Clinical trial NCT00030147
Conditions: Perimenopausal Depression Depression
Keywords: Gonadal Steroids Estrogen Receptor Mood Disorders Perimenopause Estradiol Depression Estrogen Response Element Perimenopausal Perimenopausal Depression
Sponsor: National Institute of Mental Health (NIMH)
Start date: 2002-02-01; Completion date: 2015-06-01
Enrollment: 65 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the effectiveness of the drugs raloxifene and rimostil in treating perimenopause-related depression.

Perimenopause-related mood disorders cause significant distress to a large number of women; the demand for effective therapies to treat these mood disorders is considerable. Estradiol replacement therapy (ERT) has demonstrated efficacy in treating perimenopause-related depression. Unfortunately, there are long-term risks associated with ERT. Selective estrogen receptor modulators (SERMS), such as raloxifene, and phytoestrogens, such as rimostil, have estrogen-like properties and may offer a safer alternative to ERT. The effect of SERMS and phytoestrogens on mood and cognitive functioning need to be examined in women with perimenopause-related depression.

Participants in this study will undergo a medical history, physical examination, electrocardiogram (EKG), and blood and urine tests. They will then be randomly assigned to receive one of four treatments for 8 weeks: raloxifene pills plus a placebo (an inactive substance) skin patch, rimostil pills plus placebo skin patch, estradiol skin patch plus placebo pills, or placebo patch plus placebo pills. Participants will have clinic visits every 2 weeks. During the visits, blood will be drawn and participants will meet with staff members and complete symptom self-rating scales. A urine and blood sample will be collected at the beginning and end of the study. At the end of the study, participants who received placebo or whose study medication was ineffective will be offered treatment with standard antidepressant medications for 8 weeks. Non-menstruating women will receive progesterone for 10 days to induce menstrual bleeding and shedding of the inner layer of the uterus, which may have been stimulated by the study medications.

Detailed description:
Perimenopause-related mood disorders cause significant distress to a potentially large number of women. The demand for effective therapeutic alternatives to estrogen for treating these mood disorders is considerable, as is the need to define clinical or biologic markers that may predict successful response of mood disturbances to phytoestrogens or selective estrogen receptor modulators (SERMs). Further, the study of potential biological mechanisms underlying both perimenopause-related mood disorders and their response to treatment may offer the possibility of uncovering some etiopathogenic mechanisms involved in these and related mood disorders.

Results of protocol # 90-M-0077 demonstrated the therapeutic efficacy of estradiol therapy (ET) in perimenopausal depression, independent of its effects on vasomotor symptoms. Nevertheless, the long term risks of ET to endometrial and breast tissues continue to deter many women from its use. Recently, selective estrogen receptor modulators (SERMs) and phytoestrogens (plant-derived estrogen-like compounds) have become available and are reported to display both tissue-specific profiles of estrogen agonist and antagonist actions and differential affinities for the two forms of estrogen receptor. For many women, these novel compounds would represent a safer alternative to ET for the prevention of osteoporosis and the treatment of menopausal symptoms. However, the effects of SERMs and phytoestrogens on mood and cognitive function in perimenopausal women remain undetermined.

In this protocol we wish both to investigate the effects of SERMs and phytoestrogens on mood and cognition under placebo controlled conditions and to compare these effects with estradiol therapy. This protocol will address the following questions: 1) Do selective estrogen receptor modulators or phytoestrogens improve mood and cognition in perimenopausal depressed women? 2) Are the mood and cognitive effects of SERMs and phytoestrogens comparable to those of ET? and 3) Do selective estrogen receptor modulators and phytoestrogens improve measures of bone metabolism in perimenopausal depressed women?

Arms: arm 1: Raloxifene (Evista) 60 mg per day and placebo skin patch for eight weeks arm 2: Rimostil (phytoestrogen) 1000 mg twice a day and placebo skin patch for eight weeks arm 3: 17-beta estradiol 100 micrograms a day by skin patch and placebo tablets for eight weeks arm 4: Placebo skin patch and placebo tablets for eight weeks.
Interventions: intervention 1: Raloxifene intervention 2: Rimostil intervention 3: Transdermal Estradiol intervention 4: Placebo skin patch and placebo tablets
Intervention descriptions: intervention 1: 60 mg a day orally administered intervention 2: 1000 mg twice a day administered orally intervention 3: 100 microgram per day transdermal estradiol intervention 4: matched placebo skin patch to transdermal estradiol and matched tablets to either Raloxifene or Rimostil

Protocol documents: