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


OBJECTIVE
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.


METHODS
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
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.


CONCLUSIONS
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.
Strous
Rael D
RD
Beer Yaakov Mental Health Center, P.O. Box 1, Beer Yaakov 70350, Israel. raels@post.tau.ac.il
Maayan
Rachel
R
Lapidus
Raya
R
Stryjer
Rafael
R
Lustig
Michal
M
Kotler
Moshe
M
Weizman
Abraham
A
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001008:Anxiety Disorders / Q000188:drug therapy / Q000523:psychology; D003687:Dehydroepiandrosterone / Q000097:blood / Q000627:therapeutic use*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D010919:Placebos; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012559:Schizophrenia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D012720:Severity of Illness Index; D012737:Sex Factors; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D010919:Placebos; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D006854:Hydrocortisone