Background: Dehydroepiandrosterone (DHEA) augmentation has been reported, in a preliminary fashion, to be useful in the management of schizophrenia symptoms and side effects. In this study, the intention was to investigate the efficacy and safety of DHEA administration to ongoing antipsychotic medication in a multicenter, 12-week, double-blind, randomized, placebo-controlled, crossover trial.
Methods: Fifty-five of 62 inpatients and outpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of schizophrenia completed the trial. Patients were randomly allocated to 2 treatment groups receiving either DHEA (200 mg/d) or placebo for 6 weeks with the crossover between DHEA and placebo occurring after 6 weeks. Patients continued to receive their regular antipsychotic medication for the duration of the study.
Results: Compared with placebo, DHEA administration did not produce significant improvement in clinical symptoms, side effects, and quality-of-life scores. However, 6 weeks of DHEA administration (but not placebo) was associated with a significant improvement in Positive and Negative Symptom Scale ratings compared with baseline. Furthermore, 6 weeks of DHEA treatment was associated with significant improvement in cognitive functions of visual sustained attention and visual and movement skills compared with placebo conditions. The DHEA augmentation was associated with elevations of serum concentrations of both DHEA and its sulfate ester. The DHEA treatment was well tolerated without any serious adverse effects.
Conclusion: This short-term study does not support DHEA's value as an effective adjunct in the treatment of symptoms, side effects, and quality-of-life impairment in schizophrenia, while suggesting that DHEA improves sustained attention and visual and movement skills. A long-term, large-scale study with a broader dose range is warranted to further investigate DHEA's role in the management of schizophrenia.