Neuropsychological Change in Early Phase Schizophrenia During 12 Months of Treatment With Olanzapine, Risperidone, or Haloperidol

Purdon, Scot E.; Jones, Barry D.; Stip, Emmanuel; Labelle, A.; Addington, Donald; David, S.R.; Breier, Alan; Tollefson, Gary D.

doi:10.1001/archpsyc.57.3.249

Cited by 411 publications

(278 citation statements)

References 44 publications

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“…26, NO. 5 Antipsychotics and Hippocampal Acetylcholine 589 olanzapine and clozapine, and to some extent risperidone, have been found to be beneficial in improving procedural learning tasks; these cognitive improvements have not been apparent with haloperidol treatment (Purdon et al 2000;Purdon 2000). All experiments in the present study were conducted in the presence of 0.3 M of the AChesterase inhibitor neostigmine in the perfusion solution.…”

Section: Discussionmentioning

confidence: 96%

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Effects of Typical and Atypical Antipsychotics and Receptor Selective Compounds on Acetylcholine Efflux in the Hippocampus of the Rat

Shirazi-Southall

2002

Neuropsychopharmacology

191

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Some atypical antipsychotic drugs appear to improve cognitive function in schizophrenia and since acetylcholine (ACh) is of importance in cognition, we used in vivo microdialysis to examine the effects of antipsychotics administered acutely (SC or IP) at pharmacologically comparable doses on ACh outflow in the hippocampus of the rat. The atypical antipsychotics olanzapine and clozapine produced robust increases in ACh up to 1500% and 500%, respectively. The neuroleptics haloperidol, thioridazine, and chlorpromazine, as (MDL 100,907), the 5-HT 2C (SB 242,084), the 5-HT 6 KEY WORDS : Antipsychotic; Schizophrenia; Olanzapine; Clozapine; Microdialysis; Acetylcholine Impairments in cognitive processes, such as deficits in executive function, verbal memory and attention, are prevalent in most patients with schizophrenia (Breier 1999). Some atypical antipsychotic drugs appear to improve not only the positive symptoms, but also the negative symptoms and the cognitive deficits when compared with classical neuroleptics (Kinon and Lieberman 1996;Meltzer and McGurk 1999;Remington and Kapur 2000). For example, some atypical antipsychotic drugs have been shown to improve attention, motor and executive function in schizophrenic patients (Meltzer and McGurk 1999 NO . 5 cal and clinical studies have indicated that atypical antipsychotics, such as clozapine, olanzapine and risperidone, potently inhibit serotonin 5-HT 2 receptor function and affect a variety of other receptors in the brain (Meltzer et al. 1989;Leysen et al. 1992;Bymaster et al. 1996). In particular, clozapine and olanzapine show a complex pharmacological profile, being described as "multi-acting-receptor-targeted antipsychotic agents" (MARTAs) .Acetylcholine has been shown to be an important neurotransmitter in motor function, attention and various aspects of cognition. Cholinergic synapses are prevalent in many areas of the brain, including the striatum, the prefrontal cortex and the hippocampus. Neuronal processes within the hippocampus, in particular, mediate declarative memory, and participate in cognitive mapping in both experimental animals and humans (Eichenbaum et al. 1999). It appears likely therefore that a dysfunction in cholinergic neurotransmission within the hippocampus may be responsible for the cognitive impairments often encountered in schizophrenia. In turn, the beneficial effects of some atypical antipsychotic drugs in the treatment of cognitive deficits in schizophrenia may be related to their selective action on cholinergic function in the hippocampus, as a consequence of their multireceptor pharmacological profile.Earlier in vivo microdialysis experiments have revealed a selective action of clozapine on ACh outflow in limbocortical, dopaminergic regions of the brain, such as the prefrontal cortex, as compared with classical neuroleptics (Parada et al. 1997;Moore et al. 1999). In general, antipsychotic drugs appear to either increase or have no effect on ACh efflux within the striatum, a dopaminergic region of the brain related to...

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Section: Discussionmentioning

confidence: 96%

“…**p Ͻ .01, ***p Ͻ .001 compared with the respective vehicle. olanzapine and clozapine, and to some extent risperidone, have been found to be beneficial in improving procedural learning tasks; these cognitive improvements have not been apparent with haloperidol treatment (Purdon et al 2000;Purdon 2000).…”

Section: Discussionmentioning

confidence: 99%

Effects of Typical and Atypical Antipsychotics and Receptor Selective Compounds on Acetylcholine Efflux in the Hippocampus of the Rat

Shirazi-Southall

2002

Neuropsychopharmacology

191

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“…Evaluation of the procognitive effects of atypical relative to typical antipsychotics has indicated somewhat greater benefit with atypical compared with typical antipsychotics (Bilder et al, 2002;Green et al, 2002;Harvey et al, 2000;Keefe et al, 1999;Purdon et al, 2000). In general, modest cognitive benefits from antipsychotic medications are characterized by reduction of generalized cognitive deficits across a wide range of abilities, rather than particular effects on a specific neuropsychological domain (Buchanan et al, 1994;Cassens et al, 1990;Hill et al, 2004a;Rollnik et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Efficiency of the CATIE and BACS neuropsychological batteries in assessing cognitive effects of antipsychotic treatments in schizophrenia

