The ‘unknown’ safety concern for aripiprazole once monthly

Fleischhacker et al report that treatment-emergent adverse effects are comparable for aripiprazole 400 mg once monthly and a suboptimal dose (50 mg) of aripiprazole once monthly. ¹ Also, they state that the ‘clinical relevance’ of statistically significant difference in Barnes Akathisia Rating Scale score with aripiprazole 400 mg once monthly against oral aripiprazole is ‘unknown’. Akathisia is known to be the most clinically relevant adverse effect with oral aripiprazole because of the subjective distress caused to the patient and the increased risk of agitation and suicide associated with it. Hence, a higher rate of akathisia with aripiprazole 400 mg once monthly cannot be discounted as being of ‘unknown clinical relevance’. Further, a deeper look at the apparently similar rates of ‘any treatment-emergent adverse effects’ for the two doses of aripiprazole reveals that the rates may not be similar if psychotic disorder and schizophrenia (which are efficacy outcomes and in no way can be considered as adverse effects for the purposes of this study) are removed from the list. The article minimises the possible safety concerns associated with aripiprazole 400 mg once monthly. A precise assessment of safety concerns (besides efficacy) is of utmost importance for a potential prescriber and there is potential of a prescriber being misguided by superficially reading this article. Further, efficacy outcomes of the study could have been contaminated by the noticeably high and differential discontinuation rates in the two active arms. The last observation carried forward (LOCF) method used for analysis of missing data tends to underestimate worsening in intention-to-treat (ITT) analyses. A comparison of results generated by ITT and per protocol analysis could have been more informative in assessing the efficacy outcomes.