Clinical Summary
Clinical Summary: Aripiprazole Once-Monthly for Patients Diagnosed With Schizophrenia: Number Needed to Treat, Number Needed to Harm, and Likelihood to be Helped or Harmed
For patients with schizophrenia, the real-world question is not just whether a long-acting antipsychotic works, but how likely benefit is relative to harm. This analysis translates placebo-controlled trial results for aripiprazole once-monthly 400 mg into clinically useful metrics that quantify symptom response, relapse prevention, and adverse-event tradeoffs.
Design
This was an analysis of data from 2 studies of AOM 400 for the acute or maintenance treatment of patients diagnosed with schizophrenia.
N
The analysis populations comprised 339 patients randomized to 12 weeks of treatment with either AOM 400 (n = 167) or placebo (n = 172) in the acute study and 403 patients randomized to 52 weeks of treatment with either AOM 400 (n = 269) or placebo (n = 134) in the long-term maintenance study.
Population
patients diagnosed with schizophrenia
Duration
12 weeks of treatment
Key Findings
- In the maintenance study, 242 patients (90.0%) treated with AOM 400 and 81 patients (60.4%) treated with placebo were free from impending relapse, with a corresponding NNT value of 4 (95% CI, 3–5).
- In the acute study, 60 patients (37.0%) treated with AOM 400 and 24 patients (14.4%) treated with placebo had a ≥30% reduction in PANSS total score at week 10; the corresponding NNT value was 5 (95% CI, 4–8).
- Discontinuation because of a TEAE was lower with AOM 400 than placebo in both studies: 7 patients (4.2%) versus 13 patients (7.6%) in the acute study and 19 (7.1%) versus 18 (13.4%) in the maintenance study, so NNH values were negative.
- Among commonly reported TEAEs in the acute study, weight gain of ≥7% had an NNH value of 8 (95% CI, 5–21), whereas NNH values for the other commonly reported TEAEs were all double-or triple-digit numbers.
- Based on calculated NNT and NNH values, patients treated with AOM 400 were 200 times more likely to have a reduction in symptoms than to discontinue due to a TEAE in an acute setting and were 250 times more likely to be free from impending relapse than to discontinue due to a TEAE in a maintenance setting.
Clinical Bottom Line
AOM 400 shows a favorable benefit-risk profile versus placebo in both acute and maintenance schizophrenia treatment, with single-digit NNTs for symptom response and relapse prevention and no excess TEAE-related discontinuation. Weight gain of ≥7% is the clearest short-term tolerability tradeoff to monitor.
Practice Implications
- When discussing expected benefit with patients, frame AOM 400 in concrete terms: 1 additional acute responder is expected for every 5 patients treated instead of placebo, and 1 additional patient remains free from impending relapse for every 4 treated in maintenance.
- Monitor weight early in acute treatment, because weight gain of ≥7% had an NNH of 8 (95% CI, 5–21), making this a more clinically salient adverse-effect tradeoff than other commonly reported acute TEAEs.
- Do not overinterpret maintenance tolerability as broadly generalizable; patients randomized to AOM 400 had been stabilized on AOM 400 for ≥12 weeks in an earlier phase of the study.
- Interpret the maintenance efficacy estimates in the context of trial timing, because the study was terminated early and the median time between randomization and the termination date in the 52-week randomized phase was 113 days.
