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Dr. Finch:
Hello, my name is Dr. Kristina Finch and I'm at the University of California San Diego, where I am a Clinical Sleep Medicine Doctor in addition to being on faculty. So today we're going to review the New Treatments for Residual Excessive Daytime Sleepiness in Obstructive Sleep Apnea.
So when to treat with wakefulness-promoting agent? So we want to make sure that sleep apnea has been adequately treated for at least 3 months, any comorbidities have been addressed and optimized in their treatment as well. And despite this, 14% of people with sleep apnea have been shown to have residual excessive daytime sleepiness. So you will see these patients in your office and it is important to address them. It's important to discuss their - how their sleepiness is affecting their quality of life, if there are any associated safety concerns such as driving, drowsy, poor work performance, and they can first consider a trial of over-the-counter caffeine prior to prescribed medications and ensuring that they get sufficient sleep. So we usually recommend starting with a 4- to 6-week trial, ensuring sleep apnea is well controlled, and then discontinuing a medication based on its possible side effects. We typically try to avoid stimulants for residual excessive daytime sleepiness in sleep apnea, they can come with a higher risk of cardiovascular risk, in addition to abuse potential, so these typically aren't first line but could be considered on an as-needed basis.
So wakefulness-promoting agents, the longstanding medications for in this class have been Modafinil and armodafinil. Armodafinil is – so the Modafinil is the racemic mixture, and armodafinil is just the R enantiomer. And the mechanism of action is a CNS stimulant, likely through enhanced dopamine signaling, but we don't have a great sense of how this works fully. So for dosing, Modafinil usually starts around 100 to 200 mg, can titrate up to 400 daily. And armodafinil typically starts around 150 mg, and you can titrate up to 250 if needed.
So significant side effects include a life-threatening rash, including Stevens-Johnson Syndrome with multiorgan hypersensitivity, so I always recommend that patients stop use with any signs of rash and contact me immediately. Adverse cardiovascular effects or effect warnings actually prevent this drug from being approved in Europe. So I don't prescribe it in patients with cardiovascular diagnoses like hypertension, left ventricular hypertrophy, angina, or prior MI. And it does make hormonal contraception less effective, so definitely you need to counsel your patients for alternative methods for birth control if desired.
Solriamfetol is a newer agent on the market. It is a selective dopamine and norepinephrine reuptake inhibitor. There are some thoughts of this might be more effective, but because it’s new, cost is often a barrier for patients being able to
have access to it. The dosing typically starts at 37.5 once daily, and you can double the dose as needed after 3 or greater days to a maximum of 150 mg per day. Significant side effects include cardiovascular risk, which is dose dependent, and it can increase blood pressure and heart rate. So I avoid in patients with unstable cardiovascular disease or serious arrhythmias. Psychiatric symptoms also include anxiety, insomnia, and irritability. And I would specifically use caution in patients with more severe psychiatric diagnoses including bipolar or psychosis. It does have the potential for abuse. So I always use caution in patients who have a history of drug or alcohol abuse, and it does need to be renally dosed in patients with kidney impairment.
In review of new and emerging therapies for treatment of residual sleepiness in obstructive sleep apnea, the most important thing is to really make sure that they are using their treatments, using their CPAP or whatever modality of treatment they're using for the sleep apnea for at least 3 months, and making sure that they they're comfortable with that and that everything is optimized there. And then if prescription medications are needed, we recommend close follow-up and seeing if other adjustments can be made. Modafinil and armodafinil have been around for many years, they’re kind of the tried and true, and solriamfetol is a newer agent that does hold a lot of promise.
Thank you so much for reviewing the new and emerging therapies for treatment of residual sleepiness in OSA.
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