Insomnia Patient Research Articles

Periodic limb movements and insomnia, a common but under-recognized association.

Periodic limb movements unlike restless leg syndrome is under diagnosed and unrecognized in medical arena. While robust Western trials have elucidated the association between periodic limb movements and sleep disturbances, it is not well received and recognized in India even in well sophisticated tertiary care hospital. We report a chronic insomnia patient who had sleep disturbances for past 30 years due to periodic limb movements alone. This was diagnosed through polysomnography. This case emphasizes monitoring leg movements during sleep study. This report may open new horizons in improving monitoring in sleep study in clinical setting.

Eszopiclone Treatment for Insomnia

The purpose of this post hoc analysis was to compare the treatment effect size of eszopiclone 3 mg for insomnia in patients with a diagnosis of primary insomnia and in several of the psychiatric and medical conditions that are most commonly comorbid with insomnia. Data were analyzed from 5 large, multicenter, randomized, double-blind, placebo-controlled studies of adult outpatients of at least 1 month duration published between 2006 and 2009. Diary-derived indices of sleep and daytime functioning and the Insomnia Severity Index were compared for patients with primary insomnia (DSM-IV-TR criteria, n = 828) and for those with insomnia comorbid with major depressive disorder (MDD, DSM-IV-TR criteria, n = 545), generalized anxiety disorder (GAD, DSM-IV-TR criteria, n = 595), perimenopause/postmenopause (Stages of Reproductive Aging Workshop criteria, n = 410), and rheumatoid arthritis (American College of Rheumatology criteria, n = 153). Cohen d effect sizes were calculated for each individual study as the between-treatment difference score divided by the pooled standard deviation. Effect sizes ranged from 0.40 to 0.69 (small-medium) as early as week 1 and were maintained at 0.26-0.63 at week 4 for sleep latency, wake time after sleep onset, and total sleep time. Sleep latency and total sleep time effect sizes increased from week 1 to week 4 in the primary insomnia group. At week 4, effect sizes on all 3 parameters and the Insomnia Severity Index tended to be highest for the primary insomnia patients and tended to be lowest for patients with comorbid GAD and MDD. The effect sizes for daytime functioning were small for all insomnia patient groups. Eszopiclone 3 mg is an effective treatment for insomnia across 5 clinically diverse patient populations; however, magnitude of effect is mediated by underlying comorbidity and their treatments, with largest measures of effect seen in primary insomnia and lowest in MDD and GAD. These consistent results, and the fact that clinical trials were conducted in patients being treated as appropriate for their comorbid clinical conditions, support the results' real-world generalizability and utility to clinical practice.

Reduction of protein kinase MARK4 in the brains of experimental scrapie rodents and human prion disease correlates with deposits of PrPSc

Microtubule affinity-regulating kinase 4 (MARK4) belongs to a family of kinases that are able to actively phosphorylate the neuronal microtubule-associate proteins (MAPs), such as tau, MAP2 and the ubiquitous MAP4. Abnormal changes in tubulin and the profiles of tau have been previously reported in the human brain and animal transmissible spongiform encephalopathies (TSEs), which may be associated with abnormal alterations of various cellular kinases. To elucidate the possible role of MARK4 in TSE pathogenesis, the MARK4 levels in the brain tissues of scrapie-infected rodents and human prion diseases were evaluated using western blotting and immunohistochemical assays. The results revealed that at terminal stages of the diseases, MARK4 levels in the brain tissues of the scrapie 263K-infected hamsters, 139A-infected mice and a case of Creutzfeldt-Jakob disease (CJD, G114V gCJD) correlated with amounts of PrP(Sc) deposits that were almost undetectable. On the other hand MARK4 signals were noticeable in the brain tissues of a fatal familial insomnia (FFI) patient without PrP(Sc). The reduction of MARK4 was closely related to the prolonged incubation times. These results could be reproduced in SK-N-SH and PC12 cell lines after being exposed to the synthetic peptide PrP106-126. Accordingly, the levels of phosphorylated tau at Ser262 (p-tau262) in cultured cells exposed to PrP106-126, or the ratios of p-tau262/total tau in the brain tissues of 263K-infected hamsters were also significantly decreased. According to our data there is a correlation between a TSE pathological-associated decline of MARK4 in the brain tissues with the deposits of PrP(Sc). Reduction of MARK4 will result in abnormalities of tau phosphorylation, and possibly induce further detachment of microtubules and hinder microtubule transportation.

