Pharmacologic Interventions to Treat Insomnia

The most commonly used classes of drugs to treat insomnia are traditional benzodiazepines (e.g., alprazolam, diazepam, and temazepam) and the newer class of nonbenzodiazepines (e.g., zolpidem, zoplicone, zaleplon, and eszopliclone). Although each type of medication is chemically distinct, they all act as agonists at the benzodiazepine receptor component of the gamma-aminobutyeric acid receptor chloride channel complex and preferentially bind to the alpha 1 receptor subunit, which is thought to contribute to their sedating and anticonvulsant properties. The newer class of "non-benzos" has the strongest evidence base for the treatment of insomnia in civilian populations, and these medications are generally preferred clinically because they have a more selective hypnotic effect than traditional benzodiazepines. This means that they are less likely to produce residual "hangovers" the next day, are considered safer than traditional benzodiazepines in terms of their risk for abuse and overdose, have a lower risk of withdrawal issues (though "rebound insomnia" is quite common when patients stop using the drug), and have minimal physiological tolerance issues.

Common side effects of these medications include dizziness, anxiety, drowsiness, depression, and disinhibition (Van Camp, 2009). These potential side effects warrant particular caution in operational contexts that involve using heavy or lethal machinery, complex decisionmaking, and sustained attention and vigilance. In addition to these more common side effects, other reports have documented increased rates of a range of nocturnal behaviors (ranging from "sleep sex" to "sleep driving") with potentially lethal or litigious consequences. The risk of these nocturnal behaviors appears to increase among individuals who use higher doses of the medications than recommended, who combine them with other sedating substances (such as alcohol), or who are sleep-deprived. Thus, these rarer but potentially dangerous side effects are of particular concern in servicemember populations, in which there are also high rates of alcohol use and abuse and high rates of sleep insufficiency (as described in Chapters Two and Three).

Nevertheless, evidence from civilian studies suggests that these classes of drugs are efficacious in improving insomnia symptoms, with generally moderate to large effect sizes for improving sleep quality and sleep continuity (i.e., number of awakenings and sleep latency; Benca, 2005). However, our review did not reveal any specific evidence on how efficacious these medications are in treating combat-related sleep disturbances—a notable limitation, particularly given that they remain the front-line treatments for servicemembers. Other, newer classes of drugs, including those that target the melatonin receptor agonist (i.e., Ramelteon) may hold promise for treating insomnia in servicemember populations because they tend to have an even more benign side effect profile than the non-benzodiazepines and are less likely to produce tolerance, rebound insomnia, or morning sedation. Still, to date, there is no systematic empirical evidence to support their use as front-line treatments for insomnia in service-member populations.

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