, Volume 169, Issue 3-4, pp 390-397
Date: 24 Jun 2003

Procedural learning in schizophrenia after 6 months of double-blind treatment with olanzapine, risperidone, and haloperidol

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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.

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