Efficacy of a behavioral self-help treatment with or without therapist guidance for co-morbid and primary insomnia -a randomized controlled trial

BackgroundCognitive behavioral therapy is treatment of choice for insomnia, but availability is scarce. Self-help can increase availability at low cost, but evidence for its efficacy is limited, especially for the typical insomnia patient with co-morbid problems. We hypothesized that a cognitive behaviorally based self-help book is effective to treat insomnia in individuals, also with co-morbid problems, and that the effect is enhanced by adding brief therapist telephone support.MethodsVolunteer sample; 133 media-recruited adults with insomnia. History of sleep difficulties (mean [SD]) 11.8 [12.0] years. 92.5% had co-morbid problems (e.g. allergy, pain, and depression). Parallel randomized (block-randomization, n ≥ 21) controlled "open label" trial; three groups-bibliotherapy with (n = 44) and without (n = 45) therapist support, and waiting list control (n = 44). Assessments before and after treatment, and at three-month follow-up. Intervention was six weeks of bibliotherapeutic self-help, with established cognitive behavioral methods including sleep restriction, stimulus control, and cognitive restructuring. Therapist support was a 15-minute structured telephone call scheduled weekly. Main outcome measures were sleep diary data, and the Insomnia Severity Index.ResultsIntention-to-treat analyses of 133 participants showed significant improvements in both self-help groups from pre to post treatment compared to waiting list. For example, treatment with and without support gave shorter sleep onset latency (improvement minutes [95% Confidence Interval], 35.4 [24.2 to 46.6], and 20.6 [10.6 to 30.6] respectively), and support gave a higher remission rate (defined as ISI score below 8; 61.4%), than bibliotherapy alone (24.4%, p's < .001). Improvements were not seen in the control group (sleep onset latency 4.6 minutes shorter [-1.5 to 10.7], and remission rate 2.3%). Self-help groups maintained gains at three-month follow-up.ConclusionsParticipants receiving self-help for insomnia benefited markedly. Self-help, especially if therapist-supported, has considerable potential to be as effective as individual treatment at lower cost, also for individuals with co-morbid problems.Trial RegistrationClinicalTrials.gov: NCT01105052

Should we be anxious when assessing anxiety using the Beck Anxiety Inventory in clinical insomnia patients?

Assessing for clinical levels of anxiety is crucial, as comorbid insomnias far outnumber primary insomnias (PI). Such assessment is complex since those with Anxiety Disorders (AD) and those with PI have overlapping symptoms. Because of this overlap, we need studies that examine the assessment of anxiety in clinical insomnia groups. Participants ( N = 207) were classified as having insomnia: 1) without an anxiety disorder (I-ND), or 2) with an anxiety disorder (I-AD). Mean Beck Anxiety Inventory (BAI) item responses were compared using multivariate analysis of variance (MANOVA) and follow-up ANOVAs. As a validity check, a receiver operating characteristic (ROC) curve analysis was conducted to determine if the BAI suggested clinical cutoff was valid for identifying clinical levels of anxiety in this comorbid patient group. The I-ND had lower mean BAI scores than I-AD. There were significant group differences on 12 BAI items. The ROC curve analysis revealed the suggested BAI cutoff (≥16) had 55% sensitivity and 78% specificity. Although anxiety scores were highest in those with insomnia and an anxiety disorder, those with insomnia only had scores in the mild range for anxiety. Nine items did not distinguish between those insomnia sufferers with and without an anxiety disorder. Additionally, published cutoffs for the BAI were not optimal for identifying anxiety disorders in those with insomnia. Such limitations must be considered before using this measure in insomnia patient groups. In addition, the poor specificity and high number of overlapping symptoms between insomnia and anxiety highlight the diagnostic challenges facing clinicians.

