Comparison of Sleeping Pills: Which is The Best and The Worst?

ambien, lunesta

The best sleeping pills are the ones that work for you. Because every person is different, sometimes you need to experiment to figure out what works best for you. When considering treatment options for insomnia, the relative benefits and drawbacks of sleeping pills should be taken into account.

The purpose of this review is to help you chose the right medication. Here we compare the effectiveness and safety of sedative hypnotics.

Our analysis is relied on the results of an examination of treatments for chronic insomnia by a group of medical experts from Oregon Evidence-based Practice Center3, clinical studies and articles published in the medical literature.

Types of Sleeping pills

The following medications are discussed:

Non-Benzodiazepines (Z-Drugs)

  • Zolpidem (Ambien)
  • Eszopiclone (Lunesta)
  • Zaleplon (Sonata)
  • Ramelteon (Rozerem)

Sedative antidepressants

  • Trazodone (Desyrel)
  • Amitriptyline (Elavil)
  • Doxepin (Sinequan)

Non-Benzodiazepines (Z-Drugs)

Non-benzodiazepine hypnotics currently approved in the United States are zolpidem (Ambien, Ambien CR), zaleplon (Sonata), eszopiclone (Lunesta), and ramelteon (Rozerem). They are commonly called the 'Z' drugs. They act in a similar way to benzodiazepines. Z drugs have similar long-term usage problems as benzodiazepines.

Zolpidem (Ambien)

Zolpidem (Ambien), an imidazopyridine, is one of the most commonly prescribed drugs for insomnia. It is highly effective for the treatment of insomnia on a short-term basis.

Zolpidem is a hypnotic agent with a chemical structure unrelated to benzodiazepines.

Efficacy & Benefits

Very effective. Good short term sleep aid that works for most people: hastens sleep onset, increases total sleep time and decreases the number of awakenings during the nights6. It works quickly within 15-30 min.

Many physicians consider zolpidem the best available choice as a hypnotic for short-term use when early awakening and cost are not problems.

Relatively mild next-day hangover. Zolpidem does not have that bad hangover effect that many other sleep aids have. It is less likely to cause marked residual daytime sedation than benzodiazepines4. However, zolpidem may cause grogginess if you sleep less than eight hours.

No active metabolite. Zolpidem does not accumulate during repeated use. Therefore it is less likely to cause rebound insomnia7.

Less disruption of normal sleep architecture. Unlike the benzodiazepines, zolpidem has less or no disruption of sleep architecture. It does not interfere with sleep stages 3 and 4, nor does it decrease rapid-eye-movement (REM) sleep4-6.

Approved version for long-term use. Ambien CR, a time-release pill, is approved for long-term use. The medicine is delivered in two steps. The first layer dissolves quickly, allowing to fall asleep. The second layer helps stay asleep.

Ambien is not approved for long-term use. According to the research, it may be used on an as-needed basis, with up to 5 times a week8. After 3 weeks, most people taking Ambien this way are able to reduce the intake by more than 25% without losing improvements in sleep.

Controlled-release version Ambien CR may theoretically be more effective for sleep maintenance than regular Ambien, but might also lead to more next day hangover.

Generic availability. Zolpidem is now available as a generic.

Drawbacks & Side effects

Zolpidem main drawback is that it is habit-forming.

Abuse and Dependence. Is zolpidem addictive? Undoubtedly. But it is less addictive then benzodiazepines. The research provides strong evidence that zolpidem abuse and dependence potential is much lower than that of benzodiazepines9.

Rebound insomnia. You may have difficulty sleeping (rebound insomnia) after you stop taking the drug.

Withdrawal symptoms. Ambien (zolpidem) is known to cause withdrawal symptoms in people who quickly stop the medicine after taking it daily for a long time.

Tolerance problems. Zolpidem has a tendency to not be quite as effective if it is taken nightly for longer than two weeks17.

Bizarre behaviours. Zolpidem can cause bizarre behavior (parasomnia) that goes beyond traditional sleep-walking, such as memory loss, sleep-cooking, night time snacking, making phone calls while asleep.

Increased risk of depression. Modern hypnotics zolpidem, zaleplon, eszopiclone, and ramelteon are found to increase the risks of developing depression12.

Driving impairment: On May 2013 U.S. FDA approved approved new, lower-dose labeling for zolpidem in an effort to decrease the likelihood of daytime drowsiness that could be a hazard while performing certain tasks such as driving37.

