Abstract
Rationale
First generation antipsychotics induce extrapyramidal motor symptoms (EPS), presumably through dopamine D2 receptor blockade at the dorsal striatum. This may also produce impairment of cognitive processes, such as procedural learning, that are dependent on this region. Haloperidol and, to a lesser extent, risperidone, are active in the dorsal striatum and may induce EPS and impairment of procedural learning. In contrast, the prototypical second-generation antipsychotic, clozapine, is less active in the dorsal striatum and does not induce EPS or impair procedural learning. Olanzapine is pharmacologically similar to clozapine and has a low incidence of EPS induction.
Objectives
To assess the hypothesis that olanzapine would not have a deleterious effect on procedural learning.
Methods
Thirty-nine subjects with early phase schizophrenia were randomly assigned to double blind treatment with haloperidol, risperidone, or olanzapine. They were administered the Tower of Toronto test at an unmedicated baseline and again following 6 weeks and 6 months of treatment.
Results
Procedural learning, defined as the improvement observed between two blocks of five trials of the Tower of Toronto, was preserved after 6 weeks of all three treatments but showed a substantial decline after 6 months of treatment with haloperidol or risperidone.
Conclusions
These data are consistent with the differential activity of the three medications in dorsal striatum structures and suggest that the advantages of olanzapine over haloperidol and risperidone in relation to extrapyramidal syndromes may also generalize to procedural learning. The results also suggest that the procedural learning disadvantages of haloperidol and risperidone accrue slowly but are apparent after 6 months of treatment.
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References
Bedard MA, Scherer H, Delorimier J, Stip E, Lalonde P (1996) Differential effects of D2 and D4 blocking neuroleptics on the procedural learning of schizophrenic patients. Can J Psychiatry 41:S21–S24
Bedard MA, Scherer H, Stip E, Cohen H, Rodriguez JP, Richer F (2000) Procedural learning in schizophrenia: further consideration on the deleterious effect of neuroleptics. Brain Cognit 43:31–39
Buchanan RW, Holstein C, Breier A (1994) The comparative efficacy and long term effect of clozapine treatment on neuropsychological test performance. Biol Psychiatry 36:717–725
Chouinard G, Jones B, Remington G, Bloom, Addington D, MacEwan GW, Labelle A, Beauclair L, Arnott W (1993) A Canadian multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. J Clin Psychopharmacol 13:25–40
Clare L, McKenna PJ, Mortimer AM, Baddeley AD (1993) Memory in schizophrenia: what is impaired and what is preserved. Neuropsychologia 31:1225–1241
Cohen NJ, Eichenbaum H, Deacedo BS, Corkin S (1985) Different memory systems underlying acquisition of procedural and declarative knowledge. Ann NY Acad Sci 444:54–71
Danion JM, Peretti S, Grange D, Bilik M, Imbs JL, Singer L (1992) Effects of chlorpromazine and lorazepam on explicit memory, repetition priming, and cognitive skill learning in healthy volunteers. Psychopharmacology 108:345–351
Farde L, Nordstrom AL, Wiesel FA, Pauli S, Halldin C, Sedval G (1992) Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Arch Gen Psychiatry 49:538–544
Gabrieli JDE (1998) Cognitive neuroscience of human memory. Annu Rev Psychol 49:87–115
Goldberg TE, Saint-Cyr JA, Weinberger DR (1990) Assessment of procedural learning and problem solving in schizophrenic patients by Tower of Hanoi type tasks. J Neuropsychiatr Clin Neurosci 2:165–173
Grafton ST, Mazziotta JC, Presty S, Friston KJ, Frackowiak RSJ, Phelps ME (1992) Functional anatomy of human procedural learning determined with regional cerebral blood flow and PET. J Neurosci 12:2542–2548
Granholm E, Bartzokis G, Asarnow RF, Marder SR (1993) Preliminary associations between motor procedural learning, basal ganglia T2 relaxation times, and tardive dyskinesia in schizophrenia. Psychiatr Res Neuroimaging 50:33–44
Gras-Vincendon AG, Danion JM, Grange D, Bilik M, Willard-schroeder D, Sichel JP, Singer L (1994) Explicit memory, repetition priming and cognitive skill learning in schizophrenia. Schizophr Res 13:117–126
Green MF, Marshall BD Jr, Wirshing WC, Ames D, Marder SR, McGurk S, Kern RS, Mintz J (1997) Does risperidone improve verbal working memory in treatment-resistant schizophrenia? Am J Psychiatry 154:799–804
Harrington DL, Haaland KY, Yeo RA, Marder E (1990) Procedural memory in Parkinson's disease: impaired motor but not visuo-perceptual learning. J Clin Exp Neuropsychol 12:323–339
Heindel WC, Salmon DP, Shults CW, Walicke PA, Butters N (1989) Neuropsychological evidence for multiple implicit memory systems: a comparison of Alzheimer's, Huntington's, and Parkinson's disease patients. J Neurosci 9:582–587
Kapur S, Zipursky R, Roy P, Jones C, Remington G, Reed K, Houle S (1997) The relationship between D2 receptor occupancy and plasma levels on low dose oral haloperidol: a PET study. Psychopharmacology 131:148–152
Kapur S, Zipursky RB, Remington G, Jones C, DaSilva J, Wilson AA, Houle S (1998) 5-HT2 and D2 receptor occupancy of olanzapine in schizophrenia: a PET investigation. Am J Psychiatry 155:921–928
Kapur S, Zipursky RB, Remington G (1999) Clinical and theoretical implications of 5-HT2 and D2 receptor occupancy of clozapine, risperidone, and olanzapine in schizophrenia. Am J Psychiatry 156:286–293
Kay SR, Opler LA, Fiszbein A (1992) Positive and Negative Syndrome Scale (PANSS) manual. Multi-Health Systems Inc., North Tonawanda, N.Y.
