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

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.

Reactivity of perineuronal astrocytes in the prefrontal cortex in schizophrenia: an ultrastructural morphometric study

“…В одном из последних обзоров [51] показан по-зитивный эффект эстрадиола в лечении шизофрении у женщин, но не мужчин. Недавние исследования показа-ли, что эстрадиол эффективен при резистентной к тера-пии шизофрении [52].…”

Menstrual cycle characteristics in women with persistent schizophrenia

“…Given the beneficial effects of oestradiol on psychotic symptoms (Kulkarni et al, 2014) and the negative medical consequences of oligo-amenohorrea, attention to menstrual dysfunction in women with schizophrenia is an important clinical priority. These results suggest that the severity of cyclical mood symptoms should be taken into consideration whenever attempts are made to normalise menstrual cycles in women with schizophrenia.…”

“…Admissions to psychiatric units are reported to be more common in the late luteal and early follicular menstrual phase, and lowest in the high oestradiol ovulatory phase (Lande and Karamchandani, 2002). We recently reported that adjunctive treatment with high-dose oestradiol patches has an antipsychotic effect in women with treatment-resistant schizophrenia (Kulkarni et al, 2014), further adding to the weight of evidence that hormones related to the menstrual cycle play an important role in modulating the symptoms of schizophrenia.…”

Dissecting a Genomic Role of BDNF in Schizophrenia and Psychosis

“…Likewise, given the earlier onset of schizophrenia among men as well as a peak in schizophrenia cases among menopausal-aged women, 17 it is likely that estrogenic hormones are also involved in the pathophysiology of schizophrenia. 18 Indeed, schizophrenia symptomatology fluctuates over the menstrual cycle, 19 and several recent reports have provided evidence that estradiol 20 and the selective estrogen receptor modulator raloxifene 21 may be viable adjunctive treatments for aspects of schizophrenia symptomatology. As the BDNF gene contains a putative estrogen response element, 22 enabling transcriptional control of BDNF by estrogens within the brain, it is conceivable that estrogens may partially exert their protective effects via BDNF.…”