Hostname: page-component-6bf8c574d5-h6jzd Total loading time: 0.001 Render date: 2025-02-25T09:08:16.976Z Has data issue: false hasContentIssue false
  • English
  • Français

The Effect of Clozapine on Cognition and Psychiatric Symptoms in Patients with Schizophrenia

Published online by Cambridge University Press:  03 January 2018

Terry E. Goldberg ,
Richard D. Greenberg ,
Suzanne J. Griffin ,
James M. Gold ,
Joel E. Kleinman ,
David Pickar ,
S. Charles Schulz  and
Daniel R. Weinberger
Terry E. Goldberg*
Affiliation:
IRP, NIMH, Washington, DC
Richard D. Greenberg
Affiliation:
Psychiatric Institute of Washington, DC
Suzanne J. Griffin
Affiliation:
Psychiatric Institute of Washington, DC
James M. Gold
Affiliation:
IRP, NIMH, Washington, DC
Joel E. Kleinman
Affiliation:
IRP, NIMH, Washington, DC
David Pickar
Affiliation:
IRP, NIMH, Bethesda
S. Charles Schulz
Affiliation:
Case Western Reserve University, Cleveland, OH, USA
Daniel R. Weinberger
Affiliation:
IRP, NIMH, Washington, DC
*
∗Clinical Brain Disorders Branch, Intramural Research Program, NIMH Neurosciences Center at St Elizabeths, Washington, DC 20032, USA
Get access Rights & Permissions [Opens in a new window]

Abstract

Psychiatric symptoms and cognition were assessed in 13 patients with schizophrenia, one patient with schizoaffective disorder, and one patient with psychosis not otherwise specified while they received a conventional neuroleptic and again after an average of 15 months on clozapine. Despite improvements in psychiatric symptoms, attention, memory, and higher-level problem-solving were essentially unchanged. This suggests that certain cognitive deficits are relatively independent of psychotic symptoms in schizophrenia, and are probably central and enduring features of the disorder. Cognitive disability appeared to have been rate-limiting in the sample's rehabilitation, as patients' social and vocational adjustment remained marginal during the study. We also observed that treatment with clozapine was associated with a decline in some memory functions; the potent anticholinergic properties of the drug may have been responsible for this.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 162 , Issue 1 , January 1993 , pp. 43 - 48
Copyright
Copyright © The Royal College of Psychiatrists 

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.)

