Best Sleep Medications (2023): Top Drugs for Insomnia Treatment

Approximately 10% of the adult population suffers from insomnia, another 20% experiences occasional insomnia symptoms, and it has a 40% persistence rate over a 5-year period. (R)

Some effectively manage insomnia with behavioral & lifestyle changes (exercise, zero stimulants, same sleep/wake times, etc.), temperature adjustments (cooler room), cognitive behavioral therapy (CBT), etc. – but for others these don’t do much.

A check up with a medical doctor and a sleep study are recommended to rule out underlying conditions that may contribute to insomnia (e.g. sleep apnea, infections, psychiatric disorders, etc.) – but sometimes insomnia is the only problem.

So what can you do if you’re plagued by insomnia and it’s ruining your life? Brain fog, anger & stress, feeling unwell, sweating, unproductive, etc. (These are things I experience when my insomnia flares up and goes unmanaged).

Best Sleep Medications (2023): Most Effective & Tolerable Options

For this article, I sought to determine the most effective & tolerable sleeping medications as of 2023.

There can be intra-individual variation in responses to medications and/or tolerability – so don’t assume the top ranked meds listed here are ideal for everyone.

I simply wanted to compile what I think are probably best bets to try for insomnia based off of information I compiled from ratings, UpToDate, and recent systematic reviews/meta-analyses.

If considering all these sources, the medications that are: (1) rated reasonably well; (2) endorsed by UpToDate; and (3) appear best in the recent systematic review include:

  1. Eszopiclone: Ranks high in acute and long-term efficacy in formal studies. It is also considered tolerable with fewer discontinuations – but may cause more adverse events than expected.
  2. Zolpidem: More dropouts over a long-term relative to eszopiclone in the systematic review/meta-analysis – but its weighted-average user rating is slightly higher and it is still well-tolerated.

Accounting for all evidence, the best choices on aggregate are probably eszopiclone OR zolpidem.

That said, there are some major limitations with data (e.g. lack of data for certain medications) used in systematic reviews/meta-analyses & clinical recommendations for the treatment of insomnia.

If we consider just 2 sources combined: (A) UpToDate + User Ratings OR (B) Systematic Review + User Ratings OR (C) UpToDate + Systematic Review – then best choices may be:

  1. Flurazepam (B)
  2. Triazolam (B)
  3. Gabapentin (A)
  4. Mirtazapine (A)
  5. Clonazepam (B)
  6. Zolpidem (C)
  7. Lorazepam (B)
  8. Temazepam (B)
  9. Eszopiclone (C)

It should be noted that benzodiazepines (intermediate-acting & long-acting) & eszopiclone had fewer discontinuations due to any cause than ramelteon in the systematic review AND were more effective.

Additionally, if we go by just average user ratings for medications with 50+ reviews, benzodiazepines make up 3 of the top 5 choices (flurazepam, triazolam, lorazepam).

Long-term data on benzos is lacking, but they are more effective than placebo, melatonin, ramelteon, and zaleplon (according to the recent review) – and they seem to have fewer acute discontinuations due to any cause than ramelteon.

Best Sleep Medications (Weighted Average from User Ratings)

Included below are the weighted average rankings for sleep medications based on user ratings on

  1. Flurazepam | Rating: 8.2 | Reviews: 103 | Adj. Average: 7.47
  2. Quetiapine (off-label) | Rating: 7.6 | Reviews: 516 | Adj. Average: 7.45
  3. Triazolam | Rating: 8.2 | Reviews: 60 | Adj. Average: 7.02
  4. Gabapentin (off-label) | Rating: 7.4 | Reviews: 132 | Adj. Average: 6.87
  5. Mirtazapine (off-label) | Rating: 7.0 | Reviews: 466 | Adj. Average: 6.85
  6. Clonazepam (off-label) | Rating: 7.2 | Reviews: 192 | Adj. Average: 6.84
  7. Zolpidem (Ambien) | Rating: 6.9 | Reviews: 1667 | Adj. Average: 6.8
  8. Lorazepam | Rating: 7.3 | Reviews: 124 | Adj. Average: 6.75
  9. Amitriptyline | Rating: 7.0 | Reviews: 269 | Adj. Average: 6.75
  10. Temazepam | Rating: 6.4 | Reviews: 425 | Adj. Average: 6.25
  11. Trazodone (off-label) | Rating: 6.2 | Reviews: 871 | Adj. Average: 6.12
  12. Doxylamine | Rating: 6.4 | Reviews: 215 | Adj. Average: 6.11
  13. Doxepin | Rating: 5.7 | Reviews: 306 | Adj. Average: 5.52
  14. Eszopiclone (Lunesta) | Rating: 5.6 | Reviews: 730 | Adj. Average: 5.52
  15. Olanzapine (off-label) | Rating: 5.7 | Reviews: 104 | Adj. Average: 5.2
  16. Zaleplon | Rating: 5.3 | Reviews: 133 | Adj. Average: 4.93
  17. Diphenhydramine | Rating: 4.7 | Reviews: 379 | Adj. Average: 4.58
  18. Lemborexant | Rating: 4.3 | Reviews: 220 | Adj. Average: 4.11
  19. Rozerem | Rating: 4.4 | Reviews: 103 | Adj. Average: 4.01
  20. Ramelteon | Rating: 4.0 | Reviews: 147 | Adj. Average: 3.75
  21. Suvorexant (Belsomra) | Rating: 3.6 | Reviews: 1056 | Adj. Average: 3.57
  22. Daridorexant (Quviviq) | Rating: 2.9 | Reviews: 146 | Adj. Average: 2.71

