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Comparative effect of atypical and conventional antipsychotic drugs on neurocognition in first-episode psychosis: a randomized, double-blind trial of olanzapine versus low doses of haloperidol.
Am J Psychiatry. 2004 Jun; 161(6):985-95.AJ

Abstract

OBJECTIVE

The effect of antipsychotic medication on neurocognitive function remains controversial, especially since most previous work has compared the effects of novel antipsychotic medications with those of high doses of conventional medications. This study compares the neurocognitive effects of olanzapine and low doses of haloperidol in patients with first-episode psychosis.

METHOD

Patients with a first episode of schizophrenia, schizoaffective disorder, or schizophreniform disorder (N=167) were randomly assigned to double-blind treatment with olanzapine (mean modal dose= 9.63 mg/day) or haloperidol (mean modal dose=4.60 mg/day) for the 12-week acute phase of a 2-year study. The patients were assessed with a battery of neurocognitive tests at baseline and 12 weeks after beginning treatment.

RESULTS

An unweighted neurocognitive composite score, composed of measures of verbal fluency, motor functions, working memory, verbal memory, and vigilance, improved significantly with both haloperidol and olanzapine treatment (effect sizes of 0.20 and 0.36, respectively, no significant difference between groups). A weighted composite score developed from a principal-component analysis of the same measures improved to a significantly greater degree with olanzapine, compared with haloperidol. Anticholinergic use, extrapyramidal symptoms, and estimated IQ had little effect on the statistical differentiation of the medications, although duration of illness had a modest effect. The correlations of cognitive improvement with changes in clinical characteristics and with side effects of treatment were significant for patients who received haloperidol but not for patients who received olanzapine.

CONCLUSIONS

Olanzapine has a beneficial effect on neurocognitive function in patients with a first episode of psychosis. However, in a comparison of the effects of olanzapine and low doses of haloperidol, the difference in benefit is small.

Authors+Show Affiliations

Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC 27710, USA. richard.keefe@duke.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

15169686

Citation

Keefe, Richard S E., et al. "Comparative Effect of Atypical and Conventional Antipsychotic Drugs On Neurocognition in First-episode Psychosis: a Randomized, Double-blind Trial of Olanzapine Versus Low Doses of Haloperidol." The American Journal of Psychiatry, vol. 161, no. 6, 2004, pp. 985-95.
Keefe RS, Seidman LJ, Christensen BK, et al. Comparative effect of atypical and conventional antipsychotic drugs on neurocognition in first-episode psychosis: a randomized, double-blind trial of olanzapine versus low doses of haloperidol. Am J Psychiatry. 2004;161(6):985-95.
Keefe, R. S., Seidman, L. J., Christensen, B. K., Hamer, R. M., Sharma, T., Sitskoorn, M. M., Lewine, R. R., Yurgelun-Todd, D. A., Gur, R. C., Tohen, M., Tollefson, G. D., Sanger, T. M., & Lieberman, J. A. (2004). Comparative effect of atypical and conventional antipsychotic drugs on neurocognition in first-episode psychosis: a randomized, double-blind trial of olanzapine versus low doses of haloperidol. The American Journal of Psychiatry, 161(6), 985-95.
Keefe RS, et al. Comparative Effect of Atypical and Conventional Antipsychotic Drugs On Neurocognition in First-episode Psychosis: a Randomized, Double-blind Trial of Olanzapine Versus Low Doses of Haloperidol. Am J Psychiatry. 2004;161(6):985-95. PubMed PMID: 15169686.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative effect of atypical and conventional antipsychotic drugs on neurocognition in first-episode psychosis: a randomized, double-blind trial of olanzapine versus low doses of haloperidol. AU - Keefe,Richard S E, AU - Seidman,Larry J, AU - Christensen,Bruce K, AU - Hamer,Robert M, AU - Sharma,Tonmoy, AU - Sitskoorn,Margriet M, AU - Lewine,Richard R J, AU - Yurgelun-Todd,Deborah A, AU - Gur,Ruben C, AU - Tohen,Mauricio, AU - Tollefson,Gary D, AU - Sanger,Todd M, AU - Lieberman,Jeffrey A, PY - 2004/6/1/pubmed PY - 2004/6/25/medline PY - 2004/6/1/entrez SP - 985 EP - 95 JF - The American journal of psychiatry JO - Am J Psychiatry VL - 161 IS - 6 N2 - OBJECTIVE: The effect of antipsychotic medication on neurocognitive function remains controversial, especially since most previous work has compared the effects of novel antipsychotic medications with those of high doses of conventional medications. This study compares the neurocognitive effects of olanzapine and low doses of haloperidol in patients with first-episode psychosis. METHOD: Patients with a first episode of schizophrenia, schizoaffective disorder, or schizophreniform disorder (N=167) were randomly assigned to double-blind treatment with olanzapine (mean modal dose= 9.63 mg/day) or haloperidol (mean modal dose=4.60 mg/day) for the 12-week acute phase of a 2-year study. The patients were assessed with a battery of neurocognitive tests at baseline and 12 weeks after beginning treatment. RESULTS: An unweighted neurocognitive composite score, composed of measures of verbal fluency, motor functions, working memory, verbal memory, and vigilance, improved significantly with both haloperidol and olanzapine treatment (effect sizes of 0.20 and 0.36, respectively, no significant difference between groups). A weighted composite score developed from a principal-component analysis of the same measures improved to a significantly greater degree with olanzapine, compared with haloperidol. Anticholinergic use, extrapyramidal symptoms, and estimated IQ had little effect on the statistical differentiation of the medications, although duration of illness had a modest effect. The correlations of cognitive improvement with changes in clinical characteristics and with side effects of treatment were significant for patients who received haloperidol but not for patients who received olanzapine. CONCLUSIONS: Olanzapine has a beneficial effect on neurocognitive function in patients with a first episode of psychosis. However, in a comparison of the effects of olanzapine and low doses of haloperidol, the difference in benefit is small. SN - 0002-953X UR - https://www.unboundmedicine.com/medline/citation/15169686/Comparative_effect_of_atypical_and_conventional_antipsychotic_drugs_on_neurocognition_in_first_episode_psychosis:_a_randomized_double_blind_trial_of_olanzapine_versus_low_doses_of_haloperidol_ L2 - https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.161.6.985?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -