Key Takeaways

From the Authors As published in the article
  1. While clinical trials demonstrate the efficacy, safety, and tolerability of a drug relative to placebo or other therapeutic options, they may not fully convey the drug’s benefit–risk profile. Number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH) help translate trial results into clinically useful measures for benefit–risk decisions.
  2. A favorable benefit–risk profile was demonstrated for aripiprazole once-monthly 400 mg (AOM 400) versus placebo in schizophrenia. AOM 400 recipients were 200 times more likely to achieve symptom reduction than discontinue due to an adverse event (AE) in an acute setting and 250 times more likely to remain relapse-free than to discontinue due to an AE in a maintenance setting.
  3. These findings provide clinically useful information, helping to clarify the magnitude and relevance of the benefits and risks of AOM 400 in people diagnosed with schizophrenia. A similar benefit–risk profile is expected for a once-every-2-months long-acting injectable formulation of aripiprazole in a maintenance setting, based on a comparable pharmacokinetic, safety, and efficacy profile to AOM 400.
Extended Takeaways
  1. In acute schizophrenia, the absolute response difference was substantial: 37.0% of patients receiving AOM 400 versus 14.4% receiving placebo achieved a ≥30% reduction in PANSS total score at week 10, yielding an NNT of 5 (95% CI, 4–8).
  2. For maintenance treatment, 90.0% of patients continuing AOM 400 versus 60.4% switched to placebo remained free from impending relapse, with an NNT of 4 (95% CI, 3–5), supporting strong relapse-prevention signal once patients are stabilized.
  3. Treatment-emergent AE discontinuations were numerically lower with AOM 400 than placebo in both studies—4.2% versus 7.6% acutely and 7.1% versus 13.4% in maintenance—so the NNH for this tolerability outcome was negative rather than indicating excess harm with active treatment.
  4. Among common acute adverse effects, most NNH values were double- or triple-digit, but weight gain of ≥7% was the notable exception with an NNH of 8 (95% CI, 5–21), making weight monitoring a more clinically salient tradeoff than akathisia, sedation, or injection site pain in short-term use.
  5. The maintenance tolerability estimates should be interpreted in the context of enrichment: patients randomized to AOM 400 had already been stabilized on AOM 400 for ≥12 weeks, which likely selected for individuals who both responded to and tolerated the medication.
  6. The maintenance trial ended early after a positive interim analysis, and the median time between randomization and the termination date in the 52-week randomized phase was 113 days, so the reported relapse-prevention results reflect a shorter observed double-blind exposure than the nominal 52 weeks.
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Physicians Postgraduate Press, Inc. (PPP) makes no warranties about the accuracy or completeness of any information published in The Journal of Clinical Psychiatry or other PPP materials, and disclaims liability for any use or non-use of that information. Clinicians should not rely solely on these materials and should exercise their own professional judgment when making patient care decisions on an individualized basis.

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