Estrogen in severe mental illness: a potential new treatment approach.

CONTEXT Accumulating evidence suggests that estrogens may have therapeutic effects in severe mental illnesses, including schizophrenia, via neuromodulatory and neuroprotective activity. OBJECTIVE To compare the efficacy of adjunctive transdermal estradiol with that of adjunctive placebo in the treatment of acute psychotic symptoms. DESIGN Randomized, double-blind study. SETTING Patients were recruited from inpatient acute hospital wards and outpatient clinics of 2 metropolitan Melbourne general hospitals. PARTICIPANTS One hundred two women of childbearing age with schizophrenia. All participants were in an acute or chronic phase of their illness; 73 participants were outpatients and the rest were inpatients. Intervention Patients were randomized to receive 100 microg of transdermal estradiol (n = 56) or transdermal placebo (n = 46) for 28 days. MAIN OUTCOME MEASURES Psychopathological symptoms were assessed weekly with the Positive and Negative Syndrome Scale. RESULTS The addition of 100 microg of transdermal estradiol significantly reduced positive (P < .05) and general psychopathological (P < .05) symptoms during the 28-day trial period compared with women receiving antipsychotic medication alone. CONCLUSION Estradiol appears to be a useful treatment for women with schizophrenia and may provide a new adjunctive therapeutic option for severe mental illness. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00206570.