Effect of Quetiapine, from Low to High Dose, on Weight and Metabolic Traits: Results from a Prospective Cohort Study

Abstract

Introduction The atypical antipsychotic quetiapine is known to induce weight gain and other metabolic complications. The underlying mechanisms are multifactorial and poorly understood with almost no information on the effect of dosage. Concerns were thus raised with the rise in low-dose quetiapine off-label prescription (i. e.,<150 mg/day). Methods In this study, we evaluated the influence of quetiapine dose for 474 patients included in PsyMetab and PsyClin studies on weight and metabolic parameter evolution. Weight, blood pressure, lipid, and glucose profiles were evaluated during a follow-up period of 3 months after treatment initiation. Results Significant dose-dependent metabolic alterations were observed. The daily dose was found to influence weight gain and increase the risk of undergoing clinically relevant weight gain (≥7% from baseline). It was also associated with a change in plasma levels of cholesterol (total cholesterol, LDL cholesterol, and HDL cholesterol) as well as with increased odds of developing hypertriglyceridemia, as well as total and LDL hypercholesterolemia. No impact of a dose increase on blood pressure and plasma glucose level was observed. Discussion The dose-dependent effect highlighted for weight gain and lipid alterations emphasizes the importance of prescribing the minimal effective dose. However, as the effect size of a dose increase on metabolic worsening is low, the potential harm of low-dose quetiapine should not be dismissed. Prescriptions must be carefully evaluated and regularly questioned in light of side effect onset.

Impact of low‐dose quetiapine‐use on glycosylated hemoglobin, triglyceride and cholesterol levels

“…Changes were more pronounced with increasing doses above 50 mg for all metabolic outcomes, except for HbA1c, where dose‐proportionality was modest. This finding is consistent with a recent cohort study from Switzerland where quetiapine doses ≥150 mg/day were associated with larger changes in triglycerides, TC, LDL‐C, and HDL‐C than with doses <150 mg/day 5 …”

“…This finding is consistent with a recent cohort study from Switzerland where quetiapine doses ≥150 mg/day were associated with larger changes in triglycerides, TC, LDL-C, and HDL-C than with doses <150 mg/day. 5 Two secondary, but important findings from this study are that (i) <10% of the eligible off-label, low-dose quetiapine users in the study period had records of assessed HbA1c and/or lipid parameters in the RLRR, and (ii) that the probability of having such measurements after initiation of off-label, low-dose quetiapine treatment depended on the pre-initiation level, that is, that prescribers were more likely to monitor those that have already increased HbA1c, triglyceride, or cholesterol levels.…”

“…Furthermore, the use of quetiapine might increase blood glucose levels, although this effect remains unclear, as relevant RCTs are generally short and blood glucose changes take more time. 3 Observational studies found that both cholesterol and blood glucose levels increase after quetiapine initiation, 5 and that cholesterol-lowering and antidiabetic medications are started more frequently after initiation of the second-generation antipsychotics, including quetiapine. 6 Hyperglycemia and dyslipidemia that have been associated with quetiapine use at higher doses 3,7 are important risk factors for cardiovascular disease.…”

Olanzapine‐associated dose‐dependent alterations for weight and metabolic parameters in a prospective cohort

“…Additionally, we applied mixed‐effects logistic regression models, including the above‐mentioned covariates, to assess the risk of developing metabolic abnormalities such as CRW (≥7%), EWG (≥5% weight gain during first month), 36 obesity, dyslipidaemia and elevated blood pressure, elevated fasting plasma glucose and metabolic syndrome. All analyses were performed using the R environment for statistical computing Version 3.6.0.…”

Sirolimus-Induced Severe Hypertriglyceridemia Presenting with Signs of Hyperviscosity Syndrome and as Pink Colored Blood: A Case Report

“…Especially the close temporal link with the newly prescribed drug and high trough levels link the excessive hypertriglyceridemia with sirolimus. Potentially aggravating factors elevating additionally lipid levels in this case are chronic kidney disease with mild proteinuria, medication with glucocorticoids and quetiapine [28,29]. Proteinuria leads to renal loss of lipoproteins and hence to hypertriglyceridemia, whereas administration of glucocorticoids increases triglyceride synthesis and stimulates lipoprotein lipase activity [30,31].…”