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Estradiol for treatment-resistant schizophrenia: a large-scale randomized-controlled trial in women of child-bearing age

Molecular Psychiatry volume 20, pages 695–702 (2015)Cite this article

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Abstract

Many women with schizophrenia remain symptomatic despite optimal use of current therapies. While previous studies suggest that adjunctive oestrogen therapy might be effective, large-scale clinical trials are required before clinical applications are possible. This study is the first large-scale randomized-controlled trial in women with treatment-resistant schizophrenia. This Definitive Oestrogen Patch Trial was an 8-week, three-arm, double-blind, randomized-controlled trial conducted between 2006 and 2011. The 183 female participants were aged between 18 and 45 (mean=35 years), with schizophrenia or schizoaffective disorder and ongoing symptoms of psychosis (Positive and Negative Syndrome Scale, PANSS score>60) despite a stable dose of antipsychotic medication for at least 4 weeks. Mean duration of illness was more than 10 years. Participants received transdermal estradiol 200 μg, transdermal estradiol 100 μg or an identical placebo patch. For the 180 women who completed the study, the a priori outcome measure was the change in PANSS score measured at baseline and days 7, 14, 28 and 56. Cognition was assessed at baseline and day 56 using the Repeatable Battery of Neuropsychological Status. Data were analysed using latent growth curve modelling. Both estradiol groups had greater decreases in PANSS positive, general and total symptoms compared with the placebo group (P<0.01), with a greater effect seen for 200 μg than 100 μg estradiol. The largest effect size was for the positive subscale of PANSS in the estradiol 200 μg treatment group (effect size 0.44, P<0.01). This study shows estradiol is an effective and clinically significant adjunctive therapy for women with treatment-resistant schizophrenia, particularly for positive symptoms.

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Acknowledgements

Professor Kulkarni is the Principal Investigator and Dr Wei Wang performed the statistical analysis. This trial was funded by The Stanley Medical Research Institute, Washington USA. Grant ID: 05 T-742. The design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review and approval of the manuscript; and decision to submit the manuscript for publication were performed by the authors without interference from the funder.

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Authors and Affiliations

  1. The Monash Alfred Psychiatry Research Centre, The Alfred and Monash University Central Clinical School, Monash University, Melbourne, Australia

    J Kulkarni, E Gavrilidis, W Wang, R Worsley, P B Fitzgerald, C Gurvich & T Van Rheenen

  2. IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Australia

    M Berk

  3. Prince Henry’s Institute of Medical Research, Melbourne, Australia

    H Burger

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  1. J Kulkarni
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Correspondence to J Kulkarni.

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Kulkarni, J., Gavrilidis, E., Wang, W. et al. Estradiol for treatment-resistant schizophrenia: a large-scale randomized-controlled trial in women of child-bearing age. Mol Psychiatry 20, 695–702 (2015). https://doi.org/10.1038/mp.2014.33

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