Novel ADHD Therapy More Tolerable, Less Effective Than Current Treatment Options

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Centanafadine is a serotonin-norepinephrine-dopamine triple reuptake inhibitor.

Although centanafadine has a better safety profile and demonstrates more favorable tolerability, this novel ADHD therapy is less effective than lisdexamfetamine dimesylate (Vyvanse) for adults with ADHD, according to research presented at the American Society of Health-System Pharmacists 2023 Summer Meetings and Exhibition, held June 10 to 14 in Baltimore, Maryland.

Recent phase 3 clinical trials demonstrated significant reductions in ADHD symptoms vs placebo in adults treated with centanafadine, a serotonin-norepinephrine-dopamine triple-reuptake inhibitor—a novel therapy for ADHD. Although centanafadine appeared to be well-tolerated, investigators conducted a matching-adjusted indirect comparison comparing safety and efficacy outcomes between centanafadine vs stimulants lisdexamfetamine, atomoxetine (Strattera), and nonstimulant viloxazine ER (Qelbree).

Patient-level data were pooled from two centanafadine trials (NCT03605680 and NCT03605836) and three comparator trials: NCT00334880 for lisdexamfetamine, NCT00190736 for atomoxetine, and NCT04016779 for viloxazine ER. Propensity score weighting was used to match baseline characterstics, including age, sex, race, Adult ADHD Investigator Symptom Rating Scale score, Clinical Global Impression-Severity of Illness Scale score, and—for centanafadine and viloxazine ER—body mass index. Estimated risk differences, “representing the incremental risk of each adverse event” with centanafadine vs placebo compared with comparator vs placebo, were also reported.

After matching, baseline characteristics were the same across all trials. Adverse outcomes, including dry mouth, insomnia, anxiety, nausea, lack of appetite, and fatigue, among others, were evaluated. Risk difference between centanafadine and lisdexamfetamine was -23.43% for lack of appetite, -19.27% for dry mouth, and -15.35% for insomnia; between centanafadine and atomoxetine, risk difference was -18.64% for nausea and -17.44% for dry mouth, and between centanafadine and viloxazine ER, the risk difference was -11.07% for fatigue and -10.67% for insomnia.

Additionally, investigators evaluated the reduction from baseline in AISRS/ADHD-RS score. Adults with ADHD treated with lisdexamfetamine experienced a 6.58 points greater reduction from baseline scores vs those treated with centanafadine. No statistically significant changes in AISRS score from baseline between centanafadine and atomoxetine or viloxazine ER, (2.02 and 0.90 points respectively), was noted.

“Centanafadine showed a better safety/tolerability profile than lisdexamfetamine, atomoxetine, and viloxazine ER, as evidenced by a significantly lower incidence of several adverse side effects,” the researchers noted. “Efficacy was lower than lisdexamfetamine and non-different compared to atomoxetine and viloxazine ER.”

“This study provides important insights on the relative efficacy and safety of common treatment options for adults with ADHD to help inform treatment decisions,” they concluded.

The investigators also noted that future studies are warranted to “better understand how the tradeoff between safety/tolerability and efficacy affects management in clinical practice” as well as patient treatment preferences.

Reference
1. Schein J. Assessment of centanafadine in adults with ADHD: A matching adjusted indirect comparison vs lisdexamfetamine dimesylate, atomoxetine, and viloxazine ER. Presented at: American Society of Health-System Pharmacists Summer Meetings and Exhibition; June 10-14, 2023; Baltimore, MD.
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