Medications that may interfere with sleep architecture

Drug class	Example agents
Acetylcholine modulators	Donepezil
Adenosine modulators	Theophylline, theobromine, caffeine
Alpha-2 delta ligands	Gabapentin
Antidepressants
SSRIs	Fluoxetine*, escitalopram, sertraline, paroxetine
SNRIs	Venlafaxine, duloxetine
Bupropion	Bupropion
Tricyclic antidepressants	Nortriptyline, amitriptyline
MAOIs	Phenelzine
Antihistamine, sedating	Diphenhydramine, doxylamine
Antipsychotic agents	Quetiapine
Antihypertensives	Prazosin
Benzodiazepines/NBRAs	Flurazepam*, clonazepam, lorazepam, zolpidem, eszopiclone, zaleplon
Dopamine agonists	Pramipexole, rotigotine, ropinirole
Lithium	Lithium
Melatonin agonists	Ramelteon, tasimelteon
Opioid agonists	Morphine, hydrocodone, methadone, fentanyl
Orexin/hypocretin antagonists	Suvorexant
Sodium oxybate	Sodium oxybate
Steroids	Prednisone
Stimulants	Methylphenidates, amphetamines
Wake-promoting agents	Armodafinil, modafinil, pitolisant, solriamfetol
Marijuana	Tetrahydrocannabinol*

An American Academy of Sleep Medicine task force recommends that the agents listed in the table (medications that can affect rapid eye movement [REM] sleep and/or nonrapid eye movement sleep latency) be tapered before the multiple sleep latency test (MSLT) to minimize medication and substance effects.
A 2-week washout is generally recommended; agents with an asterisk have long half-lives, and longer washout (up to 6 weeks) may be needed. The table includes commonly encountered medications or those requiring a prolonged washout period, but it is not an exhaustive list.

SSRIs: selective serotonin reuptake agonists; SNRIs: serotonin noradrenergic reuptake inhibitors; MAOIs: monoamine oxidase inhibitors; NBRAs: nonbenzodiazepine receptor agonists; CBG: cannabigerol.
* Medication agents with long half-lives and longer washout (up to 6 weeks) may be needed.

Republished with permission of American Academy of Sleep Medicine, from: Krahn LE, Arand DL, Avidan AY, et al. Recommended protocols for the Multiple Sleep Latency Test and Maintenance of Wakefulness Test in adults: guidance from the American Academy of Sleep Medicine. J Clin Sleep Med 2021; 17:2489. Copyright © 2021. Permission conveyed through Copyright Clearance Center, Inc.

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