The neurocognitive effects of low-dose haloperidol: A two-year comparison with risperidone

Michael F. Green, Stephen R. Marder, Shirley M. Glynn, Susan R. McGurk, William C. Wirshing, Donna A. Wirshing, Robert P. Liberman, Jim Mintz

Research output: Contribution to journalArticlepeer-review

197 Scopus citations


Background: Neurocognitive deficits are core features of schizophrenia that are linked to functional outcome for the disorder. Recent studies and reviews have concluded that newer antipsychotic medications are better for neurocognitive deficits than conventional antipsychotic medications; however, one difficulty in interpreting this literature is that the comparisons have mainly been with high doses of conventional medications. This study examined the neurocognitive effects of low-dose haloperidol compared with risperidone over a 2-year period. Methods: Sixty-two patients were randomly assigned to medication (starting at 6 mg of each medication) and administered neurocognitive batteries six times over the course of follow-up. At 6 months, the mean dose of haloperidol was 5.0 mg, and the mean dose of risperidone was 6.0 mg. Neurocognitive data were reduced into cluster scores and a global summary score. Results: We found no significant overall differences in treatment effects on the cluster scores or the global score. The global score revealed a significant group by time interaction, reflecting the fact that the haloperidol group tended to improve initially and then stay stable, whereas the risperidone group improved more gradually over the follow-up period. Conclusions: This study did not provide support for neurocognitive advantages of a newer antipsychotic medication over a low-dose conventional medication. We speculate that conventional medications may have neurocognitive benefits at low doses that are neutralized or reversed at higher doses.

Original languageEnglish
Pages (from-to)972-978
Number of pages7
JournalBiological Psychiatry
Issue number12
StatePublished - 15 Jun 2002
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by Grant MH41573 to Dr. Marder and by the Research Service of the Department of Veterans Affairs. The Janssen Research Foundation provided medication for this study. The authors thank Sun Hwang, M.S., M.P.H. for help with the statistical analyses and Mark McGee for help in preparing the graphics.


  • Antipsychotic medications
  • Cognitive deficits
  • Haloperidol
  • Neurocognition
  • Risperidone
  • Schizophrenia


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