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Antipsychotic Efficacy Declines in Women Aged 45 and Older

Evi Arthur

Antipsychotic efficacy drops in women older than 45 years, according to a study recently published in Schizophrenia Bulletin.

Lower estrogen levels have previously been associated with more severe disease courses. Since perimenopause lowers estrogen levels around the age of 45, and levels stay low following menopause, researchers hypothesized that this period increases relapse risk and reduces antipsychotic efficacy in women.

Related: Dementia Risk More than Doubled in Patients With Schizophrenia

“While younger women have a lower risk of relapse and generally need a lower antipsychotic dose to prevent rehospitalization than men, antipsychotic effectiveness declines in women after the age of 45,” said lead author Iris E. Sommer, MD, PhD, University Medical Center Groningen (UMCG), Groningen, Netherlands, and co-authors. “Starting in mid-40s, older women with [schizophrenia-spectrum disorders (SSD)] should be regarded as a vulnerable group that deserves special attention.”

The cohort study used Finnish registers to find patients with schizophrenia and/or schizoaffective disorder and stratified by sex and age. A total of 7676 people with schizoaffective disorder were included in the study, 59% of which were women. Hospitalization risk, or adjusted hazard ratio (aHR), was measured by comparing antipsychotic monotherapy use to nonuse periods in participants for 7 dose categories in defined daily doses (DDDs/d). Participants were divided into 5-year age groups from ages 20 to 69. Per age group, hospital admissions for psychosis were noted and compared between women and men in the same age groups.

Beginning at age 45, women were hospitalized more frequently for psychosis than men or women under 45. This decrease in efficacy was present for clozapine doses >0.6 DDDs/d, olanzapine doses >1.4 DDDs/d, and for specific doses of quetiapine (0.9–1.1 DDDs/d) and risperidone (0.6–0.9 DDDs/d). The aHRs in long-acting injectable (LAI) use and antipsychotic polytherapy showed similar trends.

“Earlier studies showed that estrogenic treatment (either HRT or raloxifene) reduces symptoms and increases the effectiveness of antipsychotic medication…in postmenopausal women with SSD,” researchers concluded. “As estrogen decline and deterioration of the clinical course already start in the mid-40s, this is the optimal age to consider such preventive actions.”

Reference
Sommer IE, Brand BA, Gangadin S, et al. Women with schizophrenia-spectrum disorders after menopause: a vulnerable group for relapse. Schizophr Bull. Published online October 5, 2022. doi.org/10.1093/schbul/sbac139

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