Cognitive Effects of Antipsychotic Drugs in First-Episode Schizophrenia and Schizophreniform Disorder: A Randomized, Open-Label Clinical Trial (EUFEST)

Duke University, Durham, North Carolina, United States
American Journal of Psychiatry (Impact Factor: 12.3). 05/2009; 166(6):675-82. DOI: 10.1176/appi.ajp.2008.08060806
Source: PubMed


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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    • "A number of studies have evaluated the impact that poor adherence to antipsychotic medication has on quality of life and hospitalizations in patients with psychosis (Gray et al., 2002; King et al., 2014; Park et al., 2014). Thus, poor medication adherence in patients following the first episode of psychosis (FEP) is associated with more frequent readmissions (Caseiro et al., 2012; Verdoux et al., 2000), and a greater risk of relapse (Kahn et al., 2008; Malla et al., 2006; Novak-Grubic and Tavcar, 2002). "
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    ABSTRACT: Both substance use and poor medication adherence are associated with poor outcome in psychosis. To clarify the contributions of substance use and poor medication adherence to poor outcome in the year following a first episode of psychosis, 205 patients were evaluated for use of tobacco, alcohol, cannabis and stimulants at their psychosis onset, and in a 1-year follow-up. Data on medication adherence and symptom remission were also collected. Patients had high rates of overall substance use before (37-65%) and after psychosis onset (45-66%). 44% showed poor medication adherence and 55% did not reach remission from psychosis. Nicotine dependence and cannabis use after psychosis onset significantly predicted both poor medication adherence and non-remission, and poor medication adherence mediated the effects of these substances on non-remission. In conclusion, medication adherence lies on the causal pathway between nicotine dependence and cannabis on the one hand and non-remission on the other.
    Full-text · Article · Dec 2015 · Schizophrenia Research
    • "Cognitive deficits are considered a core feature of schizophrenia (Kahn & Keefe, 2013) and make an impact on the long-term outcome of the illness in several ways. For example, they are significantly associated with treatment non-adherence (Keefe et al. 2007a), greater risk of relapse (Chen et al. 2005), poorer overall symptom response (Davidson et al. 2009) and impaired functionality (Bowie et al. 2008; Nuechterlein et al. 2011). As such they have become targets for intervention , both psychological (Porter et al. 2013) and pharmacological. "
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    ABSTRACT: Several questions remain unanswered regarding the magnitude and time course of cognitive improvement in response to antipsychotic treatment. The purpose of this study was to assess changes in cognitive performance in antipsychotic-naive or minimally medicated patients with first-episode schizophrenia during the first 12 months of treatment, in a case-control design. Patients were treated with flupenthixol decanoate depot injection, according to a standard algorithm. The primary outcome measure was change in MATRICS Cognitive Consensus Battery (MCCB) composite score over 12 months. The sample comprised 92 patients and 100 healthy controls matched for age, sex, ethnicity and educational status. Cognitive function was assessed by means of the MCCB. A mixed-effects model identified a significant group × time effect (p ≤ 0.0001) for the MCCB composite score, with patients showing a greater degree of change than the controls. For the other MCCB domains there were significant group × time effects at adjusted significance level for attention and vigilance (p ≤ 0.0001), visual learning (p ≤ 0.0001), verbal learning (p = 0.005) and working memory (p ≤ 0.0001), but not for reasoning and problem solving (p = 0.04), speed of processing (p = 0.03) and social cognition (p = 0.06). There were moderate correlations between change in MCCB composite score and change in symptomatology as assessed by Positive and Negative Syndrome Scale factor analysis-derived domains. Substantial improvements in cognitive function were observed over and above a practice effect, and were significantly correlated with improvements in psychopathology and functionality.
    No preview · Article · May 2015 · Psychological Medicine
    • "EUFEST was a randomized, open trial comparing the effectiveness of haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone in patients with a first episode of DSM IV schizophrenia, schizoaffective disorder, or schizophreniform disorder (Kahn et al., 2008). Patients (N=498) were recruited at 50 centers in 13 European countries and in Israel. "
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    ABSTRACT: The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) obtained a sample of 1493 chronic schizophrenia patients. The European First Episode Schizophrenia Trial (EUFEST) studied a sample of 498 patients. We have combined these two samples to study the predictors and correlates of adherence to treatment. Here we report on adherence to pharmacological treatment at the six and twelve month assessments of these trials with a combined subsample of 1154 schizophrenia patients. Individual patients׳ data were used for analyses. We used logistic regression to examine the effects of substance use, akathisia, parkinsonism, dyskinesia, hostility, and insight on pharmacological adherence. The results showed that reduced adherence to pharmacological treatment was associated with substance use (p=0.0003), higher levels of hostility (p=0.0002), and impaired insight (p<0.0001). Furthermore, poor adherence to study medication was associated with earlier discontinuation in the combined data. The clinical implications of the results point to the importance of routine assessments and interventions to address patients׳ insight and comorbid substance use and the establishment of therapeutic alliance. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.
    No preview · Article · Apr 2015 · European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology
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