Double-blind, placebo-controlled, hormonal, syndromal and EEG mapping studies with transdermal oestradiol therapy in menopausal depression.
In a double-blind, placebo-controlled study, the antidepressant and vigilance-promoting properties of transdermal oestrogen in post-menopausal depression were investigated utilizing hormonal, syndromal and EEG mapping evaluations. Sixty-nine menopausal women, aged 45-60 years without previous hormonal replacement therapy, diagnosed as major depression without psychotic or suicidal symptoms (DSM-III-R criteria), were randomly assigned to a 3-month treatment with transdermal oestradiol [Estraderm TTS (ETTS) 50 micrograms, applied twice weekly] or placebo. No other psychoactive medication was allowed. After removal of protocol violators, 32 patients were evaluable in each group, which did not differ in age, height or weight. As five patients discontinued prematurely in both groups and in one placebo patient a post-drug EEG could not be obtained, 27 patients remained in the ETTS and 26 in the placebo group for efficacy analysis. While in the placebo group, oestradiol (E2) and follicle stimulating hormone (FSH) remained unchanged, E2 increased and FSH decreased significantly in the ETTS group. Syndromal evaluation showed a significant improvement in the Kupperman Index (KI) as well as Hamilton Depression Rating Scale (HAMD) in both groups, with no inter-group difference. However, EEG mapping demonstrated significant inter-drug differences in brain function, mostly over the left temporal region. While ETTS patients showed an increase of alpha and alpha-adjacent theta activity and a decrease of beta activity, as well as an acceleration of the delta/theta centroid and a slowing of the alpha, beta and total power centroid, no changes occurred in the placebo-treated patients. These neurophysiological findings suggest improvement of vigilance by oestrogen, previously referred to as "mental tonic" effect. There were no changes, however, in the frontal alpha asymmetry index, reflecting left frontal hypo- and right frontal hyperactivation. Thus, this neurophysiological variable represents a state-independent marker for depression. The tolerability of ETTS was very good.
Saletu
B
B
Department of Psychiatry, University of Vienna, Austria.
Brandstätter
N
N
Metka
M
M
Stamenkovic
M
M
Anderer
P
P
Semlitsch
H V
HV
Heytmanek
G
G
Huber
J
J
Grünberger
J
J
Linzmayer
L
L
D000279:Administration, Cutaneous; D001931:Brain Mapping; D003692:Delayed-Action Preparations; D003863:Depression / Q000188:drug therapy* / Q000209:etiology; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy; D005260:Female; D005640:Follicle Stimulating Hormone / Q000096:biosynthesis; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D017698:Postmenopause / Q000187:drug effects*
D003692:Delayed-Action Preparations; D004958:Estradiol; D005640:Follicle Stimulating Hormone