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Association of Low-Dose Quetiapine and Diabetes

IMPORTANCE: Quetiapine has been associated with increased risk of type 2 diabetes when used in medium or high doses for the treatment of severe mental disorders. It is not known whether low doses, commonly used off-label for sedative-hypnotic purposes, are also associated with increased risk of type...

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Autores principales: Højlund, Mikkel, Lund, Lars C., Andersen, Kjeld, Correll, Christoph U., Hallas, Jesper
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105749/
https://www.ncbi.nlm.nih.gov/pubmed/33961038
http://dx.doi.org/10.1001/jamanetworkopen.2021.3209
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author Højlund, Mikkel
Lund, Lars C.
Andersen, Kjeld
Correll, Christoph U.
Hallas, Jesper
author_facet Højlund, Mikkel
Lund, Lars C.
Andersen, Kjeld
Correll, Christoph U.
Hallas, Jesper
author_sort Højlund, Mikkel
collection PubMed
description IMPORTANCE: Quetiapine has been associated with increased risk of type 2 diabetes when used in medium or high doses for the treatment of severe mental disorders. It is not known whether low doses, commonly used off-label for sedative-hypnotic purposes, are also associated with increased risk of type 2 diabetes. OBJECTIVE: To investigate whether there is an association between prescription of low-dose quetiapine and the risk of type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: This cohort study examined nationwide Danish health registers for data regarding new users of quetiapine (n = 185 938) or selective serotonin reuptake inhibitors (SSRIs) (n = 1 031 920) who were aged 18 years or older between January 1, 1998, and December 31, 2018. Individuals with schizophrenia or bipolar disorder were excluded. Quetiapine-initiators were matched 1:1 with initiators of SSRIs, using a high-dimensional propensity score (hdPS). Maximum follow-up was 5 years. Association with cumulative dose was investigated, using a case-control approach nested among quetiapine users. Data analysis was performed from May to September 2020. EXPOSURES: Dispensing of quetiapine or SSRIs. Quetiapine prescriptions were limited to tablet strengths of 25 mg and 50 mg to focus on low-dose use. MAIN OUTCOMES AND MEASURES: Incident type 2 diabetes was defined as first filling of an antidiabetic medication, first register diagnosis of type 2 diabetes or first hemoglobin A(1C) measurement greater than or equal to 6.4% (≥48 mmol/mol). Incidence rates (IRs), incidence rate ratios (IRRs), and number-needed-to-harm (NNH) were calculated for full and matched cohorts using as-treated and intention-to-treat approaches. Odds ratios (ORs) were calculated for the association with cumulative quetiapine dose. RESULTS: Altogether, 896 285 patients were included in the full cohort; 538 164 (60%) were female and the median (interquartile range) age was 47 (33-67) years. There were 57 701 low-dose quetiapine initiators and 838 584 SSRI initiators. The matched cohort consisted of 54 616 pairs. In as-treated analyses, the incidence of type 2 diabetes during treatment with low-dose quetiapine (425 cases) was 9.59 cases/1000 person-years (PY) (95% CI, 8.72-10.5/1000 PY), which was slightly higher than for SSRI users (8462 cases; IR, 8.13/1000 PY; 95% CI, 7.96-8.30/1000 PY), resulting in a significant IRR of 1.18 (95% CI, 1.07-1.30) and NNH of 684 (95% CI, 418-1873). However, the between-group difference was nonsignificant in the hdPS-matched cohort (IR, 9.49 vs IR, 9.58; IRR, 0.99; 95% CI, 0.87-1.13). The case-control analysis found no dose-response association of low-dose quetiapine with diabetes (OR for doubling of the cumulative dose: 1.02; 95% CI, 0.95-1.09; P = .54), but in sensitivity analyses higher daily doses were associated with diabetes (all tablet strengths: OR, 1.08; 95% CI, 1.03-1.13). CONCLUSIONS AND RELEVANCE: In this cohort study, use of low-dose quetiapine was not associated with excess risk of type 2 diabetes in comparison with SSRIs.
