J Head Trauma Rehabil 2006 May-Jun; 21(3): 199-212 (Read article online)

Ouellet MC, Beaulieu-Bonneau S, Morin CM

OBJECTIVES: To document the frequency of insomnia (according to DSM-IV and ICSD criteria), to describe its sociodemographic and clinical characteristics, and to identify potential predictors of insomnia in persons with traumatic brain injury (TBI). PARTICIPANTS AND PROCEDURE: Four hundred fifty-two participants aged 16 years and older with minor to severe TBI answered a questionnaire pertaining to quality of sleep and fatigue. MAIN OUTCOME MEASURES: Proportion of participants fulfilling criteria for insomnia symptoms or syndrome. Validated measures of insomnia severity, fatigue level, and psychologic distress. Results of a logistic regression analysis. RESULTS: Overall, 50.2% of the sample reported insomnia symptoms and 29.4% fulfilled the diagnostic criteria for an insomnia syndrome. For the latter participants, insomnia was a severe and chronic condition remaining untreated in almost 60% of cases. Risk factors associated with insomnia were milder TBIs, and higher levels of fatigue, depression, and pain. CONCLUSION: Insomnia is a prevalent condition after TBI requiring more clinical and scientific attention as it may have important repercussions on rehabilitation.

Sleep Med 2006 May 17; (Read article online)

Sanford SD, Lichstein KL, Durrence HH, Riedel BW, Taylor DJ, Bush AJ

BACKGROUND AND PURPOSE: This study explored the distribution of Epworth Sleepiness Scale (ESS) scores in a randomly sampled, community population and provided percentile scores that will assist in decision-making in both research and clinical settings. PATIENTS AND METHODS: Participants included 703 individuals between the ages of 20 and 98, with 116 people with insomnia (PWI) and 587 people not having insomnia (PNI). Analyses produced main effects for sleep status and ethnicity. RESULTS: PWI had higher ESS scores than PNI and African-Americans had higher ESS scores than Caucasians, although effect sizes were small. Gender, age group, and season did not impact ESS scores. Receiver operating characteristic (ROC) curve analysis proved the ESS to discriminate poorly between PWI and PNI. CONCLUSIONS: This study found higher percentages of 'sleepy' individuals than previous studies. PWI did have slightly elevated scores on the ESS, but this elevation was not necessarily predictive of an insomnia diagnosis. Results support a continuum of sleepiness/alertness among PWI.

Soc Sci Med 2006 May 17; (Read article online)

Persson A, Newman C

The concepts of health and self have become intimately entangled in contemporary western society. Health is figured as a marker of identity, as a vehicle of self-production and self-actualisation, while the individual is also made increasingly responsible for his or her health. In this paper, we explore how "self" is constituted in discourses that shape the ways in which people understand and do health and medicine, particularly discourses of neoliberalism and of the immune system. Of interest here is how the productive and unpredictable intra-action of medicine and bodies may come to trouble these discursive selves. We situate our discussion in the context of efavirenz, an antiretroviral drug prescribed and consumed for the treatment of HIV infection. This drug, commonly described as "potent", can have a number of troubling effects on a person's everyday sense of self, including insomnia, confusion, cognitive disorders, depression, depersonalisation, psychosis, and suicidal ideation. While efavirenz may be clinically effective in its capacity to suppress the virus, these effects are at odds with the implicit aim of HIV medicine to restore and secure the self by way of immunological integrity and strength. These effects also bring into focus the predicament of choice under the contemporary political conditions of neoliberalism with its emphasis on health as an enterprise of the autonomous, rational self. In exploring first-person accounts, the paper unpacks a number of the binary concepts on which contemporary discourses of health and medicine rely, such as immunity and vulnerability, potency and fragility, rationality and madness, self and non-self, and asks whether the individual under neoliberalism is being asked the impossible.

