There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
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.
Despite the frequent use of the Positive and Negative Syndrome Scale (PANSS) for rating the symptoms of schizophrenia, the clinical meaning of its total score and of the cut-offs that are used to define treatment response (e.g. at least 20% or 50% reduction of the baseline score) are as yet unclear. We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions (CGI). PANSS and CGI ratings at baseline (n = 4091), and after one, two, four and six weeks of treatment taken from a pooled database of seven pivotal, multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking. Being considered "mildly ill" according to the CGI approximately corresponded to a PANSS total score of 58, "moderately ill" to a PANSS of 75, "markedly ill" to a PANSS of 95 and severely ill to a PANSS of 116. To be "minimally improved" according to the CGI score was associated with a mean percentage PANSS reduction of 19%, 23%, 26% and 28% at weeks 1, 2, 4 and 6, respectively. The corresponding figures for a CGI rating "much improved" were 40%, 45%, 51% and 53%. The results provide a better framework for understanding the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations. Such studies may ideally use at least a 50% reduction from baseline cut-off to define response rather than lower thresholds. In treatment resistant populations, however, even a small improvement can be important, so that a 25% cut-off might be appropriate.
We examined the efficacy of estrogen in the treatment of depression in perimenopausal women with and without hot flushes. Women with perimenopause-related depression were randomized in a double-blind parallel design to receive either 17beta-estradiol or placebo for 3 weeks. Subsequently, women receiving estradiol during the first 3 weeks continued receiving estradiol for an additional 3 weeks, whereas women who had received placebo crossed over to estradiol for 3 weeks. Outcome measures included standardized mood rating scales and a visual analog scale self-report instrument. Of 34 female subjects, 16 received estradiol first and 18 received placebo first. After 3 weeks of estradiol, standardized mood rating scale scores and visual analog scale symptom scores (eg, sadness, anhedonia, and social isolation) were significantly decreased compared with baseline scores (P <.01) and were significantly lower than scores in women receiving placebo (P <.01), who showed no significant improvement. Neither the presence of hot flushes nor the duration of treatment (3 weeks vs 6 weeks) influenced outcome. A full or partial therapeutic response was seen in 80% of subjects receiving estradiol and 22% of those receiving placebo. In this preliminary study estradiol replacement effectively treats perimenopausal depression independent of its salutary effects on vasomotor symptoms.