5.4 Medications, OTC Products, Supplements & Substances: Effects on Sleep
Key Takeaways
Medication reconciliation in a sleep clinic includes prescriptions, OTC products, supplements, caffeine, alcohol, nicotine and cannabis, with doses and timing.
SSRIs and SNRIs can suppress REM, cause insomnia or vivid dreams, and worsen restless legs and periodic limb movements; beta-blockers can reduce melatonin and disturb sleep.
First-generation antihistamines such as diphenhydramine are on the AGS Beers Criteria list of drugs to avoid in older adults.
U.S. melatonin is sold as a dietary supplement, and tested products contained 74–347% of the labeled amount in one 2023 study of gummies.
Opioids, benzodiazepines, gabapentinoids and alcohol suppress breathing; the CCSH reports risky combinations to the prescriber but never changes medications.
5.4 Medications, OTC Products, Supplements & Substances: Effects on Sleep
The blueprint lists medications, over-the-counter products and supplements as knowledge areas and asks the CCSH to evaluate the impact of medications (prescription, OTC, supplements) during history taking. Many sleep complaints are side effects, and some drug combinations are dangerous for people with sleep apnea.
Medication Reconciliation in a Sleep Clinic
A complete list includes:
- prescription drugs, with dose and time of day;
- OTC products (sleep aids, decongestants, pain relievers, antacids);
- dietary supplements and herbal products (melatonin, valerian, magnesium, CBD);
- caffeine sources, alcohol, nicotine, cannabis and other substances; and
- recent starts, stops and dose changes (withdrawal also affects sleep and testing).
Ask open questions ("What do you take to help you sleep?" and "What do you take to stay awake?") and use the brown-bag method (patients bring all products) when possible.
Prescription Drugs That Affect Sleep
| Drug class | Common sleep effects |
|---|---|
| SSRIs and SNRIs (fluoxetine, sertraline, venlafaxine) | Insomnia or sedation, REM suppression, vivid dreams, REM sleep without atonia, worsened RLS/PLMS, bruxism |
| Tricyclic antidepressants | Sedation, REM suppression, anticholinergic effects, worsened RLS |
| Mirtazapine, trazodone | Sedation, next-day grogginess; mirtazapine causes weight gain and can worsen RLS |
| Bupropion | Activating; insomnia; does not usually worsen RLS |
| Beta-blockers (propranolol, metoprolol) | Lower nighttime melatonin; insomnia and vivid dreams or nightmares |
| Corticosteroids | Insomnia, especially with evening doses; weight gain |
| Diuretics | Nocturia if taken late in the day |
| Stimulants and wake-promoting drugs | Insomnia if taken late; affect MSLT results |
| Antipsychotics | Sedation, weight gain (raising OSA risk), restlessness that mimics RLS |
| Dopamine agonists | Sudden sleep episodes, RLS augmentation, impulse-control problems |
| Theophylline, levothyroxine excess, decongestants | Insomnia and arousal |
Drugs That Affect Breathing During Sleep
- Opioids: central sleep apnea, ataxic breathing and hypoventilation; they also worsen OSA.
- Benzodiazepines and Z-drugs: relax airway muscles and blunt arousal; the FDA requires a boxed warning when opioids are combined with benzodiazepines, and Z-drugs carry a boxed warning for complex sleep behaviors such as sleep-driving. In 2013 the FDA lowered the recommended starting dose of zolpidem for women because of next-morning impairment.
- Gabapentinoids (gabapentin, pregabalin): sedation; the FDA warned in 2019 about serious breathing problems when they are combined with opioids or other sedatives or used by people with respiratory risk factors.
- Alcohol: adds to all of the above.
Drugs That Affect Sleep Testing
REM-suppressing, alerting and sedating drugs alter MSLT results, which is why the prescriber may stop them about 2 weeks before testing. The CCSH reminds patients of these instructions but never stops a drug on their own.
Over-the-Counter Sleep Aids
Most OTC "PM" products contain diphenhydramine or doxylamine, first-generation antihistamines. They cause next-day drowsiness, confusion, constipation, urinary retention and dry mouth, and they can worsen restless legs. The American Geriatrics Society Beers Criteria list first-generation antihistamines as drugs to avoid in older adults, and the AASM's 2017 insomnia guideline recommends against diphenhydramine for chronic insomnia.
