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.

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.

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.

An open-label study of quetiapine for delirium.

OBJECTIVE: To evaluate the effects of quetiapine treatment in patients with delirium. MATERIAL AND METHOD: All patients with delirium were assessed. The diagnosis of delirium was confirmed by using the Confusion Assessment Method (CAM). Quetiapine at the dose between 25 and 100 mg/day was given for 7 days. The efficacy of quetiapine on delirium was evaluated by using the Delirium Rating Scale (DRS) and the Clinical Global Impression-Severity scale (CGI-S). The extrapyramidal side effects were assessed by using the Modified (9-item) Simpson-Angus Scale (MSAS). RESULTS: Twenty-two patients had delirium. Seventeen (10 males and 7 females) subjects with a mean age (SD) of 55.6 (18.6) years were included in the present study. Means (SDs) dose and duration (SD) of quetiapine treatment were 45.7 (28.7) mg/day and 6.5 (2.0) days, respectively. The DRS and CGI-S scores of days 2-7 were significantly lower than those of day 0 (p < 0. 001) for all comparisons). Only two subjects were shown to have mild tremor. CONCLUSION: Quetiapine within the range of 25-100 mg/day improves delirious condition within 24 hours of treatment. It is well-tolerated and has a very low propensity to induce extrapyramidal side effects. Further randomized, placebo-controlled trials are warranted.