The best sleeping pill depends on whether you’re dealing with occasional restless nights or ongoing insomnia, and each option comes with different tradeoffs in effectiveness, side effects, and next-day grogginess. For short-term, occasional sleeplessness, melatonin is the safest over-the-counter choice, particularly if you’re over 55. For chronic insomnia, newer prescription medications called orexin receptor antagonists offer strong sleep maintenance without the cognitive side effects of older drugs.
Over-the-Counter Options
The three most common OTC sleep aids are melatonin, diphenhydramine (the active ingredient in ZzzQuil, Benadryl, and most “PM” medications), and doxylamine (found in Unisom SleepTabs). Despite their popularity, the evidence behind them varies widely.
Diphenhydramine is surprisingly weak when tested rigorously. In controlled studies, it showed no meaningful difference from placebo in how long it took people to fall asleep or how long they stayed asleep. Even after two weeks of use, people taking diphenhydramine fell asleep in about 34 minutes compared to 37 minutes with a sugar pill. What it does reliably cause is impaired performance the next morning, with measurably worse reaction times and higher error rates on cognitive tests. This is the ingredient in most drugstore sleep aids, and many people take it without realizing how little it actually helps compared to how groggy it can make them.
Melatonin works differently. It’s not a sedative. It signals your brain that it’s time to shift into sleep mode, which makes it most useful for people whose internal clock is slightly off. Prolonged-release melatonin reduced the time to fall asleep by about 9 minutes compared to placebo in clinical trials, and the effect was strongest in adults over 55, where it cut sleep onset time by roughly 15 minutes. Crucially, melatonin caused no next-day impairment in psychomotor tests and no rebound insomnia when people stopped taking it.
Typical doses range from 1 to 5 mg, though some evidence suggests doses below 1 mg can be just as effective as higher amounts. Doses of 5 mg or less per day appear safe for both short and long-term use. A practical approach is to start with a low dose, around 1 to 3 mg, taken 30 to 60 minutes before bed. If you have trouble both falling asleep and staying asleep, combining an immediate-release and extended-release formulation (for example, 3 mg of each) is a reasonable strategy.
Valerian root and valerian-hops combinations are also sold as natural sleep aids. Valerian alone showed no benefit over placebo in clinical trials. A valerian-hops combination did improve sleep onset time, but the evidence is limited, and these supplements aren’t regulated for consistency or purity.
Prescription Sleep Medications
When OTC options aren’t enough, prescription sleep aids fall into a few main categories, and they differ significantly in how they work and what side effects they carry.
Orexin Receptor Antagonists
These are the newest class of prescription sleep medication. Rather than sedating the brain, they block a chemical signaling system that promotes wakefulness. By dialing down your brain’s “stay awake” signals, they let sleep happen more naturally. Suvorexant and lemborexant are the two most commonly prescribed versions.
These medications are effective for both falling asleep and staying asleep, and they stand out for their safety profile. A comprehensive meta-analysis found they were highly effective at inducing and maintaining sleep without impairing cognition. People taking them showed virtually no increase in driving accidents compared to placebo, which is a stark contrast to older options. Rates of next-day fatigue and drowsiness were also lower than with older prescription sleep aids.
Z-Drugs
Zolpidem (Ambien) and eszopiclone (Lunesta) are the most widely prescribed traditional sleep medications. They target the same brain receptors as older sedatives but are more targeted in their action. Zolpidem is particularly effective at shortening the time it takes to fall asleep and extending total sleep duration.
The problem is what happens the next morning. Zolpidem showed significant residual effects on memory, reaction time, and cognitive processing even when taken five hours before waking. Driving ability is measurably impaired the morning after taking it, and the risk of motor vehicle accidents increases. These aren’t rare side effects; they’re consistent findings across multiple studies. For this reason, if a prescription sleep aid is needed, orexin receptor antagonists are increasingly preferred over z-drugs.
When people stop taking zolpidem, about 20 to 30% experience one or two nights of sleep that’s worse than their baseline. This rebound insomnia is typically brief, lasting one to two nights, and one long-term study found that 12 months of nightly use did not increase the likelihood or severity of rebound compared to shorter courses.
Antidepressants Used as Sleep Aids
Two antidepressants, trazodone and mirtazapine, are frequently prescribed at low doses specifically for sleep, even when the patient isn’t depressed. This is off-label use, but it’s extremely common in clinical practice.
Both are effective. In a retrospective study, about 87% of people responded to trazodone and 87% responded to mirtazapine, with no significant difference between them. The key finding was that lower doses worked better for sleep than higher doses. For trazodone, 25 to 75 mg produced a 100% response rate, while doses of 100 to 150 mg dropped to about 43%. For mirtazapine, 7.5 to 15 mg was similarly more effective than higher doses. This is because at low doses, these medications primarily activate the brain pathways involved in drowsiness, while at higher doses, other effects kick in that can actually interfere with sleep.
Mirtazapine does tend to increase appetite and cause weight gain, which matters if you plan to take it long-term. Trazodone is less likely to cause weight gain but can leave some people feeling groggy in the morning, especially at higher doses.
Risks of Long-Term Sedative Use
Benzodiazepines like temazepam and lorazepam were once the standard prescription for insomnia, and some doctors still prescribe them. The evidence against regular use, especially in older adults, has grown substantially.
An umbrella review of meta-analyses found that benzodiazepine users had a 39% higher risk of developing dementia compared to non-users. Long-term users faced a 49% higher risk. The association followed a dose-response pattern: for every 20 daily doses per year, dementia risk increased by 22%. Both recent and past users showed elevated risk, suggesting the effects may persist after stopping.
Beyond dementia risk, benzodiazepines impair balance, slow reaction times, and increase fall risk in older adults. Short-term use of short-acting formulations is considered relatively safe, but these medications are no longer recommended as a first-line treatment for insomnia.
Sleep Apnea Changes the Equation
If you snore heavily or wake up feeling unrefreshed despite sleeping enough hours, sleep apnea may be the real issue, and certain sleep medications can make it dangerous. Opioids, benzodiazepines, and muscle relaxants all worsen sleep apnea by relaxing the airway further or suppressing the brain’s breathing drive. Opioids are particularly risky, causing both airway obstruction and central breathing pauses, and have been linked to sudden respiratory arrests during sleep.
A Cochrane review found that while some newer sleep medications like eszopiclone and zolpidem didn’t significantly worsen the number of breathing interruptions in apnea patients, certain benzodiazepines (flurazepam, triazolam) did lower blood oxygen levels during the night. If you suspect you have sleep apnea, getting that diagnosed and treated is far more important than finding the right sleeping pill.
Choosing the Right Option
For occasional sleeplessness tied to jet lag, stress, or a disrupted schedule, low-dose melatonin (1 to 3 mg) is the simplest starting point. It’s safe, non-habit-forming, and won’t leave you impaired the next day.
If your insomnia is chronic, lasting three or more nights per week for at least three months, a prescription is worth discussing. Orexin receptor antagonists offer the best balance of effectiveness and safety. Low-dose trazodone is another reasonable option, especially if anxiety or mild depression is contributing to your sleep problems.
Avoid relying on diphenhydramine-based products. Despite being the most accessible option on pharmacy shelves, the evidence for their effectiveness is weak, and the next-day impairment is real. And if you’re over 65, benzodiazepines carry risks that almost always outweigh their benefits.