Hypnotic

A hypnotic, also known as a somnifacient or soporific, and commonly known as sleeping pills, are a class of psychoactive drugs whose primary function is to induce sleep and to treat insomnia. Some hypnotics are also used to treat narcolepsy and hypersomnia by improving sleep at night and thereby reducing daytime sleepiness. Certain hypnotics can be used to treat non-restorative sleep and associated symptoms in conditions like fibromyalgia as well.
This group of drugs is related to sedatives. Whereas the term sedative describes drugs that serve to calm or relieve anxiety, the term hypnotic generally describes drugs whose main purpose is to initiate, sustain, or lengthen sleep. Because these two functions frequently overlap, and because drugs in this class generally produce dose-dependent effects, they are often referred to collectively as sedative–hypnotic drugs.
Hypnotic drugs are regularly prescribed for insomnia and other sleep disorders, with over 95% of insomnia patients being prescribed hypnotics in some countries. Many hypnotic drugs are habit-forming and—due to many factors known to disturb the human sleep pattern—a physician may instead recommend changes in the environment before and during sleep, better sleep hygiene, the avoidance of caffeine and alcohol or other stimulating substances, or behavioral interventions such as cognitive behavioral therapy for insomnia, before prescribing medication for sleep. When prescribed, hypnotic medication should be used for the shortest period of time necessary.
Among individuals with sleep disorders, 13.7% are taking or prescribed nonbenzodiazepines, while 10.8% are taking benzodiazepines, as of 2010, in the USA. Early classes of drugs, such as barbiturates, have fallen out of use in most practices but are still prescribed for some patients. In children, prescribing hypnotics is not currently acceptable—unless used to treat night terrors or sleepwalking. Elderly people are more sensitive to potential side effects of daytime fatigue and cognitive impairment, and a meta-analysis found that the risks generally outweigh any marginal benefits of hypnotics in the elderly. A review of the literature regarding benzodiazepine hypnotics and Z-drugs concluded that these drugs have adverse effects, such as dependence and accidents, and that optimal treatment uses the lowest effective dose for the shortest therapeutic time, with gradual discontinuation to improve health without worsening of sleep.
Falling outside the above-mentioned categories, the neurohormone melatonin and its analogues serve a hypnotic function.

Types

GABA_A receptor positive allosteric modulators

Benzodiazepines

s can be useful for short-term treatment of insomnia. Their use beyond 2 to 4 weeks is not recommended due to the risk of dependence. It is preferred that benzodiazepines be taken intermittently and at the lowest effective dose. They improve sleep-related problems by shortening the time spent in bed before falling asleep, prolonging sleep time, and reducing wakefulness. Like alcohol, benzodiazepines are commonly used to treat insomnia in the short-term, but worsen sleep in the long-term. While benzodiazepines can put people to sleep, while asleep, the drugs disrupt sleep architecture by decreasing sleep time, delaying time to REM sleep, and decreasing deep slow-wave sleep.
Other drawbacks of hypnotics, including benzodiazepines, are possible tolerance to their effects, rebound insomnia, and reduced slow-wave sleep and a withdrawal period typified by rebound insomnia and a prolonged period of anxiety and agitation. The list of benzodiazepines approved for the treatment of insomnia is similar among most countries, but which benzodiazepines are officially designated as first-line hypnotics prescribed for the treatment of insomnia can vary distinctly between countries. Longer-acting benzodiazepines, such as nitrazepam and diazepam, have residual effects that may persist into the next day and are, in general, not recommended.
It is not clear whether the newer nonbenzodiazepine hypnotics are better than the short-acting benzodiazepines. The efficacy of these two groups of medications is similar. According to the US Agency for Healthcare Research and Quality, indirect comparison indicates that side effects from benzodiazepines may be about twice as frequent as from nonbenzodiazepines. Some experts suggest using nonbenzodiazepines preferentially as a first-line long-term treatment of insomnia. However, the UK National Institute for Health and Clinical Excellence did not find any convincing evidence in favor of Z-drugs. A NICE review pointed out that short-acting Z-drugs were inappropriately compared in clinical trials with long-acting benzodiazepines. There have been no trials comparing short-acting Z-drugs with appropriate doses of short-acting benzodiazepines. Based on this, NICE recommended choosing the hypnotic based on cost and the patient's preference.
Older adults should not use benzodiazepines to treat insomnia unless other treatments have failed to be effective. When benzodiazepines are used, patients, their caretakers, and their physician should discuss the increased risk of harms, including evidence which shows twice the incidence of traffic collisions among driving patients, as well as falls and hip fracture for all older patients.
Their mechanism of action is primarily at GABA_A receptors.

