Thorpy M. J. (2020). Recently Approved and Upcoming Treatments for Narcolepsy. CNS drugs, 34(1), 9–27. https://doi.org/10.1007/s40263-019-00689-1

State University of New York at Buffalo

Recently approved Treatments for Narcolepsy

- First-in-class H3R antagonist/inverse agonist with wake-promoting and anticataplectic effects.
- Approved in the EU and the US for narcolepsy treatment.
- Dose range: 4.5–36 mg/day (EU), 17.8–35.6 mg/day (US).
- Mechanism of Action: Acts on histaminergic neurons in the brain, enhancing histamine release.
- PK/DDI: Rapid absorption, median tmax 3.5 h, metabolized by CYP3A4 and CYP2D6, affected by renal and hepatic impairment.
- Efficacy: Improved ESS scores, MWT sleep latency, cataplexy frequency reduction.
- Safety: Common AEs include insomnia, headache, nausea; potential for CYP interactions and QTc prolongation.

Recently approved Treatments for Narcolepsy: Pitolisant

- DA and NE reuptake inhibitor to improve wakefulness.
- Approved in the US for narcolepsy and obstructive sleep apnea.
- Dose range: 75–150 mg/day.
- Mechanism of Action: Inhibits DAT and NET, increasing DA and NE extracellular concentrations.
- PK/DDI: Linear PKs, minimal metabolism, renal clearance, dose adjustments for renal impairment.
- Efficacy: Increased MWT sleep latency, improved ESS scores, PGI-C, and CGI-C.
- Safety: Common AEs include headache, decreased appetite, nausea, anxiety, insomnia; potential for BP/HR increases and QTc prolongation.

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