Hypnotic

[8] A review of the literature regarding benzodiazepine hypnotics and Z-drugs concluded that these drugs can have adverse effects, such as dependence and accidents, and that optimal treatment uses the lowest effective dose for the shortest therapeutic time period, with gradual discontinuation in order to improve health without worsening of sleep.

These include Urethan, Acetal, Methylal, Sulfonal, Paraldehyde, Amylenhydrate, Hypnon, Chloralurethan and Ohloralamid or Chloralimid.

[12] Barbiturates emerged as the first class of drugs in the early 1900s,[13] after which chemical substitution allowed derivative compounds.

Although they were the best drug family at the time (with less toxicity and fewer side effects), they were dangerous in overdose and tended to cause physical and psychological dependence.

[19] Other sleep remedies that may be considered "sedative–hypnotics" exist; psychiatrists will sometimes prescribe medicines off-label if they have sedating effects.

Examples of these include mirtazapine (an antidepressant), clonidine (an older antihypertensive drug), quetiapine (an antipsychotic), and the over-the-counter allergy and antiemetic medications doxylamine and diphenhydramine.

Off-label sleep remedies are particularly useful when first-line treatment is unsuccessful or deemed unsafe (as in patients with a history of substance abuse).

Barbiturates are drugs that act as central nervous system depressants, and can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia.

[21] Examples of quinazolinones include cloroqualone, diproqualone, etaqualone (Aolan, Athinazone, Ethinazone), mebroqualone, Afloqualone (Arofuto), mecloqualone (Nubarene, Casfen), and methaqualone (Quaalude).

[22][23] Like alcohol, benzodiazepines are commonly used to treat insomnia in the short-term (both prescribed and self-medicated), but worsen sleep in the long-term.

[23] However, the UK National Institute for Health and Clinical Excellence (NICE) 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.

[19][31] Examples include zopiclone (Imovane, Zimovane), eszopiclone (Lunesta), zaleplon (Sonata), and zolpidem (Ambien, Stilnox, Stilnoct).

[33] 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.

[34] Melatonin, the hormone produced in the pineal gland in the brain and secreted in dim light and darkness, among its other functions, promotes sleep in diurnal mammals.

[medical citation needed] This results in their primarily affecting peripheral histamine receptors, and therefore having a much lower sedative effect.

[44][45] Some of the more serious adverse effects have been observed to occur at the low doses used for this off-label prescribing, such as dyslipidemia and neutropenia,[46] [47][48][49] and a recent network meta-analysis of 154 double-blind, randomized controlled trials of drug therapies vs. placebo for insomnia in adults found that quetiapine had not demonstrated any short-term benefits in sleep quality.

[52] It found a wide range of effect sizes (standardized mean difference (SMD)) in terms of efficacy for insomnia.