Pharmacotherapy for schizophrenia in postmenopausal women

ABSTRACT

Introduction: Reduced estrogen levels at menopause mean a loss of the neuroprotection that is conferred, from puberty until menopause, on women with schizophrenia. The postmenopausal stage of schizophrenia requires therapeutic attention because women with this diagnosis almost invariably experience increased symptoms and increased side effects at this time. So far, few targeted therapies have been successfully developed.

Areas covered: This non-systematic, narrative review is based on the relevant published literature indexed in PubMed. A digital search was combined with a manual check of references from studies in the field of gender differences, menopause and schizophrenia. Aside from the inclusion of a few early classic papers, the review focuses on 21st century basic, psychopharmacologic, and clinical literature on the treatment of women with schizophrenia after menopause.

Expert opinion: Beyond a relatively low dose threshold, all antipsychotic medications have adverse effects, which become more prominent for women at the time of menopause. Estrogen modulators may not help all symptoms of schizophrenia but are, nevertheless, relatively safe and, when used as adjuncts, help to keep antipsychotic doses low, thus reducing the side effect burden. The field is currently moving towards precision medicine and individual genetic profiles will help to determine the efficacy of available treatments in the future.

KEYWORDS:

• Antipsychotics
• estrogens
• menopause
• raloxifene
• schizophrenia

Declaration of Interest

A Gonzalez-Rodriguez has received honoraria and/or travel cost compensation from Pfizer Inc, Janssen Pharmaceuticals, Lundbeck-Otsuka and Ferrer. MV Seeman has acted as a consultant for Clera Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Article highlights

• The estrogen protection hypothesis in schizophrenia has received support from basic, animal, epidemiological and clinical studies.

• Antipsychotic response deteriorates over time in postmenopausal women with schizophrenia.

• Antipsychotic medication induces co-morbidities, especially severe at and after menopause.

• A significant correlation between gonadal hormone levels and clinical improvement in postmenopausal women with schizophrenia has been reported, but remains controversial.

• Estrogen-based hormone replacement therapies for the treatment of schizophrenia have the potential of improving symptoms and repairing cognitive deficits without inducing serious medical morbidity.

• Pharmacogenetic studies indicate that genetic variants in estrogen receptor genes may modulate the beneficial effects of SERMs. New basic and clinical advances will shed further light on these important observations.

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Additional information

Funding

This manuscript has not been funded.