To study the effect of adjunctive bazedoxifene - a selective estrogen receptor modulator (SERM) in a double blind, placebo-controlled adjunctive study in the treatment of women with schizophrenia. All patients receive standardized antipsychotic medication.

Despite advances in the treatment of schizophrenia, pharmacotherapy remains sub- optimal, and the prognosis for many patients is poor. We have pioneered work showing that estradiol has a positive role in the treatment of psychosis symptoms and cognitive deficits seen in people with schizophrenia. However, with the longer-term work from studies such as the Women's Health Initiative, it has become clear that long-term use of estradiol with progesterone may have associated increased risks of breast and other cancers. Hence, we began working with the Selective Estrogen Receptor Modulator - raloxifene, which appears to be safer for longer term use with respect to the development of breast and other cancers. Building on our and others work, raloxifene used as an adjunctive treatment in schizophrenia appears to produce inconsistent and varying responses in different sub-populations; gender, menopausal status, age, drug dose and delivery mode. We now propose to conduct a double-blind, randomized, placebo controlled trial of a third generation SERM - bazedoxifene - which is 4 times more selective for the alpha than the beta oestrogen receptor subtype. Bazedoxifene appears to be safer with respect to long term use than older SERMs, has additional actions on the glucocorticoid receptor, and together this different pharmacology speculatively has greater potential than other SERMs to impact favorably on both psychosis symptoms and cognition in men and women with schizophrenia. This study will test 160 women to determine if bazedoxifene, as an adjunctive hormone modulator, is effective for positive and cognitive symptoms of schizophrenia.

Inclusion Criteria:

• Physically well.
• A current DSM-V diagnosis of schizophrenia or related disorder.
• 18- 65 years
• Able to give informed consent.
• PANSS total score between 40 and 90.
• Documented normal PAP smear and pelvic examination in the preceding two years.
• Stable psychotropic medication for previous 4 weeks
• Normal breast screen (for women aged over 40 years)
• IQ > 70 (as determined by the WAIS IV subtests)
• English language proficiency (in order to provide informed consent and complete cognitive test battery)

Exclusion Criteria:

• Patients with known abnormalities in the hypothalamo-pituitary gonadal axis, thyroid dysfunction, central nervous system tumours, active or past history of a venous thromboembolic event.
• Patients with a history of severe traumatic brain injury or significant neurological or unstable medical illness such as epilepsy and diabetes or known active cardiac, renal or liver disease; presence of illness causing immobilisation.
• Patients whose psychotic illness is directly related to illicit substance use or who have a history of substance dependence during the last six months (with the exclusion of caffeine and/or nicotine dependence).
• Women aged 40 or over who have not had a normal mammogram in the last 24 months
• Use of any form of estrogen, progestin or androgen as hormonal therapy in preceding 4 weeks including the pill (excluding IUD or Hormone Implants).
• Pregnant (HCG will be measured at screening)
• Breastfeeding
• Planned changes to psychotropic medication or psychotherapy regimen.

Women

Participants will be randomised to receive either activie treatment or identically packaged placebo