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Add-on estradiol effective for some women with schizophrenia

Transdermal estradiol was an effective add-on treatment for women with schizophrenia, particularly those aged older than 38 years, findings published in JAMA Psychiatry showed.

“New directions in treatment of schizophrenia are urgently needed, but as in other fields of medicine, many promising new directions for treatment have been reported, but not later replicated,” Mark Weiser, MD, from the Stanley Medical Research Institute, and colleagues wrote. “Well-replicated sex differences in the age of onset and course of schizophrenia indicate that estradiol might influence the course of schizophrenia.”

Researchers conducted an 8-week randomized, placebo-controlled trial to replicate the results of the effect of estradiol on schizophrenia in 200 premenopausal women aged 19 to 46 years with schizophrenia or schizoaffective disorder. Women were randomly allocated to receive a 200-g estradiol patch or placebo patch changed twice a week plus their antipsychotic treatment to determine the positive subscale of the Positive and Negative Syndrome Scale (PANSS).

On average, positive PANSS score was 19.6 for both groups combined at baseline and 14.4 in the placebo group vs. 13.4 in the estradiol group at week 8.

Weiser and colleagues found that women receiving add-on estradiol had statistically significant improvement in PANSS positive subscale scores (difference = –0.94; 95% CI, –1.64 to –0.24) and in PANSS total score (difference = –4.1; 95% CI, –6.73 to–1.47) as well as the PANSS subscales for negative symptoms and general psychopathology compared with those receiving placebo. They also found significantly greater improvements with estradiol vs. placebo in Clinical Global Impression Scale (CGI)–Severity score and Montgomery Depression Scale (MADRS) score.

However, post hoc analyses revealed that these effects were only evident in the 100 participants older than 38 years (46 in placebo group vs. 54 in estradiol group), with no benefit observed in younger women on estradiol over placebo (difference = 0.08 points on the PANSS positive subscale; 95% CI, –0.91 to 1.07). Breast tenderness and weight gain were more common in the estradiol than the placebo group.

“The finding of differential effects by age should be replicated,” Weiser and colleagues wrote. “Although promising, the results of the meta-analysis are not robust enough to support clinical application at this point. FDA-level studies should be performed and submitted for approval with schizophrenia as an indication.” – by Savannah Demko

Disclosure: One researcher reports owning stock in the site management organization that supported the site conducting the trial.