Dehydroepiandrosterone augmentation in the management of negative, depressive, and anxiety symptoms in schizophrenia

Negative symptoms of schizophrenia are a prominent feature of the illness, and frequently remain refractory to treatment. Dehydroepiandrosterone (DHEA), along with its sulfated form, DHEA-S, is an important circulating neurosteroid with several vital neurophysiological functions, including the regulation of neuronal excitability and function.

Since the administration of DHEA has demonstrated improvement in mood, sense of well-being, interest, activity, and energy in several subpopulations, we investigate the efficacy of DHEA in the management of the negative symptoms of schizophrenia.

Thirty DSM-IV-diagnosed schizophrenic patients with prominent negative symptoms (inpatients in a large referral state hospital) were randomized to receive either DHEA or placebo in double-blind fashion, in addition to regular antipsychotic medication, dose-stabilized prior to study entry. The DHEA was titrated up to a dose of 100 mg in divided doses during 6 weeks.

Results indicated significant improvement in negative symptoms (P<.001), as well as in depressive (P<.05) and anxiety (P<.001) symptoms in individuals receiving DHEA. This effect was especially noted in women. The improvement in negative symptoms was independent of improvement in depression. No differences were noted on the positive symptom subscale of the Positive and Negative Syndrome Scale (PANSS) or on the total PANSS score as compared with placebo. Subjects receiving DHEA demonstrated a significant increase in DHEA (P<.05) and DHEA-S (P<.01) plasma levels, without changes in cortisol levels. Increases in DHEA and plasma DHEA-S levels were correlated with improvement in negative symptoms (P<.05), but not with improvement in depressive and anxiety symptoms. No obvious adverse effects were experienced by participating subjects.

Our preliminary observations report for the first time in double-blind fashion the efficacy of DHEA augmentation in the management of negative, depressive, and anxiety symptoms of schizophrenia. The findings from this study raise important issues regarding the role of neurosteroids in general, and DHEA in particular, in the ongoing symptomatology and pharmacotherapy of schizophrenia.