I consolidated all “brand name” reviews with the generic so that there were more data for each specific chemical being used to treat insomnia (e.g. Ambien & zolpidem were combined).

Worth noting is that the weighted averages for “brand name” formulas were nearly identical to generics (e.g. Restoril & Temazepam) – which should be expected.

How was the adjusted average determined?

A simple formula that accounted for: (A) rating out of 10 & (B) number of reviews.

The formula was as follows: (Rating * # of Reviews) / (# of Reviews + 10).

This formula takes into account sample size, reduces the impact of outliers, and generally provides a more accurate & fairer representation than the standard average.

Best Sleep Medications (Basic Rankings)

I also did a “top ranking” list for medications with at least 50 reviews – focused entirely on the ranking given by users… nothing more.

  1. Flurazepam – Ranking: 8.2/10 | Reviews: 103
  2. Triazolam – Ranking: 8.2/10 | Reviews: 60
  3. Quetiapine – Ranking: 7.6/10 | Reviews: 516
  4. Gabapentin – Ranking: 7.4/10 | Reviews: 132
  5. Lorazepam – Ranking: 7.3/10 | Reviews: 124
  6. Clonazepam – Ranking: 7.2/10 | Reviews: 192
  7. Zolpidem – Ranking: 7/10 | Reviews: 550
  8. Amitriptyline – Ranking: 7/10 | Reviews: 269
  9. Mirtazapine – Ranking: 7/10 | Reviews: 466
  10. Doxylamine – Rating: 6.4/10 | Reviews: 215
  11. Temazepam – Rating: 6.4/10 | Reviews: 425
  12. Trazodone – Rating: 6.2/10 | Reviews: 871
  13. Doxepin – Rating: 5.7/10 | Reviews: 306
  14. Olanzapine – Rating: 5.7/10 | Reviews: 104
  15. Eszopiclone – Rating: 5.6/10 | Reviews: 413

Analysis based on rating distribution…

I’ve analyzed the rating distribution data from the page you’ve provided and created several lists: medications with the most high ratings; medications with the most middle/moderate ratings; and medications with the most low ratings.

Top sleep medications (most high ratings) (8-10)

  1. Zolpidem: 59% (31% 10-rating, 16% 9-rating, 12% 8-rating)
  2. Trazodone (off-label): 49% (17% 10-rating, 18% 9-rating, 14% 8-rating)
  3. Quetiapine (off-label): 68% (37% 10-rating, 16% 9-rating, 15% 8-rating)
  4. Mirtazapine (off-label): 54% (27% 10-rating, 14% 9-rating, 13% 8-rating)
  5. Temazepam: 48% (25% 10-rating, 13% 9-rating, 10% 8-rating)

Sleep medications with the most middle ratings (4-7)

  1. Zolpidem: 25% (5% 7-rating, 4% 6-rating, 5% 5-rating, 3% 4-rating)
  2. Trazodone (off-label): 30% (9% 7-rating, 8% 6-rating, 7% 5-rating, 6% 4-rating)
  3. Quetiapine (off-label): 22% (7% 7-rating, 5% 6-rating, 6% 5-rating, 4% 4-rating)
  4. Mirtazapine (off-label): 25% (10% 7-rating, 5% 6-rating, 6% 5-rating, 4% 4-rating)
  5. Temazepam: 32% (10% 7-rating, 9% 6-rating, 7% 5-rating, 6% 4-rating)

Most hated sleeping medications (most low ratings: 1-4)

It seems like the most hated medications are orexin receptor antagonists.