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spelling pubmed-81057492021-05-24 Association of Low-Dose Quetiapine and Diabetes Højlund, Mikkel Lund, Lars C. Andersen, Kjeld Correll, Christoph U. Hallas, Jesper JAMA Netw Open Original Investigation IMPORTANCE: Quetiapine has been associated with increased risk of type 2 diabetes when used in medium or high doses for the treatment of severe mental disorders. It is not known whether low doses, commonly used off-label for sedative-hypnotic purposes, are also associated with increased risk of type 2 diabetes. OBJECTIVE: To investigate whether there is an association between prescription of low-dose quetiapine and the risk of type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: This cohort study examined nationwide Danish health registers for data regarding new users of quetiapine (n = 185 938) or selective serotonin reuptake inhibitors (SSRIs) (n = 1 031 920) who were aged 18 years or older between January 1, 1998, and December 31, 2018. Individuals with schizophrenia or bipolar disorder were excluded. Quetiapine-initiators were matched 1:1 with initiators of SSRIs, using a high-dimensional propensity score (hdPS). Maximum follow-up was 5 years. Association with cumulative dose was investigated, using a case-control approach nested among quetiapine users. Data analysis was performed from May to September 2020. EXPOSURES: Dispensing of quetiapine or SSRIs. Quetiapine prescriptions were limited to tablet strengths of 25 mg and 50 mg to focus on low-dose use. MAIN OUTCOMES AND MEASURES: Incident type 2 diabetes was defined as first filling of an antidiabetic medication, first register diagnosis of type 2 diabetes or first hemoglobin A(1C) measurement greater than or equal to 6.4% (≥48 mmol/mol). Incidence rates (IRs), incidence rate ratios (IRRs), and number-needed-to-harm (NNH) were calculated for full and matched cohorts using as-treated and intention-to-treat approaches. Odds ratios (ORs) were calculated for the association with cumulative quetiapine dose. RESULTS: Altogether, 896 285 patients were included in the full cohort; 538 164 (60%) were female and the median (interquartile range) age was 47 (33-67) years. There were 57 701 low-dose quetiapine initiators and 838 584 SSRI initiators. The matched cohort consisted of 54 616 pairs. In as-treated analyses, the incidence of type 2 diabetes during treatment with low-dose quetiapine (425 cases) was 9.59 cases/1000 person-years (PY) (95% CI, 8.72-10.5/1000 PY), which was slightly higher than for SSRI users (8462 cases; IR, 8.13/1000 PY; 95% CI, 7.96-8.30/1000 PY), resulting in a significant IRR of 1.18 (95% CI, 1.07-1.30) and NNH of 684 (95% CI, 418-1873). However, the between-group difference was nonsignificant in the hdPS-matched cohort (IR, 9.49 vs IR, 9.58; IRR, 0.99; 95% CI, 0.87-1.13). The case-control analysis found no dose-response association of low-dose quetiapine with diabetes (OR for doubling of the cumulative dose: 1.02; 95% CI, 0.95-1.09; P = .54), but in sensitivity analyses higher daily doses were associated with diabetes (all tablet strengths: OR, 1.08; 95% CI, 1.03-1.13). CONCLUSIONS AND RELEVANCE: In this cohort study, use of low-dose quetiapine was not associated with excess risk of type 2 diabetes in comparison with SSRIs. American Medical Association 2021-05-07 /pmc/articles/PMC8105749/ /pubmed/33961038 http://dx.doi.org/10.1001/jamanetworkopen.2021.3209 Text en Copyright 2021 Højlund M et al. JAMA Network Open. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the CC-BY License.
spellingShingle Original Investigation
Højlund, Mikkel
Lund, Lars C.
Andersen, Kjeld
Correll, Christoph U.
Hallas, Jesper
Association of Low-Dose Quetiapine and Diabetes
title Association of Low-Dose Quetiapine and Diabetes
title_full Association of Low-Dose Quetiapine and Diabetes
title_fullStr Association of Low-Dose Quetiapine and Diabetes
title_full_unstemmed Association of Low-Dose Quetiapine and Diabetes
title_short Association of Low-Dose Quetiapine and Diabetes
title_sort association of low-dose quetiapine and diabetes
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105749/
https://www.ncbi.nlm.nih.gov/pubmed/33961038
http://dx.doi.org/10.1001/jamanetworkopen.2021.3209
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