Risperidone and haloperidol in first-episode psychosis: a long-term randomized trial.
ABSTRACT The first episode of psychotic illness is a key intervention point. The initial experience with medication can affect willingness to accept treatment. Further, relapse prevention is a treatment cornerstone during the first years of illness because active psychotic illness may affect lifetime outcomes. Thus, initial treatment of active symptoms and subsequent relapse prevention are central goals of pharmacotherapy. This study compared long-term effectiveness of risperidone versus haloperidol in first-episode psychosis patients.
First-episode psychosis patients (N=555, mean age=25.4 years) participated in a double-blind, randomized, controlled flexible-dose trial that compared risperidone (mean modal dose=3.3 mg) and haloperidol (mean modal dose=2.9 mg). The median treatment length was 206 days (maximum=1,514).
Positive and Negative Syndrome Scale scores and Clinical Global Impression ratings improved significantly relative to baseline, with no significant differences between groups. Three-quarters of the patients achieved initial clinical improvement, defined as >20% reduction in total Positive and Negative Syndrome Scale score. However, among those who achieved clinical improvement, 42% of the risperidone group experienced a relapse compared with 55% of the haloperidol group. The median time to relapse was 466 days for risperidone-treated subjects and 205 days for those given haloperidol. These differences were statistically significant based on Kaplan-Meier survival analysis. Adverse effects distinguished the treatments: there were significantly more extrapyramidal signs and symptoms and adjunctive medication use in the haloperidol group and greater prolactin elevation in the risperidone group. There was less weight gain with haloperidol initially but no significant differences between groups at endpoint.
Relatively low doses of antipsychotic drugs lead to significant symptom amelioration in the majority of first-episode psychosis patients. In the long term, risperidone prevents relapse in more patients and for a longer time and also induces less abnormal movements than haloperidol.
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ABSTRACT: Objective:Given that atypical antipsychotic medications have been increasingly prescribed for improving weight gain in anorexia nervosa (AN), we conducted a systematic review and meta-analyses to estimate the influence of atypical antipsychotics on BMI, eating disorder, and psychiatric symptoms in individuals with AN. Method:Independent reviewers selected studies and extracted study characteristics, methodologic quality, and outcomes for the intention-to-treat group from randomized clinical trials comparing the effect of atypical antipsychotic use to placebo or an active control treatment on BMI. Results:Compared with placebo, atypical antipsychotics were associated with a nonsignificant increase in BMI (weighted mean difference, WMD = 0.18, 95% CI: −0.36, 0.72; I2 = 26%) and a nonsignificant effect on the drive for thinness and body dissatisfaction. Compared with placebo or active control, these medications led to an increase in anxiety and overall eating disorder symptoms. However, there was a significant reduction over placebo or active control on level of depression. © 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2013)International Journal of Eating Disorders 05/2013; 46(4). · 3.03 Impact Factor
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ABSTRACT: Major psychiatric disorders such as schizophrenia, major depressive and bipolar disorders are severe, chronic and debilitating, and are associated with high disease burden and healthcare costs. Currently, diagnoses of these disorders rely on interview-based assessments of subjective self-reported symptoms. Early diagnosis is difficult, misdiagnosis is a frequent occurrence and there are no objective tests that aid in the prediction of individual responses to treatment. Consequently, validated biomarkers are urgently needed to help address these unmet clinical needs. Historically, psychiatric disorders are viewed as brain disorders and consequently only a few researchers have as yet evaluated systemic changes in psychiatric patients. However, promising research has begun to challenge this concept and there is an increasing awareness that disease-related changes can be traced in the peripheral system which may even be involved in the precipitation of disease onset and course. Converging evidence from molecular profiling analysis of blood serum/plasma have revealed robust molecular changes in psychiatric patients, suggesting that these disorders may be detectable in other systems of the body such as the circulating blood. In this review, we discuss the current clinical needs in psychiatry, highlight the importance of biomarkers in the field, and review a representative selection of biomarker studies to highlight opportunities for the implementation of personalized medicine approaches in the field of psychiatry. It is anticipated that the implementation of validated biomarker tests will not only improve the diagnosis and more effective treatment of psychiatric patients, but also improve prognosis and disease outcome.Progress in Neurobiology 11/2014; · 10.30 Impact Factor
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ABSTRACT: The clinical expression of schizophrenia is generally reported to be expressed by three to five different factors (i.e. positive, negative, disorganization, excitability, anxiety-depression symptoms). It is often claimed that antipsychotic medications are particularly helpful for positive symptoms, but not for the others, suggesting a differential efficacy for different aspects of the disorder. We formally tested this claim. Using Structural Equation Modeling in two large [1884 patients] clinical trials in schizophrenia, we compared the model of a common general effect of antipsychotics to models whereby the antipsychotics have multiple and differential effects on the different factors of the illness. We validated the generalizability of the model in further trials involving antipsychotics in chronic [1460 patients] and first-episode patients [1053 patients]. Across different populations, different trials and different antipsychotics - the best-fitting model suggests that symptom response in schizophrenia is underpinned by a single general effect with secondary and minor lower-order effects on specific symptom domains. This single-factor model explained nearly 80% of the variance, was superior to the assumption of unique efficacy for specific domains; and replicated across antipsychotics and illness stages. Despite theoretical and pharmacological claims the differential efficacy of antipsychotics on the various dimensions of schizophrenia is not supported in the prevailing data. The implication of this finding for the measurement of treatment response and our understanding of the neurobiology of antipsychotic action, for clinical practice and for future drug development are discussed.European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 04/2014; · 3.68 Impact Factor