References

American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders (3rd edn, revised) (DSM–III–R). Washington, DC: APA.Google Scholar
Benton, A. L., Hamsher, K. deS., Varney, N. R., et al (1978a) Facial Recognition. New York: Oxford University Press.Google Scholar
Benton, A. L., Hamsher, K. deS., Varney, N. R., et al (1978b) Judgment of Line Orientation. New York: Oxford University Press.Google Scholar
Bornstein, R. A. & Yang, V. (1991) Neuropsychological performance in medicated and unmedicated patients with Tourette's disorder. American Journal of Psychiatry, 148, 468–471.Google Scholar
Brier, A., Schreiber, J. L., Dyer, J., et al (1991) NIMH longitudinal study of chronic schizophrenia: prognosis and predictors of outcome. Archives of General Psychiatry; 48, 239–246.Google Scholar
Cassens, G., Inglis, A. K., Appelbaum, P. S., et al (1990) Neuroleptics: effects on neuropsychological function in chronic schizophrenic patients. Schizophrenia Bulletin, 16, 477–499.CrossRefGoogle ScholarPubMed
Claghorn, J., Honigfeld, G., Abuzzahab, F. S., et al (1987) The risks and benefits of clozapine versus chlorpromazine. Journal of Clinical Psychopharmacology, 7, 377–384.Google Scholar
Classen, W. & Laux, G. (1988) Sensorimotor and cognitive performance of schizophrenic inpatients treated with haloperidol, flupenthixol, or clozapine. Pharmacopsychiatry, 21, 295–297.Google Scholar
Cleghorn, J. M., Kaplan, R. D., Szechtman, B., et al (1990) Neuroleptic drug effects on cognitive function in schizophrenia. Schizophrenia Research, 3, 211–219.Google Scholar
Coyle, J. T., Price, D. L. & DeLong, M. R. (1983) Alzheimer's disease: a disorder of central cholinergic innervation. Science, 219, 1184–1190.Google Scholar
DeFeillips, N. A. & McCampbell, E. (1979) The Booklet Category Test. Odessa: Psychological Assessment Resources.Google Scholar
Drachmas, D. A. & Leavitt, J. (1974) Human memory and the cholinergic system. Archives of Neurology, 30, 113–121.CrossRefGoogle Scholar
Farde, L., Wiesel, A. L., Nordstrom, G., et al (1989) D1- and D2-dopamine receptor occupancy during treatment with conventional and atypical neuroleptics. Psychopharmacology, 99 (suppl.), S28.Google Scholar
Gold, J. M. & Hurt, S. W. (1990) The effects of haloperidol on thought disorder and IQ in schizophrenia. Journal of Personality Assessment, 54, 390–400.Google Scholar
Goldberg, T. E., Weinberger, D. R., Pliskin, N. H., et al (1987) Further evidence for dementia of the prefrontal-type in schizophrenia? A controlled study of teaching the Wisconsin Card Sorting Test. Archives of General Psychiatry, 44, 1066–1072.CrossRefGoogle ScholarPubMed
Goldberg, T. E., Ragland, J. D., Torrey, E. F., et al (1990) Neuropsychological assessment of monozygotic twins discordant for schizophrenia. Archives of General Psychiatry, 47, 1066–1072.CrossRefGoogle ScholarPubMed
Goldberg, T. E., Torrey, E. F., Gold, J. M., et al (1993) Learning and memory in monozygotic twins discordant for schizophrenia. Psychological Medicine (in press).CrossRefGoogle Scholar
Guy, W. (1976) ECDEU Assessment Manual for Psychopharmacology, US Department of Health and Human Services Publication (ADM) 76–338, pp. 534–535. Rockville, MD: US Government Printing Office.Google Scholar
Heaton, R. K. (1981) The Wisconsin Card Sorting Test Manual. Odessa: Psychological Assessment Resources.Google Scholar
Heaton, R. K. & Crowley, T. J. (1981) Effects of psychiatric disorders and their somatic treatments on neuropsychological test results. In Handbook of Clinical Neuropsychology (eds Filskov, D. & Boll, T. J.), pp. 481–525. New York: Wiley.Google Scholar
Hollingshead, A. B. & Redlich, F. C. (1958) Social Class and Mental Illness. New York: Wiley.CrossRefGoogle Scholar
Jastak, S. & Wilkinson, G. S. (1985) WRAT-R2 . Wilmington: Jastak Associates.Google Scholar
Kane, J., Honigfeld, G., Singer, J., et al (1988) Clozapine for the treatment-resistant schizophrenic: a double-blind comparison with chlorpromazine. Archives of General Psychiatry, 45, 789–796.CrossRefGoogle ScholarPubMed
Kay, S. R. & Lindenmayer, J.-P. (1991) Stability of psychopathology dimensions in chronic schizophrenia: response to clozapine treatment. Comprehensive Psychiatry, 32, 28–35.CrossRefGoogle ScholarPubMed
