Anti-Estrogens - A Potential Treatment for Bipolar Affective Disorder in Women?

• Status: Completed
• Trial end date: 2007-12-01
• Target enrollment: 0
• Participant gender: Female

Summary

OBJECTIVE:

To test the use of two adjunctive hormonal agents in a 28 day three-arm, double-blind, placebo-controlled study in the treatment of acute mania/hypomania.

HYPOTHESIS:

That women receiving adjunctive Tamoxifen or Progesterone will demonstrate a more rapid and more substantial decrease in manic symptoms over the course of the study than women receiving adjunctive placebo.

STUDY POPULATION:

Sixty females with a current diagnosis of Bipolar Affective Disorder or Schizoaffective disorder - Manic Phase, according to the operationalised criteria of the Diagnostic and Statistical Manual, 4th edition (DSM-IV) of the American Psychiatric Association.

STUDY MEDICATION:

Tamoxifen. One third of patients (twenty) will be randomized to receive adjunctive Tamoxifen at 40 mg/day for 28 days. The Tamoxifen will be administered within a plain capsule to maintain "blinding" of treatment arm.

Progesterone. One third of patients (twenty) will be randomized to receive adjunctive oral Provera (progesterone) at 20 mg/day. The Progesterone will be administered within a plain capsule identical to that used with Tamoxifen.

Placebo. The remaining one third of patients will be randomized to receive adjunctive placebo (inert substance). The placebo substance will be administered within a plain capsule identical to that used with Tamoxifen and Progesterone.

STUDY EVALUATIONS:

Data will be collected over a 28-day period for each patient. Visits will be performed at baseline, and then at weekly intervals. A total of five visits will be completed for each patient. The following evaluations will be performed:

• Psychiatric evaluation to determine diagnosis. (Baseline visit only)

• General clinical evaluation including medical history, current conditions and a non-invasive physical examination, body weight, vital signs. (Baseline visit only)

• Medication history (baseline and evaluation visits).

• Demographics (baseline visits only).

• Completion of clinical rating scales; CARS-M, PANSS, MADRS, AIMS, Barnes Akathisia scale (BA), and Simpson-Angus scale (SA) (baseline and evaluation visits). A Menstrual Cycle Interview and a cognitive assessment (RBANS) will be performed at baseline and endpoint (day 28) visit.

• Laboratory tests including; Serum levels of mood stabilizer, luteinizing hormone (LH), follicle-stimulating hormone (FSH), Estrogen, Progesterone, Prolactin, dehydroepiandrosterone (DHEA), Testosterone and protein kinase C(PKC) (baseline and evaluation visits).

• Inclusion/exclusion checklist (baseline visit only).

• Informed consent (baseline visit only).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Alfred
• Collaborators: National Health and Medical Research Council, Australia; Stanley Medical Research Institute
• Treatments: Estrogen Antagonists; Estrogen Receptor Modulators; Estrogens; Progesterone; Tamoxifen

Criteria

Inclusion Criteria:

• Female patients who have a current diagnosis of Bipolar Affective Disorder (Manic phase) or Schizoaffective Disorder (Bipolar type in manic phase).

• Female patients who are able to give informed consent.

Exclusion Criteria:

• Female patients who are pregnant or lactating.

• Female patients with postpartum psychosis or related disorder.

• Female patients with known abnormalities in the hypothalamo-pituitary gonadal-axis, thyroid dysfunction, central nervous system tumors.

• Female patients taking estrogen preparations such as the oral contraceptive pill.

• Female patients currently taking interacting drugs including warfarin, aminoglutethimide, diuretics, methyldopa, theophylline, fluoxetine, calcium channel blockers and non-steroidal anti-inflammatory drugs.

• Female patients whose psychotic illness is directly due to illicit drugs or who have a history of substance abuse or dependence during the last 6 months.

• Females with any significant unstable medical illness such as cardiovascular disease, renal disease, Addisons disease, thromboembolic disorders, epilepsy, diabetes etc.