How many elderly patients with insomnia use over-the-counter sleep aids that contain antihistamines? Could these drugs be the reason for morning confusion? Do they affect daytime cognitive function? Do they contribute to drowsiness, dizziness, fatigue and impaired performance? Dr. Ronald Pies cites several studies and discusses the use of OTC antihistamines in an article titled, To Sleep, Perchance to Take OTC Antihistamines in the June, 2003 issue of Psychiatric Times.

A recent study found use of diphenhydramine is increasing among older people (Basu et al. 2003). The most common antihistamines used in OTC sleep aids are diphenhydramine hydrochloride (brand names include: Benedryl, Sominex and Unisom SoftGels and doxylamine, Unisom Sleep Tabs, in 25 mg to 50 mg dosages. Even though their efficacy and safety is poorly documented, first generation antihistamines such as diphenhydramine (Benedryl) seem to be used frequently in nursing homes in spite of their effects on daytime cognitive function.

As sleep inducing agents, H1 antagonists suppress the wake promoter pathway and cause the person to sleep. Generally, histamine-1 receptor antagonists (H1 blockers) are divided into first-generation and second- generation agents. First-generation agents are stronger sedatives and have greater effect on autonomic receptors (Katzung and Julius, 2001). Second-generation agents including fexofenadine (Allegra) and loratadine (Claratin) are less sedating because of reduced absorption into the central nervous system. Besides their antihistaminic effects, these drugs also produce significant atropine-like effects on peripheral receptors.

First generation H1 blockers can affect psychomotor performance without causing sleep (Okamura et al. 2000). Side effects included drowsiness, dizziness, grogginess and fatigue that are consistent with the sedating effect of diphenhydramine (Rickels et al. 1983). In a recent search in PubMed for literature on this topic, out of thirteen studies, only two were conducted on elderly subjects. This is disturbing because of the widespread use of this substance in treating sleep disorders in seniors especially in nursing homes.

In a random, double-blind study of 50 mg diphenhydramine given twice a day to healthy men between the ages of 18 to 50, both objective and subjective measures of sleepiness was significantly higher on day one than on day four. Performance was greatly impaired on day one but had essentially disappeared by day four (Richardson et al 2002). Conclusion: tolerance was reached by day three and since tolerance was reached so quickly, it is unlikely that taking diphen-hydramine for more than a few days would be beneficial to most people with chronic insomnia. However, it seems likely that in patients with dementia, the effects could lead to confusion after the sleep-inducing effects have worn off.

There is also the potential for abuse of OTC antihistamines. In 1997, a liquid-filled capsule with 50 mg of diphenhydramine (Sleepia) was introduced in Great Britain. Statements in the advertising included: “non-habit forming” and “helps restore natural sleep” (Roberts et al. 1997). A few months after its introduction, pharmacists in Scotland noticed “requests for excessive quantities of the product by patients on the supervised methadone programme.” Apparently, the drug was being injected. Soon after, the manufacturer withdrew the product from Great Britain. With its documented abuse in liquid form, the potential of abuse in non-injectable forms must be considered.

Another potentially serious complication is drug-to-drug interaction. Since patients may be using OTC antihistamines without their doctors’ knowledge, the possibility of unexpected drug reactions is considerable. Diphenhydramine inhibits the CYP systems (Lessard et al. 2001) which helps metabolize many psychotropic drugs and other medications including antidepressants, anti-inflammatory drugs and codeine, which are often prescribed for the elderly, suggests the possibility of interactions should not be ignored.

Conclusion: most OTC sleep aids have not been studied adequately. Diphenhydramine does seem to be superior to a placebo in most double blind, placebo-controlled studies. But the studies were of short duration and utilized patients with mild to moderate insomnia and, in several cases, only subjective measures of quality, quantity and maintenance were used. There are no recent studies of the long-term (three weeks plus) effect of the drug on chronic insomnia. It appears the drug loses its effectiveness after a few days and, even though side effects eventually diminish, they cause severe daytime cognitive dysfunction in the elderly. There is also a huge potential for abuse of diphen-hydramine as well as the real possibility of dangerous drug interactions with other medications commonly prescribed for seniors. Available evidence suggests that diphenhydramine (and related drugs) are not a viable treatment plan for patients with chronic insomnia and should not be used daily or for more than three weeks consecutively.

To quote Dr. Peis, “So why has that patient in the nursing home been taking 50 mg of diphenhydramine every night for the last two months?”

This summary is from an article in the June, 2003 Psychiatric Times by Ronald Pies, M.D., titled To Sleep, Perchance to Take OTC Antihistamines.