Side effects: headache (19%); somnolence (15%); dizziness (12%); drowsiness (8%); nausea (7%); myalgia (7%); dyspepsia (5%); arthralgia, back pain (4%); hallucinations (4%); anxiety, disorientation, drugged feeling, fatigue, lethargy, memory disorders (3%).

Controlled substance. Zolpidem is classified as a schedule IV controlled substance (like benzodiazepines).

User ratings and reviews of Ambien on DailyStrength
Ambien (Zolpidem) - reviews, ratings, comments by patients on DrugLib
Ambien (Zolpidem) reviews on ViewPoints

Sonata (Zaleplon)

Sonata (Zaleplon) is the weakest of the sedative pills with ultra-short half-life of about 1 hour. The drug may be taken at bedtime or later as long as the patient can sleep for at least 4 hours. Because it is rapidly eliminated from the body it may be best for people who have difficulty falling asleep, not those who wake up often throughout the night.

Efficacy & Benefits

Helps get to sleep. Sonata works effectively to decrease the amount of time it takes to get to sleep. The drug does not increase total sleep time or decrease the number of awakenings. Sonata is removed from the body too quickly to help these conditions.

It works very quickly (within 10-20 minutes of taking it) and should be taken right before going to bed. Sonata has more rapid onset of effect than zolpidem (Ambien).

Possible middle-of-the-night dosing. It can be taken during the night if you have problems staying asleep11. Zaleplon wears off in about four hours.

Low risk of next day hangover. It's one of the sleeping pills that supposedly does not triggers hangover or next day grogginess, even when taken in the middle of the night11. Zaleplon is metabolized much more quickly than other sleep aids, so is far less likely to leave you feeling sleepy in the morning.

Minimal-to-absent rebound insomnia. Another potential benefit is minimal rebound insomnia after discontinuation of the drug10.

Risks & Drawbacks

Side effects: headache, pain, and dizziness10, 16. If you have less than six hours to sleep, it is much more likely that you will still feel sedated or lethargic when you get up.

Memory loss. There is a chance that you may experience a certain type of memory loss (amnesia). This can usually be avoided by taking Sonata only when you are able to get 4 or more hours of sleep before you need to be active again.

Dependence. Zaleplon may cause dependence, especially if it has been used regularly for an extended time (more than a few weeks) or if it has been used in high doses. In such cases, if you suddenly stop this drug, withdrawal reactions may occur.

Withdrawal. Withdrawal symptoms may occur when the medication is stopped suddenly after being used daily for a long time. Such reactions can include unusual depressed or anxious mood, stomach cramps, vomiting, sweating, fatigue, irritability.

Tolerance. Sonata can lose its effectiveness if used for long periods of time.

Rebound insomnia. You may have more trouble falling asleep the first few nights after you stop taking Sonata than before starting this hypnotic.

Bizarre behaviours. Rarely Sonata can cause bizarre behavior (parasomnia), such as sleepwalking, sleep-eating, making phone calls, or having sex while not fully awake. Often, people do not remember these events.

Controlled substance. Sonata is classified as a Schedule IV controlled substance by federal regulation.

Increased risk of depression. May increase the risks of developing depression12.

Sonata (Zaleplon) reviews, ratings, comments by patients on DrugLib

Lunesta (Eszopiclone)

Eszopiclone (Lunesta) is a short acting non-benzodiazepine sedative hypnotic and belongs to the class of drugs known as cyclopyrrolones. Eszopiclone is the active stereoisomer of zopiclone.

Unlike other sleep aids, eszopiclone can be taken on a long-term basis.

Efficacy & Benefits

Lunesta helps you to fall asleep and stay asleep. But it should only be used when you expect to get eight hours of sleep. Lunesta takes effect within an hour and keeps working for about six hours.

Approved for long-term use. It has the distinction of being approved for long-term use by the U.S. FDA. In clinical trials, patients used eszopiclone for up to 6 months15.

Mild next day hangover. At recommended doses, eszopiclone (despite its relatively long half-life) appear to cause less day-after grogginess than Ambien (zolpidem) or benzodiazepines.

Low risk of tolerance. Does not lose its effectiveness over time. Important advantage of Lunesta is that studies found that no tolerance to the drug develops13, 15.

Rebound insomnia. Relatively low risk of rebound insomnia31.

Eszopiclone is less likely than the benzodiazepines to change sleep patterns.

Eszopiclone has fewer anticholinergic side effects than racemic zopiclone.

