Amisulpride, aripiprazole, and olanzapine in patients with schizophrenia-spectrum disorders (BeSt InTro): a pragmatic, rater-blind, semi-randomised trial

This pragmatic RCT (n=144) found randomisation to first-line amisulpride was more efficacious than aripiprazole and olanzapine at 52 weeks (mean reduction in PANSS total score of 32.7 points [SD 3.1] vs 21.9 [3.9], p=0.027 and 23.3 [2.9], p=0.025, respectively).

SPS commentary:

The authors acknowledge the limitations of their study due to its pragmatic design, including the lack of a placebo group, and the fact that treatment allocation was open to all aside from the research team assessing the participants. The randomisation was to a sequence of study drugs; if the first could not be used because of previous inefficacy or tolerability issues, then the second drug in the sequence could be offered (a drug other than that first in sequence was chosen in 16.7% of cases). The first study drug in the sequence was the basis of the intention-to-treat analysis, and the drug ultimately chosen was the basis of the per-protocol analyses. Of note, the differences between the groups in terms of reduction in PANSS total score at week 52 were not statistically significant in the per-protocol analysis (reduction of 29.1 [2.9] in the amisulpride group, 23.5 [3.9] in the aripiprazole group [p=0.242] and 24.6 [3.3] in the olanzapine group [p=0.290]).

Further limitations to this study include the lack of adjustment for multiple comparisons, and the substantial attrition. Also of note is the fact that 215 patients assessed for eligibility were excluded, despite the trial being designed to mimic real-life clinical practice, with broad inclusion criteria.

The Lancet Psychiatry