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Schizophr Res. 2009 Nov;115(1):24-9. doi: 10.1016/j.schres.2009.01.004. Epub 2009 Feb 3.

Reduction of functional disability with atypical antipsychotic treatment: a randomized long term comparison of ziprasidone and haloperidol.

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  • 1Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.



Recent interest has focused on the definition and measurement of clinical remission in people with schizophrenia. This study examined the process of development of "functional remission" in a long-term comparative double-blind study of haloperidol and the atypical antipsychotic medication ziprasidone.


Community dwelling patients with schizophrenia were randomized to treatment with haloperidol (n=47) or ziprasidone dosed either once or twice daily (n=139). They were re-examined at follow-up intervals that ranged up to 196 weeks. Their community functioning was examined with the Heinrichs-Carpenter Quality of Life Scale (QLS). Total scores for occupational and interpersonal functioning and achievement of improvement milestones across the individual items were both analyzed.


Mixed model repeated measures analyses detected a significant (p<.05) treatment effect over time favoring ziprasidone for interpersonal functioning. While the mixed model was not significant for role functioning, the mean change at endpoint was significantly greater than 0 for the ziprasidone group but not the haloperidol group. Analyses of the distributions of change scores across the items showed that the number of items where endpoint scores were 5 or 6 (reflecting minimal to no impairment) was significantly higher in ziprasidone treated patients, (p=.03).


Long term treatment with ziprasidone was associated with greater functional gains than treatment with haloperidol, even when the time course of dropout was controlled. Both treatment retention and functional gains favored the atypical treatment in this long-term study. Future long-term studies will be needed to clarify the determinants of these functional changes.

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