What are the strongest sleeping pills?
/mtm/ramelteon.htmlThere are many different types of sleeping pills available. Some require a prescription, while others are available over the counter. In general, prescription sleeping pills are stronger than those found over the counter. Experts recommend combining cognitive-behavioral therapies together with medication whenever possible.
Prescription sleeping pills include:
- Antidepressants (e.g., doxepin, trazodone)
- Antipsychotics (e.g., quetiapine, risperidone)
- Benzodiazepines (e.g., triazolam, temazepam)
- Benzodiazepine receptor agonists (e.g., eszopiclone, zaleplon, zolpidem)
- Melatonin receptor agonists (ramelteon)
- Orexin receptor antagonists (e.g., suvorexant, lemborexant)
Over-the-counter sleeping pills include:
- Antihistamines (e.g., diphenhydramine, doxylamine)
- Magnesium
- Melatonin
- L-tryptophan
- Valerian
Antidepressants
Some antidepressants can cause drowsiness as a side effect, and this can be helpful for sleep problems. Doxepin (Silenor) is a tricyclic antidepressant that is FDA-approved for treating insomnia characterized by difficulty staying asleep. It is only available with a prescription, but is not a controlled substance. Other tricyclic antidepressants (e.g., amitriptyline, nortriptyline) have been prescribed off-label for treating insomnia, but this is rare since these medications have many potential side effects.
Trazodone and mirtazapine (Remeron) are not FDA approved to treat insomnia (they are approved to treat depression), but they are sometimes prescribed off-label for treating insomnia. Both medications require a prescription.
Antipsychotics
No antipsychotic is FDA approved for treating insomnia, and use of these medications are not recommended by the American Academy of Sleep Medicine for sleep problems. However, they might be helpful for some patients who are being treated for psychiatric disorders already due to their sedating effects. Some examples of antipsychotics that may be prescribed for insomnia are quetiapine (Seroquel), olanzapine (Zyprexa), and risperidone (Risperdal). These medications require a prescription, but are not controlled substances.
Benzodiazepines
There are a few different benzodiazepines that are FDA approved to treat insomnia, including:
- Estazolam
- Flurazepam
- Quazepam
- Temazepam (Restoril)
- Triazolam (Halcion)
All benzodiazepines require a prescription, and are classified as a Schedule IV controlled substance because of their risk for abuse, addiction, and dependence. They differ in terms of how long they last, but are generally recommended for short-term use only (e.g., a few weeks). These medications work by enhancing the effects of a neurotransmitter called gamma-aminobutyric acid (GABA) in the brain. This has a calming effect, which can reduce anxiety and promote sleep.
Benzodiazepine receptor agonists
Benzodiazepine receptor agonists, also called nonbenzodiazepines or “Z drugs,” are also prescription-only sleep aids. They include eszopiclone (Lunesta), zolpidem (Ambien), and zaleplon (Sonata). Similar to benzodiazepines, these medications are classified as Schedule IV controlled substances. Nonbenzodiazepines also interact with GABA receptors, but in a more specific way. Eszopiclone can be used for long-term treatment of insomnia, while the others are approved for short-term use.
Melatonin receptor agonists
Currently, ramelteon (Rozerem) is the only FDA-approved, prescription melatonin receptor agonist for the treatment of insomnia. It is not a controlled substance, since it has not been proven to have potential for misuse and addiction. Instead of interacting with GABA receptors like benzodiazepines and nonbenzodiazepines, it targets melatonin receptors in the brain. It is approved for the treatment of insomnia characterized by trouble falling asleep, and clinical studies were up to 6 months long.
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Orexin receptor antagonists
A newer class of prescription medications has recently come onto the market called orexin receptor antagonists. Examples include suvorexant (Belsomra), lemborexant (Dayvigo), and daridorexant (Quviviq). They all require a prescription and have been classified as Schedule IV controlled substances. These medications have been FDA approved for treating insomnia characterized by trouble falling and staying asleep. They work by blocking orexin receptors in the brain, which are thought to play a role in wakefulness.
Over-the-counter sleep aids
A few over-the-counter sleep aids include antihistamines (e.g., diphenhydramine (ZzzQuil), doxylamine (Unisom)), melatonin, L-tryptophan, and valerian. The American Academy of Sleep Medicine does not recommend over-the-counter sleep aids for treating either sleep onset or sleep maintenance insomnia. This is based on a review of studies looking at the safety and effectiveness of these medications on sleep, which have not shown strong enough evidence supporting their use. However, some people still choose to try them occasionally for sleeplessness.
With most over-the-counter sleep aids, it is not recommended to take them for more than 2 weeks without consulting a healthcare provider. This is because insomnia can be a sign of an underlying medical condition that may require alternative treatment.
Things to consider when taking a sleeping pill
There are several things to consider before taking medication to help you sleep. These include potential side effects, medical conditions, other medications you are taking, risk of addiction, tolerance, and rebound insomnia.
