© Copyright 2003 The British Pharmacological Society
University of Surrey
Summer Meeting June 2003
clinical trial of adjunctive estrogen treatment in women with cronic
schizophrenia: a double blind and placebo controlled study
2, A.A. Nejatisafa1 & H. Amini1.
Hospital, Tehran University of Medical Sciences; 2Institute
of Medicinal Plants, Tehran, Iran.
Schizophrenia is a chronic
progressive disease and it affects more than 1% of the population. The
etiology of schizophrenia remains unknown in a majority of cases (Mohammadi
and Akhondzadeh, 2001). The estrogen hypothesis of schizophrenia postulates
that estrogen exerts a protective effect against schizophrenia and that
has partly explained the observed sex differences in premorbid adjustment,
onset age, treatment response and illness course. It has been suggested
that estrogen supplementation can augment the treatment effects of antipsychotics
(Grigoriadis and Seeman, 2002). The purpose of the present investigation
was to access the efficacy of ethinylestradiol as an adjuvant agent in
the treatment of premenopausal women with chronic schizophrenia in a 8
week double blind and placebo controlled trial.
Eligible participations in the study were 32 women of child-bearing age
with acute schizophrenia. All patients were inpatients and were Caucasian,
in the active phase of illness, and met DSM-IV criteria for chronic schizophrenia.
The minimum score of 60 on positive and negative syndrome scale (PANSS)
was required for entry into the study. Patients were allocated in a random
fashion, 16 to haloperidol 15 mg/day plus ethinylestradiol 0.05 mg/day
and 16 to haloperidol 15 mg/day plus placebo for a 8-week, double-blind,
placebo-controlled study. Patients were assessed by a psychiatrist at
baseline and after 2, 4, 6 and 8 weeks after the medication started. The
mean decrease in PANSS score from baseline was used as the main outcome
measure of schizophrenia to treatment. A two-way repeated measures analysis
of variance (time- treatment interaction) was used. The two groups as
a between-subjects factor (group) and the five measurements during treatment
as the within-subjects factor (time) were considered. In addition, a one-way
repeated measures analysis of variance with a two-tailed post-hoc Tukey
mean comparison test were performed in the change from baseline in each
group. To compare the two groups at baseline and the outcome of two groups
at the end of the trial, an unpaired Student's t-test with a two-sided
P value was used. To compare the demographic data, Fisher's exact test
Although both protocols significantly decreased the score of the positive,
negative and general psychopathological symptoms over the trial period,
the combination of haloperidol and ethinylestradiol showed a significant
superiority over haloperidol alone in the treatment of positive symptoms,
general psychopathology symptoms as well as PANSS total scores (Greenhouse-Geisser
corrected: F=6.17, d.f.=1, P=0.019; F=4.27, d.f =1, P=0.047 and F=6.72,
d.f.=1, P=0.015 respectively). No significant differences were observed
between the two protocols on the negative scores (F=0.088, d.f.=1, P=0.76).
The results of this study suggest that estrogen may be an effective adjuvant
agent in the management of women of child-bearing age with acute schizophrenia.
Nevertheless, results of larger controlled trials are needed, before recommendation
for a broad clinical application can be made.
Grigoriadis, S. & Seeman, M.V. (2002). Can. J. Psychiatry 47,
Mohammadi, M.R. & Akhondzadeh, S. (2001). IDrugs 4,