In a recent study, an indirect treatment comparison was performed to examine the relative efficacy and tolerability of aripiprazole once monthly and paliperidone palmitate once monthly. The authors concluded that the results may suggest relative advantages for aripiprazole once monthly over paliperidone palmitate once monthly in the short-term treatment of schizophrenia. However, the validity of the study is compromised as an indirect treatment comparison using extant data may violate important assumptions. Other methodological issues identified further highlight the challenges of performing indirect treatment comparisons.