Denmark: The use of low-dose quetiapine is not associated with an increased risk of type 2 diabetes (T2D) in people with mental illness in comparison with SSRIs use, finds a recent study in JAMA Network Open.
Quetiapine is a second-generation antipsychotic medication labeled for treatment of the bipolar affective disorder, schizophrenia, and as adjunctive treatment in major depression. Its use has increased worldwide and quetiapine has now become the most commonly prescribed antipsychotic medication. However, when used in medium or high doses for the treatment of severe mental disorders, quetiapine has been associated with increased T2D risk. It is not known whether low doses, commonly used off-label for sedative-hypnotic purposes, are also associated with increased diabetes risk.
Against the above background, Mikkel Højlund, University of Southern Denmark, Odense, Denmark, and colleagues aimed to investigate whether there is an association between prescription of low-dose quetiapine and the risk of type 2 diabetes in this cohort study.
For this purpose, the researchers 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. People with bipolar disorder or schizophrenia were excluded.
Using a high-dimensional propensity score (hdPS), quetiapine-initiators were matched 1:1 with initiators of SSRIs. They were followed for a maximum of 5 years. Association with cumulative dose was investigated, using a case-control approach nested among quetiapine users.
Quetiapine prescriptions were limited to tablet strengths of 25 mg and 50 mg to focus on low-dose use.
Altogether, 896 285 patients were included in the full cohort; 538 164 (60%) were female and the median age was 47 years. There were 57 701 low-dose quetiapine initiators and 838 584 SSRI initiators. The matched cohort consisted of 54 616 pairs.
Key findings of the study include:
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), which was slightly higher than for SSRI users (8462 cases), resulting in a significant IRR of 1.18 and NNH of 684.
The between-group difference was nonsignificant in the hdPS-matched cohort (IR, 9.49 vs IR, 9.58; IRR, 0.99).
The case-control analysis found no dose-response association of low-dose quetiapine with diabetes (OR for doubling of the cumulative dose: 1.02), but in sensitivity analyses higher daily doses were associated with diabetes (all tablet strengths: OR, 1.08).
"The results of this cohort study suggest that there is not a significant excess risk of type 2 diabetes with use of low-dose quetiapine in comparison with SSRIs," wrote the authors. "As this study focused on low-dose quetiapine alone, future studies should focus on higher doses or concomitant use with other antipsychotics or antidepressants."
Reference:
The study titled, "Association of Low-Dose Quetiapine and Diabetes," is published in JAMA Network Open.
DOI: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779687