Neurocognitive Effects of Clozapine, Olanzapine, Risperidone, and Haloperidol in Patients With Chronic Schizophrenia or Schizoaffective Disorder

Bilder, Robert M.; Goldman, Robert; Volavka, Jan; Czobor, Pál; Hoptman, Matthew J.; Sheitman, Brian; Lindenmayer, Jean Pierre; Citrome, Leslie; McEvoy, Joseph P.; Kunz, Michal; Chakos, Miranda; Cooper, Thomas B.; Horowitz, Terri L.; Lieberman, Jeffrey A.

doi:10.1176/appi.ajp.159.6.1018

Cited by 487 publications

(326 citation statements)

References 29 publications

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“…Specifically, clozapine has demonstrated limited or no effects on executive function (Meltzer and McGurk, 1999;Hoff et al, 1996;Bellack et al, 2004). Risperidone has been shown either to be not effective (Bellack et al, 2004;Remillard et al, 2005;Lee et al, 2007) or slightly effective, as measured by Wisconsin Card Sorting Test (Meltzer and McGurk, 1999;Harvey et al, 2005), and olanzapine produces effects in the same range as risperidone (Meltzer and McGurk, 1999;Bilder et al, 2002;Keefe et al, 2007). In a small clinical trial, sertindole has shown superiority to haloperidol on executive function performance (Gallhofer et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Reversal of Subchronic PCP-Induced Deficits in Attentional Set Shifting in Rats by Sertindole and a 5-HT6 Receptor Antagonist: Comparison Among Antipsychotics

Rodefer

Nguyen

Karlsson

et al. 2007

Neuropsychopharmacol

116

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Currently accepted treatments for schizophrenia can effectively control positive symptoms but have limited impact on cognitive deficits in schizophrenia. The purpose of these experiments was to address this unmet need by characterizing the effects of classical and secondgeneration antipsychotics on cognitive impairments associated with schizophrenia. An additional aim was to characterize the part(s) of the pharmacological profile of drugs that were important to reverse deficits. Cognitive deficits were assessed using a frontally mediated attentional set-shifting task in rats that is analogous to tasks used in humans and nonhuman primates that assess executive function. Mirroring findings in patients with schizophrenia, the classical antipsychotic haloperidol was ineffective in treating set-shifting deficits induced by subchronic treatment with phencyclidine (PCP). Similarly, second-generation antipsychotics, risperidone, clozapine, and olanzapine were ineffective. In contrast, selected doses of sertindole and the 5-HT 6 receptor antagonist SB 271046 attenuated PCPinduced set-shifting deficits. Finally, the 5-HT 2A receptor antagonist M100907 was without effect. Further examination revealed that repeated treatment (21 days) with sertindole, but not olanzapine, also was effective in reversing the executive function deficit. These data suggest that the combination of 5-HT 6 antagonistic activity and the absence of antimuscarinic activity may represent key characteristics of the pharmacological profile for improved antipsychotic drugs for schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Reversal of Subchronic PCP-Induced Deficits in Attentional Set Shifting in Rats by Sertindole and a 5-HT6 Receptor Antagonist: Comparison Among Antipsychotics

Rodefer

Nguyen

Karlsson

et al. 2007

Neuropsychopharmacol

116

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“…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). A subsequent 14-week study by Bilder et al (2002) confirmed that 10-40 mg olanzapine was superior to 10-30 mg haloperidol (particularly with regard to attention), but also found improvements in memory, which were most marked for 4-16 mg risperidone, implicating that different SGAs may differ in their patterns of cognitive effects. However, a large study of Harvey et al (2003), comparing the cognitive effects of 5-20 mg olanzapine or 2-6 mg/day risperidone over 8 weeks in 377 patients, found no differences between both treatments, while performance of all patients improved for several domains.…”

Section: Introductionmentioning

confidence: 92%

“…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%

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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“…[14][15][16]57,58 Also, in these studies, different antipsychotics have been tested against each other. 57,58 In contrast, EPO has been able as an add-on treatment, on top of a stable antipsychotic medication regime, to specifically target cognition in a group of chronic schizophrenic patients with clearly defined, persistent cognitive decline. Even though the principal question Figure 4 Repeated-measures ANCOVA: effect of EPO versus placebo treatment on S100B serum levels in male chronic schizophrenic patients.…”

Section: H Ehrenreich Et Almentioning

confidence: 99%

Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin

et al. 2006

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Schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component, comprising cognitive decline and loss of cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on strategy, recombinant human erythropoietin (rhEPO) in addition to stable antipsychotic medication, may be able to improve cognitive function even in chronic schizophrenic patients. Therefore, we designed a doubleblind, placebo-controlled, randomized, multicenter, proof-of-principle (phase II) study. This study had a total duration of 2 years and an individual duration of 12 weeks with an additional safety visit at 16 weeks. Chronic schizophrenic men (N = 39) with defined cognitive deficit (X1 s.d. below normal in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)), stable medication and disease state, were treated for 3 months with a weekly short (15 min) intravenous infusion of 40 000 IU rhEPO (N = 20) or placebo (N = 19). Main outcome measure was schizophrenia-relevant cognitive function at week 12. The neuropsychological test set (RBANS subtests delayed memory, language-semantic fluency, attention and Wisconsin Card Sorting Test (WCST-64) -perseverative errors) was applied over 2 days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both placebo and rhEPO patients improved in all evaluated categories. Patients receiving rhEPO showed a significant improvement over placebo patients in schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no effects on psychopathology or social functioning. Also, a significant decline in serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that rhEPO is the first compound to exert a selective and lasting beneficial effect on cognition should encourage new treatment strategies for schizophrenia.

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Neurocognitive Effects of Clozapine, Olanzapine, Risperidone, and Haloperidol in Patients With Chronic Schizophrenia or Schizoaffective Disorder

Abstract: Patients with a history of suboptimal response to conventional treatments may show cognitive benefits from newer antipsychotic drugs, and there may be differences between atypical antipsychotic drugs in their patterns of cognitive effects.

Cited by 487 publications

References 29 publications

Reversal of Subchronic PCP-Induced Deficits in Attentional Set Shifting in Rats by Sertindole and a 5-HT6 Receptor Antagonist: Comparison Among Antipsychotics

Reversal of Subchronic PCP-Induced Deficits in Attentional Set Shifting in Rats by Sertindole and a 5-HT6 Receptor Antagonist: Comparison Among Antipsychotics

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

Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin

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