Pharmacy Times, Volume 0, 0

Z Drugs May Require More Safety Studies in HIV Patients

Although the prescribing information for eszopiclone discussesstudies in which high doses of the drug inducedtumors in laboratory animals, the relevance of these data tohuman safety is unknown. Researchers in the UnitedKingdom, 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 prescribedzopiclone or chemically similar eszopiclone for insomnia.

As reported in the Journal of Clinical Oncology (November2005), approximately 5% (32 of these patients) were diagnosedwith cancer after at least 2 weeks of eszopiclone orzopiclone treatment. Most of the 32 cancers were of typescommon to HIV-positive populations, but some were lesstypical and also were diagnosed in patients undergoing antiretroviraltherapy. The authors suggested that further studiesare needed to assess the risk of human cancer associatedwith these 2 insomnia medications.

Stroke and Sleep Problems Are Linked

Poor sleep and stroke are linked, according to a review ofsleep disorders in stroke patients reported in Seminars inNeurology (March 2005). The consequences of stroke (eg,brain damage, pain) may make sleep disorders frequent. Ofthe patients who experienced a stroke, 60% to 70%, for example,have sleep-disordered breathing (SDB), which primarilymanifests as obstructive sleep apnea (OSA). The OSA patient'sairway is blocked and his or her sleep cycle is interruptedmany times throughout the night. In addition to the more typicalcauses of sleep problems—depression, anxiety, certainmedications, and SDB—stroke complications may contributeto sleep-wake disorders (SWDs). As many as 40% of strokepatients are afflicted with SWDs such as insomnia, daytimesleepiness, or increased sleep (hypersomnia).

Interestingly, SDB also puts a patient at risk for stroke: SDBsymptoms such as snoring and excessive daytime sleepinessare independent risk factors for stroke. Additionally, SDB hasbeen statistically associated with poor stroke-associated outcomesand increased long-term mortality. Fortunately, a varietyof agents, including hypnotic drugs, are potential treatmentsfor stroke patients who experience sleep disorders.

Sleep Deprivation Affects Brain Function

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

Using functional magnetic resonance imaging (fMRI, or brainmapping), the researchers examined the effects of restrictedsleep on the healthy brain's performance of verbal tasks. Theyrecently reported their data in the Journal of the InternationalNeuropsychological Society (September 2006). The researchersfound that sleep deprivation for 36 hours changed how theparietal lobes of the brain functioned during the recall of memorizedwords. In contrast to well-rested patients, when thesleep-deprived patients recalled the words, interactionsbetween the prefrontal areas of the lobes decreased and intraparietallobe activity increased. Additionally, the relative difficultyof the memorized words caused differences in parietal activityduring recall: "easy" words required different interactionsbetween brain regions, compared with "hard" words. Theauthors concluded that sleep deprivation and word difficultyproduce different effects on the neural networks involved inverbal learning.

Study Characterizes Insomnia Patients

A comprehensive review ofinsomnia literature revealsinteresting characteristics ofthe "typical" insomnia patient,as reported in Encephale(November-December 2002).

Insomnia rates are higher indivorced, separated, or widowedindividuals and in the lesseducated, the unemployed, andthose in lower socioeconomicgroups. Women report insomniafar more frequently thanmen do. People who experiencevarious forms of personalconflict or stress (eg, grief, hospitalization,work-related problems)also experience insomniamore frequently than others.Insomnia is more common inthose with poor nighttime routines,such as going to sleep tooearly, reading or watching TV inbed, or eating a late-eveningmeal. Several medical or physiologicfactors can contribute topoor sleep, including restlesslegs syndrome, narcolepsy, centralnervous system injuries,and chronic pain.

Several hypotheses are presentedto explain how someforms of insomnia are caused.Psychological stress is fundamentalin these hypotheses:unresolved conflict, overwhelminganguish, past trauma,and hopelessness are discussedas potential contributorsto poor sleep. The authoralso emphasized that insomniais best treated with therapiesthat address the multipledimensions of the disease.