Examining maladaptive beliefs about sleep across insomnia patient groups

Objectives Unhelpful beliefs about sleep have been linked to insomnia, and increasing one's cognitive flexibility about sleep has been linked to posttreatment sleep improvement. This study evaluated whether levels of such beliefs differ across insomnia groups and whether there are particular beliefs that differ for specific insomnia subtypes. Methods Participants ( N=1384) were people with insomnia and good sleepers ranging from 18 to 89 years old (mean=42.6; S.D.=19.4). Data from previous studies at five insomnia clinical sites were pooled to examine responses on the Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS) across differing insomnia groups. Results Group analyses revealed that those from community-based insomnia clinics and those who are hypnotic-dependent generally had the highest levels of unhelpful sleep-related beliefs. With the exception of beliefs about sleep needs (wherein only community sleep clinic patients had high scores relative to good sleepers), all insomnia groups had higher scores on the 16-item DBAS (DBAS-16) than good sleepers. A validity analysis suggested that a DBAS-16 index score of >3.8 represented the level of unhelpful beliefs associated with clinically significant insomnia, although a slightly lower cutoff may be useful for identifying an unhelpful degree of sleep-related beliefs in highly screened primary-insomnia-only and medical patient groups. Conclusions This study offers descriptive data for the use of DBAS-16 across insomnia subgroups, which will help the user understand what degree of maladaptive sleep beliefs is most strongly associated with clinically significant levels of insomnia. Results also may have implications for cognitive targeting during treatment for particular insomnia groups.

Periodic leg movements during sleep and periodic limb movement disorder in patients presenting with unexplained insomnia

The aim of this study was to evaluate quantitatively the presence and the characteristics of periodic leg movements during sleep (PLMS) in a group of consecutive patients presenting with daytime impairment related to insomnia of unknown etiology and whose polysomnographic features differ from those of healthy individuals only for a significantly increased arousal index in NREM sleep. We recruited 20 consecutive adult patients with insomnia according to the ICSD-2 criteria, 20 patients with RLS, and 12 age-matched normal controls. The time structure of their polysomnographically recorded leg movements during sleep was analyzed by means of an approach particularly able to consider their periodicity. A subgroup of 12 patients with a relatively high number of periodic LM activity was detected with a statistically based approach using two indexes: total LM index and Periodicity index. This subgroup had high PLMS index, Periodicity index was also high and PLMS showed a progressive decrease during the night, being highest in the first hours of sleep. The characteristics of PLMS were identical within this insomnia subgroup and RLS patients. PLMS was a common finding in our patients with insomnia and a detailed analysis of their periodicity revealed that a subgroup of these patients had to be finally diagnosed with Periodic Limb Movement Disorder. Polysomnography with the subsequent analysis of PLMS periodicity is able to differentiate between insomnia patient subgroups.

Indiplon: A Nonbenzodiazepine Sedative–Hypnotic for the Treatment of Insomnia

To review the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and adverse effects of indiplon in the treatment of transient and chronic insomnia in adult and geriatric patients. A literature search was conducted using MEDLINE (1966-May 2008), International Pharmaceutical Abstracts (1970-May 2008), and Cochrane database (2007) for the key words indiplon or NBI-34060. References cited in the articles were reviewed for additional information. Abstract data were included only in the absence of significant published data. English-language literature reporting animal and human clinical studies was reviewed to evaluate data on the pharmacology, pharmacokinetics, pharmacodynamics, efficacy, and adverse effects of indiplon. Clinical trials selected for inclusion were limited to those with human subjects, with the accepted inclusion of pharmacology data in animals. Indiplon is a nonbenzodiazepine sedative-hypnotic that exhibits its sedating activity through its interaction with the gamma-aminobutyric acid alpha receptor complex. Indiplon immediate-release (IR) as well as modified-release (MR) forms have shown improvement compared with placebo in patients with DSM-IV-TR primary insomnia in various areas of subjective and objective sleep measurements. Specifically, improvements in total sleep time, latency to persistent sleep, latency to sleep onset, wake after sleep onset, and sleep quality have been noted in clinical trials. Trials evaluating both indiplon IR and MR have so far not identified any major serious adverse effects. Limited clinical trial data exist on use of indiplon in a "true" transient insomnia patient population. Based on recent Food and Drug Administration requests, clinical trial data assessing direct comparisons of indiplon IR with other approved nonbenzodiazepine sedative-hypnotics are needed to clearly define the differences among these agents.