Potential side effects
Side effects are an important consideration when choosing a sleep aid. Even over-the-counter sleep aids can cause side effects. For example, headache, dizziness, and nausea have been reported by people taking melatonin. Antihistamines have many potential side effects, such as dry mouth, dizziness, and constipation. Prescription sedative/hypnotics like zolpidem and eszopiclone have a risk of next-day impairment and complex sleep behaviors. Newer medications, like daridorexant, have been associated with headaches. Be sure to discuss all possible side effects with your healthcare provider.
Medical conditions
Discuss your full medical history with your healthcare provider before taking a sleep aid. Some medications, like ramelteon, are not recommended if you have severe liver problems. For others, like eszopiclone, doxepin, daridorexant, and zolpidem, your healthcare provider might prescribe a lower dose if you have liver problems.
Drug interactions
With most sleep aids, it is not recommended to take them with other medications or substances that cause sedation. This includes alcohol, pain medications (e.g., opioids), and muscle relaxants. Doing so can raise your risk of serious side effects, like dizziness, breathing problems, and falls.
Additionally, some sleep aids are broken down by enzymes in the liver. If you are taking another medication that affects these same enzymes, the levels of sleep medication can go up or down in your body. This can lead to more side effects or loss of effectiveness. Share all of your medications with your healthcare provider so they can screen for interactions.
Controlled substances
Some sleep medications are classified as controlled substances by the Drug Enforcement Administration (DEA). This is because they have been shown to have a rise of misuse, addiction, and dependence. Tolerance can also develop from taking certain sleep aids, which means you need to take a higher dose to achieve the same effects. If you have a history of substance abuse, depression, or other mood problems, discuss the best sleep aid with your healthcare provider.
Rebound insomnia
When you stop taking a sleeping medication, you can develop rebound insomnia. This means your sleeping problems come back and become worse than before. This is more likely when you take a sleep aid for a long period of time and if it is considered a “short-acting” medication, but talk with your healthcare provider about your individual risk of having rebound insomnia. Stopping some medications too quickly can also lead to withdrawal symptoms.
Antihistamines, dual orexin receptor antagonists, and melatonin receptor agonists seem to have the lowest risk of rebound insomnia and withdrawal symptoms after stopping the medication.
If you have been taking sleeping medication for a long time or at a high dose, ask your healthcare provider whether it is safe to stop taking it all of a sudden. In some cases, you may need to slowly taper down the dose until you are able to stop safely.
This is not all the information you need to know about sleeping pills for safe and effective use and does not take the place of your doctor’s directions. Review the full product information and discuss this information and any questions you have with your doctor or other health care provider.
References
Farzam, K., et. al. 2023. Antihistamines. In: StatPearls [Internet]. Accessed 11/19/2024 at https://www.ncbi.nlm.nih.gov/books/NBK538188/
Lie, J. D., et. al. 2015. Pharmacological Treatment of Insomnia. In: Pharmacy and Therapeutics. PMCID: PMC4634348 PMID: 26609210
National Center for Complementary and Integrative Health. January 2024. In the News: Magnesium Supplements for Sleep Disorders. Accessed 11/19/2024 at https://www.nccih.nih.gov/health/in-the-news-magnesium-supplements-for-sleep-disorders
National Center for Complementary and Integrative Health. May 2024. Melatonin: What You Need To Know. Accessed 11/19/2024 at https://www.nccih.nih.gov/health/melatonin-what-you-need-to-know
Ramelteon [package insert]. Updated March 2022. Actavis Pharma, Inc. Accessed 11/19/2024 at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a89dae05-6c39-4072-b8ee-c4c35b46f7d4
Sateia, M. J., et. al. 2017. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline. In: Journal of Clinical Sleep Medicine. DOI: https://doi.org/10.5664/jcsm.6470
U.S. Food and Drug Administration. 2016. FDA Drug Safety Communication: FDA warns of next-day impairment with sleep aid Lunesta (eszopiclone) and lowers recommended dose. Accessed 11/19/2024 at https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-next-day-impairment-sleep-aid-lunesta-eszopiclone-and-lowers
U.S. Food and Drug Administration. 2018. Questions and answers: Risk of next-morning impairment after use of insomnia drugs; FDA requires lower recommended doses for certain drugs containing zolpidem (Ambien, Ambien CR, Edluar, and Zolpimist). Accessed 11/19/2024 at https://www.fda.gov/drugs/drug-safety-and-availability/questions-and-answers-risk-next-morning-impairment-after-use-insomnia-drugs-fda-requires-lower
Watson, N. F., et. al. 2023. Alliance for Sleep Clinical Practice Guideline on Switching or Deprescribing Hypnotic Medications for Insomnia. In: Journal of Clinical Medicine. DOI: https://doi.org/10.3390/jcm12072493
ZzzQuil [package insert]. Updated December 2023. Lil' Drug Store Products, Inc. Accessed 11/19/2024 at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0b2777be-85d4-443d-b65f-6750e0ba97ba
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Can you take melatonin while pregnant?
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