Hill

Sweeney

Hamer

et al. 2008

J. Inter. Neuropsych. Soc.

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Efficient and reliable assessments of cognitive treatment effects are essential for the comparative evaluation of procognitive effects of pharmacologic therapies. Yet, no studies have addressed the sensitivity and efficiency with which neurocognitive batteries evaluate cognitive abilities before and after treatment. Participants were primarily first episode schizophrenia patients who completed baseline (n 5 367) and 12-week (n 5 219) assessments with the BACS (Brief Assessment of Cognition in Schizophrenia) and CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) neuropsychological batteries in a clinical trial comparing olanzapine, quetiapine, and risperidone. Exploratory factor analysis revealed that performance on both batteries was characterized by a single factor of generalized cognitive deficit for both baseline performance and cognitive change after treatment. Both batteries estimated similar levels of change following treatment, although the BACS battery required half the administration time. Because a unitary factor characterized baseline cognitive abilities in early psychosis as well as cognitive change after treatment with atypical antipsychotic medications, short batteries such as the BACS may efficiently provide sufficient assessment of procognitive treatment effects with antipsychotic medications. Assessment of cognitive effects of adjunctive therapies targeting specific cognitive domains or impairments may require more extensive testing of the domains targeted to maximize sensitivity for detecting specific predicted cognitive outcomes. (JINS, 2008, 14, 209-221.)

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“…Among the advantages of these 'second-generation' antipsychotics (SGAs) (also referred to as 'atypical' or 'modern' antipsychotics) over 'first-generation' antipsychotics (FGAs) (also referred to as 'typical', 'traditional', or 'conventional' antipsychotics) are reduced extrapyramidal side effect profiles (Rosenheck et al, 1997;Simpson and Lindenmayer, 1997), reduced risk for tardive dyskinesia (Chouinard, 1995;Lieberman et al, 1994), greater effects on the negative and positive symptoms (Kane et al, 1988;Marder and Meibach, 1994;Beasley et al, 1996), and possibly beneficial effects on cognitive functioning (Purdon et al, 2000;Harvey et al, 2003;Bilder et al, 2002). SGAs have diverse receptor profiles, and the mechanism of action is still controversial (Seeman, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…In early randomized controlled trials, risperidone was found to be superior to haloperidol with regard to verbal working memory and verbal declarative memory (Kern et al, 1999). A randomized clinical trial of Purdon et al (2000) compared cognitive effects of haloperidol with two SGAs (olanzapine and risperidone) over 12 months and found olanzapine to be superior to risperidone and haloperidol in a global cognitive measure, with few reliable treatment differences for single tests or cognitive domains. This study has been criticized for high dropout rates, which were different between treatments (Weiss et al, 2002), and for a high average dosage of risperidone (Sharma, 2002).…”

Section: Introductionmentioning

confidence: 99%

Cognitive Improvement in Schizophrenic Patients does not Require a Serotonergic Mechanism: Randomized Controlled Trial of Olanzapine vs Amisulpride

Wagner

Quednow

Westheide

et al. 2004

Neuropsychopharmacol

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Combined serotonin-2A (5-HT 2A ) and dopamine-2 (D 2 ) receptor blockade has been proposed as a candidate mechanism by which second-generation antipsychotics (SGAs) improve both cognition and negative symptoms in schizophrenic patients, in contrast to antipsychotics of the first generation. The SGA amisulpride, however, only binds to D 2 /D 3 receptors, which makes it an interesting tool to test this assumption. In a randomized controlled trial, 52 schizophrenic patients were allocated to treatment with either olanzapine (10-20 mg/day) or amisulpride (400-800 mg/day). A comprehensive neuropsychological test battery and clinical ratings were used to assess participants at inclusion and after 4 and 8 weeks. Cognitive improvements of moderate size were observed, with effect sizes similar to those obtained in previous studies on the cognitive effects of SGAs. Importantly, amisulpride was not inferior to olanzapine for any cognitive domain. Combined 5-HT 2A /D 2 receptor blockade is probably not necessary for cognitive improvement by SGAs.

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Neuropsychological Change in Early Phase Schizophrenia During 12 Months of Treatment With Olanzapine, Risperidone, or Haloperidol

Cited by 411 publications

References 44 publications

Effects of Typical and Atypical Antipsychotics and Receptor Selective Compounds on Acetylcholine Efflux in the Hippocampus of the Rat

Effects of Typical and Atypical Antipsychotics and Receptor Selective Compounds on Acetylcholine Efflux in the Hippocampus of the Rat

Efficiency of the CATIE and BACS neuropsychological batteries in assessing cognitive effects of antipsychotic treatments in schizophrenia

Cognitive Improvement in Schizophrenic Patients does not Require a Serotonergic Mechanism: Randomized Controlled Trial of Olanzapine vs Amisulpride

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