Refractory schizophrenia

Departamento e Instituto de Psiquiatria, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
Revista Brasileira de Psiquiatria (Impact Factor: 1.77). 11/2007; 29 Suppl 2:S41-7.
Source: PubMed


The aim of the present paper is to review the various aspects of refractory schizophrenia regarding issues such as definitions, clinical aspects, psychobiological correlates, pharmacological and non-pharmacological treatment options and predictors of treatment response.
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Refractory schizophrenia affects at least one third of patients with schizophrenia and the best evidence shows that is monotherapy with clozapine remains the mainstay for the treatment of such condition. Antipsychotic polipharmacy is not supported by current evidence and recent clinical trials have shown that clozapine augmentation with antipsychotics has no benefit over placebo.

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    • "mg/day). These differences may be related to local healthcare systems, patients' clinical profiles and family economic status, and clinicians' prescribing habits.21,24) "
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    ABSTRACT: Clozapine is one of the most commonly used antipsychotic drugs in China. To date, few studies have investigated the patterns the prescription of clozapine nationwide. The present study examined these patterns in China in 2006 and identified the demographic and clinical characteristics associated with the use of clozapine. Using a standardized protocol and data collection procedure, we surveyed 5,898 patients with schizophrenia in 10 provinces with differing levels of economic development. Overall, clozapine had been prescribed for 31.9% (n=1,883) of the patients; however we found considerable variation among the 10 provinces. The frequency of clozapine use was highest in Sichuan (39.3%) and lowest in Beijing (17.3%). The mean daily dose of clozapine was 210.36±128.72 mg/day, and 25.1% of the patients were treated with clozapine in combination with other antipsychotics. Compared with the group not receiving clozapine, clozapine-user had been treated for longer durations and had experienced a greater number of relapses and hospitalizations. Furthermore, those in the clozapine-user had lower family incomes, were less able to seek psychiatric services, and more likely to be male and have a positive family history of schizophrenia. A multiple logistic regression analysis revealed that age, sex, professional help-seeking behaviors, duration of illness, economic status, educational level, and clinical manifestations were associated with the use of clozapine. Clozapine use is common in China. However, use of the antipsychotic varies among provinces, and demographic and clinical factors play important roles in the prescription of clozapine.
    Full-text · Article · Aug 2012 · Clinical Psychopharmacology and Neuroscience
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    • "However, as reviewed by Chung and Remington (2005) there are no predictors of clozapine response that are either specific or, in fact, particularly sensitive. In a Brazilian cohort Henna-Neto and Elkis (2007) did not observe specific predictors of non-response to clozapine. According to these authors there were no demographic differences between responder and non-responder subjects, and despite the greater disease severity of non-responder patients, they did not differ in terms of number of hospitalizations. "
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    ABSTRACT: Schizophrenia is a severe mental illness affecting around 1% of adults with a high degree of morbidity and mortality. Affected individuals are at increased risk for unemployment, handicap, obesity, diabetes mellitus, hearth attack and suicide. Antipsychotic drugs are the best treatment for this disease, but about 20% of patients display drug resistance, or refractoriness, and may receive a special neuroleptic named Clozapine. Despite its superiority from other neuroleptics, only 30-60% of drug-resistant patients are responsive to clozapine. Clozapine's action results from interactions between dopaminergic and serotonergic neurotransmitter systems and since clozapine appears to exert its effect strongly through the serotonergic systems, alterations in serotonin synaptic levels may influence antipsychotic response. The serotonin transporter (5-HTT) is responsible for pre-synaptic re-uptake of serotonin, making this transporter a logical candidate gene for prediction of clozapine response and to increase understanding about mechanisms of refractoriness. Therefore, we investigated the influence of two polymorphisms in the 5-HTT gene (HTTLPR/rs25531 and VNTR Stin2) in clozapine response in a sample of 116 schizophrenic individuals of European descent from South-Brazil. Significant differences between responders and non-responders to clozapine were observed for the HTTLPR/rs25531 polymorphism. Nonresponders to clozapine showed a higher frequency of S'-allele (P = 0.01) and also were more likely to be S'/S' homozygous or S'/L' heterozygous than those who did respond (P = 0.04). After controlling for confounding variables, logistic regression analyses confirmed this association (OR = 3.15; 95% CI: 1.13-8.80). The observed association suggests that increased availability of extracellular serotonin concentrations at all synapses may reduce clozapine effect.
    Full-text · Article · May 2010 · Journal of Psychiatric Research
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    ABSTRACT: A high percentage of schizophrenic patients suffer from auditory verbal hallucinations (AVH). The chronic nature of AVH presents a serious therapeutic challenge, as up to one third of these patients are resistant to antipsychotic pharmacotherapy. Low-frequency repetitive transcranial magnetic stimulation (rTMS) is a therapeutic option that may disrupt or attenuate treatment-resistant AVH. In this chapter, we review the literature on the application of rTMS from the initial studies, more than a decade ago, to the current randomized controlled trials (RCT), which also include ‘super-refractory’ schizophrenia (SRS) patients, active comparator stimulation strategies and imaging-guided stimulations. We also consider 3 meta-analyses, which found moderate rates of AVH attenuation in response to rTMS. We believe that larger maintenance and follow-up studies with clearer definitions of treatment resistance are required to confirm the beneficial effects of rTMS in AVH. In addition, the underlying mechanism of action of rTMS at different cortical sites related to speech networks needs further clarification. We suggest that future trials should focus on standardizing; methods for assessing AVH changes, time courses of response, placebo strategies, RCT designs, and also the further development of potential response markers, and inclusion of both unmedicated and SRS patients.Copyright © 2010 S. Karger AG, Basel
    No preview · Article · Jan 2010 · Recent advances in biological psychiatry
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