The therapeutic effect of medicines is determined by more than their pharmacological properties. Factors such as the colour of a tablet, its taste and even its price have been found to significantly influence efficacy.1,2 This insight has sparked optimism about the potential to enhance drug effects by tweaking these and other features to optimize therapeutic outcomes. In this issue of Brain, Schenk and colleagues3 add a somewhat counter-intuitive factor to the list of features that could be targeted to boost the efficacy of a drug: side effects.