Centanafadine for ADHD

Centanafadine is a

• Noradrenaline reuptake inhibitors
• Dopamine reuptake inhibitors
• Serotonin reuptake inhibitors (weak)

Two randomized, double-blind, placebo-controlled, parallel-group phase 3 studies were conducted in adults with ADHD using 200 mg/d or 400 mg/d centanafadine sustained-release tablets.¹²
At Day 42, both studies showed improvements in AISRS total score compared to placebo with Effect sizes of -0.28 for 200 mg/d and -0.24 for 400 mg/d in Study 1 and -0.37 for 200 mg/d and -0.40 for 400 mg/d in Study 2.

Centanafadine was well tolerated and the overall rate of adverse events was low, but dose-dependent.
A 52-week study found fewer side effects with centanafadine than with lisdexamfetamine, methylphenidate and atomoxetine, with a worse Effect size than lisdexamfetamine and comparable Effect size to methylphenidate³⁴ and thus showed the best adjusted overall benefit (Effect size in relation to side effects).⁵
(Falling) asleep problems were less frequent with centanafadine than with MPH, with comparable efficacy in relation to ADHD.⁶

Centanafadine is currently being studied in several clinical trials for its efficacy and safety in children and adolescents with ADHD (NCT05279313, NCT05428033, NCT05257265).⁷
An RCT in adolescents aged 13 to 17 years found an efficacy of 328.8 mg, but not of 164.4 mg centanafadine. At 328.8 mg, 50.3 % showed undesirable side effects, compared to 23.8 % with placebo. The most common side effects were decreased appetite, nausea, headache and rash. 0.6 % suffered serious side effects (one each of increased liver enzymes and aggressiveness) with 164.4 mg and 0.6 % with placebo (somnolence).⁸
A 12-month study found only mild side effects in adults, which are also typical for stimulants, such as⁹

• Sleep disorders (8.0 %)
• Nausea (7.7 %)
• Diarrhea (7.0 %)
• Headaches (7.0 %)
• (12.3%) discontinued treatment due to side effects

Centanafadine did not affect the QTc time.¹⁰