Risks & Drawbacks

Withdrawal. Although Lunesta is not a highly addictive substance stopping it abruptly can lead to withdrawal symptoms that include anxiety, unusual dreams, sweating, shakiness, fatigue.

Bizarre behaviours. There have been lots of documented cases of sleep walking, sleep driving, sleep-cooking, sleep-eating, and other bizarre behaviours after taking Lunesta.

Increased risk of depression. May increase the risks of developing depression12.

Bad taste. Leaves a unpleasant metallic taste (unrelated to the taste of the pill itself) in the mouth that is hard to get rid of.

Side effects: peculiar or bitter taste (17-34%), dizziness (5-7%), dry mouth (5-7%), drowsiness (4-9%)14.

Controlled substance. Lunesta (Eszopiclone) is classified as a Schedule IV controlled substance by federal regulation.

Lunesta (Eszopiclone) reviews, ratings, comments by patients on DrugLib
Lunesta reviews on ViewPoints

Rozerem (Ramelteon)

Rozerem (ramelteon) is a melatonin receptor agonist. Rozerem works by interacting with melatonin receptors in the brain. It is specifically indicated for insomnia characterized by difficulty in falling asleep.

Efficacy & Benefits

Rozerem helps with sleep-onset problems but is not recommended for restarting sleep if you wake up during the night.

It has a different mechanism of action from its competitors. While hypnotics work to slow down the central nervous system (act as a generalized CNS depressants at the GABA receptors), Rozerem instead mimics melatonin, a chemical that helps regulate the body's natural sleep-wake cycle.

However, as with the other sleeping pills, Rozerem will not address any underlying medical problems causing the insomnia.

No abuse potential. The major benefit of Rozerem is that it is not potentially addictive. Unlike many other hypnotics, clinical trials of Rozerem did not yield evidence of physical dependence or abuse potential. This is good choice for people who have trouble falling asleep but do not want to risk having a dependence on a sleep aid.

Not a controlled substance. Rozerem is the only FDA-approved hypnotic that is not a controlled substance.

No withdrawal and rebound insomnia. Another good thing about Rozerem is lack of withdrawal symptoms and rebound insomnia after its discontinuation. In all clinical studies, no regimens of Rozerem produced evidence of rebound insomnia at any time point following treatment.

Rozerem is unlikely to cause the bizarre sleep-related behavior.

Risks & Drawbacks

Relatively weak sleeping aid. The main drawback of Rozerem is that it may not work sufficiently. Simply it is not as effective as sedatives in helping with insomnia. Other causes may be involved in insomnia that Rozerem doesn't address.

Sexual side effects. Rozerem can cause changes in certain hormone levels, including testosterone and prolactin18. These changes could lead to sexual side effects, including decreased libido, milk-like nipple discharge, fertility problems.

Expensive. Rozerem also costs more, since it is not yet available as a generic.

Next-day drowsiness. Despite its claims, there are risks of drowsiness and lack of concentration after taking Rozerem.

Side effects: headache, fatigue, and somnolence.

Rozerem ratings and patient comments on Askapatient database
User reviews and ratings for Rozerem on Drugs.com
User ratings and reviews of Rozerem on DailyStrength

Sedative Antidepressants

The sedating antidepressants most commonly used to help with sleep include trazodone (Desyrel), amitriptyline (Elavil), and doxepin (Sinequan). They have been used for many years to promote sleep.

A major benefit of antidepressants is that these medicines are not potentially addictive and are not a controlled substances. And if you suffer from depression in addition to insomnia, the right antidepressant might effectively treat both conditions.

All of the low-dose sedating antidepressants have half-lives greater than the usual sleep period.

Desyrel (Trazodone)

Trazodone is widely used for insomnia in the United States1.

Efficacy & Benefits

Trazodone is good choice for those who suffer from mild depression and insomnia. It is especially effective for the treatment of insomnia caused by other antidepressants19.

Studies of people with various kinds of insomnia have found that main effect of trazodone on sleep architecture is an increase in slow-wave (stages 3 and 4) sleep20.

Unscheduled status. Unlike hypnotics, antidepressants have a lower potential for abuse or dependency35.

Perceived safety. Trazodone has a long safety record.

Inexpensive. Available as a generic formulation.

Low risk of daytime grogginess. Unlike benzodiazepine hypnotics, trazodone causes less performance-impairing effects21.

Risks & Drawbacks

Day-time sedation. Even trazodone, the shortest-acting of sedating antidepressants and the least sedating, at a dose of 50 mg is associated with reports of daytime somnolence in 23% of patients compared with 8% for placebo.

