Key considerations for women living with schizophrenia

In this symposium presented at the 35th ECNP Congress in Vienna, Austria (15th−18th Oct), titled ‘Schizophrenia in women,’ Dr Donatella Marazziti (University of Pisa, Italy), Dr Heidi Taipale (Karolinska Institute, Stockholm, Sweden, Niuvanniemi Hospital, Kuopio, Finland), Dr Sofia Brissos (Centro Hospitalar Psiquiátrico de Lisboa, Lisbon, Portugal) and Dr Claudia Carmassi (University of Pisa, Italy) presented a number of studies regarding this topic. While, in general, women living with schizophrenia have a later onset and fewer negative symptoms, they are also more likely to be misdiagnosed, have more physical comorbidities and experience more affective symptoms. Due to differences in body composition and drug metabolism; antipsychotic absorption, distribution, bioavailability and activity may differ in women than men. However, in clinical trials study results may not be analysed by sex. One particular issue for women is with prolactin-increasing antipsychotics, which are associated with higher rates of breast cancer and low energy fractures in women taking such drugs.

A wide range of differences in schizophrenia in women and men

Compared to men, women living with schizophrenia, in general, have fewer negative symptoms, a later onset, lower mortality and are better at seeking help. However, while these are all positives, going deeper reveals inequalities. For instance, although prior to first hospitalisation for schizophrenia-spectrum disorder men are more likely to have a substance use disorder,1 women with such are less likely to reduce substance use in the first year following initial treatment for psychosis.2

While it is purported that women living with schizophrenia have a better illness course than men, long range studies have found that recovery rates are similar,3 as are functional outcomes4 and hospitalisation for psychiatric reasons in the decade after diagnosis.5 Additionally, after the age of 40, women are more likely to relapse than men.1

Women living with schizophrenia have lower mortality and fewer negative symptoms, but also more physical comorbidities and greater drug side-effects

Other negatives include that women are more often misdiagnosed and experience longer delays in receiving care, are more likely to experience affective symptoms, physical comorbidities and personality disorders, and more often develop treatment-related obesity, metabolic syndrome, cardiovascular diseases, endocrine-induced adverse events and tardive dyskinesia. There are also effects of the menstruation cycle, pregnancy, contraception and age-related endocrine changes to take into account in women.6

 

Important differences regarding antipsychotic treatment for women with schizophrenia

Women in general are under-represented in clinical trials, especially those aged >45 years, and study results are rarely analysed by sex.7 This is important as women differ from men with regard to drug metabolism, absorption and excretion; drug distribution to the brain and the rest of the body; and target site (for instance, dopamine receptor) bioavailability, sensitivity and activity. There are also increased rate of adverse events.8 This can be due to differences in body composition; for instance, women in general have smaller organs, less muscle tissue and more fatty tissue, which can affect the drug volume of distribution.9

One particular issue with schizophrenia treatment important to women’s health is that some antipsychotics can increase prolactin levels as dopamine D2 receptor blockage can decrease dopamine’s tonic inhibition of prolactin secretion. Symptoms of hyperprolactinemia include decreased libido, infertility, oligomenorrhea, hypogonadism and amenorrhea. Increases in prolactin in response to antipsychotics are higher in women, especially those who are premenopausal.10

Hyperprolactinemia can be a particular issue for women taking prolactin-increasing antipsychotics

In a study including 30,785 women in Finland diagnosed with schizophrenia between 1972−2014, of which 1069 women were diagnosed with invasive breast cancer between 2000−2017, the odds ratio of developing breast cancer was 1.56 in women taking a prolactin-increasing antipsychotic for ≥5 years compared to those taking a non-prolactin-increasing antipsychotic. Higher daily doses were also associated with breast cancer development (odds ratio 1.33−1.39).11 These findings have been replicated in a US cohort.12 This points to a need, said Dr Taipale, to consider using antipsychotics without prolactin-increasing properties where possible and recommend cancer screening for all women living with schizophrenia.

Increased prolactin is also associated with decreases in bone mineral density.13 Work presented during the symposium found that longer duration (≥4 years) and increasing dose per day of prolactin-increasing antipsychotics was associated with low energy fractures. These were similar for both women and men.

 

Educational financial support for this Satellite symposium was provided by Gedeon Richter.

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

References
  1. Sommer IE, et al. NPJ Schizophr. 2020; 6: 12.
  2. Lange EH, et al. Compr Psychiatry. 2014; 55: 274-282.
  3. Brand BA, et al. Lancet Psychiatry. 2022; 9: 330-336.
  4. Ayesa-Arriola R, et al. NPJ Schizophr. 2020; 6 :33.
  5. Jääskeläinen E, et al. Schizophr Bull. 2013; 39: 1296-1306.
  6. Mazza M, et al. J Pers Med. 2021;11 (12).
  7. Feuerstein IM, et al. J Womens Health (Larchmt). 2018; 27: 1195-1203.
  8. Brand BA, et al. Psychol Med. 2021; 52: 1-15.
  9. Seeman MV. Am J Psychiatry. 2004; 161: 1324-1333.
  10. Peuskens J, et al. CNS Drugs. 2014; 28: 421-453.
  11. Taipale H, et al. Lancet Psychiatry. 2021; 8: 883-891.
  12. Rahman T, et al. J Clin Psychopharmacol. 2022; 42: 7-16.
  13. Tseng PT, et al. 2015; 94: e1967.
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