King, D. J. (1990) The effect of neuroleptics on cognitive and psychomotor function. British Journal of Psychiatry, 157, 799–811.Google Scholar
Kolb, B. & Whishaw, I. Q. (1983) Performance of schizophrenic patients on tests sensitive to left or right frontal, temporal, or parietal function in neurological patients. Journal of Nervous and Mental Disease, 171, 435–443.CrossRefGoogle ScholarPubMed
Lalonde, F. (1985) Psychometric characteristics of a short form of the Category Test. Journal of Clinical and Experimental Neuropsychology, 6, 270.Google Scholar
Lezak, M. D. (1976) Neuropsychological Assessment. New York: Oxford University Press.Google Scholar
Louis, T. A., Lavori, P. W., Bailar, J. C., et al (1984) Crossover and self-controlled designs in clinical research. New England Journal of Medicine, 310, 24–31.Google Scholar
Medalia, A., Gold, J. M. & Merriam, A. (1988) The effects of neuroleptics on neuropsychological test results of schizophrenics. Archives of Clinical Neuropsychology, 3, 249–271.CrossRefGoogle ScholarPubMed
Meltzer, H. Y. (1989) Clinical studies in the mechanism of action of clozapine: the dopamine–serotonin hypothesis of schizophrenia. Psychopharmacology, 99 (suppl.), 18.CrossRefGoogle ScholarPubMed
Meltzer, H. Y., Bastani, B., Kwon, K. Y., et al (1989) A prospective study of clozapine in treatment-resistant schizophrenic patients. I. Preliminary report. Psychopharmacology, 99 (suppl.), 68.Google Scholar
Overall, J. E. & Gorham, D. R. (1962) The Brief Psychiatric Rating Scale. Psychological Reports, 10, 799–812.Google Scholar
Perlick, D., Stastny, P., Katz, I., et al (1986) Memory deficits and anticholinergic levels in chronic schizophrenia. American Journal of Psychiatry, 143, 230–232.Google Scholar
Povlsen, V. J., Noring, U., Fog, R., et al (1985) Tolerability and therapeutic effect of clozapine. Acta Psychiatrica Scandinavica, 71, 176–185.Google Scholar
Reitan, R. M. (1979) Manual for Administration of Neuropsychological Test Batteries for Adults and Children. Tucson: Ralph M. Reitan.Google Scholar
Richelson, E. (1980) Neuroleptics and neurotransmitter receptors. Psychiatric Annals, 10, 21–26.CrossRefGoogle Scholar
Richelson, E. (1984) Neuroleptic affinities for human brain receptors and their use in predicting adverse effects. Journal of Clinical Psychiatry, 45, 331–336.Google Scholar
Saletu, B., Grunberger, J., Kinzmayer, L., et al (1987) Comparative placebo-controlled pharmacodynamic studies with zotepine and clozapine utilizing pharmaco-EEG and psychometry. Pharmacopsychiatry, 20, 12–27.Google Scholar
Silverstein, A. B. (1985) Two and four subtest short forms of the WAIS–R: a close look at validity and reliability. Journal of Clinical Psychology, 41, 95–97.Google Scholar
Snyder, S., Greenberg, D. & Yamamura, H. I. (1974) Antischizophrenic drugs and brain cholinergic receptors. Affinity for muscarinic sites predicts extrapyramidal effects. Archives of General Psychiatry, 31, 58–61.CrossRefGoogle ScholarPubMed
Snyder, S. & Yamamura, H. I. (1977) Antidepressants and the muscarinic acetylcholine receptor. Archives of General Psychiatry, 34, 236–239.Google Scholar
Spitzer, R. L., Williams, J. B. W., Gibbon, M., et al (1990) SCID. Washington, DC: American Psychiatric Press.Google Scholar
Spohn, H. E. & Strauss, M. E. (1989) Relation of neuroleptic and anticholinergic medications to cognitive functions in schizophrenia. Journal of Abnormal Psychology, 98, 367–380.CrossRefGoogle ScholarPubMed
Taylor, M. A. & Abrams, R. (1984) Cognitive dysfunction in schizophrenia. American Journal of Psychiatry, 141, 186–201.Google Scholar
Torrey, E. F. (1988) Surviving Schizophrenia: A Family Manual. New York: Harper & Row.Google Scholar
Tune, L. E., Strauss, M. E., Lew, M. F., et al (1982) Serum levels of anticholinergic drugs and impaired recent memory in chronic schizophrenic patients. American Journal of Psychiatry, 139, 1460–1462.Google ScholarPubMed
Van Tol, H. H. M., Bunzow, J. R., Guan, H.-C., et al (1991) Cloning of the gene for a human dopamine D4 receptor with higher affinity for the antipsychotic clozapine. Nature, 350, 610–611.Google Scholar
Wechsler, D. (1981) WAIS–R. New York: Psychological Corporation.Google Scholar
Wechsler, D. & Stone, L. P. (1985) The Wechsler Memory Scale. New York: Psychological Corporation.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.