Rebound insomnia. Trazodone has also been associated with rebound insomnia after withdrawal.

Side effects include drowsiness, dry mouth, nausea, vomiting, constipation, headache and blurred vision.

Risk of drug-induced priapism. The main serious side effects (priapism) can only occur in men.

Trazodone reviews on ViewPoints

Amitriptyline (Elavil)

Amitriptyline is commonly prescribed in low doses for insomnia.

Efficacy & Benefits
  • In clinical trials amitriptyline increased total sleep time and decreased the number of awakenings during the night in depressed people24.
  • Additional benefit of providing some analgesic effect as compared to the hypnotics.
  • Very inexpensive.
  • Low rate of side effects when used in low doses.
  • Suitable for long-term treatment.

Risks & Drawbacks
  • Strong anticholinergic properties and as a result severe anticholinergic side effects.
  • Tend to suppress REM sleep.
  • Cardiotoxicity.
  • Potentially lethal overdose.
  • Risk of weight gain.

Elavil user ratings & reviews for insomnia on Ask a Patient
Amitriptyline user reviews for insomnia at Drugs.com

Doxepin (Sinequan)

Doxepin has long been known to have significant sleep promoting effects. Low dose doxepin is effective treatment for insomnia due to its sedating effects22. This antidepressant currently is being evaluated by the FDA for use as a possible insomnia treatment.

Efficacy & Benefits

Doxepin 1 mg, 3 mg, and 6 mg is effective for people suffering from chronic insomnia23. All three doses improved wake time during sleep, total sleep time, and sleep efficiency relative to placebo.

Suitable for long-term treatment.

Risks & Drawbacks
  • Cardiovascular side effects.
  • Potentially lethal overdose.
  • Substantial anticholinergic and sedative effects.

Key Points: Non-benzodiazepines vs Benzodiazepines

Newer-generation non-benzodiazepine hypnotics offer multiple advantages over traditional benzodiazepines including:

  • Effectiveness. Ambien (zolpidem), Lunesta (eszopiclone), and Sonata (zaleplon) have efficacies similar to those of the hypnotic benzodiazepines in the management of insomnia33. For some people Rozerem (ramelteon) seems to be less effective than benzos and the Z drugs.
  • Addiction, abuse and dependence potential. All four of the newer medicines are less likely to cause dependence and abuse problems - and that may be their biggest advantage over the older drugs25.
  • Withdrawal and rebound Insomnia. The risk for withdrawal symptoms, rebound insomnia, and tolerance is lower with non-benzodiazepine hypnotics than with benzodiazepines.
  • Next-day impairment. Another favorable feature of newer hypnotics is modest day-after psychomotor depression.
  • Sleep architecture. Unlike the benzodiazepines, non-benzodiazepines cause minimal disruption of sleep architecture.

Easy-to-understand comparison chart that covers important points to consider:

 
Ambien (Zolpidem)
Ambien CR
(Zolpidem CR)
Lunesta
(Eszopiclone)
Sonata (Zaleplon)
Rozerem (Ramelteon)
Company
Sanofi-Aventis
Sanofi-Aventis
Sepracor
King
Takeda
FDA approval date
1992
2005
2004
1999
2005
How it works Binds to a specific type of GABA receptor in the brain. Binds to a specific type of GABA receptor in the brain. Binds to a specific type of GABA receptor in the brain. Binds to a specific type of GABA receptor in the brain. Stimulates melatonin receptors in the brain area that controls the sleep-wake cycle.
Half-life
2.5
2.8
6
1
1-2.6
Helps You
Fall Asleep?
Yes
Yes
Yes
Yes
Yes
Average Time to
Fall Asleep
30 to 45 minutes 30 minutes 50 minutes 15-20 minutes 75 minutes
Helps You Stay
Asleep?
Yes
Yes
Yes
No
No
Risk of
Rebound
Insomnia?
Yes
Yes
Yes
Low
No
Risk of
Dependency
Yes
Yes
Yes
Yes
No
Generic
Yes
No
No
No
No

Head-to Head Comparisons

While Sonata (zaleplon) may be best indicated for the delayed onset of sleep, Ambien (zolpidem) and Lunesta (eszopiclone) may be better indicated for maintaining a complete night's sleep26.

Of the three, zaleplon has the shortest half-life, so it may be best when the main problem is getting to sleep, or when you don’t want to sleep for more than four or five hours (for example, on a cross-country airplane trip).

