Patients with a schizophrenia spectrum disorder experience substantial impairments in multiple domains of everyday life, including the ability to maintain social relationships, sustain employment, and live independently. These problems often persist, even after successful treatment of psychosis. Currently, no consistent evidence exists for the efficacy of interventions to reduce cognitive and negative symptoms, while in fact these are the factors that determine functioning to a great extent.
Premenopausal women with schizophrenia have less psychotic and negative symptoms, and better cognitive and social functioning, in comparison to men and older women. This is largely due to protective effects of estrogens in the brain. Administering estrogens has positive effects on psychotic symptoms, but exerts long term side effects, especially in men.
Raloxifene is a selective estrogen receptor modulator, with a beneficial side effect profile in women and in men. It has been shown to be effective in reducing symptoms in postmenopausal women with schizophrenia. Recently, positive results were found in premenopausal women and in men. It is important to replicate these results in an independent sample and to investigate the effects of raloxifene on functioning.
For this reason, we propose to augment antipsychotic medication with 120mg raloxifene or placebo for 12 weeks in premenopausal women, postmenopausal women, and men with schizophrenia, schizoaffective disorder or schizophreniform disorder, in a double blind randomized controlled trial. We will measure short and long term effects on functioning, symptom severity, social and cognitive functioning, quality of life, and health care costs.
If raloxifene proves to be effective, this will offer a safe, simple, and cheap way to improve functioning in patients. Importantly, raloxifene is a commercially available and extensively tested component, and therefore can be implemented into clinical guidelines rather swiftly.