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

Scot E. Purdon, Neil Woodward, Stacy R. Lindborg, Emmanuel Stip

Research output: Contribution to journalArticlepeer-review

62 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)390-397
Number of pages8
Issue number3-4
Publication statusPublished - Sept 2003
Externally publishedYes


  • Dorsal striatum
  • Haloperidol
  • Olanzapine
  • Procedural learning
  • Risperidone
  • Schizophrenia

ASJC Scopus subject areas

  • Pharmacology


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