Narcolepsy has no cure, but its main symptoms can usually be treated. The medicines used in Ireland and the UK today are modafinil, pitolisant, solriamfetol and sodium oxybate, alongside planned naps. Some people also take stimulants or certain antidepressants for cataplexy. These treat symptoms. None of them replaces the orexin (hypocretin) that is lost in narcolepsy type 1.
That is what makes the new orexin drugs different. Oveporexton (brand name Orzeyful) switches on the orexin 2 receptor directly. The US Food and Drug Administration (FDA) approved it on 5 August 2026 for adults with narcolepsy type 1. It is not authorised in the EU or the UK. NICE expects to publish its appraisal in April 2027. Several similar drugs are still in trials.
This guide explains each option, what the trials found, and what you can actually get in Ireland and the UK. If you are still waiting for a diagnosis, start with why narcolepsy takes years to diagnose.
Narcolepsy has several symptoms, and different medicines target different ones:
The 2021 European guideline, from the European Academy of Neurology and two European sleep societies, says treatment should be tailored. Your symptoms, other conditions, side effects and drug interactions all shape the choice.
Medicines are not the only tool. The European guideline gives scheduled daytime naps a strong recommendation for daytime sleepiness, in adults and children. The NHS also advises a regular bedtime and wake time, planned naps and enough sleep at night. It suggests avoiding alcohol.
Modafinil is a wake-promoting medicine. In 2010 the European Medicines Agency (EMA) reviewed it across the EU. It concluded the benefits outweighed the risks only in narcolepsy. It removed its other uses, including idiopathic hypersomnia and sleep apnoea.
The EMA review linked modafinil to rare serious skin reactions. It also linked it to psychiatric effects, such as suicidal thoughts, and to high blood pressure and irregular heartbeat. The UK product information says it can make hormonal contraception less effective. It also says modafinil is suspected to cause birth defects if taken in pregnancy.
Pitolisant works on the brain's histamine system to promote wakefulness. In the main 8-week trial (Harmony 1, 94 adults), it reduced sleepiness compared with placebo. It did not differ significantly from modafinil. It also cut cataplexy attacks by 65%, against 10% on placebo.
A second trial used a lower top dose (Harmony Ibis). In its most cautious analysis, it showed no significant effect on sleepiness against placebo. In Harmony CTP, a trial in people with frequent cataplexy, weekly attacks on pitolisant were about half those on placebo.
Pitolisant can make the contraceptive pill less effective. Its product information says to avoid combining them and to use another reliable method.
Solriamfetol is thought to work by blocking the reuptake of dopamine and noradrenaline. In its 12-week trial, the 150 mg group stayed awake 7.7 minutes longer than placebo on a stay-awake test. The 75 mg group improved on the sleepiness questionnaire, but not on the stay-awake test. Solriamfetol can raise blood pressure and heart rate, so these are checked before and during treatment.
Sodium oxybate is the sodium salt of GHB. In Europe it is taken as a liquid at bedtime and again 2.5 to 4 hours later. The European guideline strongly recommends it for both daytime sleepiness and cataplexy.
In one trial, people on the highest dose started with a median of 23.5 cataplexy attacks a week. Their median fall was 16 attacks a week, against 4 on placebo. In a separate trial, people on long-term treatment who were switched to placebo had a large rise in attacks.
It has serious cautions. It can slow breathing, so people are assessed for sleep apnoea before starting. It must not be combined with alcohol, opioids or barbiturates. It is not used in people with major depression. It has well-known abuse potential.
Two newer versions exist in the US only. Lumryz is a once-nightly sodium oxybate, approved by the FDA in 2023. Xywav is a mixed-salt oxybate containing much less sodium. We found neither on the EU or UK medicine registers.
The European guideline gives methylphenidate and amphetamine-type stimulants a weak recommendation for sleepiness. For cataplexy in adults it strongly recommends sodium oxybate, venlafaxine or clomipramine. NICE notes that in England, sleepiness is usually treated first with modafinil, then dexamfetamine or methylphenidate.
In narcolepsy type 1, the brain loses the cells that make orexin. Orexin-receptor agonists act like orexin at its receptor. They are the first medicines aimed at the missing signal itself, rather than other alertness systems.
Two phase 3 trials, First Light and Radiant Light, were published in the New England Journal of Medicine in September 2026. They enrolled 273 people with narcolepsy type 1, from a permitted age range of 16 to 70. Participants took oveporexton or placebo twice each morning for 12 weeks.
The main measure was how long people could stay awake in a quiet, dark room (normal is 20 minutes or more). In the FDA label:
The side effects were common. In the pooled trials, 58% had insomnia, mostly starting in the first two days. Most cases settled within a week. Passing urine more often affected 53% to 58%, against 5% on placebo. Some had urgency, extra saliva or raised muscle enzymes.
The FDA label says oveporexton has potential for abuse. Its US controlled-drug schedule was still pending when the label was issued. It must not be taken with strong CYP3A inhibitors, a group of interacting medicines. The trials lasted 12 weeks, so longer-term effects are not yet established.
Oveporexton is approved only for narcolepsy type 1. People with type 2 usually still make orexin, and they were not in these trials.
These are investigational. None is approved anywhere we checked. Registry entries list studies of:
A trial is research, not a treatment option. Results may be positive or negative.
We checked the HSE's list of reimbursable items (last updated 8 October 2026):
The NCPE also reviewed pitolisant for children aged 6 and over in 2023. It recommended it not be considered for reimbursement at the submitted price.
We searched ClinicalTrials.gov, the EU clinical trials register and ISRCTN on 3 November 2026. We found no orexin-agonist trial listing a site in Ireland or the UK. Sites were in mainland Europe, North America, Asia and Australia.
If you are waiting for a specialist, our guide to getting referred in Ireland explains the routes.
Narcolepsy can affect mood, and some of these medicines carry psychiatric warnings. If you have thoughts of suicide or self-harm, contact Samaritans on 116 123 (Ireland and UK). In Ireland, you can also text 50808. In an emergency, call 112 or 999.
No. It acts on the orexin 2 receptor while you take it. It does not restore the lost orexin cells. Its trials lasted 12 weeks.
Not as an approved medicine. It is not authorised by the EMA or MHRA. We found no trial site in either country. NICE expects to publish its appraisal in April 2027, but that is a schedule, not a promise.
We found no EU or UK authorisation for Lumryz, the once-nightly version. In Europe, sodium oxybate is taken twice a night.
Modafinil, pitolisant and solriamfetol are licensed for narcolepsy with or without cataplexy. Oveporexton is approved only for type 1. Several orexin agonists are being tested in type 2.
In the EU, modafinil is licensed only for narcolepsy, after the EMA's 2010 review. Any other use would be off-label.
This article is general information, not medical advice. It does not replace advice from your GP, sleep specialist or pharmacist. Do not start, stop or change a medicine without your prescriber.
Reviewed by: Proco Team
Last updated: November 2026