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W103

ARIPIPRAZOLE ONCE-MONTHLY FOR PATIENTS LIVING WITH SCHIZOPHRENIA: NUMBER NEEDED TO TREAT, NUMBER NEEDED TO HARM, AND LIKELIHOOD TO BE HELPED OR HARMED

Leslie Citrome — Karimah S. Bell Lynum2, Zhen Zhang2, Anne M. Hutson Walker3, Norman Atkins, Jr.2, Murat Yildirim4, Leslie Citrome5 1New York Medical College, 2Otsuka Pharmaceutical Development and Commercialization Inc., 3Lundbeck LLC, 4H. Lundbeck A/S, 5New York Medical College

2026 ASCP Annual Meeting

Introduction

Choosing an antipsychotic for patients living with schizophrenia requires an understanding of its benefits and risks. This analysis assessed the benefit–risk profile of acute and maintenance treatment with aripiprazole once-monthly 400 mg (AOM 400) in patients living with schizophrenia, using effect size metrics including number needed to treat (NNT), number needed to harm (NNH), and the likelihood of being helped or harmed (LHH).

Methods

Data came from two double-blind studies of patients living with schizophrenia. In Study 291 (NCT01663532), adults experiencing an acute psychotic episode were randomized to AOM 400 or placebo for 12 weeks. In Study 246 (NCT00705783), patients stabilized on oral aripiprazole and then AOM 400 were randomized to continue AOM 400 or switch to placebo for up to 52 weeks. Key efficacy outcomes included ≥30% reduction in Positive and Negative Syndrome Scale (PANSS) total score at Week 10 (Study 291) and freedom from relapse at Week 52 (as defined in Study 246). The rate of discontinuations due to treatment-emergent adverse events (TEAEs) was the selected safety/tolerability outcome in both studies. NNT, NNH, and LHH were calculated for these outcomes. In this analysis, NNT and NNH described the number of patients needed to be treated with AOM 400 vs placebo for 1 additional patient to benefit (NNT) or be harmed (NNH). Generally, lower NNT values and higher NNH values indicate a more favorable benefit–risk profile. Negative NNH values, which occur when a safety outcome occurs more often with placebo than AOM 400, were imputed as 1000. LHH is the ratio of NNH to NNT; a LHH > 1 indicates a higher likelihood of benefit than harm.

Results

In Study 291, 60/162 patients (37.0%) in the AOM 400 group and 24/167 patients (14.4%) in the placebo group achieved ≥30% reduction in PANSS total score at Week 10, resulting in a NNT of 5 (95% confidence interval [CI]: 4, 8). The rate of discontinuations due to TEAEs was lower with AOM 400 (n=7/167; 4.2%) than placebo (n=13/172; 7.6%), resulting in a NNH of −30 (95% CI: not significant). Using an imputed NNH of 1000, the LHH was 200. In Study 246, 242/269 patients (90.0%) in the AOM 400 group and 81/134 patients (60.4%) in the placebo group were free from relapse at study end, resulting in a NNT of 4 (95% CI: 3, 5). The rate of discontinuations due to TEAEs was lower with AOM 400 (n=19/269; 7.1%) than placebo (n=18/134; 13.4%) resulting in a NNH of −16 (95% CI: not significant). Using an imputed NNH of 1000, the LHH was 250.

Conclusions

Patients living with schizophrenia, experiencing an acute psychotic episode, and receiving AOM 400, were 200 times more likely to achieve treatment benefit over 10 weeks than discontinue due to a TEAE. Additionally, patients living with schizophrenia were 250 times more likely to maintain efficacy over 52 weeks than discontinue treatment due to a TEAE. W104. MEDETOMIDINE-AN EMERGING ADULTERANT Thersilla Oberbarnscheidt*1 1University of Pittsburgh Medical Center, Western Psychiatric Hospital

Drug-related morbidity and mortality in the United States are the highest of any country, a worsening situation further complicated by a dangerous and changing drug supply. Specifically, opioids are a factor in over 7 out of 10 overdose deaths and remain responsible for around 80,000 deaths per year. The landscape of illicit opioids continues to undergo changes. Opioid overdose deaths are described in three waves: wave 1 began in the 1990s with prescription opioids, wave 2 saw a shift to heroin overdose deaths in 2010, and 2013 marked the third wave in which synthetic overdose deaths saw the addition of adulterants to opioids, namely fentanyl. Initially, wave 3 oversaw an increasing content of Xylazine added to fentanyl; however, in recent years fentanyl laced with Medetomidine has been on the rise. Medetomidine is an alpha-2 receptor agonist that is 100-200 times more potent than xylazine, typically used in veterinary medicine. The exposure to medetomidine can cause prolonged sedation, hypotension, bradycardia, and central nervous system depression. An overdose due to a fentanylmedetomidine combination is more difficult to reverse due to the lack of responsiveness to the antidote naloxone. Also, medetomidine is more likely to cause severe withdrawal symptoms than fentanyl alone and fentanyl laced with xylazine, with patients reporting its use being more likely to present to an emergency department. Common symptoms are tachycardia, severe hypertension, waxing and waning of alertness, tremor, and intractable nausea and vomiting. The treatment of these withdrawal symptoms has been more challenging and prolonged than previous experiences with pure fentanyl. This poster will illustrate the evolution of medetomidine and its pharmacology, as well as discuss typical intoxication and withdrawal symptoms with current treatment approaches. Utilized sources were Pubmed, Ovid, Medline, PsychInfo, EMBASE.