Oestrogen modulators as augmentation to antipsychotics for the treatment of post- and perimenopausal psychosis: a systematic review.

Abstract

Background: It is theorised that oestrogen provides neuroprotection against psychosis. Oestrogen levels drop during post- and perimenopausal periods, creating a window for the onset of psychotic symptoms. Oestrogen treatment using hormonal therapy (HT) or selective oestrogen receptor modulators (SERMs) as an adjunct to antipsychotics could provide a new treatment option for post- and perimenopausal women.

Objective: This review investigated the effectiveness of oestrogen agents as adjunctive treatment to antipsychotic medications in post- and perimenopausal women with psychosis.

Design: Systematic review.

Data sources and methods: A systematic search of major databases identified trials examining oestrogen or SERMs as adjuncts to antipsychotics in women aged 40+ with psychosis. Studies were assessed for quality using the Cochrane Risk of Bias tool and the Joanna Briggs Institute (JBI) critical appraisal tools.

Results: Ten studies met inclusion criteria: one using oestrogen HT and nine using raloxifene. Reductions in total Positive and Negative Syndrome Scale (PANSS) scores support evidence for the adjunctive use of raloxifene in improving psychotic symptoms. Of the nine included clinical trials, six reported statistically significant improvements with oestrogen-modulating agents: four in total PANSS reduction, and two in positive PANSS domain only. Quality assessments identified publication bias, inconsistent data reporting and variability in study design.

Conclusion: Raloxifene shows potential as an adjunctive treatment in post- and perimenopausal psychosis, but further high-quality clinical trials are needed to inform practice and develop hormone-informed treatment protocols.

Trial registration: Not registered.