His CPAP Numbers Are Excellent. He’s Still Falling Asleep at Red Lights.
His apnea is fixed, by every number that matters. What CPAP hasn’t fixed is falling asleep behind the wheel — a real, separate problem with real, separate drugs, neither of which is simply “more CPAP.”
G.M., a 51-year-old man, restores old pickup trucks in his garage most weekends, a hobby he picked up from his own father and now shares with his teenage nephew, who comes over most Saturdays to help. He was diagnosed with moderate-to-severe obstructive sleep apnea three years ago after a routine physical picked up on loud snoring and witnessed breathing pauses, and he has used CPAP nightly since with excellent, well-documented adherence — download data his sleep center reviews at each visit shows him averaging over seven hours of use most nights, and his apnea-hypopnea index on therapy has consistently been well-controlled. He supervises crews on commercial construction sites, work that regularly puts him within arm’s reach of heavy, moving machinery for most of his day.
Despite that genuinely strong adherence, he continues to report significant daytime sleepiness, scoring 16 on the Epworth Sleepiness Scale at today’s visit — solidly in the significant-sleepiness range — and disclosed, with visible discomfort and after some hesitation, that he has caught himself nodding off at red lights twice in the past month during his commute home, once badly enough that a car horn behind him was what woke him. He has no cardiac history beyond mild, well-controlled hypertension managed on a single low-dose medication, and no other chronic medical conditions.
His physician confirmed at today’s visit, reviewing his records carefully, that his CPAP mask fit and pressure settings remain appropriate and that his residual sleepiness is not explained by inadequate apnea treatment, poor adherence — which his download data clearly rules out — or an alternative sleep disorder identified on repeat testing. That combination raises the question of a wake-promoting agent specifically for his persistent daytime sleepiness despite otherwise genuinely well-controlled OSA, a real, separate problem from the apnea itself.
In clinic, after he disclosed the near-misses at red lights
This is a well-recognized clinical entity — residual excessive daytime sleepiness despite objectively adequate CPAP therapy — and solriamfetol is a reasonable first choice. In the TONES 3 trial, solriamfetol produced significant, dose-dependent improvements in both objective wakefulness testing and subjective ESS scores in exactly this population, and it’s FDA-approved specifically for this indication.
Given his hypertension, though, I’d flag the dosing ceiling directly: the US product labeling caps solriamfetol at 150 mg daily — the label's stated reason being that doses above 150 mg don't add enough effectiveness to outweigh their dose-related adverse reactions, blood pressure prominent among them, which is why the 300 mg arm tested in TONES 3 never became an approved dose — worth naming now, not discovering later.
That’s the right caution, and I’d push it a little further given his occupational context. Solriamfetol’s blood-pressure effect is real and dose-dependent even within the capped range, and for a man managing hypertension who also needs sustained, reliable alertness around heavy machinery all day, I think pitolisant deserves equal first-line consideration rather than being treated as the second option.
One thing has to be said plainly before we go further, because it changes what we are actually proposing: in the United States pitolisant is approved only for narcolepsy — excessive daytime sleepiness since 2019, cataplexy since 2020. It is not FDA-approved for residual sleepiness in obstructive sleep apnea. That indication exists in Europe, where it is marketed as Ozawade and was approved by the EMA in 2021 on the HAROSA trials. So for this patient, in this country, pitolisant is an off-label recommendation and solriamfetol is the drug that actually carries the indication for his exact problem. That doesn’t settle the question — off-label prescribing on good evidence is ordinary medicine — but it is not a detail to leave out of a comparison that otherwise reads as two equally-approved defaults.
Pitolisant works through a different mechanism entirely — histamine H3 receptor antagonism, indirectly boosting histaminergic wake-promoting signaling rather than direct dopamine/norepinephrine reuptake inhibition — and the HAROSA I trial, in patients adherent to CPAP with residual sleepiness, showed real ESS improvement without the same blood-pressure signal, with only a small, clinically non-significant QTc increase seen over a full year of use in the long-term follow-up data.
You’re right that the labeling asymmetry is real, and I don’t want to wave it away — but I’d weigh it differently than it might first appear. An FDA indication tells us a sponsor ran trials for that population in this country; it isn’t a statement that the unapproved drug is unproven for it. HAROSA I and II were real randomized trials in exactly this population, and the EMA reviewed them and approved on that basis. What the off-label status does change is practical, and it’s worth being honest about: insurance coverage will be harder, prior authorization is likely, and the conversation with him has to include that we are prescribing outside the US label.
Weighing those together, for his specific situation — hypertension, a job where next-day cardiovascular strain matters as much as alertness does — I’d still start with pitolisant rather than treating the two options as interchangeable defaults. It isn’t that solriamfetol is unsafe at the capped dose; it’s that when two comparably effective options exist and one has a real, named blood-pressure signal in a patient who already has hypertension, that difference should drive the first choice. If coverage turns out to be the obstacle it often is, solriamfetol at the lowest effective dose with genuine blood-pressure monitoring is a legitimate fallback, not a failure of the plan.
Agreed: pitolisant started as first-line wake-promoting therapy given his hypertension, with CPAP continued unchanged and blood pressure monitored at follow-up regardless of which agent he ultimately needed.
Not fully settled at the start of the visit, but resolved by its end:
Solriamfetol as the reasonable default with the dosing ceiling as a caveat, reflecting its status as the more established, more extensively trial-tested option.
For a hypertensive patient in a safety-sensitive occupation, the blood-pressure difference between the two options should determine the first choice directly, not sit as an asterisk on the more familiar drug.
G.M. was told plainly that both drugs are real, effective options for his exact problem, that pitolisant was chosen specifically because of his own blood pressure and job rather than because solriamfetol is a worse drug in general, and that pitolisant is being prescribed outside its US label for this use — approved here for narcolepsy, approved for his indication in Europe but not by the FDA. He was told to expect an insurance conversation before the first fill.