Insomnia Treatment: DORAs


An overview of dual orexin receptor agonists (DORAs) therapy for the treatment of insomnia in female patients.

Charlene Gamaldo, MD: This class of medications works by settling down the orexin conductor, which is responsible for the intersecting of the various wake neurochemicals. The efficacy data have been quite good across all 3 medications. There haven’t been head-to-head studies on them. All of them with their own randomized crossover placebo trials have shown good efficacy. The efficacy suggests that it may be perhaps more efficacious in some situations than the GABA [gamma-aminobutyric acid]–related drugs.

Within the different medications available in that class, there’s no head-to-head study. Efficacy seems to be about the same. There have been differences in terms of daytime functioning. Suvorexant was the first of the class of orexin medications to come out. A study was done looking at its impact on daytime functioning from the standpoint of daytime sleepiness and cognitive functioning. It didn’t show that it was necessarily better than placebo in terms of providing benefit to daytime functioning.

A study was done with lemborexant with driving capability and alertness specifically vs placebo. Patients on lemborexant did show better driving capabilities and tension. That’s of interest in terms of improving not only the sleep experience but also the safety of component of addressing insomnia. Finally, daridorexant is the youngest on the block in this class. There’s been significant work looking at various aspects of daytime functioning and showing higher functioning compared with placebo in terms of sleepiness and cognitive functioning. Interestingly, studies also show a favorable safety profile for older patients. This is something that was of interest, particularly because there were some concerns about nighttime falls among older patients with the medications that work through the GABA system.

There’s a question about not only the efficacy of DORA [dual orexin receptor agonist] medications but also the failure rate. Some patients find that it doesn’t work, or they have to come off the medication because of efficacy or safety and tolerability. In my experience, the safety and efficacy have been good. More than two-thirds of the patients I have on the medications find some benefit over what they were doing in the past. It becomes a bit complicated in terms of knowing what that means vs some of the other medications. It’s not typical for that to be the first-line medication, primarily because of the influence of insurance companies. Older medications are tried first. If it goes on to the DORA medication, it’s because they failed the other. Because of that, it’s hard to say which is better in terms of head-to-head comparison. But it suggests that all these folks are trying these medications because they failed the others. I’ve seen a reasonable response rate. I haven’t had too many people come off it because of primary adverse effects. There may be a few headaches. That’s 1 I can think of. The failure rate has been mainly from an efficacy standpoint. It didn’t seem to make much difference, but that was probably I’d estimate a third of the patients. Two-thirds saw some benefit.

Transcript Edited for Clarity

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