J Sleep Res 2006 Jun; 15(2): 212-21 (Read article online)

Marchetti LM, Biello SM, Broomfield NM, Macmahon KM, Espie CA

Summary Cognitive models of insomnia suggest that selective attention may be involved in maintaining the disorder. However, direct assessment of selective attention is limited. Using the inducing change blindness (ICB) paradigm we aimed to determine whether there is attentional preference for sleep-related stimuli in psychophysiological insomnia (PI) relative to delayed sleep phase syndrome (DSPS) and good sleepers (GS). In the ICB task, a visual scene, comprising both sleep-related and neutral stimuli, 'flickers' back and forth with one element (sleep or neutral) of the scene changing between presentations. Therefore, a 2 x 3 totally between-participants design was employed. The dependent variable was the number of flickers it took for the participant to identify the change. Ninety individuals (30 per group) were classified using ICSD-R criteria, self-report diaries and wrist actigraphy. As predicted, PI detected a sleep-related change significantly quicker than DSPS and GS, and significantly quicker than a sleep-neutral change. Unexpectedly, DSPS detected a sleep-related change significantly quicker than GS. No other differences were observed between the two controls. These results support the notion that there is an attention bias to sleep stimuli in PI, suggesting that selective attention tasks such as the ICB may be a useful objective index of cognitive arousal in insomnia. The results also suggest that there may be an element of sleep preoccupation associated with DSPS. Results are discussed with reference to other experiments on attentional processing in insomnia.

Sleep Med 2006 May 12; (Read article online)

Bateson AN

BACKGROUND AND PURPOSE: The benzodiazepine binding site on the GABA(A) receptor is the target for the majority of hypnotics, including the nonbenzodiazepine 'Z drugs' (zaleplon, zolpidem, zopiclone and eszopiclone). Concerns still exist over long-term benzodiazepine use, and efforts are, therefore, being made to search for new hypnotic agents and alternative receptor target sites, with novel mechanisms of action. PATIENTS AND METHODS: Clinically useful compounds, including GABA mimetics and GABA-uptake inhibitors, have been found by developing structurally rigid analogs of GABA. RESULTS: The GABA-site agonist 4,5,6,7-tetra hydroisoxazolo[5,4-c]pyridin-3-ol (THIP) shows high potency for extrasynaptic GABA(A) receptor subtypes, which are not primary targets for classical benzodiazepines or the Z drugs. Hence, THIP targets a novel set of GABA(A) receptors. The antiepileptic drug, tiagabine, is a specific blocker of the GAT-1 GABA-transporter, increasing GABA levels following synaptic GABA release. It is proposed that this promotes extrasynaptic GABA(A) receptor activity. In contrast, two other GABA analogs, pregabalin and gabapentin, are not GABA mimetics but appear to act at calcium channels responsible for neurotransmitter release, rather than at the GABA receptors. CONCLUSIONS: All of these GABA analogs modify sleep behaviors and so are potentially effective hypnotic drugs that provide an alternative to the benzodiazepine binding site of the GABA(A) receptor.

J Occup Rehabil 2006 May 16; (Read article online)

Lillefjell M, Krokstad S, Espnes GA

Introduction: This study aimed to investigate the outcome and outcome predictors of multidisciplinary rehabilitation in terms of working ability. Methods: One hundred and forty three (n=143) patients with musculoskeletal pain (mean age=45.7, SD=8.9) were included. Work status, pain, functional health status and psychosocial factors were collected previous to treatment, after a 5 week intensive training and a 52 week follow-up period.Demographics and data on personal characteristics were also collected. Results: Workability increased from 57.4 to 80% during treatment period. Stepwise multivariate logistic regression indicated that age, sleeplessness, cognitive function, overall health, pain experience, and anxiety were the strongest predictors of work ability. Pain severity and depression were not found to be significant predictors of work ability. Conclusions: These data suggest that emotional distress, cognitive function and overall health are important priority areas in rehabilitation programmes to improve work ability.

