Sex Differences Between Female and Male Individuals in Antipsychotic Efficacy and Adverse Effects in the Treatment of Schizophrenia

Megan Galbally; Karen Wynter; Dan Siskind; Christoph U Correll; Korinne Northwood; Susanna Every-Palmer

doi:10.1007/s40263-024-01089-w

Sex Differences Between Female and Male Individuals in Antipsychotic Efficacy and Adverse Effects in the Treatment of Schizophrenia

CNS Drugs. 2024 May 7. doi: 10.1007/s40263-024-01089-w. Online ahead of print.

Authors

Megan Galbally^{1

2}, Karen Wynter^{3

4}, Dan Siskind^{5

6}, Christoph U Correll^{7

8

9

10}, Korinne Northwood^{5

6}, Susanna Every-Palmer¹¹

Affiliations

¹ School of Clinical Sciences, Monash Medical Centre, Monash University, 246 Clayton Road, Clayton, VIC, 3168, Australia. megan.galbally@monash.edu.
² Health Futures Institute, Murdoch University, Perth, WA, Australia. megan.galbally@monash.edu.
³ School of Clinical Sciences, Monash Medical Centre, Monash University, 246 Clayton Road, Clayton, VIC, 3168, Australia.
⁴ Faculty of Health, Deakin University, Geelong, VIC, Australia.
⁵ Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
⁶ Metro South Addiction and Mental Health Hospital and Health Service, Brisbane, QLD, Australia.
⁷ Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA.
⁸ Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.
⁹ Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany.
¹⁰ German Center for Mental Health (DZPG), Partner Site Berlin, Berlin, Germany.
¹¹ Department of Psychological Medicine, University of Otago, Wellington, New Zealand.

PMID: 38713452
DOI: 10.1007/s40263-024-01089-w

Abstract

Background and objective: Antipsychotics are core treatments for people living with psychotic disorders. Understanding individualised factors that influence both efficacy and adverse responses will improve outcomes. The objective of this study was to examine sex differences in antipsychotic-related efficacy and tolerability.

Methods: This was a secondary analysis of data from phase 1 and 1a of Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE); participants with schizophrenia were randomly assigned to double-blinded treatment with oral olanzapine, quetiapine, risperidone, ziprasidone or perphenazine. Measures included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions (CGI) scale and Calgary Depression Rating Scale, as well as self-reported side effects, medication compliance, dosage, weight measurements and various blood parameters.

Results: There were 1460 participants including 380 female and 1080 male individuals. Very few differences existed between male and female participants in response, adverse reactions, compliance or antipsychotic dosage. However, significantly more female participants than male participants reported constipation (28% vs 16%), dry mouth (50% vs 38%), gynecomastia/galactorrhea (11% vs 3%), incontinence/nocturia (16% vs 8%) and self reported weight gain (37% vs 24%) [all p < 0.001]. Within the risperidone treatment group, there was a significantly greater increase in prolactin levels (p < 0.001) among female participants (n = 61) than male participants (n = 159). No overall differences in clinician-rated measures, weight gain or other laboratory indicators were found.

Conclusions: While overall sex differences were limited across efficacy and tolerability for antipsychotic treatment, there were some specific findings with risperidone. Further examination of sex differences within antipsychotic trials will be important to improve efficacy and reduce adverse responses across as well as individualising care for people with schizophrenia.