Article

Risperidone and Haloperidol in First-Episode Psychosis: A Long-Term Randomized Trial

Hurwich Professor, Bar Ilan University, Ramat Gan, Israel.
American Journal of Psychiatry (Impact Factor: 12.3). 05/2005; 162(5):947-53. DOI: 10.1176/appi.ajp.162.5.947
Source: PubMed

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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Available from: Lili C Kopala, Nov 15, 2015
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    • "To cross-validate the first results, 1137 participants with chronic schizophrenia from a different trial were analyzed (Lieberman et al., 2005). Data for the last set of analyses ('generalizability') came from two RCT contributing with 1053 firstepisode patients (Schooler et al., 2005; Kahn et al., 2008). "
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    Full-text · Article · Apr 2014 · European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology
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    • "To cross-validate the first results, 1137 participants with chronic schizophrenia from a different trial were analyzed (Lieberman et al., 2005). Data for the last set of analyses ('generalizability') came from two RCT contributing with 1053 firstepisode patients (Schooler et al., 2005; Kahn et al., 2008). "
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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 Modelling 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.
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    • "In addition, concerns about side effects such as EPS have been replaced by other distressing side-effects, including weight gain, hyperglycemia and dyslipidemia. Studies specifically comparing the SGAs with the FGAs for first-episode schizophrenia have had mixed results, with small or limited advantages to secondary outcomes for SGAs.[141516171819] "
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