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.
Depressant
In general, benzodiazepines are safe and effective in the short term, although cognitive impairments and paradoxical effects such as aggression or behavioral disinhibition occasionally occur. A minority react reverse and contrary to what would normally be expected. For example, a state of panic may worsen considerably following intake of a benzodiazepine. Long-term use is controversial due to concerns about adverse psychological and physical effects, increased questioning of effectiveness, and, because benzodiazepines are prone to cause tolerance, physical dependence, and, upon cessation of use after long-term use, a withdrawal syndrome. Due to adverse effects associated with the long-term use of benzodiazepines, withdrawal from benzodiazepines, in general, leads to improved physical and mental health. The elderly are at an increased risk of suffering from both short- and long-term adverse effects.