Adjunctive transdermal oestradiol improves positive symptoms and general psychopathology in women with schizophrenia.

ED FROM Kulkarni J, de Castella A, Fitzgerald PB, et al. Estrogen in severe mental illness—A potential new treatment approach. Arch Gen Psychiatry 2008;65:955–60. Correspondence to: Jayashri Kulkarni, Alfred Psychiatry Research Centre, The Alfred and Monash University, School of Psychology, Psychiatry and Psychological Medicine, The Alfred Hospital, First Floor, Old Baker Bldg, Commercial Road, Melbourne, Victoria, 3004, Australia; [email protected] Source of funding: Stanley Medical Research Institute and the National Health and Medical Research Council of Australia. C O M M EN TA R Y E pidemiological investigations have demonstrated that schizophrenia is expressed differently with regard to age at onset, severity of symptoms, course and outcome between genders. Oestrogens and other gonadal hormones influence human emotions, cognition and behaviour and might have an impact on schizophrenic symptomatology. Clinical and animal studies have demonstrated the protective effect of oestrogen in schizophrenia while previous open label and double blind, placebo controlled clinical trials had pointed out the beneficial effect on controlling psychotic symptoms in women receiving oestradiol as an adjunctive therapy to antipsychotics. The present study indicates that addition of 100 g of transdermal oestradiol in a clinically heterogeneous (acutely ill, chronic, treatment resistant) sample of women with schizophrenia significantly improves the efficacy of antipsychotics to reduce positive symptoms in the short term (4 weeks). Women were of childbearing age with normal oestradiol levels; no significant adverse side effects were reported in the active treatment group. Notably, thorough analysis of the results (total PANSS total and positive symptoms scores) seems to show that the significant differences between groups might be mediated by lack of response to treatment in the control group. Unfortunately, the effect size of the reported clinical changes is not reported. The fact that no significant differences were found in negative symptom improvement is also somewhat disappointing. I believe that the improvement in negative and cognitive symptoms is the real challenge that psychopharmacology should face in schizophrenia during the next few years. The clinical heterogeneity of the sample and the short evaluative time span weaken the study’s design and, therefore, generalisation of these findings to clinical practice. While it is not currently possible to recommend oestrogens as adjunctive therapy in schizophrenia, the available evidence is strong enough to justify the continuation of well designed studies to reveal what benefit oestrogens may bring to the treatment of schizophrenia. Benedicto Crespo-Facorro, MD, PhD, Rocio PerezIglesias, MD, PhD, Ignacio Mata, MD, PhD Centro de Investigacion Biomedica en Red en Salud Mental (CIBERSAM), Department of Psychiatry, University of Cantabria, Schizophrenia Research Program, Hospial Marques de Valdecilla, Santander, Spain Competing interests: BCF has received unrestricted research funding from AstraZeneca, Pfizer, Bristol-Myers Squibb and Johnson & Johnson, and consultant fees from Pfizer. 1. Chua WL, de Izquierdo SA, Kulkarni J, et al. Estrogen for schizophernia. Cochrane Database Syst Rev 2005;4: CD004719. 2. Riecher-Rössler A, de Geyter C. The forthcoming role of treatment with oestrogens in mental health. Swiss Med Wkly 2007;137:65–72. Therapeutics EBMH May 2009 Vol 12 No 2 55 group.bmj.com on April 20, 2017 Published by http://ebmh.bmj.com/ Downloaded from