How do you treat idiopathic hypersomnia inadequately responding to modafinil?

I agree with @Dr. First Last. I usually start my patients on modafinil or armodafinil. If those do not work, I will try solriamfetol. I will supplement with as needed amphetamines as well. I do not often go straight to sodium oxybate/low-sodium oxybate, as you need the right patient for this medication. They have to be in a safe living situation and have no need to wake in the middle of the night. This leaves out college students living in dorms. This also leaves out parents with young children ...

I would try a traditional stimulant first, and if they have side effects, then switch to low-sodium oxybate.

Although I agree with modafinil or armodafinil as a first-line, amphetamines are problematic both in the mood disorders associated with idiopathic hypersomnolence and in college students. Solriamfetol is intriguing, but since IH is an off-label indication, insurers routinely deny it. Overall, sodium oxybate has had a rather excellent side effect profile when it is carefully monitored. Sodium oxybate appears to be a game changer for the ten patients taking it under my care.

The one patient I work with who has idiopathic hypersomnia also has other dysautonomias, so I referred out to a sleep specialist. It took over two years for them to get approved for Xywav because their sleep study was slightly off, and not many physicians prescribed GHB. My patient experienced a brief psychotic episode when the titration was too rapid. The titration was resumed at a slower pace and was well tolerated. They continue to take modafinil, with partial efficacy, but Xywav has signific...

In reviewing the AASM practice guidelines 2021 (1), clarithromycin also has RCT evidence to support it, but must be used cautiously in those with comorbid heart disease, and being wary of the development of antibiotic resistance. Flumazenil also has interesting retrospective data to support it (2) [I am biased as I am grateful to have had a small part in this paper], but was ultimately deemed insufficient/inconclusive for the AASM guideline (1, 3).

That said, I have not tried sodium-oxybate yet, ...