Dietary Supplements
In the United States, supplements are not approved by the FDA for safety and effectiveness before sale, and label accuracy varies.
| Product | What the evidence shows | Cautions |
|---|---|---|
| Melatonin | Useful when timed for circadian rhythm disorders and jet lag; small effects on sleep latency; the AASM recommends against it for chronic insomnia | Content varies widely: a 2023 study of U.S. melatonin gummies found 74–347% of the labeled amount; pediatric melatonin ingestions reported to poison centers rose sharply over the last decade; look for third-party quality marks (such as USP Verified) |
| Valerian | Weak evidence; the AASM recommends against it for chronic insomnia | Rare liver injury reports |
| Kava | Some anxiety benefit | FDA advisory about severe liver injury |
| Magnesium | Limited evidence for sleep | Diarrhea; caution in kidney disease |
| L-tryptophan | The AASM recommends against it for chronic insomnia | Historic contamination outbreak (eosinophilia-myalgia syndrome) |
| CBD and cannabis products | Only one prescription CBD product is FDA-approved, for certain seizure disorders; sleep evidence is limited | Unregulated content, drowsiness, liver enzyme changes, drug interactions |
| St. John's wort | Used for low mood | Induces liver enzymes and reduces the effect of many drugs, including hormonal contraceptives |
| Energy drinks and caffeine pills | Can contain 200 mg or more of caffeine per serving | The FDA considers up to about 400 mg/day generally safe for healthy adults; more causes insomnia and palpitations |
The CCSH's Role and Scope
- Reconcile all products and their timing at intake and follow-up.
- Recognize likely medication causes of insomnia, sleepiness, nightmares, RLS, nocturia or central apnea.
- Report concerns and dangerous combinations (for example, opioids plus benzodiazepines in a patient with untreated OSA) to the prescriber, documenting the communication.
- Educate patients on timing and safety (no alcohol with sedatives, avoid driving if drowsy) and on what the prescriber has decided.
- Collaborate with pharmacists, who are valuable partners for interaction checks.
The CCSH does not start, stop or change doses. Changing a medication's timing is also the prescriber's decision.
Worked Example: What a Reconciliation Can Reveal
A 58-year-old man referred for "insomnia and fatigue" brings his medicines to the visit.
| Finding | Possible sleep effect | Action |
|---|---|---|
| Metoprolol taken at 9 PM | Lower melatonin; vivid dreams | Report to the prescriber, who may consider a different time or drug |
| Fluoxetine started 2 months ago | Insomnia, vivid dreams, worse leg restlessness | Report the timing to the prescriber; note for any planned MSLT |
| Prednisone burst taken in the evening | Insomnia | Ask whether the dose can be given in the morning |
| OTC "PM" product nightly | Next-day grogginess, worse RLS, confusion risk | Educate; report use |
| Two energy drinks after 3 PM | High caffeine late in the day | Set a caffeine cutoff goal |
| Melatonin 10 mg at random times | Poorly timed; dose content uncertain | Discuss timing and quality with the clinician |
Several "insomnia" causes are reversible here. Documenting them clearly and communicating with the prescriber can resolve the complaint without adding another sleep medicine.
A 78-year-old patient takes an OTC 'PM' pain reliever containing diphenhydramine every night for sleep. What is the most important point to raise with the provider?
Diphenhydramine is the AASM's recommended first-line treatment for chronic insomnia in adults over 65
First-generation antihistamines are on the Beers Criteria list to avoid in older adults because of confusion and falls
Diphenhydramine improves restless legs, so the dose should be increased if her legs bother her
Antihistamines have no effect on next-day alertness or balance, so no change is needed as long as she is not driving
A parent asks whether store-bought melatonin gummies are a reliable dose for her child. What is accurate?
Melatonin is an FDA-approved drug, so every gummy contains exactly the labeled dose
Melatonin cannot cause harm in children, so any amount can be given without guidance
Gummies are always weaker than labeled, so parents should routinely double the dose recommended on the package
U.S. melatonin is a dietary supplement, and tested gummies contained 74–347% of the labeled amount
During reconciliation, a patient with untreated severe OSA reports taking oxycodone, gabapentin and nightly alcohol. What should the CCSH do?
Tell the patient to stop the oxycodone and gabapentin immediately until the CPAP is set up
Document the combination and promptly alert the prescribers and sleep physician to the breathing risk
Advise the patient to take all three together at bedtime so that they help him tolerate the mask
Take no action, since prescription and OTC medications do not affect breathing in patients with obstructive apnea
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