Doxepin
At very low doses, doxepin has not shown discontinuation or withdrawal effects nor rebound insomnia. Sustained effectiveness without apparent tolerance was demonstrated in clinical studies of up to 12 weeks duration. This appears to be in contrast to over-the-counter antihistamines like diphenhydramine and doxylamine and all other first-generation antihistamines, which are associated with rapid development of tolerance and dependence (by day 3 or 4 of continuous dosing) and loss of hypnotic effectiveness. It is for this reason that, unlike doxepin, they are not recommended for the chronic management of insomnia and are advised for only short-term treatment (i.e., 1 week). It is not entirely clear why doxepin and first-generation antihistamines are different in this regard, but it has been suggested that it may have to do with the lack of selectivity for the H receptor of the latter or may have to do with the use of optimal doses. Unlike very-low-dose doxepin, most first-generation antihistamines also have marked anticholinergic activity as well as associated side effects such as dry mouth, constipation, urinary retention, and confusion. This is particularly true in older people, and antihistamines with concomitant anticholinergic effects are not recommended in adults over the age of 65. Anticholinergic activity notably may interfere with the sleep-promoting effects of H receptor blockade.
Hydroxyzine
Hydroxyzine, sold under the brand names Atarax among others, is a medication of the antihistamine type. It is used in the treatment of itchiness, anxiety, and nausea, including that due to motion sickness. It is used either by mouth or injection into a muscle.
Common side effects include sleepiness, headache, and a dry mouth. Serious side effects may include QT prolongation. It is unclear if use during pregnancy or breastfeeding is safe. Hydroxyzine works by blocking the effects of histamine. It is in the piperazine family of chemicals.
It was first made by Union Chimique Belge in 1956 and was approved for sale by Pfizer in the United States later that year. In the United Kingdom 28 doses cost less than a pound. In the United States the wholesale cost in 2018 was about 0.05 USD per dose. In the United States about 8 million prescriptions were written for hydroxyzine in 2016.