Ambien (zolpidem) vs Sonata (zaleplon)
  • Effectiveness: There is evidence that zaleplon is more efficacious than zolpidem for sleep latency (time to sleep onset)36, but zolpidem is more efficacious than zaleplon for sleep duration and sleep quality26.
    Zaleplon has a more rapid onset of effect and a shorter elimination half-life.
    Ambien may be a better choice for those with difficulty falling and staying asleep.
  • Next-day effects: Zaleplon at recommended doses is free of residual hypnotic or sedative effects when taken as little as 2 h before waking. In contrast, residual effects of zolpidem are still apparent when the drug is taken 5 h before waking27.
  • Patient's preference: In general, most insomniacs are likely to prefer zolpidem to zaleplon28.

Ambien (zolpidem) vs Lunesta (eszopiclone)
  • Effectiveness: Indirect comparisons based on placebo-controlled trials29,30 provide evidence that the drugs are similar for sleep onset and sleep maintenance insomnia. However, eszopiclone may be more effective for increasing sleep duration.
  • Next-day effects: Some people find that Ambien causes more the next-day hangover effects32. Lunesta is much better in that aspect.
  • Rebound insomnia: The rebound insomnia is more common with Ambien than Lunesta31.
  • Tolerance: A significantly higher number of Ambien users report developing a tolerance to the drug than is the case with Lunesta15,17. Developing tolerance means that with regular use the drug loses its effectiveness and that increasing the dosage is required to maintain its effectiveness.
  • Bad taste: The most common side effect with Lunesta is an unpleasant metallic taste in the mouth.

Rozerem (ramelteon) vs Non-benzodiazepines
  • Effectiveness: Rozerem tends to be less effective than sedatives in helping with insomnia.
  • Mode of action: Rozerem works differently than other sleeping pills. While hypnotics work to slow down the central nervous system, Rozerem instead mimics melatonin.
  • Potential for abuse, addiction or dependency: Unlike many other hypnotics, clinical trials of Rozerem did not yield evidence of physical dependence or abuse potential.
    Rozerem is not a controlled substance and is the first, and only, non-scheduled hypnotic that is FDA approved for insomnia.
  • Effect on reproductive hormones: Rozerem may affect the reproductive hormones by increasing prolactin and potentially decreasing testosterone levels. This may cause missed menstrual periods, nipple drainage, decreased sex drive, or problems getting pregnant.

Trazodone vs Ambien (zolpidem)
  • Effectiveness: Compared to trazodone, Ambien is somewhat more effective in treating insomnia34. However, as an antidepressant, trazodone has the advantage of treating insomnia while treating concurrent conditions like depression or psychological disorders. Ambien actually may increase the risk of developing depression.
  • Potential for abuse, addiction and dependency: Trazodone offers a lower potential for abuse or dependency in comparison with Ambien35.
  • Side effects: Ambien may cause memory loss (amnesia), parasomnias (such as sleepwalking, nocturnal eating), whereas trazodone can produce hypotension, constipation, and priapism.
Further reading
References
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  • 2. National Institutes of Health State of the Science Conference statement on Manifestations and Management of Chronic Insomnia in Adults. Sleep. 2005;28:1049–1057.
  • 3. Carson S, McDonagh MS, Thakurta S, et al. Drug Class Review on Newer Drugs for Insomnia. Oregon Health & Science University; 2008 Oct.
  • 4. Uchimura N, Nakajima T, Hayash K, Nose I, Hashizume Y, Ohyama T, Habukawa M, Kotorii N, Kuwahara H, Maeda H. Effect of zolpidem on sleep architecture and its next-morning residual effect in insomniac patients: a randomized crossover comparative study with brotizolam. Prog Neuropsychopharmacol Biol Psychiatry. 2006 Jan;30(1):22-9.
  • 5. Dujardin K, Guieu JD, Leconte-Lambert C, Leconte P, Borderies P, de La Giclais B. Comparison of the effects of zolpidem and flunitrazepam on sleep structure and daytime cognitive functions. A study of untreated unsomniacs. Pharmacopsychiatry. 1998 Jan;31(1):14-8. PubMed
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    http://www.medicalnewstoday.com/youropinions.php?opinionid=6309&p=2
    Lunesta vs. Ambien discussion on LoveShack.org
    http://www.loveshack.org/forums/t67312/
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  • 37. FDA Drug Safety Communication: FDA approves new label changes and dosing for zolpidem products and a recommendation to avoid driving the day after using Ambien CR.

Published: May 23, 2009
Last updated: Augusr 21, 2014

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