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Effect of first-generation perphenazine and second-generation antipsychotics on depressive symptoms in schizophrenia: all antipsychotics improved symptoms; quetiapine was superior to risperidone for people with major depression at baseline

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Are second-generation antipsychotics (SGAs) effective for the treatment of depressive symptoms in chronic schizophrenia? And does this effect differ from first-generation perphenazine?


1424 people with DSM-IV schizophrenia who were able to take an oral antipsychotic medication. Exclusions: people with schizoaffective disorder, mental retardation or other cognitive disorders, unstable serious medical condition, past adverse reactions to a proposed treatment, treatment-resistant schizophrenia and first episode of schizophrenia, and individuals who were pregnant or breastfeeding.


Multiple sites in the USA; January 2001 and December 2004.


Capsules of olanzapine (7.5 mg), quetiapine (200 mg), risperidone (1.5 mg), perphenazine (8 mg) or ziprasidone (40 mg). Medications were flexibly dosed with one to four capsules. Concomitant medications were permitted, with the exception of additional antipsychotics.


Depression assessed using the Calgary Depression Scale for Schizophrenia (CDSS).

Patient follow-up

Up to 18 months.



Randomised controlled trial.


Not concealed.


Partially double blinded. Exceptions: people with tardive dyskinesia (TD) were not considered in …

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