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Home » Meet the First H3 Antagonist

Meet the First H3 Antagonist

November 15, 2019
Chris Aiken, MD
From The Carlat Psychiatry Report
Issue Links: Learning Objectives | Editorial Information | PDF of Issue
Chris Aiken, MD. Editor-in-Chief of The Carlat Psychiatry Report. Practicing psychiatrist, Winston-Salem, NC.

On August 15, 2019, pitolisant (Wakix) received FDA approval for narcolepsy, making it the first release of a histamine-3 (H3) antagonist.


Unlike other narcolepsy medications, pitolisant is not a controlled substance and lacks abuse potential. Those other options for narcolepsy are the stimulants (methylphenidate and amphetamine), the modafinils, sodium oxybate (Xyrem), and the newly released solriamfetol (Sunosi), a dopamine and norepinephrine reuptake inhibitor that we reviewed in the June/July issue of TCPR. Pitolisant has been compared to modafinil in 2 head-to-head trials, where pitolisant had similar efficacy but better tolerability (total n = 260) (Romigi A et al, Drug Des Devel Ther 2018;12:2665–2675).


Pitolisant’s main side effects are insomnia, headache, nausea, and anxiety. As a weak CYP3A4 inducer, it may decrease oral contraceptives.


The H3 histamine receptor is mainly found in the brain, where it regulates wakefulness, appetite, and memory. Pitolisant blocks the H3 receptor, and this blockade causes downstream effects of increased dopamine and acetylcholine in the prefrontal cortex. That profile has led to investigations of pitolisant in ADHD, dementia, obesity, and cognitive symptoms of schizophrenia. So far the results have not proved as promising as the narcolepsy findings, but most of those trials are incomplete or unpublished. It’s an intriguing mechanism, and we expect to learn more about its psychiatric effects in the future (Syed YY, Drugs 2016;76(13):1313–1318).

General Psychiatry
KEYWORDS histamine narcolepsy neurology news_of_note pitolisant wakix
Aiken eic 150x150
Chris Aiken, MD

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www.thecarlatreport.com
Issue Date: November 15, 2019
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Table Of Contents
CME Post-Test - Adult ADHD, TCPR, November/December 2019
Highlights From This Issue
Adult-Onset ADHD
Micronutrients in Mental Health
Adult ADHD: What Else Could It Be?
Stimulants as Cognitive Enhancers
A Practical Guide to Light Therapy
Meet the First H3 Antagonist
An Antipsychotic Patch
Pharmacology for GAD: Complex Choices
Olanzapine for Anorexia Nervosa
In Brief: Antipsychotic Update
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