Prominent depressive symptomatology occurs quite commonly (approximately 25% of patients) during the post-psychotic phases of schizophrenia. Despite anecdotal experience which suggests that antidepressant drugs are useful in treating this state, data to support this practice are quite limited. The data generated by the initial phases of this research grant represent the most compelling evidence which currently exists that, indeed, the addition of antidepressant medication to the neuroleptic regimen of patients with stable post-psychotic depression syndromes may be beneficial. The current research plan is designed to clarify and amplify these findings, particularly in the area of identifying the optimal duration of acute and maintenance treatment and also in the area of characterizing clinical and biological features of the syndrome potentially predictive of treatment response. Patients between the ages of 18 and 60, in good physical health, who meet Research Diagnostic Criteria for schizophrenia or schizoaffective disorder, whose psychotic symptomatology has largely abated, and who have a persistent syndrome of """"""""depression"""""""", will be studied. Patients will be stabilized on an optimal dose of fluphenazine decanoate and benztropine - the latter to rule out the akinesia syndrome. A full symptom and historical profile and the results of a dexamethasone suppression test and TRH test will be obtained for later reference. Patients will then enter a nine week double-blind trial during which either placebo or imipramine (IMI), to a maximum dose of 200 mg/day will be added to their medication regimen. Patients will have their clinical condition rated with SADS summary scales for depression and psychosis, as well as scales for demoralization, quality of life, and global functioning. Blood samples for plasma IMI and desipramine will also be obtained. Patients who had received placebo and remained depressed will subsequently be allowed to participate in an open nine week trial of IMI, similar to the double-blind trial. For those patients benefiting from the addition of IMI, a double-blind IMI discontinuation study after six months will test the value of continuation and maintenance IMI treatment. The information gained from this study will lead to more rational therapeutic use of antidepressant medications among the broad spectrum of schizophrenic patients who suffer from signs and symptoms suggestive of clinical depression.
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