Sleep Initiation and Maintenance Disorders: Nutt DJ

Wilson SJ, Rich AS, Rich NC, Potokar J, Nutt DJ. · Psychopharmacology Unit, University of Bristol, Dorothy Hodgkin Building, Bristol, UK. · Int Clin Psychopharmacol. · Pubmed #15076015 No free full text.

Abstract: This study aimed to explore new methodologies in insomnia research, namely whether actigraphy was suitable to show hypnotic effects over weeks in insomnia, and to compare an automated method of questionnaire data collection with traditional methods. Thirty-eight insomniacs took part in a 5-week, double-blind, placebo-controlled study of the effects of 2 weeks of administration of temazepam 20 mg on sleep. Outcome measures were actigraphy and daily St Mary's Hospital Sleep Questionnaires (SMHSQ). Actigraphy was performed using Actiwatch (CNT) and analysed using both the automated Actiwatch sleep analysis software and non-parametric analysis of rest-activity rhythms. The questionnaires were administered as straightforward pencil-and-paper for half of the time and an automated telephoned system for the other half. The experimental paradigm allowed within-subject comparison of traditional and automated data collection, both on and off drug. Actigraphy showed a high degree of inter-subject variability but, nevertheless, some sleep variables (Fragmentation Index, Actual Sleep Time %) showed significant improvement during drug treatment, and Sleep Efficiency and Actual Sleep Time were significantly worsened during the first post-drug week. Nonparametric circadian rhythm analysis showed no significant effect. Subjective data from the SMHSQ showed significant drug effects and there was no significant difference in scores between the automated and pencil-and-paper methods; automated data collection was slightly more acceptable to patients and minimized data entry and management. Effect sizes using within-subject and between-subject comparisons were calculated for the subjective and objective measures to inform future studies

Paterson LM, Wilson SJ, Nutt DJ, Hutson PH, Ivarsson M. · Psychopharmacology Unit, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, UK. · Psychopharmacology (Berl). · Pubmed #17225163 No free full text.

Abstract: RATIONALE: Insomnia is a common and disabling complaint for which there is a need for improved treatments. Successful drug discovery relies on the use of appropriate animal models to assess likely outcome in the clinic. OBJECTIVES: The purpose of this study was to develop a translational, caffeine-induced model of insomnia in rats and healthy volunteers. We used sleep onset latency (SOL) as a comparable sleep measure between the two species. The model was validated by two effective sleep-promoting agents with different pharmacology, zolpidem and trazodone, which have GABA-ergic and serotonergic mechanisms, respectively. MATERIALS AND METHODS: In rats, radiotelemetry transmitters with electroencephalogram and electromyogram electrodes were implanted for sleep recording. Animals were administered with caffeine alone (10 mg/kg) or in combination with zolpidem (10 mg/kg) or trazodone (20 mg/kg), or vehicle, in crossover experiments. Home polysomnography was performed in 12 healthy male volunteers in a randomised, placebo-controlled, 4-week crossover study. Subjects received placebo, caffeine (150 mg) or caffeine in combination with zolpidem (10 mg) or trazodone (100 mg). Subjective sleep effects in volunteers were assessed using the Leeds Sleep Evaluation Questionnaire. RESULTS: Caffeine caused a significant prolongation in objective SOL in rats and humans. This effect was sensitive to zolpidem and trazodone, both of which attenuated the caffeine-induced increase in SOL. Furthermore, both hypnotics restored the disruption in subjective measures of sleep onset caused by caffeine in volunteers. CONCLUSIONS: This model therefore provides a promising paradigm in which we can study novel treatments for sleep disorders and an opportunity for direct comparison of results between rodents and humans.

Nutt DJ. · Psychopharmacology Unit, University of Bristol, Bristol, UK. · J Psychopharmacol. · Pubmed #15728430 No free full text.

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Nutt DJ, Wilson S. · Psychopharmacology Unit, School of Medical Sciences, Bristol, UK. · J Psychopharmacol. · Pubmed #10667457 No free full text.

This publication has no abstract.

Chevalier H, Los F, Boichut D, Bianchi M, Nutt DJ, Hajak G, Hetta J, Hoffmann G, Crowe C. · · J Psychopharmacol. · Pubmed #10667452 No free full text.

Abstract: The epidemiology of severe insomnia and its effect on quality of life and healthcare consumption was assessed in a survey of the general population of five northern European countries. Applying established consumer sampling techniques, insomnia sufferers were selected from the general population using a questionnaire, conducted by face-to-face interview, and severity of insomnia was ranked (severe, mild/moderate, no sleep complaint) using a specific algorithm. Population samples were matched according to case control methodology for age, gender and geographical region. A second questionnaire gathered information on sleep problems, quality of life (SF-36 scores) and healthcare consumption. The prevalence of severe insomnia ranged from 4% to 22%, was higher in females than in males, but did not increase significantly with age. Patients with severe insomnia had been experiencing sleeping problems for a median of 2-6 years. In all countries, insomnia had a negative impact on quality of life, and the degree of impairment in quality of life was directly related to the severity of insomnia. Individuals with severe insomnia also showed a higher level of healthcare consumption. Despite this, severe insomnia did not appear to feature prominently in the doctor-patient relationship.