Abstract | Importance: Objective: 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: 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 A1C 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:
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Authors | Mikkel Højlund, Lars C Lund, Kjeld Andersen, Christoph U Correll, Jesper Hallas |
Journal | JAMA network open
(JAMA Netw Open)
Vol. 4
Issue 5
Pg. e213209
(05 03 2021)
ISSN: 2574-3805 [Electronic] United States |
PMID | 33961038
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antipsychotic Agents
- Serotonin Uptake Inhibitors
- Quetiapine Fumarate
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Topics |
- Adult
- Aged
- Antipsychotic Agents
(administration & dosage, adverse effects)
- Case-Control Studies
- Denmark
(epidemiology)
- Diabetes Mellitus, Type 2
(chemically induced, epidemiology)
- Female
- Humans
- Incidence
- Intention to Treat Analysis
- Male
- Middle Aged
- Quetiapine Fumarate
(administration & dosage, adverse effects)
- Risk Factors
- Selective Serotonin Reuptake Inhibitors
(adverse effects)
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