Sleep Med 2006 May 13; (Read article online)

Lichstein KL

BACKGROUND AND PURPOSE: Patients with hypnotic-dependent insomnia and those with secondary (comorbid) insomnia have previously been regarded as being unsuitable for inclusion in studies of cognitive behavioral therapy (CBT). This paper reviews CBT clinical trials that have mainly been published in the past 15 years with these two disorders. PATIENTS AND METHODS: CBT studies that targeted patients taking sleep medication and exhibiting current insomnia qualified for hypnotic-dependent insomnia and patients with comorbid conditions that presented a high risk of producing insomnia such as depression and chronic pain were included as secondary insomnia. RESULTS: In recent years, studies in patients with hypnotic-dependent insomnia have shown that supervised hypnotic gradual withdrawal programs can reduce patients' use of hypnotic medications and, when combined with CBT, can also significantly improve parameters such as sleep-onset latency and sleep efficiency. Secondary, or comorbid, insomnia accounts for 60% of all cases of insomnia. A number of reports now show that CBT can lead to improvements in sleep efficiency, latency and quality in a wide range of medical and psychiatric conditions, with similar improvements being seen regardless of the primary disorder. Indeed, it is now believed that insomnia should not be considered as 'secondary' to other causes, pariticularly in patients with chronic illness. In these individuals, the secondary component of insomnia is likely to be greatly reduced, particularly by the time they are referred to a sleep specialist. CONCLUSIONS: Previous theory-based beliefs that hypnotic-dependent insomnia and secondary insomnia were unresponsive to CBT intervention have been shown to be unfounded. Data support the psychological treatment of both these conditions.

Sleep Med 2006 May 13; (Read article online)

Hajak G

BACKGROUND AND PURPOSE: Insomnia is a chronic disorder that may require long-term treatment with hypnotic drugs. Newer drugs, such as zolpidem, zaleplon, zopiclone and eszopiclone, provide tools to maintain efficacy over a period of at least 6 months, without the marked rebound or dependence effects that are seen with traditional benzodiazepines over this period. However, even with newer drugs, the need for long-term therapy should be balanced against the symptom variability that occurs in insomnia patients over time. PATIENTS AND METHODS: Patients may not require a hypnotic drug every night, because there will be nights when no insomnia occurs and when medication is superfluous. Non-nightly (discontinuous) dosing strategies allow symptoms to be addressed as they arise. This article focuses on data obtained for a variety of non-nightly administration schedules of zolpidem. RESULTS: Results from trials treating more than 6000 patients demonstrate that discontinuous treatment with zolpidem is effective and that intermittent replacement with placebo can be carried out safely. In addition, large-scale studies show that zolpidem is effective when taken 'as needed' in daily life settings and that there is a trend for patients to spontaneously self-limit drug intake when using these flexible schedules. CONCLUSIONS: Non-nightly zolpidem, therefore, offers an approach to treatment of patients with chronic insomnia that does not result in the inappropriate daily use of drugs.

J Sleep Res 2006 Jun; 15(2): 125-32 (Read article online)

Adan A, Fabbri M, Natale V, Prat G

Summary The aim of this work was to present the Sleep Beliefs Scale (SBS), a 20-item reviewed version of the Sleep Hygiene Awareness by Lacks and Rotert [Behav. Res. Ther., 1986, 28: 104-112]. We also examined for the first time the influence of circadian typology in sleep beliefs. Voluntary and unpaid psychology students participated in the study (n = 510; 182 men and 328 women), from Italy and Spain, aged between 18 and 33 (22.80 +/- 4.14 years). The mean score of SBS was 13.05 (SD = 3.46; range 2-20) in the total sample, with a distribution positive skewness to high score (correct beliefs) (Z = 1.82; P = 0.003). The internal consistency was good (Cronbach's alpha = 0.714) and factor analysis extracted three factors labelled 'Sleep-incompatible behaviours' (eight items), 'Sleep-wake cycle behaviours' (seven items) and 'Thoughts and attitudes to sleep' (five items). Circadian typology influences the total score and that of the three factors, as well the majority of the items that compose the SBS. The morning-type showed the best scores, the evening-type the worst, and the neither-type the medium scores. Moreover, in the men sample, the differences between circadian typology groups were higher than in the women sample. The SBS showed good psychometric properties; however, further studies in other countries, with clinical and non-student samples, and more aged subjects are needed so as to validate this psychometric instrument. The circadian typology is an individual difference that presented significant relationships with the sleep beliefs, the possibility of the evening-type being a risk factor for a worse sleep hygiene, and the maintenance of sleep problems such as insomnia may all be investigated in depth in future research.

