Newer Sedative and Hypnotic Agents

In recent years, a variety of alternatives to the benzodiazepines have become available to treat both anxiety and insomnia. Buspirone (Buspar) has been shown to reduce anxiety in generalized anxiety disorders, but it does not suppress panic attacks, and is not used as a primary treatment of obsessive-compulsive disorder. Buspirone is not abused by alcoholics and drug addicts, and it does not produce withdrawal symptoms on abrupt discontinuation. Like the antidepressants, buspirone requires several weeks of daily dosing to produce antianxiety effects, which are less dramatic from patients' point of view than are the effects produced by the benzodiazepines (Sussman & Stein, 2002).

The antidepressants as a class have been shown to possess antipanic and antianxiety effects opening a new range of uses for these medicines in the treatment of anxiety disorders. The selective serotonin reuptake inhibitors (SSRIs) have emerged as the first-line treatment for many anxiety disorders (Davidson, 2003; DuPont, 1997; Jefferson, 1997). Although the earlier antianxiety and anti-insomnia medicines focused exclusively on the benzodiazepine receptors in the GABA system, the recognition of the importance of serotonin and norepinephrine neurotransmitters in the management of anxiety and insomnia, and the success of buspirone, have stimulated a search for a new generation of antianxiety medicines that are not controlled substances (e.g., they are not abused by alcoholics and drug addicts). Recognition of the withdrawal symptoms associated with abrupt discontinuation of some antidepressants (especially those with shorter half-lives and more anticholinergic properties) have shown that withdrawal is not limited to controlled stubstances (DuPont, 1997).

Two nonbenzodiazepine hypnotic agents have been introduced. Zolpidem (Ambien) and Zaleplon (Sonata) are rapid-onset, short duration of action medicines that act on the benzodiazepine receptors of the GABA system. They have been shown to reduce insomnia. They have largely replaced the benzo-diazepines as hypnotic medicines, although they lack the anxiolytic, anti-convulsant, and muscle-relaxant properties of the benzodiazepines (Scharf, Mayleben, Kaffeman, Krall, & Ochs, 1991). Zolpidem and zaleplon are reinforcing to alcoholics and drug addicts, underscoring the fact that the abuse potential of both drugs appears to be similar to that of benzodiazepines. Both medicines impair memory and performance of complex tasks in ways that are similar to the acute effects of benzodiazepines. They do not affect stage 4 sleep, as do the benzodiazepines.

Both zaleplon and Zolpidem are effective in relieving sleep-onset insomnia, and both have been approved by the FDA for use up to 7-10 days at a time. Both medicines clinically appear to have sustained hypnotic activity over longer periods of time. Zolpidem has a half-life of about 2 hours, which is consistent with therapeutic activity over a typical 8 hours of sleep. Zaleplon has a 1hour half-life that offers the possibility of dosing in the middle of the night for broken sleep. For this reason zaleplon is approved for use both at bedtime and in midsleep periods of insomnia.

In recent years, the antiepilepsy medicines, including valproate (Depakote) and gabapentin (Neurontin), have been used as augmenting agents in the treatment of anxiety (Lydiard, 2002).


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