Associations between off-label low-dose olanzapine or quetiapine and cardiometabolic mortality
(2022) In Journal of Psychiatric Research 149. p.352-358- Abstract
Olanzapine and quetiapine are routinely used off-label at lower doses, though it remains unclear whether treatment is associated with mortality. Here, we examined the associations between low-dose olanzapine/quetiapine, defined as 5 mg/day of olanzapine equivalents (OE) with cardiometabolic mortality in a population-based, longitudinal cohort of individuals who sought specialized psychiatric services. Through cross-linked Swedish registries, 428,525 individuals without psychotic, bipolar, or cardiometabolic disorders, or previous treatment with antipsychotics or cardiometabolic-related drugs were followed for up to 10.5 years. Extended stratified Cox proportional hazards regressions were employed to estimate the hazard ratios (HR) of... (More)
Olanzapine and quetiapine are routinely used off-label at lower doses, though it remains unclear whether treatment is associated with mortality. Here, we examined the associations between low-dose olanzapine/quetiapine, defined as 5 mg/day of olanzapine equivalents (OE) with cardiometabolic mortality in a population-based, longitudinal cohort of individuals who sought specialized psychiatric services. Through cross-linked Swedish registries, 428,525 individuals without psychotic, bipolar, or cardiometabolic disorders, or previous treatment with antipsychotics or cardiometabolic-related drugs were followed for up to 10.5 years. Extended stratified Cox proportional hazards regressions were employed to estimate the hazard ratios (HR) of cardiometabolic mortality as a function of cumulative OE exposures, adjusted for age, sex, inpatient care, and time-dependent psychiatric diagnoses and treatments. Individuals were followed for a total of 2.1 million person-years. Treatment with olanzapine/quetiapine occurred in 18,317 of the cohort. In total, 2606 cardiometabolic-related deaths occurred. Treatment status (treated vs. untreated) was not significantly associated with cardiometabolic mortality (adjusted HR 0.86, 95% CI 0.64–1.15, P = 0.307). However, compared to no treatment, treatment for <6 months was significantly associated with a reduced risk (adjusted HR 0.56, 95% CI 0.37–0.87, P = 0.010) whereas treatment for 6–12 months was significantly associated with an increased risk (adjusted HR 1.89, 95% CI 1.22–2.92, P = 0.004), but not significantly beyond 12 months. Among those treated, each year exposed to an average 5 mg/day was significantly associated with increased cardiometabolic mortality (adjusted HR 1.45, 95% CI 1.06–1.99, P = 0.019). Overall, low-dose olanzapine/quetiapine treatment was weakly associated with cardiometabolic mortality. Clinicians should consider potential cardiometabolic sequelae at lower doses.
(Less)
- author
- Berge, Jonas LU ; Abri, Paul LU ; Andell, Pontus LU ; Movahed, Pouya LU and Ragazan, Dragos C.
- organization
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Cardiometabolic, Mortality, Olanzapine, Quetiapine, Register
- in
- Journal of Psychiatric Research
- volume
- 149
- pages
- 352 - 358
- publisher
- Elsevier
- external identifiers
-
- scopus:85118997329
- pmid:34785037
- ISSN
- 0022-3956
- DOI
- 10.1016/j.jpsychires.2021.11.023
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2021
- id
- 3662006b-603d-4d2f-9376-fb09182fe101
- date added to LUP
- 2021-12-03 08:07:57
- date last changed
- 2024-04-20 17:06:26
@article{3662006b-603d-4d2f-9376-fb09182fe101,
abstract = {{<p>Olanzapine and quetiapine are routinely used off-label at lower doses, though it remains unclear whether treatment is associated with mortality. Here, we examined the associations between low-dose olanzapine/quetiapine, defined as 5 mg/day of olanzapine equivalents (OE) with cardiometabolic mortality in a population-based, longitudinal cohort of individuals who sought specialized psychiatric services. Through cross-linked Swedish registries, 428,525 individuals without psychotic, bipolar, or cardiometabolic disorders, or previous treatment with antipsychotics or cardiometabolic-related drugs were followed for up to 10.5 years. Extended stratified Cox proportional hazards regressions were employed to estimate the hazard ratios (HR) of cardiometabolic mortality as a function of cumulative OE exposures, adjusted for age, sex, inpatient care, and time-dependent psychiatric diagnoses and treatments. Individuals were followed for a total of 2.1 million person-years. Treatment with olanzapine/quetiapine occurred in 18,317 of the cohort. In total, 2606 cardiometabolic-related deaths occurred. Treatment status (treated vs. untreated) was not significantly associated with cardiometabolic mortality (adjusted HR 0.86, 95% CI 0.64–1.15, P = 0.307). However, compared to no treatment, treatment for <6 months was significantly associated with a reduced risk (adjusted HR 0.56, 95% CI 0.37–0.87, P = 0.010) whereas treatment for 6–12 months was significantly associated with an increased risk (adjusted HR 1.89, 95% CI 1.22–2.92, P = 0.004), but not significantly beyond 12 months. Among those treated, each year exposed to an average 5 mg/day was significantly associated with increased cardiometabolic mortality (adjusted HR 1.45, 95% CI 1.06–1.99, P = 0.019). Overall, low-dose olanzapine/quetiapine treatment was weakly associated with cardiometabolic mortality. Clinicians should consider potential cardiometabolic sequelae at lower doses.</p>}},
author = {{Berge, Jonas and Abri, Paul and Andell, Pontus and Movahed, Pouya and Ragazan, Dragos C.}},
issn = {{0022-3956}},
keywords = {{Cardiometabolic; Mortality; Olanzapine; Quetiapine; Register}},
language = {{eng}},
pages = {{352--358}},
publisher = {{Elsevier}},
series = {{Journal of Psychiatric Research}},
title = {{Associations between off-label low-dose olanzapine or quetiapine and cardiometabolic mortality}},
url = {{http://dx.doi.org/10.1016/j.jpsychires.2021.11.023}},
doi = {{10.1016/j.jpsychires.2021.11.023}},
volume = {{149}},
year = {{2022}},
}