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.

27 Reads
    • "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. "
    [Show abstract] [Hide abstract]
    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.
    Psychological Medicine 05/2015; 45(13):1-11. DOI:10.1017/S0033291715000860 · 5.94 Impact Factor
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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 · 4.37 Impact Factor
  • Source
    • "However, the typical pharmacotherapy in schizophrenia is not as effective as one would hope in treating cognitive impairments (36). Two large trials, the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) (37) and the European First-Episode Schizophrenia Trial (EUFEST) (38) showed mild to moderate improvement after atypical antipsychotic treatment in long-term or first-episode schizophrenia and schizophreniform disorder, respectively. Later studies report that most antipsychotics, especially atypical antipsychotics, may at best produce mild remediation of cognitive deficits (Cohen’s d between 0.20 and 0.40), while domain-specific cognitive treatment effects have not been revealed (39–41). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cognitive impairment is an important aspect of schizophrenia, where cognitive remediation therapy (CRT) is a promising treatment for improving cognitive functioning. While neurobiological dysfunction in schizophrenia has been the target of much research, the neural substrate of cognitive remediation and recovery has not been thoroughly examined. The aim of the present article is to systematically review the evidence for neural changes after CRT for schizophrenia. The reviewed studies indicate that CRT affects several brain regions and circuits, including prefrontal, parietal, and limbic areas, both in terms of activity and structure. Changes in prefrontal areas are the most reported finding, fitting to previous evidence of dysfunction in this region. Two limitations of the current research are the few studies and the lack of knowledge on the mechanisms underlying neural and cognitive changes after treatment. Despite these limitations, the current evidence suggests that CRT is associated with both neurobiological and cognitive improvement. The evidence from these findings may shed light on both the neural substrate of cognitive impairment in schizophrenia, and how better treatment can be developed and applied.
    Frontiers in Psychiatry 08/2014; 5:103. DOI:10.3389/fpsyt.2014.00103
Show more

Similar Publications