Once-Monthly Aripiprazole Demonstrates Favorable Benefit–Risk Profile in Schizophrenia Treatment
Key Clinical Summary:
- Aripiprazole once-monthly 400 mg (AOM 400) demonstrated strong efficacy in acute schizophrenia, with 37.0% of patients achieving ≥30% Positive and Negative Syndrome Scale (PANSS) reduction vs 14.4% on placebo (number needed to treat [NNT] = 5).
- In maintenance treatment, 90.0% of patients remained relapse-free vs 60.4% with placebo (NNT = 4).
- Lower discontinuation rates due to adverse events yielded negative number needed to harm (NNH) and high likelihood to be helped or harmed (LHH up to 250).
Once-monthly aripiprazole 400 mg (AOM 400) demonstrated a favorable risk-benefit profile as an acute and long-term maintenance treatment in patients with schizophrenia, according to post hoc analysis results published in The Journal of Clinical Psychiatry.
Study Findings
The analysis evaluated efficacy and tolerability data from 2 trials comparing AOM 400 with placebo in patients with schizophrenia. Outcomes were assessed in both acute and maintenance settings using standardized clinical measures.
In the acute treatment study, 60 of 167 patients (37.0%) receiving AOM 400 achieved at least a 30% reduction in Positive and Negative Syndrome Scale (PANSS) total score at 10 weeks, compared with 24 of 168 patients (14.4%) on placebo. This corresponded to a number needed to treat (NNT) of 5 (95% CI, 4–8), indicating that 5 patients would need to be treated for 1 additional patient to benefit.
In the maintenance study, conducted over a median observation period of 113 days, 242 of 269 patients (90.0%) treated with AOM 400 remained free from impending relapse, compared with 81 of 134 patients (60.4%) receiving placebo. The resulting NNT was 4 (95% CI, 3–5).
Safety analysis showed fewer discontinuations due to treatment-emergent adverse events (TEAEs) in the AOM 400 groups compared with placebo in both studies. This produced negative number needed to harm (NNH) values, suggesting a lower risk of harm relative to placebo. Likelihood to be helped or harmed (LHH) values were 200 for acute treatment and 250 for maintenance therapy, indicating a substantially greater likelihood of benefit than harm.
Clinical Implications
The findings reinforce the clinical utility of AOM 400 as both an acute and long-term maintenance therapy for schizophrenia. Low NNT values suggest robust efficacy, particularly in relapse prevention, which remains a major challenge in schizophrenia management.
The negative NNH values indicate that AOM 400 may be better tolerated than placebo in terms of discontinuation due to adverse events. This has practical implications for adherence, a critical factor in long-term outcomes.
High LHH values further contextualize the benefit–risk balance, offering clinicians a quantitative framework for treatment decisions. In routine practice, these data may support the selection of long-acting injectable antipsychotics (LAIs) for patients at risk of relapse or poor adherence.
Expert Commentary
“The analysis was conducted post hoc, and the findings can be considered hypothesis-generating and require prospectively designed studies to confirm,” noted first author and Psych Congress Consultant Leslie Citrome, MD, MPH, Department of Psychiatry and Behavioral Sciences, New York Medical College, Valhalla, New York, and study coauthors.
However, the researchers concluded that the findings “provide insight into the magnitude and clinical relevance of the benefits and risks associated with AOM 400 and may be useful to support informed decision-making in clinical practice.”
