Background: Antiglucocorticoids, such as ketoconazole, have been investigated as antidepressant agents in major depression and other conditions. Despite evidence that a significant number of patients with schizophrenia and schizoaffective disorder are both hypercortisolemic and depressed, the antidepressant effects of antiglucocorticoids have never been assessed in these populations. Methods: Fifteen symptomatic patients with diagnoses of schizophrenia or schizoaffective disorder, who were at least partially treatment-resistant, were treated with ketoconazole, up to 800 mg/day, (n = 8) or placebo (n = 7) for four weeks in a double-blind manner. The study medication was added to a pre-stabilized antipsychotic and/or antidepressant medication regimen. Results: Ketoconazole treatment, compared to placebo, was associated with significant improvements in observer-rated depression, but not in subjectively rated depression, positive or negative psychotic symptom ratings, or cognitive performance scores. Conclusions: These pilot data partially support the hypothesis that antiglucocorticoids reduce depressive symptoms in patients with schizophrenia and schizoaffective disorder, although objective and subjective ratings may not be similarly affected during a four-week course of treatment. Further studies with larger sample sizes, more extensive endocrine assessments and longer duration of drug administration seem warranted.
Bibliographical noteFunding Information:
This project was funded by: The National Alliance for Research on Schizophrenia and Affective Disorders, The National Alliance for the Mentally Ill and The Stanley Foundation. Active ketoconazole and placebo capsules were provided at no cost by ]aiisseri Pharmaceuticals.