Insomnia Insomnia

174 Attarian
Secondary Insomnias
Restless legs syndrome (RLS) is a common condition found in varying degrees
in up to 10% of the population. The four cardinal symptoms are as follow:
1. A desire to move the legs.
2. Accompanying paresthesias that are characterized as uncomfortable or indescribable.
3. Motor restlessness.
4. Worsening of symptoms at night and at rest.
Symptoms of RLS may worsen with administration of tricyclic antidepressants
or selective serotonin reuptake inhibitors and during pregnancy.
Menopause-related insomnia is a high level of sleep disturbance occurring in
about 42% of middle-aged women. Other secondary insomnias include insomnia
due to other sleep disorders, insomnia due to poor sleep hygiene, neurological, psychiatric,
other sleep disoders or other medical conditions, and medication-induced
insomnia. Secondary insomnias most often respond to the treatment of the underlying
cause. In this chapter, only the pharmacological treatments of primary
insomnias, menopause-related insomnia, and RLS are discussed.
HISTORICAL PERSPECTIVES
In the late 1800s, two compounds similar to alcohol were used to treat insomnia:
paraldehyde and chloral hydrate. Synthesized by Justin Liebig in 1832, chloral hydrate
is the oldest synthetic hypnotic agent. It has been used since 1869 as a hypnotic.
It is still used for this purpose, but only rarely (2). These two medications fell
out of favor because of adverse effect profiles and problems with withdrawal after
the advent of barbiturates in the early 20th century. Barbiturates were widely used
as treatments of choice for insomnia for about half a century. In the 1950s, problems
with tolerance, addiction, withdrawal, and overdose became apparent. Meprobamate
was introduced to solve these issues, but it and its congeners turned out to
have the same problems of addiction, tolerance, and withdrawal as the barbiturates.
In 1960, chlordiazepoxide was introduced as the first benzodiazepine. Since then,
the safety and efficacy of this class has made the former methods of pharmacological
treatment of insomnia obsolete. There is much controversy regarding the incidence
of addiction, tolerance, and dependence with benzodiazepine use. Because
of this, many natural products have been studied as insomnia drugs. In 1970 Ltryptophan,
an amino acid precursor of serotonin, was found to be effective in the
treatment of insomnia (3). In 1989, cases of eosinophilia-myalgia syndrome from
all over the world were being reported in association with manufactured L-tryptophan
(4–6). In November 1989, the substance was recalled. By July 1990, only in
the United States, 1531 cases were reported, with 27 resulting in death despite treatment
and discontinuation of the drug (5). By the early 1990s, L-tryptophan became
obsolete as a hypnotic.