Ramelteon doesn’t seem to be well-liked, perhaps because it’s too similar to melatonin.

Nonbenzodiazepines like zolpidem & eszopiclone have a lot of low ratings too, but they also have high ratings as well.

  1. Suvorexant / Belsomra: 63% (1-rating: 35%; 2-rating: 7%; 3-rating: 7%; 4-rating: 6%)
  2. Lemborexant / Dayvigo: 55% (1-rating: 33%; 2-rating: 11%; 3-rating: 6%; 4-rating: 5%)
  3. Ramelteon / Rozerem: 49% (1-rating: 48%; 2-rating: 4%; 3-rating: 5%; 4-rating: 4%)
  4. Zolpidem / Ambien / Ambien CR: 38% (1-rating: 15%; 2-rating: 4%; 3-rating: 4%; 4-rating: 3%)
  5. Eszopiclone / Lunesta: 37% (1-rating: 24%; 2-rating: 5%; 3-rating: 4%; 4-rating: 3%)

What about long-term efficacy (based on user ratings)?

It would be easy to analyze this if allowed me to filter all medications by time of use, but I am unable to do this at present.

So I dug through each medication individually, sorted reviews by “time on medication,” and glossed over how satisfied long-term users were.

Every medication I clicked through indicated that at least a subset of people were extremely satisfied with its effect – even after 5-10+ years.

This means that nearly all sleep medications have potential to work well over a long-term for a subset of users.

Note: I could’ve gone through and done weighted averages solely for the subset of long-term users – but this would’ve taken too much time.

Limitations with sleep medication data

There are a variety of limitations associated with estimating the efficacy of sleep medications with user reviews from

  • Confounds: Reviews may conflate efficacy and side effects – making it difficult to determine the actual effectiveness of a medication. (For example: One reviewer might give a medication a 10/10 because it works really well without factoring in tolerability whereas another reviewer may give a medication a 1/10 due to side effects even though it worked really well for sleep).
  • Fake reviews: Some reviews might be fabricated – which could distort the perception of a medication’s effectiveness. For example, a pharmaceutical company could hire a marketing team to write fake reviews for their drug to distort public perception of efficacy.
  • Bias: A review site may attract extreme opinions – particularly from dissatisfied users, leading to an unbalanced view of the medication’s performance.
  • Misreporting: Users may not provide accurate information about duration of use, dosage, or other factors in their review. (For example: Someone decides to click that they’ve been using a medication for 10+ years when they really only used for 6 months).
  • Outdated: People may no longer use – leading to a lack of current data on medication efficacy… perhaps much of the data is really old.
  • Sample sizes: Some medications might have few reviews – making it challenging to draw reliable conclusions about their effectiveness.
  • Indirect comparison: Reviews don’t provide a direct comparison between medications – making it difficult to determine whether one drug is more effective than another.

Which sleep medications are best for insomnia based on formal research?

To determine this I analyzed UpToDate – which provides up-to-date information on the best science-based treatments for specific medical conditions.

UpToDate: Pharmacotherapy for insomnia in adults (R)

As of 2023, Neubauer et al. state that all medications with regulatory approval are appropriate to prescribe as first-line pharmacotherapy for insomnia – except older benzodiazepine hypnotics.

Why? They state that older benzo hypnotics have: (1) long half-lives (e.g. estazolam, flurazepam, quazepam); (2) higher risk of dependence & habituation; and (3) safer options exist.

Isolated sleep-onset insomnia

Difficulty falling asleep at the desired time (such that it takes 30+ minutes to fall asleep).

Once asleep, persons with sleep-onset insomnia tend to sleep well with minimal middle-of-the-night awakening.

  • Ramelteon: Melatonin receptor agonist
  • Eszopiclone, Zaleplon, Zolpidem: Nonbenzodiazepine BZRA
  • Melatonin (supplement)
  • Sedating antidepressant: Amitriptyline, Mirtazapine, Trazodone
  • Diphenhydramine OR doxylamine (OTC)

Sleep maintenance insomnia (or mixed)

Difficulty sleeping through the night (such that patient wakes up and it takes 30+ minutes to fall back asleep OR the patient consistently wakes up too early).

Onset of sleep may also take longer than desired – but this wouldn’t be the only complaint.

