A Mayo Clinic study reemphasizes that REM suppressing drugs can cause false negatives for people with suspected narcolepsy who are taking a multiple sleep latency test.

By Lisa Spear

Excessive sleepiness can go hand in hand with depression, so it is not surprising that many patients who undergo diagnostic testing for narcolepsy are on antidepressants. But there’s historically been a lack of scientific data on how these medications may influence the results of diagnostic tests.

“It’s common for us to see patients who are referred to us for an evaluation of excessive sleepiness who are on antidepressant medications,” says psychiatrist Bhanu Kolla, MD, who treats narcolepsy patients at the Mayo Clinic in Rochester, Minn. “And for the longest time, we have known that antidepressants can interfere with this testing, and the  AASM [American Academy of Sleep Medicine] guidelines state that we should at least attempt to get these patients off these medications before doing the testing. That was based mostly on conjecture, so we were assuming that these medications interfere.”

To evaluate how antidepressants may impact narcolepsy testing, Kolla and his colleagues conducted research, which now shows that these medications may skew the results of the multiple sleep latency test (MSLT), a daytime diagnostic study for individuals with suspected narcolepsy. The study showed that when patients taper off antidepressants prior to taking the MSLT, they experience an increase in the number of sleep-onset rapid eye movement periods and a reduction in the time it takes to fall asleep.

“I wouldn’t call it surprising. It was sort of reemphasizing what we already knew,” says Kolla.

Patients involved in the study were undergoing an MSLT at Mayo Clinic between 2014 and 2018. Up to a third of the 502 adult patients involved in the study were on rapid eye movement (REM) suppressing antidepressants at the time of the initial assessment. Of those, 70% were able to discontinue the medication. The remainder of the patients could not be weaned off before undergoing the MSLT.

“This is also common, clinically, to see that the depression is quite severe. The patients do not feel comfortable, or you know from prior experience that they have had depressive relapses,” says Kolla. “There are a fair number of patients who still go through the testing with the medication.”

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The results of the research were presented in August as an abstract during Virtual SLEEP 2020 and published in an abstract in a supplement to the journal Sleep.

To avoid any problems during the process of removing a patient from antidepressants, Kolla suggests that providers work with the prescribing provider, psychiatrist, or primary care clinician to understand the patient’s history and previous attempts at discontinuing the medication to try to plan for the ideal testing circumstance.

It is important to have a comprehensive plan and timeline to taper the patient off of antidepressants. If patients are not able to come off of their medications before the MSLT, then providers need to be aware of how that might impact the results.

If a patient undergoes testing while still on these medications, providers should have a high clinical suspicion that the result could be a false negative. That is, the antidepressants are suppressing the early REM sleep that is needed to meet the criteria for narcolepsy. In this case, physicians should consider identifying a laboratory that provides a cerebrospinal fluid hypocretin/orexin test, an alternate means to identify narcolepsy.

If you are conducting MSLTs with antidepressants, “it is quite likely that the results are influenced by the medications and are not interpretable,” says Kolla. “Look at other options.”

Lisa Spear is associate editor of Sleep Review.