Antipsychotic Use and Risk of Low-Energy Fractures in People With Schizophrenia: A Nationwide Nested Case-Control Study in Finland.

Abstract

BACKGROUND:

Low-energy fractures (LEF) are more frequent in people with schizophrenia than the general population, and the role of prolactin-increasing antipsychotics is unknown.

STUDY DESIGN:

We conducted a nested case-control study using Finnish nationwide registers (inpatient, specialized outpatient care, prescription drug purchases). We matched each person with schizophrenia aged 16-85 years and incident LEF (cases) with 5 age/sex/illness duration-matched controls with schizophrenia, but no LEF. We investigated the association between cumulative exposure (duration, and Defined Daily Doses, DDDs) to prolactin-increasing/sparing antipsychotics and LEF. Adjusted conditional logistic regression analyses were performed. Sensitivity analyses were conducted.

STUDY RESULTS:

Out of 61 889 persons with schizophrenia between 1972 and 2014, we included 4960 cases. Compared with 24 451 controls, 4 years or more of exposure to prolactin-increasing antipsychotics was associated with increased risk of LEF (adjusted odds ratio (aOR) from aOR = 1.22, 95%CI = 1.09-1.37 to aOR = 1.38, 95%CI = 1.22-1.57, for 4-< 7 />13 years of exposure, respectively), without a significant association for prolactin-sparing antipsychotics. All cumulative doses higher than 1000 DDDs of prolactin-increasing antipsychotics were associated with LEF (from aOR = 1.21, 95%CI = 1.11-1.33, 1000-<3000 DDDs, to aOR = 1.64, 95%CI = 1.44-1.88, >9000 DDDs). Only higher doses of prolactin-sparing antipsychotics reached statistical significance (aOR = 1.24, 95%CI = 1.01-1.52, 6000-<9000 DDDs, aOR = 1.45, 95%CI = 1.13-1.85, >9000 DDDs). Sensitivity analyses confirmed the main analyses for prolactin-increasing antipsychotics. For prolactin-sparing antipsychotics, significant associations were limited to extreme exposure, major LEF, older age group, and males.

CONCLUSIONS:

Long-term exposure to prolactin-increasing antipsychotics at any dose, and high cumulative doses of prolactin-sparing antipsychotics is associated with significantly increased odds of LEF. Monitoring and addressing hyperprolactinemia is paramount in people with schizophrenia receiving prolactin-increasing antipsychotics.

• Authors: Marco Solmi, Markku Lähteenvuo, Christoph U Correll, Antti Tanskanen, Jari Tiihonen, Heidi Taipale
• Journal: Schizophrenia bulletin (Schizophr Bull) Vol. 49 Issue 1 Pg. 78-89 (01 03 2023) ISSN: 1745-1701 [Electronic] United States
• PMID: 36334051 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Antipsychotic Agents
• Prolactin

Topics

• Aged
• Humans
• Male
• Antipsychotic Agents (adverse effects)
• Case-Control Studies
• Finland (epidemiology)
• Prolactin
• Schizophrenia (drug therapy, epidemiology, chemically induced)
• Female