Nonbenzodiazepines

s are a class of psychoactive drugs that are "benzodiazepine-like" in nature. Nonbenzodiazepine pharmacodynamics are almost entirely the same as benzodiazepine drugs, and therefore entail similar benefits, side effects, and risks. Nonbenzodiazepines, however, have dissimilar or different chemical structures, and are unrelated to benzodiazepines on a molecular level.
Examples include zopiclone, eszopiclone, zaleplon, and zolpidem. Since the generic names of all drugs of this type start with Z, they are often referred to as Z-drugs.
Research on nonbenzodiazepines is new and conflicting. A review by a team of researchers suggests the use of these drugs for people who have trouble falling asleep, as next-day impairments were minimal. The team noted that the safety of these drugs had been established, but called for more research into their long-term effectiveness in treating insomnia. Other evidence suggests that tolerance to nonbenzodiazepines may be slower to develop than with benzodiazepines. A different team was more skeptical, finding little benefit over benzodiazepines.

Barbiturates

s are drugs that act as central nervous system depressants, and can therefore produce a broad spectrum of effects, from mild sedation to total anesthesia. They are also effective as anxiolytics, hypnotics, and anticonvulsant effects; however, these effects are somewhat weak, preventing barbiturates from being used in surgery in the absence of other analgesics. They have dependence liability, both physical and psychological. Barbiturates have now largely been replaced by benzodiazepines in routine medical practice – such as in the treatment of anxiety and insomnia – mainly because benzodiazepines are significantly less dangerous in overdose. However, barbiturates are still used in general anesthesia, for epilepsy, and for assisted suicide. The principal mechanism of action of barbiturates is believed to be positive allosteric modulation of GABA_A receptors. Barbiturates are derivatives of barbituric acid. Examples include amobarbital, pentobarbital, phenobarbital, secobarbital, and sodium thiopental.

Quinazolinones

s are also a class of drugs that function as hypnotics/sedatives that contain a 4-quinazolinone core. Examples of quinazolinones include cloroqualone, diproqualone, etaqualone, mebroqualone, afloqualone, mecloqualone, and methaqualone. This class of drugs has been largely discontinued and is no longer used clinically.

Neurosteroids

metabolizes into neurosteroids including allopregnanolone and pregnanolone which act as potent GABA_A receptor positive allosteric modulators. As a result, oral progesterone can dose-dependently produce side effects including dizziness, drowsiness, sedation, somnolence, fatigue, anxiety reduction, euphoria, and cognitive impairment. For this reason, oral progesterone is often taken at night before bed. Oral progesterone taken before bed has been found to improve multiple sleep outcomes in clinical studies. Zuranolone is a synthetic analogue of allopregnanolone that likewise acts as a GABA_A receptor positive allosteric modulator but is orally active. It is under development for the treatment of insomnia and is in phase 3 clinical trials for this indication as of September 2025.

Others

Other GABA_A receptor positive allosteric modulators with hypnotic effects include alcohol, chloral hydrate, urethane, isoflurane, allopregnanolone, and propofol, among others.

GABA_A receptor agonists

The GABA_A receptor agonist gaboxadol, a synthetic derivative of the neurotransmitter γ-aminobutyric acid and an analogue of the alkaloid muscimol, underwent formal clinical development for the treatment of insomnia and reached phase 3 clinical trials for this indication in the 1990s and 2000s. It was found to effectively improve sleep onset and duration in people with insomnia. In addition, and unlike other hypnotics like benzodiazepines, gaboxadol improved slow wave sleep, preserved sleep architecture, and did not suppress REM sleep. Moreover, in contrast to benzodiazepines, tolerance did not appear to develop to gaboxadol's hypnotic effects.
The development of gaboxadol was discontinued in 2007. This was due to high rates of psychiatric and hallucinogenic effects in drug users at supratherapeutic doses, failure of a 3-month efficacy trial, and other cited reasons. Moreover, there was tension concerning hypnotics in the pharmaceutical industry at the time owing to bizarre reports of zolpidem -induced delirium that emerged in the media in 2006, which may have made the developer of gaboxadol more concerned about potential liability issues. According to journalist Hamilton Morris, the discontinuation of gaboxadol's late-stage development may have deprived people with insomnia access to an effective, safe, and non-addictive treatment. There has been some further study of gaboxadol as a hypnotic by David Nutt and colleagues following the discontinuation of its development.
Muscimol, the compound from which gaboxadol was derived, is a naturally occurring constituent of Amanita mushrooms such as Amanita muscaria and is a potent GABA_A receptor agonist similarly. However, muscimol is less selective, more toxic, and far less-researched than gaboxadol. Muscimol is reported to induce sleep in humans in addition to its well-known hallucinogenic effects that occur at sufficiently high doses. The drug shows similar effects on sleep in rodents as gaboxadol. By the mid-2020s, microdosing of muscimol and Amanita mushrooms for claimed therapeutic benefits, the most prominently cited of which is improved sleep, has become increasingly prominent.