Raloxifene and Rimostil for Perimenopause-Related Depression
Condition: Perimenopausal Depression; Depression
MeSH terms: Depression; Depressive Disorder
Study type: Interventional
Phase: Phase 4

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?
    

Intervention name(s): Raloxifene; Rimostil; Transdermal Estradiol; Placebo skin patch and placebo tablets
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 60 mg a day orally administered; 1000 mg twice a day administered orally; 100 microgram per day transdermal estradiol; matched placebo skin patch to transdermal estradiol and matched tablets to either Raloxifene or Rimostil
Other intervention name(s): Evista; Alora
Intervention MeSH terms: Raloxifene Hydrochloride; Estradiol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Gonadal Steroids; Estrogen Receptor; Mood Disorders; Perimenopause; Estradiol; Depression; Estrogen Response Element; Perimenopausal; Perimenopausal Depression