HTR4 and major depressive disorder: The overlap between Kaplan–Meier curves in the early phase of follow-up argues against obvious selection bias, which can manifest as effects that appear too early.24 Finally, the findings from interrupted time-series analysis provide further evidence that initiation of prucalopride may decrease the risk of depression, and complements the emulated target trial design: the former benefits from better control of unmeasured time-invariant covariates, whereas the latter distinguishes the effect of 5-HT4R agonism from a generic anti-constipation effect.