Phenotypic variability in fatal familial insomnia (D178N-129M) genotype

To report the clinical and pathologic features of patients with the D178N-129M mutation living in Germany. Patients with clinically suspected Creutzfeldt-Jakob disease (CJD) were seen in an ongoing, prospective epidemiologic study from June 1993 to August 1997 throughout Germany. Suspect patients were referred to the CJD unit by the participating hospitals or physicians. Patients were seen by a physician, and each patient underwent a detailed neurologic examination. Prion protein gene (PRNP) analysis was performed to distinguish patients with familial forms of CJD. The constellation D178N-129M was identified in eight individuals; in one patient, the diagnosis was made by neuropathologic examination. Four affected men and five women belong to eight unrelated families. A family history of a neurodegenerative disorder was recalled in only five patients. In contrast to the first reported fatal familial insomnia (FFI) patient, none of our patients complained of severe, untreatable insomnia in the early stages. Dysautonomia was observed in varying degrees in most patients. The clinical course of these patients resembled sporadic CJD. In six patients, brain tissue was available for neuropathologic study. In one patient, the neuropathologic examination showed changes that were more reminiscent of forms of sporadic CJD; in the remaining five, the histopathology was typical of FFI. The clinical presentation in patients with FFI may vary to a great extent. Genotyping of the patients was crucial in providing laboratory confirmation of the diagnosis of FFI, even when there was no family history of a prion disease.

Long-term, nightly benzodiazepine treatment of injurious parasomnias and other disorders of disrupted nocturnal sleep in 170 adults

To assess the efficacy, dose stability, safety, and abuse potential of long-term, nightly benzodiazepine treatment of chronic disorders of disrupted nocturnal sleep. During a 12-year period, one author evaluated and treated 170 adult referrals for > or = 6 months with nightly benzodiazepine therapy for longstanding, sleep-disruptive disorders: injurious sleepwalking and sleep terrors (69); rapid eye movement sleep behavior disorder (52); chronic, severe insomnia (25); and restless legs syndrome/periodic limb movement disorder (24). Complete/substantial control of the sleep disorders was achieved by 146 patients (86%); 8% had adverse effects requiring medication changes; 2% had relapses of alcohol or chemical abuse requiring hospitalization; another 2% at times misused their medications. A total of 136 patients received clonazepam nightly for a mean 3.5 (+/- 2.4) years, with no significant difference in inital versus final mean dose: 0.77 mg (+/- 0.46) versus 1.10 mg (+/- 0.96). Similar results were obtained with chronic alprazolam treatment and with other benzodiazepine treatments. Long-term, nightly benzodiazepine treatment of injurious parasomnias and other disorders of disrupted nocturnal sleep resulted in sustained efficacy in most cases, with low risk of dosage tolerance, adverse effects, or abuse. Data from this study on the treatment of chronic, severe insomnia (a small subset of all insomnia) are not generalizable to the typical insomnia patient.

Treating insomnia: A practical guide for managing chronic sleeplessness, circa 1975

Insomnia means a complaint of sleep loss. Between 13% and 32% of surveyed populations suffer frequent insomnia, 1–3 and 7%–10% of the population use sleeping pills. 4,5 Alcohol and minor tranquilizers are also used to ease insomnia. The ubiquity of such drugs and the persistence of insomnia suggest that drugs alone do not remedy insomnia. The possibility of drug habituation, the distortion of sleep patterns, morning hangovers, 6,7 the possible accumulation of long-lived metabolites, 8 and the risk of aggravated sleep disturbances upon withdrawal from sleeping pills 9,10 further complicate the use of hypnotics. Presently, there are few clinics offering specialized services for the treatment of sleep disorders. The physician is compelled to treat severe cases of insomnia and yet may feel that there is little to offer the insomnia patient besides hypnotic drugs. Some physicians, however, rarely prescribe sleeping pills for insomnia. 11,12 This paper, therefore, will offer practical suggestions on insomnia management, many of which do not depend primarily on the use of hypnotic drugs.

REDUCTION OF RESPIRATION FOR INSOMNIA

To the Editor: —I start with the assumption that every insomnia patient has been carefully examined for any pathologic condition, especially for intestinal disorders, and that all medical and surgical conditions have been met. The suggestions offered herein are for that class of patients that cannot forget their business when they want to sleep and should be asleep, or those who have troubles or worries from which they are unable to travel or take a vacation. My first efforts began about ten years ago, along the popular line of mental gymnastics, in an attempt to control the mental states. Since the dreaming state lies between consciousness and sound sleep, just at the threshold of sleep the idea was to make them dream themselves to sleep. Directions were to avoid reasoning and analysis, to direct any train of thoughts into the absurd and grotesque. Mention is made of this method because