Frequently Asked Questions

The number needed to treat (NNT) was 5 for acute symptom response with aripiprazole once-monthly 400 mg (AOM 400) versus placebo. In the 12-week acute study, 60 of 167 patients (37.0%) receiving AOM 400 and 24 of 172 patients (14.4%) receiving placebo achieved a 30% or greater reduction in PANSS total score at week 10, yielding an NNT of 5 (95% CI, 4 8). This means 1 additional patient was expected to respond for every 5 treated with AOM 400 instead of placebo.

AOM 400 was associated with an NNT of 4 for remaining free from impending relapse in the maintenance study. In the randomized maintenance phase, 242 of 269 patients (90.0%) continuing AOM 400 and 81 of 134 patients (60.4%) switched to placebo were free from impending relapse, giving an NNT of 4 (95% CI, 3 5). The same NNT of 4 was also identified for patients free from clinical worsening and for patients categorized as responders.

Discontinuation due to treatment-emergent adverse events was numerically lower with AOM 400 than with placebo in both trials, so the number needed to harm (NNH) for this outcome was negative rather than showing excess harm with active treatment. In the acute study, 7 of 167 patients (4.2%) on AOM 400 and 13 of 172 (7.6%) on placebo discontinued because of a treatment-emergent adverse event. In the maintenance study, the corresponding rates were 19 of 269 (7.1%) for AOM 400 and 18 of 134 (13.4%) for placebo.

Weight gain of 7% or more from baseline was the most clinically notable short-term tolerability tradeoff reported in this analysis. In the acute study, the NNH for weight gain of at least 7% was 8 (95% CI, 5 21), whereas NNH values for other commonly reported adverse events such as akathisia, injection site pain, sedation, and increased weight were all in the double- or triple-digit range. The authors noted that no patient in the acute study discontinued because of weight gain.

Likelihood to be helped or harmed (LHH) compares benefit with risk by dividing the NNH for a harm outcome by the NNT for a benefit outcome; values greater than 1 indicate benefit is more likely than harm. All LHH values in this analysis were greater than 1. Based on the calculated NNT and NNH values, patients treated with AOM 400 were 200 times more likely to have symptom reduction than to discontinue because of a treatment-emergent adverse event in the acute setting and 250 times more likely to remain free from impending relapse than to discontinue because of a treatment-emergent adverse event in the maintenance setting.

The maintenance results should be interpreted in the context of both enrichment and shorter observed follow-up than the nominal study duration. Patients randomized to AOM 400 in the maintenance phase had already been stabilized on AOM 400 for at least 12 weeks earlier in the study, which the authors said likely enriched the sample with patients who tolerated AOM 400. The study was also stopped early after a positive interim analysis, and although the randomized phase was intended to last 52 weeks, the median time from randomization to the termination date was 113 days.

The analysis used data from two randomized, double-blind, placebo-controlled trials of AOM 400 in schizophrenia. The acute study randomized 339 patients to 12 weeks of AOM 400 (n=167) or placebo (n=172), and the main efficacy outcome for this analysis was a 30% or greater reduction in PANSS total score at week 10. The maintenance study randomized 403 stabilized patients to continue AOM 400 (n=269) or switch to placebo (n=134), and the main efficacy outcome for this analysis was being free from impending relapse during the maintenance phase.

This was a post hoc, descriptive analysis, so the authors considered the findings hypothesis-generating rather than definitive. They also noted that NNT and NNH depend on binary outcomes and therefore do not capture the full granularity of continuous data, and that the values were derived from highly selected clinical trial populations that may not generalize to real-world patients with schizophrenia. In addition, the maintenance sample was enriched with patients who had already tolerated AOM 400, and negative NNH values were imputed as 1,000 for LHH calculations.