DHEA Augmentation Improves Schizophrenic Symptoms

Laurie Barclay, MD

February 13, 2003

Feb. 13, 2003 — Dehydroepiandrosterone (DHEA) augmentation markedly improved negative, depressive, and anxiety symptoms in patients with schizophrenia, according to the results of a small, randomized, double-blind trial reported in the February issue of the Archives of General Psychiatry.

"In humans, DHEA has demonstrated efficacy in the improvement of mood, with increased energy, interest, confidence, and activity levels in various populations," write Rael D. Strous, MD, from the Beer Yaakov Mental Health Center in Israel, and colleagues. "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."

At a large referral state hospital, 30 inpatients meeting DSM-IV criteria for schizophrenia with prominent negative symptoms received either DHEA or placebo in double-blind fashion, in addition to regular antipsychotic medication. Dosages of medications were stabilized before study entry, and DHEA was titrated up to a dose of 100 mg in divided doses over the six-week study period.

There was significant improvement in negative symptoms (P < .001), depressive symptoms (P < .05), and anxiety symptoms (P < .001) in subjects receiving DHEA, especially in women. Improvement in negative symptoms was not related to improvement in depression.

Compared with placebo, there was no difference in DHEA-treated subjects in the positive subscale of the Positive and Negative Syndrome Scale (PANSS) or on the total PANSS score, which the authors attribute to continued use of standard antipsychotic medication in both groups.

DHEA and DHEA-S plasma levels significantly increased (P < .05 and P < .01, respectively) in subjects receiving DHEA, but cortisol levels did not change. Increases in DHEA and DHEA-S plasma levels were correlated with improvement in negative symptoms (P < .05), but not with improvement in depressive and anxiety symptoms. No adverse effects were reported.

Study limitations include the relatively small sample size, short duration, and lack of standardization of antipsychotic medication. In addition to potential adverse effects on behavior, the authors note other adverse effects reported with DHEA administration including oily skin, acne, voice deepening, and hirsutism, as well as the theoretical potential for DHEA to exacerbate hormone-sensitive tumors when metabolized to testosterone and estrogen.

"DHEA demonstrates potent neuroprotective qualities and plays an important role in neurodevelopment," the authors write. "Whether DHEA administration at an earlier stage of the illness may serve as a protective factor remains unknown and merits further investigation."

Arch Gen Psychiatry. 2003;60:133-141

Reviewed by Gary D. Vogin, MD

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