REVIEW OF: Sommer I et al, Schizophr Bull 2023;49(1):136–143

STUDY TYPE: Retrospective cohort study

We know that times of low estrogen, for example premenstrually and around perimenopause, place many women at risk for mood change. But might some women also face a higher risk of psychosis exacerbation? This study examined whether women with schizophrenia spectrum disorders were more likely to relapse once they reached age 45 years and older.

The authors identified individuals hospitalized with schizophrenia or schizoaffective disorder between 1972 and 2014 from Finnish nationwide registers (n=61,889). They stratified patients by sex and age, grouping ages into five-year periods, and compared doses for the four most common antipsychotic medications: clozapine, olanzapine, quetiapine, and risperidone.

Younger women needed fewer hospitalizations for psychosis and lower doses of antipsychotics than men. But after age 45, the situation flipped. Women ages 45–49 to 65–69 were significantly more likely to be hospitalized for psychosis than men, and the gap widened as they got older (all p values <0.00001). Older women were also more prone to relapse on standard doses of antipsychotics compared to women age <45 and to men of any age. Older women also required higher antipsychotic doses for stabilization. Clozapine and olanzapine showed the largest drop in effectiveness as women reached age 45 and above.

The study’s strengths include its large sample size and the use of many subjects as their own controls within different age groups. The use of age to estimate menopause onset was a limitation, as was the lack of information about whether any women were also on estrogen supplementation.

The authors hypothesized that diminished estrogen levels heighten female patients’ susceptibility to psychosis exacerbations and that menopause might influence the metabolism of antipsychotic medications.

CARLAT TAKE

During and especially after perimenopause, women with schizophrenia spectrum disorders appear particularly vulnerable to relapse and may need higher doses of antipsychotic medications. As your female patients with schizophrenia approach menopause, closely monitor them for signs of relapse, especially if they’re on clozapine or olanzapine.