- Objectives: Although depression is a recognized side effect of many medications, the association of this condition with neuroleptics has received limited attention in the literature. Atypical antipsychotics may demonstrate a beneficial effect on affective symptoms. On the other hand, they may also cause depression both in those with and without a history of psychiatric illness. Although ziprasidone has been reported to have antidepressive properties, we are not aware of reports regarding ziprasidone-induced depression. Methods: We describe 3 cases of ziprasidone-associated depression in patients treated for schizophrenia who had no previous history of depressive illness. To the best of our knowledge, this is the first description of such an association. Conclusions: This case series suggests that atypical antipsychotics may have a causal relationship in the development of depression in schizophrenic patients. This is noteworthy because these medications have been found in the past to have an antidepressant action. If neuroleptic-induced depression is mistaken for negative symptoms of schizophrenia, this condition may go untreated. Further data based on controlled studies are required.