Keefe RS, Silva SG, Perkins DO, Lieberman JA (1999) The effects of atypical antipsychotic drugs on neurocognitive impairment in schizophrenia: a review and meta-analysis. Schizophr Bull 25:201–222
Kern RS, Green MF, Marshall Jr. BD, Wirshing WC, Wirshing D, McGurk S, Marder SR, Mintz J (1998) Risperidone vs. haloperidol on reaction time, manual dexterity, and motor learning in treatment-resistant schizophrenia patients. Biol Psychiatry 44:726–732
Kimura V, Corr PJ, Mulligan OF, Cotter PA, Checkley SA, Gray JA (1997) Effects of acute administration of d-amphetamine and haloperidol on procedural learning in man. Psychopharmacology 129:271–276
Kornetsky C, Humphries O (1957) Relationship between effects of a number of centrally acting drugs and personalty. AMA Arch Neurol Psychiatry 77:325–327
Kornetsky C, Pettit M, Wynne R (1959) A comparison of the psychological effects of acute and chronic administration of chlorpromazine and secobarbital (quinalbarbitone) in schizophrenia patients. J Ment Sci 105:190–198
Leucht S, Pitschel-Walz G, Abraham D, Kissling W (1999) Efficacy and extrapyramidal side-effects of the new antipsychotics olanzapine, quetiapine, risperidone, and sertindole compared to conventional antipsychotics and placebo. A meta-analysis of randomized controlled trials. Schizophr Res 35:51–68
Martone M, Butters N, Payne M, Becker JT, Sax DS (1984) Dissociations between skill learning and verbal recognition in amnesia and dementia. Arch Neurol 41:965–970
Obeso JA, Rodriguez MC, DeLong MR (1997) Basal ganglia pathophysiology: a critical review. In: Obeso JA, DeLong MR, Ohye C, Marsden CD (eds) The basal ganglia and new surgical approaches for Parkinson's disease. Lippinicott-Raven, Philadelphia, pp 3–18
Peretti CS, Danion JM, Kauffmann-Muller F, Grange D, Patat A, Rosenzweig P (1997) Effects of haloperidol and amisulpride on motor and cognitive skill learning in healthy volunteers. Psychopharmacology 131:329–338
Poldrack RA, Prabhakaran V, Seger CA, Gabrieli JD (1999) Striatal activation during acquisition of a cognitive skill. Neuropsychology 13:564–574
Purdon SE (1999) Cognitive improvement in schizophrenia with novel antipsychotic medications. Schizophr Res 35:S51–60
Purdon SE, Mohr E, Ilivitsky V, Jones BD (1994) Huntington's disease: pathogenesis, diagnosis and treatment. J Psychiatr Neurosci 19:359–367
Purdon SE, Jones BD, Stip E, Labelle A, Addington D, David SR, Breier A, Tollefson GD (2000) Neuropsychological change in early phase schizophrenia during 12 months of treatment with olanzapine, risperidone, or haloperidol. Arch Gen Psychiatry 57:249–258
Purdon SE, Malla A, LaBelle A, Lit W (2001a) Neuropsychological change in schizophrenia after 6 months of double blind treatment with quetiapine or haloperidol. J Psychiatr Neurosci 26:137–149
Purdon SE, LaBelle A, Boulay L (2001b) Neuropsychological change in schizophrenia with 6 weeks of clozapine. Schizophr Res 48:57–67
Purdon SE, Woodward ND, Mintz AR, Labelle A (2002) Procedural learning following 6 weeks treatment with clozapine. Schizophr Res 53:165–166
Reading PJ, Dunnett SB, Robbins TW (1991) Dissociable roles of the ventral, medial, and lateral striatum on the acquisition and performance of a complex visual stimulus-response habit. Behav Brain Res 45:147–161
Saint-Cyr JA, Taylor AE, Lang AE (1988) Procedural learning and neostriatal dysfunction in man. Brain 111:941–959
Schmand B, Brand N, Kuipers T (1992) Procedural learning of cognitive and motor skills in psychotic patients. Schizophr Res 8:157–170
Schwartz BL, Rosse RB, Veazay C, Deutsch SI (1996) Impaired motor skill learning in schizophrenia: implications for corticostriatal dysfunction. Biol Psychiatry 39:241–248
Spohn HE, Strauss ME (1989) Relation of neuroleptic and anticholinergic medication to cognitive functions in schizophrenia. J Abnorm Psychol 98:367–380
Stevens A, Schwarz J, Schwarz B, Ruf I, Kolter T, Czekalla J (2002) Implicit and explicit learning in schizophrenics treated with olanzapine and with classic neuroleptics. Psychopharmacology 160:299–306
Tandon R, Milner K, Jibson MD (1999) Antipsychotics from theory to practice: integrating clinical and basic data. J Clin Psychiatry 60:21–28
Acknowledgements
This work was supported by an investigator initiated grant from Eli Lilly and Company.
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A preliminary draft of this paper was presented at the 29th Annual Meeting of the International Neuropsychological Society, Chicago, February 14–18, 2001; and the 5th Biennial Mt Sinai Conference on Cognition in Schizophrenia, Whistler, BC, April 28 to May 2, 2001
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Purdon, S.E., Woodward, N., Lindborg, S.R. et al. Procedural learning in schizophrenia after 6 months of double-blind treatment with olanzapine, risperidone, and haloperidol. Psychopharmacology 169, 390–397 (2003). https://doi.org/10.1007/s00213-003-1505-z
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DOI: https://doi.org/10.1007/s00213-003-1505-z