Drugs Today (Barc) 2006 Apr; 42(4): 255-63 (Read article online)

Owen RT

To date the mainstay of the pharmacological treatment of insomnia has involved the modulation of the gabaminergic system via benzodiazepines or the Z-drugs, zolpidem, zopiclone or zaleplon. A new approach has explored the melatoninergic system, namely activation of MT1 and MT2 receptors in the suprachiasmatic nucleus of the hypothalamus. Ramelteon (TAK-375) is a novel sleep-promoting agent that acts as an agonist at these receptors; its preclinical pharmacology, mode of action, pharmacokinetics, drug interactions, clinical efficacy, and safety and tolerability are reviewed here. (c) 2006 Prous Science. All rights reserved.

Sleep Med 2006 May 16; (Read article online)

Roth T, Seiden D, Sainati S, Wang-Weigand S, Zhang J, Zee P

BACKGROUND AND PURPOSE: To assess the efficacy and safety of ramelteon, a selective MT(1)/MT(2) receptor agonist, for chronic insomnia treatment. PATIENTS AND METHODS: Randomized, double-blind, placebo-controlled 35-night outpatient trial with weekly clinic visits at multiple centers. Patients include older adults (>/=65 years; N=829) with chronic insomnia. Placebo, ramelteon 4mg, or ramelteon 8mg were taken nightly for five weeks, and patient-reported sleep data were collected using sleep diaries. Primary efficacy was sleep latency at week 1. Sustained efficacy was examined at weeks 3 and 5. Rebound insomnia and withdrawal effects were evaluated during a 7-day placebo run-out. RESULTS: Both doses of ramelteon produced statistically significant reductions in sleep latency vs. placebo at week 1 (ramelteon 4mg: 70.2 vs. 78.5min, P=.008; ramelteon 8mg: 70.2 vs. 78.5min, P=.008). Patients continued to report reduced sleep latency at week 3 with ramelteon 8mg (60.3 vs. 69.3min, P=.003), and at week 5 with ramelteon 4mg (63.4 vs. 70.6min, P=.028) and ramelteon 8mg (57.7 vs. 70.6min; P<.001). Statistically significant increases in total sleep time were observed with ramelteon 4mg at week 1 (324.6 vs. 313.9min, P=.004) and week 3 (336.0 vs. 324.3min, P=.007) compared with placebo. There was no evidence of significant rebound insomnia or withdrawal effects following treatment discontinuation. The incidence of adverse events was similar among all treatment groups; most were mild or moderate. CONCLUSIONS: In older adults with chronic insomnia, ramelteon significantly reduced patient reports of sleep latency over five weeks of treatment with no significant rebound insomnia or withdrawal effects.

J Clin Psychopharmacol 2006 Jun; 26(3): 284-289 (Read article online)

Blin O, Micallef J, Audebert C, Legangneux E

ABSTRACT:: Short-acting hypnotic drugs, such as zolpidem, have minimal residual effects but may not provide optimal efficacy throughout the night for all insomnia patients. A modified-release formulation of zolpidem, zolpidem-MR, has been developed to overcome this limitation. This was a phase I, double-blind, 3-way crossover, placebo-controlled study to investigate the residual psychomotor and cognitive effects of a single oral dose of zolpidem-MR 12.5 mg in 18 healthy young adults. Flurazepam 30 mg was used as a positive control. No comparison with standard immediate-release zolpidem was made. Five neuropsychological tests and 2 subjective tests were performed 8 hours after dosing. The safety of zolpidem-MR was also investigated. Performance on the Critical Flicker Fusion Frequency test, Choice Reaction Time, Immediate and Delayed Word Recall, and the Compensatory Tracking Task was significantly impaired by flurazepam but not by zolpidem-MR (with the exception of the Compensatory Tracking Task) or placebo. No significant effects were observed on the Digit Symbol Substitution Test. The Leeds Sleep Evaluation Questionnaire showed that both drugs improved the ease of getting to sleep and perceived quality of sleep, whereas only flurazepam significantly impaired the ease of awakening. Neither drug scored significantly better than placebo on the Bond and Lader contentedness scale, but both induced a significant difference in calmness; only flurazepam significantly reduced alertness. The safety profile of zolpidem-MR was comparable to placebo. In conclusion, the study showed the good tolerance of zolpidem-MR in terms of residual neuropsychological effects as well as a beneficial effect on sleep quality in young healthy adults.

