Dose–response association of acute-phase quetiapine treatment with risk of new-onset hypothyroidism in schizophrenia patients

Abstract

Aims: To assess association between quetiapine treatment and risk of new-onset hypothyroidism in schizophrenia patients. Methods: We conducted a retrospective cohort study in a tertiary hospital in China between January 2016 and December 2018. Schizophrenia patients with normal thyroid tests at admission were included. Hypothyroidism, which was defined as thyroid-stimulating hormone >4.20 mU/L and free thyroxine <12.00 pmol/L, or on L-thyroxine prescriptions, was the outcome measure, and quetiapine treatment between admission and subsequent thyroid test was the exposure measure of this study. Adjusted relative risks and 95% confidence intervals were used to assess the independent association of quetiapine treatment with risk of new-onset hypothyroidism. The dose–response association was further analysed by 3 quetiapine doses: low (≤ 0.6 g/d). Results: A total of 2022 eligible patients were included in the final analysis. Sixty patients (15.0%) in the quetiapine group developed hypothyroidism, while 56 patients (3.5%) in the nonquetiapine group developed hypothyroidism. Relative risk (95% confidence interval) of developing hypothyroidism for quetiapine use was 4.01 (2.86–5.64) after adjusting for several potential confounding factors. A strong dose–response association between quetiapine use and risk of developing hypothyroidism was observed: adjusted relative risks (95% confidence intervals) were 1.00 (0.25–2.59), 4.22 (2.80–6.25) and 5.62 (3.66–8.38), respectively, for low-, medium- and high-dose quetiapine, as compared with no quetiapine. Conclusion: Acute phase quetiapine treatment for schizophrenia patients was strongly associated with increased risk of developing new-onset hypothyroidism, with a clear dose–response association.