Double-blind antiglucocorticoid treatment in schizophrenia and schizoaffective disorder: A pilot study

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.