Sleep Med 2006 May 13; (Read article online)

Morin CM

Despite the interest in combining theropeutics many issues remain to be resolved regarding the combination of behavioral treatment and pharmacotherapy for insomnia. Studies examining the relative advantages of cognitive behavioral therapy (CBT) and pharmacotherapy have found that improvements may be achieved more quickly with drug treatment but are more sustained with CBT. Combining modes of treatment is not necessarily superior to monotherapy because long-term effects can vary between patients. Various modes of combination are possible, with one or other type of treatment being started or discontinued depending on the phase of treatment and the patient's response. Which treatment to initiate first, or whether to run treatments concurrently, depends on factors such as the nature of the insomnia, treatment history, comorbid conditions, acceptability of treatment to the patient, and treatment cost or availability. Issues of dosage, treatment duration or whether treatment should be given continuously or intermittently will have an effect on how these treatment types can be integrated to provide the best outcome for the patient. A detailed look at the efficacy of behavioral and pharmacological therapies with regard to different outcome measures gives some indication of how these different types of treatment may act in a complementary fashion; observations that may be exploited in the integration of behavioral with pharmacological approaches in clinical practice.

J Clin Psychopharmacol 2006 Jun; 26(3): 311-315 (Read article online)

von Knorring AL, Olsson GI, Thomsen PH, Lemming OM, Hultén A

ABSTRACT:: In a European, multicenter, double-blind study, 244 adolescents, 13 to 18 years old, with major depression were randomized to treatment with citalopram (n = 124) or placebo (n = 120). One third of the patients in both groups withdrew from the study. No significant differences in improvement of scores from baseline to week 12 between citalopram and placebo were found. The response rate was 59% to 61% in both groups according to the Schedule for Affective Disorders and Schizophrenia for school-aged children-Present episode version (Kiddie-SADS-P) (depression and anhedonia scores /=50% reduction). Remission (MADRS score

J Psychiatry Neurosci 2006 May; 31(3): 168-176 (Read article online)

Chouinard G

Most drugs are prescribed for several illnesses, but it took several years for psychotropic drugs to have multiple clinical indications. Our search for serotonergic drugs in affective illnesses and related disorders led to new off-label indications for fluoxetine, sertraline, tryptophan, clonazepam, alprazolam, tomoxetine, buproprion, duloxetine, risperidone and gabapentin. Various clinical trial designs were used for these proof-of-concept studies. Novel therapeutic uses of benzodiazepines, such as in panic disorder and mania, were found with the introduction of 2 high-potency benzodiazepines, clonazepam and alprazolam, which were thought to have serotonergic properties. Our initial clinical trials of fluoxetine and sertraline led to their approved indications in the treatment of obsessive-compulsive disorder, and our trials of gabapentin led to new indications in anxiety disorders (generalized anxiety, panic attack and social phobia) and sleep disorders (insomnia).

Eur J Epidemiol 2006; 21(4): 323-4 (Read article online)

Hubálek Z, Lukácová L, Halouzka J, Sirůcek P, Januska J, Precechtelová J, Procházka P

We report West Nile virus infection of the central nervous system in a 69-year-old man, residing in North Moravia (Czech Republic), who visited the USA from 6 July to 31 August 2002. He developed fever with fatigue at the end of his US stay, and was hospitalized in Ostrava after his return on 3 September with fever (up to 39.5 degrees C), fatigue, anorexia, moderate laryngotracheitis, dizziness, insomnia, blurred speech, and a marked bradypsychism. EEG demonstrated a slow bifrontal theta-delta activity, and CT of the brain a slight hydrocephalus. A significant increase of antibodies neutralizing West Nile virus was detected between the first (1:16) and second (1:256) blood serum sample. The patient recovered gradually and was released from hospital on 16 September. This is the first recorded human case of West Nile fever (WNF) imported to the Czech Republic. Nine similar cases of WNF import from the USA have already been reported in other European countries - France, Denmark, the Netherlands, and Germany.

