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: 13.56). 05/2009; 166(6):675-82. DOI: 10.1176/appi.ajp.2008.08060806
Source: PubMed

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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    • "The European First Episode Schizophrenia Trial (EUFEST) was a pragmatic study comparing four second generation antipsychotics (amisulpride, olanzapine, quetiapine and ziprasidone ) with the first generation antipsychotic, haloperidol, used in low doses, in nearly 500 patients. The main results of the study were published in 2008 (Kahn et al., 2008), and some specific issues such as cognitive symptoms (Davidson et al., 2009), depression (Rybakowski et al., 2012); metabolic symptoms (Fleischhacker et al., 2013), persistent negative symptoms (Galderisi et al., 2013) or hyperprolactinemia (Riecher-Rössler et al, 2013) were addressed in subsequent papers. As to EPS, the initial analysis showed that the secondgeneration antipsychotic drugs used in EUFEST induced fewer extrapyramidal side-effect than haloperidol, even at low doses (Kahn et al., 2008). "
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    ABSTRACT: The European First Episode Schizophrenia Trial (EUFEST) included first-episode schizophrenia patients, assessing the efficacy of five antipsychotic drugs (haloperidol, amisulpride, olanzapine, quetiapine and ziprasidone) over one year. Baseline frequency of extrapyramidal symptoms (EPS) in this group of patients (n=490) was as follows: parkinsonism 10.8%, akathisia 10.0%, dystonia 1.8%, and dyskinesia 0.6%. The frequency of parkinsonism at baseline was greater in patients with a brief prior exposure to antipsychotics (≤2 weeks) compared with antipsychotic-naïve ones, and was positively correlated with the intensity of negative symptoms and negatively with depressive symptoms. After one month of treatment, the increase of parkinsonism was highest in patients receiving haloperidol (+13%), that of akathisia in patients treated with ziprasidone (+14%), and 10.1% of the patients were taking anticholinergic drugs, most frequently in the haloperidol group (24%). In 291 patients remaining on treatment after one year, both parkinsonism and akathisia had decreased: the frequency of parkinsonism was 3%, highest in the haloperidol group (9.1%), that of akathisia was 3%, highest in the quetiapine group (7.5%), and 4% of patients were taking anticholinergic drugs, most frequently those receiving haloperidol (10.5%). The results obtained suggest that in first-episode schizophrenia patients during the first year of antipsychotic treatment (in this case amisulpride, haloperidol in low doses, olanzapine, quetiapine and ziprasidone), EPS present as manageable clinical problems.
    European Neuropsychopharmacology 09/2014; 24(9). DOI:10.1016/j.euroneuro.2014.07.001 · 5.40 Impact Factor
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    • "Woodward et al. in a recent meta-analysis found no evidence that higher doses of haloperidol may perhaps be associated with lower cognitive score improvements (Woodward et al. 2005). However, the dose of haloperidol used in our study (3.64 mg) is relatively low compared to the range of doses used in previous investigations in FEP (Davidson et al. 2009). Thus, in agreement with Buchanan et al. recommendations (Buchanan et al. 2010), there is insufficient evidence to support a recommendation for the preferential use of SGAs over FGAs to achieve gains in the treatment of cognitive impairments. "
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    ABSTRACT: INTRODUCTION: The initially postulated superior neurocognitive effectiveness of second-generation antipsychotics is currently under debate. METHODS: A prospective, randomized, open-label study was carried out to compare the long-term neurocognitive effectiveness of haloperidol, olanzapine, and risperidone in the first episode of schizophrenia spectrum disorders. A final sample of 79 patients randomized to haloperidol (N = 28), olanzapine (N = 23), or risperidone (N = 28) who completed clinical and cognitive evaluations at baseline and 3-year follow-up was included in the final analysis. Forty-one healthy individuals were also included in the final analysis. The main outcome measure was cognitive changes at 3-year follow-up. Due to the fact that some of the patients had switched their initially prescribed antipsychotic medication during the course of the study (6 out of 28 in haloperidol group, 18 out of 23 in olanzapine group, and 24 out of 28 in risperidone group continued with the initial study drug at 3-year assessment), we have also conducted a per protocol analysis. RESULTS: Overall, cognitive changes were similar in the three treatment groups and controls, although a greater improvement in Rey Auditory Verbal Learning Test, Digit Symbol, and Iowa Gambling Test was found in the treatment groups. The better performance observed on Rey Auditory Verbal Learning Test and Digit Symbol in olanzapine treatment group was likely explained by the lower prevalence of use of antimuscarinic drugs. These results were essentially similar to those found in the intention-to-treat analysis. CONCLUSIONS: The major conclusion of this study is that haloperidol, olanzapine, and risperidone have not demonstrated substantial neurocognitive effectiveness, improving cognitive deficits present in the early phases of the illness. The study also underscores the importance of exploring new drugs for the treatment of cognitive impairments and associated functional disabilities in schizophrenia.
    Psychopharmacology 03/2013; 227(4). DOI:10.1007/s00213-013-2994-z · 3.99 Impact Factor
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    • "Thus, type of antipsychotic drug seems not to have any substantial effect on social cognitive functioning. Similar reports include: Davidson et al. (2009) (17), Penn et al. (2009) (15), and Sergi et al. (2007) "
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    ABSTRACT: Social cognition captures affect recognition, social cue perception, "theory of mind," empathy, and attributional style. The aim of our study was to assess social cognition in schizophrenia inpatients being treated with first-generation antipsychotic drugs (FGAs), n=28 (perphenazine and haloperidol, FGAs) or with second-generation antipsychotic drugs (SGAs), n=56 (olanzapine and clozapine, SGAs). Eighty-four patients completed the Facial Expression Recognition Test, the Voice Emotion Recognition Test, the Short Recognition Memory Test for Faces, and the Reading the Mind in the Eyes Test. Patients also completed the Visual Object and Space Perception Test (VOSP) as a control task, which would not engage social cognition. The patients were compared with fifty healthy controls matched for age and gender. ResulTS: There were no significant differences on social cognitive performance between the FGA- and SGA-treatment groups. Nor was olanzapine superior to clozapine, FGAs or both. However, patients treated with FGAs performed significantly worse on VOSP compared to both groups treated with SGAs, a 10% difference. We cannot conclude that SGAs were associated with better social cognition than FGAs. However, there were small but significant advantages for SGAs in non-social visual processing function, as evaluated with the VOSP.
    Clinical Schizophrenia & Related Psychoses 04/2012; 6(1):14-20. DOI:10.3371/CSRP.6.1.2
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