Dose-related hypoglycemia in venlafaxine poisoning: a retrospective cohort study

Context Several case reports describe hypoglycemia in the context of venlafaxine overdose, while investigations at therapeutic dose suggested a neutral effect on glucose homeostasis. Studies on hypoglycemia in venlafaxine intoxication are lacking. Methods Single-center retrospective cohort study of non-diabetic patients presenting with a laboratory-confirmed antidepressant overdose to the department of clinical toxicology of a tertiary care hospital over a 12-year period. Our main goal was to investigate the association of hypoglycemia as the primary outcome with venlafaxine exposure using multiple logistic regression. Multi-drug exposures were included. We further aimed to describe the association of blood glucose (BG)/hypoglycemia with antidepressant dose, seizures and length of hospital stay. Results 525 antidepressant intoxications were included, 85 of which involved venlafaxine. Hypoglycemia occurred in 34.1% (29/85) of venlafaxine intoxications and in 10.7% (47/440) of non-venlafaxine antidepressant overdoses. Venlafaxine exposure was significantly associated with hypoglycemia (adjusted odds ratio (OR): 6.6, 95% confidence interval (CI): 3.5-12.6). Venlafaxine-associated hypoglycemia was mainly mild (BG: 51-70 mg/dL), in 75.8% of cases, to moderate (BG: 31-50 mg/dL), in 20.7%, with one case of severe hypoglycemia (BG: 30 mg/dL). BG was significantly inversely correlated with dose in the venlafaxine group (Spearman's correlation coefficient: -0.47, p = 0.002) but not in other commonly prescribed antidepressants. Regardless of venlafaxine exposure, hypoglycemia was associated with seizures (adjusted OR: 5.3, 95% CI: 2.6-10.6) and with a 2.7 day increase in hospital length of stay (95% CI: 1.3-4.2). Conclusion A dose-related, mild to moderate hypoglycemia occurred in over one-third of venlafaxine poisonings. In overdose of other antidepressants, hypoglycemia was seen less frequently and without significant dose-dependency. Regardless of venlafaxine exposure, hypoglycemia was associated with seizures and prolonged length of stay, although these factors are likely primarily determined by other toxicities. BG monitoring in venlafaxine overdose should be considered.