While all antidepressants help regulate sleep, some antidepressants, such as amitriptyline, doxepin, mirtazapine, trazodone, and trimipramine, can have an immediate sedative effect, and are prescribed to treat insomnia. Amitriptyline, doxepin, and trimipramine all have antihistaminergic, anticholinergic, antiadrenergic, and antiserotonergic properties, which contribute to both their therapeutic effects and side effect profiles, while mirtazapines actions are primarily antihistaminergic and antiserotonergic and trazodones effects are primarily antiadrenergic and antiserotonergic. Mirtazapine is known to decrease sleep latency (i.e., the time it takes to fall asleep), promoting sleep efficiency and increasing the total amount of sleeping time in people with both depression and insomnia.Agomelatine, a melatonergic antidepressant with claimed sleep-improving qualities that does not cause daytime drowsiness, is approved for the treatment of depression though not sleep conditions in the European Union and Australia. After trials in the United States, its development for use there was discontinued in October 2011 by Novartis, who had bought the rights to market it there from the European pharmaceutical company Servier.A 2018 Cochrane review found the safety of taking antidepressants for insomnia to be uncertain with no evidence supporting long term use. Melatonin agonists
Melatonin receptor agonists such as melatonin and ramelteon are used in the treatment of insomnia. The evidence for melatonin in treating insomnia is generally poor. There is low-quality evidence that it may speed the onset of sleep by 6 minutes.
Studies of brain metabolism using positron emission tomography (PET) scans indicate that people with insomnia have higher metabolic rates by night and by day. The question remains whether these changes are the causes or consequences of long-term insomnia. Genetics
Heritability estimates of insomnia vary between 38% in males to 59% in females. A genome-wide association study (GWAS) identified 3 genomic loci and 7 genes that influence the risk of insomnia, and showed that insomnia is highly polygenic. In particular, a strong positive association was observed for the MEIS1 gene in both males and females. This study showed that the genetic architecture of insomnia strongly overlaps with psychiatric disorders and metabolic traits. It has been hypothesised that the epigenetics might also influence insomnia through a controlling process of both sleep regulation and brain-stress response having an impact as well on the brain plasticity. Substance-induced
Alcohol-induced
Alcohol is often used as a form of self-treatment of insomnia to induce sleep. However, alcohol use to induce sleep can be a cause of insomnia. Long-term use of alcohol is associated with a decrease in NREM stage 3 and 4 sleep as well as suppression of REM sleep and REM sleep fragmentation. Frequent moving between sleep stages occurs, with awakenings due to headaches, the need to urinate, dehydration, and excessive sweating. Glutamine rebound also plays a role as when someone is drinking; alcohol inhibits glutamine, one of the bodys natural stimulants. When the person stops drinking, the body tries to make up for lost time by producing more glutamine than it needs.