Am J Manag Care 2006 May; 12(8 Suppl): S221-9 (Read article online)

Ancoli-Israel S

Chronic insomnia may coexist with chronic physical and psychiatric conditions, and its prevalence is often higher among patients with these conditions than in the general population. Evidence suggests that insomnia as a feature of chronic disease tends to be more severe and persistent than insomnia that does not occur in the context of chronic illness. Furthermore, comorbid insomnia can have a profound negative impact on patients' quality of life and overall functioning, and may be associated with greater healthcare resource utilization. In some cases, treatment of the underlying disorder may improve sleep, whereas in other cases, treatment of the sleep symptoms may actually improve the underlying disorder. In addition, chronic insomnia may be a precursor to certain psychiatric comorbidities. Further research is needed not only to clarify the efficacy and safety of specific therapeutic approaches but also to further investigate the possibility that successful treatment of sleep disturbances may improve objective and subjective parameters of the disorders themselves. This article reviews the specific associations between chronic insomnia and a wide range of chronic physical and psychiatric disorders.

Neurology 2006 May 9; 66(9): 1418-24 (Read article online)

Landolt HP, Glatzel M, Blättler T, Achermann P, Roth C, Mathis J, Weis J, Tobler I, Aguzzi A, Bassetti CL

BACKGROUND: The prevalence and characteristics of sleep-wake disturbances in sporadic Creutzfeldt-Jakob disease (sCJD) are poorly understood. METHODS: Seven consecutive patients with definite sCJD underwent a systematic assessment of sleep-wake disturbances, including clinical history, video-polysomnography, and actigraphy. Extent and distribution of neurodegeneration was estimated by brain autopsy in six patients. Western blot analyses enabling classification and quantification of the protease-resistant isoform of the prion protein, PrPSc, in thalamus and occipital cortex was available in four patients. RESULTS: Sleep-wake symptoms were observed in all patients, and were prominent in four of them. All patients had severe sleep EEG abnormalities with loss of sleep spindles, very low sleep efficiency, and virtual absence of REM sleep. The correlation between different methods to assess sleep-wake functions (history, polysomnography, actigraphy, videography) was generally poor. Brain autopsy revealed prominent changes in cortical areas, but only mild changes in the thalamus. No mutation of the PRNP gene was found. CONCLUSIONS: This study demonstrates in sporadic Creutzfeldt-Jakob disease, first, the existence of sleep-wake disturbances similar to those reported in fatal familial insomnia in the absence of prominent and isolated thalamic neuronal loss, and second, the need of a multimodal approach for the unambiguous assessment of sleep-wake functions in these patients.

Am J Manag Care 2006 May; 12(8 Suppl): S246-52 (Read article online)

Fullerton DS

An important question for managed care organizations is whether insomnia is associated with increased consumption of healthcare resources. Even though a large number of adults complain of insomnia, few actually receive a diagnostic code for the condition. Consequently, it has been challenging to consistently measure both direct medical costs and indirect costs attributable to insomnia. Recent data have provided a clearer picture showing that insomnia is a costly medical condition. This paper summarizes current understanding of the prevalence of insomnia and explores its impact on health-related quality of life, workplace productivity, and healthcare resource utilization.

Am J Manag Care 2006 May; 12(8 Suppl): S230-45 (Read article online)

Morin AK

Insomnia is a prevalent condition that remains underdiagnosed and undertreated. Recognizing and treating insomnia are important in decreasing morbidity and restoring quality of life for those who experience sleep disturbances. Appropriate treatment of insomnia should involve multiple interventions designed to address not only the symptoms of insomnia itself, but also any coexisting factors that may be contributing to the sleep disturbances. A combination of pharmacologic and nonpharmacologic therapies may be particularly efficacious in those with chronic and debilitating insomnia. Pharmacotherapy is the most frequently used intervention for insomnia in cases where the goal of therapy is immediate relief of symptoms, insomnia is accompanied by significant distress or impairment, nonpharmacologic approaches alone are ineffective, or the patient prefers medication. The ideal hypnotic has the following characteristics: rapid absorption, rapid sleep induction, optimal duration of action, preservation of sleep architecture, and a favorable safety profile. This review will discuss currently available treatment options for insomnia, the benefits of each, and appropriate treatment regimens.