  • Daridorexant, Lemborexant, Suvorexant: DORAs
  • Doxepin (low dose)
  • Eszopiclone, Zaleplon, Zolpidem: Nonbenzodiazepine BZRA
  • Sedating antidepressant: Amitriptyline, Mirtazapine, Trazodone.
  • Gabapentin
  • Diphenhydramine OR doxylamine (OTC)

Note: Authors recommend combining medication with CBT-I, healthy sleep habits, treating relevant comorbidities, etc. (Medication shouldn’t be the only intervention).

2022: Comparative effects of pharmacological interventions for insomnia in adults (R)

Crescenzo et al. conducted a systematic review and network meta-analysis comparing pharmacological interventions for acute & long-term management of insomnia disorder in adults.

They included data from 170 trials (36 interventions & 47,950 participants) in the systematic review & 154 double-blind RCTs (30 interventions & 44,089 participants) in the meta-analysis.

Most effective sleep medications (acute treatment)

These medications were more effective than a placebo with estimates of certainty ranging from: “High” to “Moderate.”

  1. Benzodiazepines
  2. Doxylamine
  3. Eszopiclone
  4. Lemborexant
  5. Seltorexant
  6. Zolpidem
  7. Zopiclone

Benzodiazepines, eszopiclone, zolpidem, and zopiclone were found to be more effective than melatonin, ramelteon, and zaleplon. The certainty of these findings ranged from moderate to very low.

Most effective sleep medications (long-term)

These medications were found to be more effective than placebo, ramelteon, and zolpidem when used over a long-term.

  1. Eszopiclone
  2. Lemborexant

Most tolerable medications for insomnia (lower discontinuations & side effects)

Intermediate-acting benzodiazepines, long-acting benzodiazepines, and eszopiclone had fewer discontinuations due to any cause than ramelteon, which is an important consideration for tolerability.

  1. Doxepin
  2. Seltorexant
  3. Zaleplon

Best sleep medications (overall – considering efficacy & tolerability)

Eszopiclone and lemborexant appeared to be the best sleep medications overall when considering both effectiveness and tolerability.

That said, authors state that eszopiclone might cause more adverse events than expected and lemborexant has inconclusive safety data.

  1. Eszopiclone (although it might cause substantial adverse events)
  2. Lemborexant (however, safety data is inconclusive)

There are other limitations associated with this study, including:

  • Comparison quality: Many were rated as low or very low quality – particularly for long-term timepoints due to inadequate reporting of randomization and allocation concealment.
  • Bias risk: Poor risk of bias information could be a reporting issue – but the study provided full details on the risk of bias of all included studies.
  • Geometry of networks: The geometry of networks for long-term timepoints showed single-standing nodes connected only to placebo – which might limit reliability of results.
  • Excluded patients: Patients with physical comorbidities and treatment-resistant insomnia were excluded from the study – limiting the applicability of the results to these clinical subgroups.
  • Combo interventions: Some trials combined sleep hygiene education with pharmacological interventions – which could influence efficacy to some extent.
  • Average treatment effects: The study only analyzed average treatment effects and couldn’t investigate individual patient-level modifiers of treatment response.
  • Inconsistent adverse events: Data on specific adverse events were reported inconsistently across studies.

How do sleep medications work (mechanisms of action)

Sleep medications work through different mechanisms of action to induce and maintain sleep.

GABA & BZD receptors: Enhance the effect of GABA, an inhibitory neurotransmitter, to promote relaxation and sleepiness. Benzodiazepines bind to specific sites on the GABA-A receptor, increasing the affinity of GABA for the receptor to induce sedation. (Examples: benzodiazepines & nonbenzodiazepines like Temazepam & Zolpidem).

Orexin receptors: Orexin is a neuropeptide that promotes wakefulness. Blocking neuropeptides A & B from binding to orexin receptors (OX1R & OX2R) decreases activation of the orexin system and induces sleep. (Examples: Suvorexant & Lemborexant).

Melatonin receptors: Melatonin is a hormone synthesized by the pineal gland that regulates the sleep/wake cycle. Melatonin supplements & medications that function as melatonin agonists – bind to melatonin receptors to promote sleep onset. (Example: Ramelteon).

Histamine receptors: Histamine is a neurotransmitter that promotes wakefulness. Medications that block histamine receptors to decrease histamine activity (i.e. antihistamines) can induce drowsiness and promote sleep. (Examples: Diphenhydramine, Doxylamine, Quetiapine).

