NOVEMBER 01, 2006

Z Drugs May Require More Safety Studies in HIV Patients

Although the prescribing information for eszopiclone discusses studies in which high doses of the drug induced tumors in laboratory animals, the relevance of these data to human safety is unknown. Researchers in the United Kingdom, concerned about the potential role of Z drugs (zopiclone, eszopiclone, zolpidem, and zaleplon) as carcinogens, investigated the cancer incidence in a population of >600 individuals infected with HIV who were prescribed zopiclone or chemically similar eszopiclone for insomnia.

As reported in the Journal of Clinical Oncology (November 2005), approximately 5% (32 of these patients) were diagnosed with cancer after at least 2 weeks of eszopiclone or zopiclone treatment. Most of the 32 cancers were of types common to HIV-positive populations, but some were less typical and also were diagnosed in patients undergoing antiretroviral therapy. The authors suggested that further studies are needed to assess the risk of human cancer associated with these 2 insomnia medications.

Stroke and Sleep Problems Are Linked

Poor sleep and stroke are linked, according to a review of sleep disorders in stroke patients reported in Seminars in Neurology (March 2005). The consequences of stroke (eg, brain damage, pain) may make sleep disorders frequent. Of the patients who experienced a stroke, 60% to 70%, for example, have sleep-disordered breathing (SDB), which primarily manifests as obstructive sleep apnea (OSA). The OSA patient's airway is blocked and his or her sleep cycle is interrupted many times throughout the night. In addition to the more typical causes of sleep problems—depression, anxiety, certain medications, and SDB—stroke complications may contribute to sleep-wake disorders (SWDs). As many as 40% of stroke patients are afflicted with SWDs such as insomnia, daytime sleepiness, or increased sleep (hypersomnia).

Interestingly, SDB also puts a patient at risk for stroke: SDB symptoms such as snoring and excessive daytime sleepiness are independent risk factors for stroke. Additionally, SDB has been statistically associated with poor stroke-associated outcomes and increased long-term mortality. Fortunately, a variety of agents, including hypnotic drugs, are potential treatments for stroke patients who experience sleep disorders.

Sleep Deprivation Affects Brain Function

Previous studies have found that brain function is impacted by both sleep deprivation and task difficulty, but the specific mechanism(s) for these impacts are unclear. Sleep deprivation, for example, may make cognitive tasks more difficult for the brain and may alter the activity of certain brain networks.

Using functional magnetic resonance imaging (fMRI, or brain mapping), the researchers examined the effects of restricted sleep on the healthy brain's performance of verbal tasks. They recently reported their data in the Journal of the International Neuropsychological Society (September 2006). The researchers found that sleep deprivation for 36 hours changed how the parietal lobes of the brain functioned during the recall of memorized words. In contrast to well-rested patients, when the sleep-deprived patients recalled the words, interactions between the prefrontal areas of the lobes decreased and intraparietal lobe activity increased. Additionally, the relative difficulty of the memorized words caused differences in parietal activity during recall: "easy" words required different interactions between brain regions, compared with "hard" words. The authors concluded that sleep deprivation and word difficulty produce different effects on the neural networks involved in verbal learning.

Study Characterizes Insomnia Patients

A comprehensive review of insomnia literature reveals interesting characteristics of the "typical" insomnia patient, as reported in Encephale (November-December 2002).

Insomnia rates are higher in divorced, separated, or widowed individuals and in the less educated, the unemployed, and those in lower socioeconomic groups. Women report insomnia far more frequently than men do. People who experience various forms of personal conflict or stress (eg, grief, hospitalization, work-related problems) also experience insomnia more frequently than others. Insomnia is more common in those with poor nighttime routines, such as going to sleep too early, reading or watching TV in bed, or eating a late-evening meal. Several medical or physiologic factors can contribute to poor sleep, including restless legs syndrome, narcolepsy, central nervous system injuries, and chronic pain.

Several hypotheses are presented to explain how some forms of insomnia are caused. Psychological stress is fundamental in these hypotheses: unresolved conflict, overwhelming anguish, past trauma, and hopelessness are discussed as potential contributors to poor sleep. The author also emphasized that insomnia is best treated with therapies that address the multiple dimensions of the disease.