uneventfully with supportive management. Notwithstanding the benign outcome in this instance, age, co-ingested drugs, active metabolites and medical co-morbidity are critical issues in overdose with atypical antipsychotics. As prescription of these drugs continues to increase in developing countries, systematic studies evaluating their clinical toxicity and management are necessary. The issues associated with overdose of multiple psychotropic agents and appropriate management policies are highlighted.

[Occurrence of malignant neuroleptic syndrome due to the intake of risperidone in low-risk patients]

Neuroleptic Malignant Syndrome [NMS] is a rare but potentially fatal problem induced by the consumption of antipsychotic drugs, especially traditional drugs which are more common in youngsters and males. This paper describes the first reported case of a clinical presentation of NMS [induced by the consumption of Risperidone] in an old woman, who was suffering from psychotic processes. Due to psychotic depression and with differential diagnosis of schizoaffective, the woman had been prescribed a low and medium dosage of Risperidone, but she suddenly and unexpectedly developed clinical NMS. Despite special treatments and services, she passed away after 14 days. In spite of rare universal reports regarding the development of NMS induced by the consumption of Risperidone, so far no occurrence of NMS in aged women has been reported