2026 August Update: Centanafadine, Oveporexton, and New Guidance on OCD, Lithium, and Insomnia

<jats:p>After completing this activity, participants should be able to: Identify the mechanism, indication, and eligible population of the two first-in-class agents approved this period, centanafadine (a norepinephrine-dopamine-serotonin reuptake inhibitor for ADHD from age 6) and oveporexton (an orexin receptor 2 agonist for narcolepsy type 1 in adults), and differentiate centanafadine from the non-stimulants it is being grouped with, given a label that classifies it as a CNS stimulant, carries a boxed warning for abuse, and rests on placebo-controlled trials establishing no advantage over existing agents. Apply the period's new guidance to three prescribing decisions: extending an SSRI trial in OCD to at least 12 weeks at the maximally tolerated dose before judging it failed, targeting the lowest effective serum lithium level given that 0.60–0.79 mmol/L carries a 2.9-fold increase in chronic kidney disease and 0.80–0.99 mmol/L a 4.3-fold increase, and offering CBT-I alone ahead of combination treatment in chronic insomnia. Evaluate what the period's label and safety changes do and do not establish, including why lumateperone's randomized-withdrawal design cannot support a comparison with another antipsychotic, why subcutaneous initiation of lecanemab leaves the ARIA monitoring burden unchanged, and how to counsel men of reproductive potential taking valproate following the EMA's revised position.</jats:p>