Cognitive Effects of Antipsychotic Drugs in First-Episode Schizophrenia and Schizophreniform Disorder: A Randomized, Open-Label Clinical Trial (EUFEST)
ABSTRACT Cognitive impairment, manifested as mild to moderate deviations from psychometric norms, is present in many but not all schizophrenia patients. The purpose of the present study was to compare the effect of haloperidol with that of second-generation antipsychotic drugs on the cognitive performance of patients with schizophreniform disorder or first-episode schizophrenia.
Subjects were 498 patients with schizophreniform disorder or first-episode schizophrenia who were randomly assigned to open-label haloperidol (1 to 4 mg/day [N=103]), amisulpride (200 to 800 mg/day [N=104]), olanzapine (5 to 20 mg/day [N=105]), quetiapine (200 to 750 mg/day [N=104]), or ziprasidone (40 to 160 mg/day [N=82]). The Rey Auditory Verbal Learning Test, Trail Making Test Part A and Part B, WAIS Digit Symbol Test, and Purdue Pegboard Test were administered at baseline and the 6-month follow-up evaluation.
Compared with scores at baseline, composite cognitive test scores improved for all five treatment groups at the 6-month follow-up evaluation. However, there were no overall differences among the treatment groups. In addition, there was a weak correlation between the degree of cognitive improvement and changes in Positive and Negative Syndrome Scale scores.
Treatment with antipsychotic medication is associated with moderate improvement in the cognitive test performance of patients who have schizophreniform disorder or who are in their first episode of schizophrenia. The magnitude of improvement does not differ between treatment with haloperidol and treatment with second-generation antipsychotics. Moreover, cognitive improvement is weakly related to symptom change.
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ABSTRACT: Cognitive impairment is a core feature of schizophrenia. The present randomized open study enrolled antipsychotic-naïve patients who were experiencing their first episode of schizophrenia. After baseline neurocognitive tests and clinical assessment, subjects were randomly assigned to olanzapine, risperidone and aripiprazole treatment groups. A battery of neurocognitive tests showed that risperidone produced cognitive benefits in all five cognitive domains, including verbal learning and memory, visual learning and memory, working memory, processing speed, and selective attention; olanzapine improved processing speed and selective attention; and aripiprazole improved visual learning and memory, and working memory. However, the three atypical antipsychotic drugs failed to reveal any significant differences in the composite cognitive scores at the study endpoint. In addition, the three drugs all significantly improved clinical measures without significant differences between the drugs after 6 months. These results suggest that the atypical antipsychotics, olanzapine, risperidone and aripiprazole may improve specific cognitive domains with similar global clinical efficacy. In clinical practice, it may be feasible to choose corresponding atypical antipsychotics according to impaired cognitive domains.Neural Regeneration Research 01/2013; 8(3):277-86. DOI:10.3969/j.issn.1673-5374.2013.03.011 · 0.23 Impact Factor
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ABSTRACT: While the frequency and importance of antipsychotic switching in patients with schizophrenia, there is insufficient evidence with regard to switching strategy. Quetiapine is one of the drugs of choice for switch because of its unique receptor profile. However, there were no data on the long-term clinical and neurocognitive effect of quetiapine in patients who had responded inadequately to prior antipsychotics. The purpose of this study is to examine the long-term efficacy and tolerability of quetiapine in patients with schizophrenia who switched from other antipsychotics because of inadequate therapeutic response. We hypothesized that quetiapine would show long-term effectiveness in broad symptom dimensions including negative and neurocognitive symptoms while having good tolerability. Twenty-nine subjects with schizophrenia who did not respond to their current monotherapy of antipsychotic or who could not tolerate the treatment were switched to quetiapine and assessed at baseline and at 3, 6, and 12 months. The outcome measures included the brief assessment of cognition in schizophrenia (BACS), the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions Scale (CGI), the Schizophrenia Quality of Life Scale Japanese version (JSQLS), the Athens Insomnia Scale (AIS), and the Drug Attitude Inventory with 30 items (DAI-30). The Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS), HbA1c, prolactin (PRL), and body weight were also evaluated. Statistically significant improvements were observed in all subscores of the PANSS, the GAF, and the symptoms and side effects subscale of the JSQLS, the DIEPSS, the AIS, and the PRL level, and nearly significant improvements were observed in the DAI-30. Quetiapine monotherapy was associated with significant improvement in the verbal memory test, even after controlling for the practice effect. Although quetiapine was well tolerated, three subjects dropped out because of the worsening of the psychotic symptoms and two additional subjects dropped out because of somnolence. In this open-label, single-arm study of 29 patients, quetiapine improved both the clinical symptoms and the neurocognitive impairment in chronic schizophrenia patients who failed to respond to prior antipsychotic treatment.
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ABSTRACT: Movement disorders are common in individuals with schizophrenia, even in those who are not exposed to antipsychotic medications. Extrapyramidal symptoms (EPS) are among the most common abnormal movements in schizophrenia, but their relationship with other features of the illness such as cognition is not well characterized. Three hundred and twenty-five individuals with schizophrenia who were not receiving any antipsychotic or anticholinergic medication and participated in the baseline visit of the Clinical Antipsychotic Treatment of Intervention Effectiveness study were included in the present study. EPSs were assessed using the Simpson-Angus Scale, while cognition was measured with a comprehensive neuropsychological test battery. The relationship between EPS and cognitive test performance was evaluated both dimensionally and categorically. Greater severity of EPS was significantly associated with worse cognitive test performance evaluated using a composite score. Eighty-six patients were identified as having parkinsonism and these patients performed worse on cognitive tests than non-parkinsonian patients. These findings remained significant even after accounting for other variables such as severity of psychopathology, sedation, akathisia and dyskinesia. The present results demonstrate that severity of EPS is reliably linked with poorer scores on tests of cognition. While this may reflect a common pathophysiology underlying neuromotor and neurocognitive deficits, it may also be the case that parkinsonian symptoms such as rigidity and bradykinesia impede test taking ability. Regardless of mechanism, inferences regarding cognitive impairment should take into account the presence of EPS, as well as other variables that may mediate cognitive test findings. Copyright © 2014 Elsevier B.V. All rights reserved.Schizophrenia Research 12/2014; 161(2-3). DOI:10.1016/j.schres.2014.11.018 · 4.43 Impact Factor