DOUBLE-BLIND, PLACEBO-CONTROLLED, HORMONAL, SYNDROMAL AND EEG MAPPINGSTUDIES WITH TRANSDERMAL ESTRADIOL THERAPY IN MENOPAUSAL DEPRESSION

In a double-blind, placebo-controlled study, the antidepressant and vi gilance-promoting properties of transdermal oestrogen in post-menopaus al depression were investigated utilizing hormonal, syndromal and EEC mapping evaluations. Sixty-nine menopausal women, aged 45-60 years wit hout previous hormonal replacement therapy, diagnosed as major depress ion without psychotic or suicidal symptoms (DSM-III-R criteria), were randomly assigned to a 3-month treatment with transdermal oestradiol [ Estraderm TTS (ETTS) 50 mu g, applied twice weekly] or placebo. No oth er psychoactive medication was allowed. After removal of protocol viol ators, 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 o btained, 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 a nd 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 int er-group difference. However, EEG mapping demonstrated significant int er-drug differences in brain function, mostly over the left temporal r egion. While ETTS patients showed an in crease of alpha and alpha-adja cent theta activity and a decrease of beta activity, as well as an acc eleration 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 suggestimprovement of vigi lance 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 mark er for depression. The tolerability of ETTS was very good.