Neurocognitive Effects of Antipsychotic Medications in Patients With Chronic Schizophrenia in the CATIE Trial

Keefe, Richard S.E.; Bilder, Robert M.; Davis, Sonia M.; Harvey, Philip D.; Palmer, Barton W.; Gold, James M.; Meltzer, Herbert Y.; Green, Michael F.; Capuano, George; Stroup, T. Scott; McEvoy, Joseph P.; Swartz, Marvin S.; Rosenheck, Robert A.; Perkins, Diana O.; Davis, C. E.; Hsiao, John K.; Lieberman, Jeffrey A.

doi:10.1001/archpsyc.64.6.633

Cited by 965 publications

(613 citation statements)

References 84 publications

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“…Reductions in GABAergic interneurones in these areas have been found in post-mortem analysis from patients with schizophrenia (Benes et al, 1991;Benes and Berretta, 2001;Beasley et al, 2002;Zhang and Reynolds, 2002). We have shown that atypical but not classical antipsychotics can reverse these cognitive deficits; however, in the clinic there is differing evidence for the efficacy of atypical antipsychotics in improving cognition with the CATIE study (Lieberman, 2006;Keefe et al, 2007) and the UK Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS; Jones et al, 2006; suggesting that antipsychotics actually have a limited effect. Cognitive dysfunction is a core characteristic of schizophrenia (Sullivan et al, 1994;Elvevag and Goldberg, 2000;Kuperberg and Heckers, 2000), occurring in 75-85% of patients (Reichenberg et al, 2006), and is becoming increasingly important as impaired cognition has been implicated in poor long-term functional outcome (Marder and Fenton, 2004) which can often persist when other symptoms may be improved with treatment (Gold et al, 1991;Heinrichs, 2005).…”

Section: Introductionmentioning

confidence: 81%

Role of 5-HT receptor mechanisms in sub-chronic PCP-induced reversal learning deficits in the rat

et al. 2009

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Section: Introductionmentioning

confidence: 81%

Role of 5-HT receptor mechanisms in sub-chronic PCP-induced reversal learning deficits in the rat

et al. 2009

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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%

“…Novel antipsychotic compounds (second-generation or 'atypical' antipsychotics) such as clozapine (Fitton and Heel, 1990), olanzapine (Fulton and Goa, 1997), and sertindole (Kane and Tamminga, 1997;Azorin et al, 2006) have some beneficial effect on negative symptoms and reduced potential to produce extrapyramidal side effects, but these agents have demonstrated inconsistent effects on cognitive function in patients with schizophrenia. Depending on the type of cognitive domain measured, second-generation antipsychotics have been reported to produce improvement (Mortimer 1997;Meltzer and McGurk, 1999;Keefe et al, 2007), no effect (Hoff et al, 1996;Meltzer and McGurk, 1999), and impairment (Goldberg et al, 1993). The effect of sertindole on cognitive function has not been investigated extensively; however, a small clinical trial indicates a beneficial effect on some cognitive substrates, including executive function, in individuals diagnosed with schizophrenia (Gallhofer et al, 2007).…”

Section: Introductionmentioning

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

115

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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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“…These deficits are present at disease onset (e.g., Saykin et al, 1994), stable over time (e.g., Gold et al, 1999;Hoff et al, 1999;Kurtz et al, 2005;Stirling et al, 2003), and are only modestly affected by pharmacologic intervention for symptoms (e.g., Harvey & Keefe, 2001;Keefe et al, 2007). Particular significance has been attached to these deficits, as there are a growing number of studies showing that deficits in elementary neurocognitive function are linked to a variety of aspects of functional outcome cross-sectionally and in some cases longitudinally as well.…”

Section: Introductionmentioning

confidence: 99%

Symptoms versus neurocognition as predictors of change in life skills in schizophrenia after outpatient rehabilitation

Kurtz

Wexler

Fujimoto

et al. 2008

Schizophrenia Research

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A growing body of literature has shown that neurocognitive deficits in schizophrenia account for 20-60% of the variance in measures of outcome, and in many studies, are more closely related to outcome than symptoms (Green et al., 2000;. Most of these studies have been cross-sectional, few longitudinal studies have investigated the degree to which neurocognition and symptoms predict ability to benefit from outpatient rehabilitation, and no longitudinal studies use measures of everyday life-skills that are performance-based. In the current study we investigated the relationship between five measures of neurocognitive function, crystallized verbal ability, visual sustained vigilance, verbal learning, problem-solving, and processing speed, and two measures of symptoms, total positive and negative symptoms, and change on a performance-based measure of everyday life-skills after a year of outpatient rehabilitation. Rehabilitation consisted of both psychosocial and cognitive interventions. Forty-six patients with schizophrenia or schizoaffective disorder were studied. Results of a linear regression model revealed that verbal learning predicted a significant amount of the variance in change in performance-based measures of everyday life skills after outpatient rehabilitation, even when variance for all other variables in the model was accounted for. Measures of crystallized verbal ability, sustained visual vigilance, problem-solving, processing speed and symptoms were not linked to functional status change. These findings emphasize the importance of verbal learning for benefiting from psychosocial and cognitive rehabilitation interventions, and suggest the development of alternative rehabilitation strategies for those who do not benefit.

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Neurocognitive Effects of Antipsychotic Medications in Patients With Chronic Schizophrenia in the CATIE Trial

Cited by 965 publications

References 84 publications

Role of 5-HT receptor mechanisms in sub-chronic PCP-induced reversal learning deficits in the rat

Role of 5-HT receptor mechanisms in sub-chronic PCP-induced reversal learning deficits in the rat

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

Symptoms versus neurocognition as predictors of change in life skills in schizophrenia after outpatient rehabilitation

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