Adrenergic receptors: Norepinephrine and epinephrine are stimulatory neurotransmitters that promote wakefulness and alertness. Medications that block adrenergic receptors can decrease their activation and promote sleep. (Example: Trazodone & Quetiapine).

Muscarinic receptors: Acetylcholine is a neurotransmitter that promotes wakefulness and alertness. Medications that block muscarinic receptors (i.e. anticholinergics) can decrease acetylcholine activity to promote drowsiness & sleep. (Examples: Diphenhydramine & Doxylamine).

Voltage-gated ion channels: Medications that modulate voltage-gated ion channels can alter neuronal excitability and induce sleepiness. (For example, sodium channel blockers decrease neuronal activity to promote sleep.) (Examples: Gabapentin, Pregabalin, Carbamazepine).

Other mechanisms of action for sleep medications…

Below are other mechanisms of action that may prove useful for induction of sleep. However, none of these are primary mechanisms of action associated with approved sleep meds.

Understand that most of these are not dominant mechanisms of action for any approved sleep medication – but they may help in some cases.

  • Serotonin receptors: Medications that target specific serotonin receptors (e.g. 5-HT2A) have been shown to help with sleep in some studies. (Example: Trazodone).
  • Cannabinoid receptors: Cannabinoids like CBD & THC can alter sleep through interaction with the endocannabinoid system. CBD is thought to increase total sleep time & improve sleep quality, whereas THC is thought to decrease REM sleep. (Example: CBD Oil).
  • Opioid receptors: Activation of mu-opioid receptors (MOR), modulation of the HPA axis, altering the release of histamine, and inhibiting noradrenergic activity – may promote relaxation, drowsiness, and sleep in some cases. (Example: Morphine).
  • Dopamine receptors: Modulation of dopamine receptors (e.g. blocking D2Rs) may promote sleep by decreasing arousal & wakefulness. Dopamine also helps regulate the circadian rhythm and in some cases, modulating dopamine may treat sleep disorders like RLS & PLMD.

My personal struggle with insomnia…

Insomnia is something I’ve struggled with for several years and it emerged about 1-2 months after I had COVID in 2020.

Looking back, I don’t think my insomnia is related to COVID but I can’t definitively rule it out… I never used to have difficulty staying asleep and now I wake up in the middle of the night every night.

I’ve tried a variety of nonpharmacological interventions including: stress management, zero caffeine intake, morning sunlight exposure, outdoor exercise, waking up at the same time each day, a temperature-controlled mattress topper, altered food/water intake, etc.

I’ve also experimented with various supplements, including: melatonin (low & high dose), magnesium threonate, magnesium glycinate, taurine, glycine, lemon balm, hops, valerian, diphenhydramine, doxylamine, B vitamins, theanine, apigenin, chamomile, etc.

I’ve also tried various medications including: diphenhydramine, doxylamine, gabapentin, alprazolam, zolpidem, oxcarbazepine, clonidine, etc.

Most effective interventions? Alprazolam & zolpidem (not together), zero caffeine OR early AM caffeine, and cool room temperature (58-66 F or 14.44-18.88 C)… the cool room temp probably matters most (way more than temp-controlled mattress top).

An ideal strategy for dealing with insomnia?

Below are my thoughts on managing insomnia. Consult a medical doctor if you have severe and/or chronic insomnia.

1. Medical examination: Rule out and/or treat medical conditions that may be causing insomnia (e.g. infection, sleep apnea, etc.).

2. Nonpharmacological approaches: Exhaust all nonpharmacological interventions (CBT, sleep/wake schedule, zero caffeine, no electronics before bed, stress management, exercise, sun exposure, cool room temperature, etc.).

3. Consider supplements: Try various dietary supplements (e.g. melatonin, magnesium threonate, etc.) – see if they’re effective. (Work with a doctor to ensure safe).

4. Try sleep medications: If tolerance occurs, it may be worth developing some sort of a cycling or rotation strategy (e.g. GABAergic -> antihistamine OR trazodone -> GABAergic -> antihistamine OR trazodone) – verify safety with a medical doctor. (Or simply use “as needed” if possible.)

This cycling strategy may not work due to withdrawal/rebound effects from the previous medication… but perhaps combined with nonpharmacological interventions it’ll work well.

Have you tried any medications for insomnia?

If you’ve tried medications for sleep/insomnia – which have you tried? (What dose did you take?)

How long have you used sleep medications?

How would you rate the effectiveness of these medications?

Have you experienced any significant and/or unwanted side effects?

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