Hostname: page-component-cd4964975-ppllx Total loading time: 0 Render date: 2023-03-28T00:54:09.677Z Has data issue: true Feature Flags: { "useRatesEcommerce": false } hasContentIssue true

Beyond Control of Acute Exacerbation: Enhancing Affective and Cognitive Outcomes

Published online by Cambridge University Press:  07 November 2014


From the perspective of efficacy, the main advantages of the group of new antipsychotic drugs, including ziprasidone, clozapine, quetiapine, olanzapine, and risperidone, are their ability to improve cognitive function. Other advantages are more selective, eg, clozapine in treatment-resistant schizophrenia, while the advantages for positive and negative symptoms in neuroleptic responsive patients are modest and sometimes difficult to demonstrate. The advantage for cognitive function is important because of abundant evidence that cognitive function is a key predictor of work and social function acquisition. The drug-induced cognitive improvement can synergize with typical rehabilitation programs and more experimental cognitive retraining programs to optimize these areas of improvement. Improved cognition also has implications for better compliance and decreased caretaker burden. It is also important to consider the efficacy of antipsychotics to improve mood and negative symptoms and to provide a biological framework for their ability to achieve these advantages over typical neuroleptic drugs. This article will provide new data on efficacy of this class of drugs relative to each other and to typical neuroleptics. Current theories linking efficacy in cognition to unique effects on cortical dopaminergic and cholinergic function and improved patterns of connectivity in the brain during cognitive task performance will be discussed. Finally, pharmacologic strategies to augment affect and cognitive improvements due to the new antipsychotic drug therapies will be discussed.

Academic Supplement
Copyright © Cambridge University Press 2003

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)



1.Kraepelin, E. Dementia Praecox and Paraphrenia. Barclay RM, trans. Edinburgh, Scotland: E&S Livingstone; 1999.Google Scholar
2.Bleuler, E. Dementia Praecox or the Group of Schizophrenias. Zinkin J, trans. New York, NY: International Universities Press; 1950.Google Scholar
3.Andreasen, NC. A unitary model of schizophrenia: Bleuler's “fragmented phrene” as schizencephaly. Arch Gen Psychiatry. 1999;56:781787.CrossRefGoogle ScholarPubMed
4.Saykin, AJ, Shtasel, DL, Gur, RE, et al.Neuropsychological deficits in neuroleptic-naive patients with first-episode schizophrenia. Arch Gen Psychiatry. 1994;51:124131.CrossRefGoogle ScholarPubMed
5.Palmer, BW, Heaton, RK, Paulsen, JS, et al.Is it possible to be schizophrenic yet neuropsychologically normal? Neuropsychology. 1997;11:437446.CrossRefGoogle ScholarPubMed
6.Meltzer, HY, McGurk, SR. The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia. Schizophr Bull. 1999;25:233255.CrossRefGoogle Scholar
7.Green, MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry. 1996;153:321330.Google Scholar
8.Green, MF. Interventions for neurocognitive deficits: editor's introduction. Schizophr Bull. 1999;25:197200.CrossRefGoogle ScholarPubMed
9.McGurk, SR, Meltzer, HY. The role of cognition in vocational functioning in schizophrenia. Schizophr Res. 2000;45:175184.CrossRefGoogle Scholar
10.Heaton, RK, Crowley, TJ. Effects of psychiatric disorders and their somatic treatment on neuropsychological test results. In: Filskov, SB, Boll, TJ, eds. Handbook of Clinical Neuropsychology. New York, NY: John Wiley & Sons; 1981:481525.Google Scholar
11.Cassens, G, Inglis, AK, Appelbaum, PS, Gutheil, TG. Neuroleptics: effects on neuropsychological function in chronic schizophrenic patients. Schizophr Bull. 1990;16:477499.CrossRefGoogle ScholarPubMed
12.Spohn, HE, Strauss, ME. Relation of neuroleptic and anti-cholinergic medication to cognitive functions in schizophrenia. J Abnorm Psychol. 1989;98:367380CrossRefGoogle Scholar
13.Meltzer, HY. Treatment-resistant schizophrenia-the role of clozapine. Curr Med Res Opin. 1997;14:120.CrossRefGoogle ScholarPubMed
14.Harvey, PD, Keefe, RS. Studies of cognitive change in patients with schizophrenia following novel antipsychotic treatment. Am J Psychiatry. 2001;158:176184.CrossRefGoogle ScholarPubMed
15.Sawaguchi, T, Goldman-Rakic, PS. D1 dopamine receptors in prefrontal cortex: involvement in working memory. Science. 1991;251:947950.CrossRefGoogle ScholarPubMed
16.Granon, S, Poucet, B, Thinus-Blanc, C, Changeux, JP, Vidal, C. Nicotinic and muscarinic receptors in the rat prefrontal cortex: differential roles in working memory, response selection and effortful processing. Psychopharmacology (Berl). 1995;119:139144.CrossRefGoogle ScholarPubMed
17.Kuroki, T, Meltzer, HY, Ichikawa, J. Effects of antipsychotic drugs on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens. J Pharmacol Exp Ther. 1999;288:774781.Google ScholarPubMed
18.Ichikawa, J, Dai, J, O'Laughlin, IA, Fowler, WL, Meltzer, HY. Atypical, but not typical, antipsychotic drugs increase cortical acetylcholine release without an effect in the nucleus accumbens or striatum. Neuropsychopharmacology. 2002;26:325339.CrossRefGoogle ScholarPubMed
19.Tollefson, GD, Sanger, TM. Negative symptoms: a path analytic approach to a double-blind, placebo- and haloperidol-controlled clinical trial with olanzapine. Am J Psychiatry. 1997;154:466474.Google ScholarPubMed
20.Moller, HJ. Novel antipsychotics and negative symptoms. Int Clin Psychopharmacology. 1998;13(suppl 3):S43S47.CrossRefGoogle ScholarPubMed
21.Arató, M, O'Connor, R, Meltzer, HY, ZEUS Study Group. A 1-year, double-blind, placebo-controlled trial of ziprasidone 40, 80 and 160 mg/day in chronic schizophrenia: the Ziprasidone Extended Use in Schizophrenia (ZEUS) study. Int Clin Psychopharmacol. 2002;17:207215.CrossRefGoogle Scholar
22.Manos, G, Stock, EG, Jody, D, Archibald, DG, Tourkodimitris, S, Marcus, RN. Long-term effects of aripiprazole on the negative symptoms of schizophrenia. Poster presented at: 156th Annual Meeting of the American Psychiatric Association; May 17-22, 2003; San Francisco, Calif.Google Scholar
23.Daniel, DG, Zimbroff, DL, Potkin, SG, Reeves, KR, Harrigan, EP, Lakshminarayanan, M. Ziprasidone 80 mg/day and 160 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 6-week placebo-controlled trial. Ziprasidone Study Group. Neuropsychopharmacology. 1999;20:491505.CrossRefGoogle ScholarPubMed
24.Keck, PE Jr, Strakowski, SM, McElroy, SL. The efficacy of atypical antipsychotics in the treatment of depressive symptoms, hostility, and suicidality in patients with schizophrenia. J Clin Psychiatry. 2000;61(suppl 3):49.Google ScholarPubMed
25.Spivak, B, Shabash, E, Sheitman, B, Weizman, A, Mester, R. The effects of clozapine versus haloperidol on measures of impulsive aggression and suicidality in chronic schizophrenia patients: an open, nonrandomized, 6-month study. J Clin Psychiatry. 2003;64:755760.CrossRefGoogle ScholarPubMed