According to an editorial, off-label prescribing matters because it is usually (but not always) linked to substantial uncertainty about the balance of benefit and harm. It advises that prescribers should therefore be cautious when they prescribe an off-label medicine on the basis of an extrapolation of evidence for a different indication, in a different patient group, or for a substantially different dose or formulation. It adds that equally, on-label prescribing also often involves extrapolation, most commonly because the patient needing treatment is very different from the patients included in trials. As a result, most people with well characterised major depressive disorder in everyday practice would be ineligible for the trials on which licensing and treatment recommendations are based. It notes that evidence also shows that patients who would be ineligible for trials are less likely to respond to antidepressants and more likely to experience adverse events.