ABSTRACT
In Lewy body dementia (LBD), disturbances of sleep and/or arousal including insomnia, excessive daytime sleepiness, rapid eye movement (REM) sleep behavior disorder, obstructive sleep apnea, and restless leg syndrome are common. These disorders can each exert a significant negative impact on both patient and caregiver quality of life; however, their etiology is poorly understood. Little guidance is available for assessing and managing sleep disorders in LBD, and they remain under-diagnosed and under-treated. This review aims to (1) describe the specific sleep disorders which occur in LBD, considering their putative or potential mechanisms; (2) describe the history and diagnostic process for these disorders in LBD; and (3) summarize current evidence for their management in LBD and consider some of the ongoing and unanswered questions in this field and future research directions.
Subject(s)
Lewy Body Disease , REM Sleep Behavior Disorder , Sleep Wake Disorders , Humans , Lewy Body Disease/diagnosis , Clinical Relevance , Quality of Life , Sleep , Sleep Wake Disorders/etiologyABSTRACT
STUDY OBJECTIVE: To assess the interaction between therapeutic dosages of ropinirole and L-dopa plus a decarboxylase inhibitor administered at steady state in patients with Parkinson's disease. DESIGN. Open, 6-week, overlap trial with random allocation. PATIENTS: Thirty patients with Parkinson's disease not previously treated with dopamine agonists, of whom 28 produced evaluable pharmacokinetic data for ropinirole and 23 for L-dopa. INTERVENTION: Group A (14 patients) received L-dopa for weeks 1-5 and ropinirole in increasing increments for weeks 2-6; group B (16) received ropinirole for weeks 1-5 and L-dopa for weeks 5 and 6. MEASUREMENTS AND MAIN RESULTS: Primary end points were AUC0-8 and Cmax for ropinirole, and AUC0-8, AUC0-infinity and Cmax for L-dopa. Secondary end points were Tmax for ropinirole, and Tmax and half-life for L-dopa. Coadministration with L-dopa at steady state did not affect rate or extent of availability of ropinirole: point estimates of the geometric mean ratio for ropinirole plus L-dopa compared with ropinirole alone for both Cmax and AUC0-8 approximated to unity. The small (16%) increase in peak concentrations of L-dopa on administration with ropinirole is unlikely to be of clinical consequence, as peak concentrations of L-dopa are typically highly variable. CONCLUSION: There are no pharmacokinetic grounds for adjusting dosages of either ropinirole or L-dopa when given in combination.
Subject(s)
Antiparkinson Agents/pharmacokinetics , Dopamine Agonists/pharmacokinetics , Indoles/pharmacokinetics , Levodopa/pharmacokinetics , Parkinson Disease/metabolism , Aged , Antiparkinson Agents/adverse effects , Antiparkinson Agents/therapeutic use , Area Under Curve , Carbidopa/pharmacology , Dopamine Agonists/adverse effects , Dopamine Agonists/therapeutic use , Drug Therapy, Combination , Enzyme Inhibitors/pharmacology , Female , Humans , Indoles/therapeutic use , Levodopa/adverse effects , Levodopa/therapeutic use , Male , Middle Aged , Parkinson Disease/drug therapyABSTRACT
1. The effects of single doses of a novel 5-HT3 receptor antagonist, BRL 46470A (0.1 microgram, 0.01 mg, 1 mg or 50 mg) and lorazepam (2.5 mg) on psychometric performance and the EEG were investigated in a randomised, double-blind, crossover, placebo controlled study of 16 healthy male volunteers. 2. There was strong evidence that lorazepam had a marked effect on the EEG, increasing power in the 1 Hz to 7 Hz and 13 Hz to 20 Hz wavebands, whilst reducing power in the 8 Hz to 12 Hz waveband. Lorazepam also produced an impairment of daytime function as assessed by psychometric performance and subjective measures. 3. In contrast, there was little evidence to suggest that BRL 46470A had any effect on the EEG or that it impaired daytime function.
Subject(s)
Bridged Bicyclo Compounds, Heterocyclic , Bridged Bicyclo Compounds/pharmacology , Electroencephalography/drug effects , Indoles/pharmacology , Lorazepam/pharmacology , Psychomotor Performance/drug effects , Serotonin Antagonists , Adult , Awareness/drug effects , Double-Blind Method , Humans , Male , Reaction Time/drug effectsABSTRACT
1. The effects of granisetron (160 micrograms kg-1 body weight) and haloperidol (3 mg) on psychometric performance and the EEG were investigated in a randomised, single-blind, crossover, placebo controlled study of 12 healthy male volunteers. 2. There was evidence that haloperidol impaired psychometric performance; however its effects on the EEG were not clear cut. In contrast there was very little evidence to suggest that granisetron had any impact on performance or the EEG. 3. The findings from this study suggest that granisetron does not impair daytime function and that it can be co-administered with haloperidol without producing unwanted synergistic effects.
Subject(s)
Electroencephalography/drug effects , Haloperidol/pharmacology , Indazoles/pharmacology , Psychomotor Performance/drug effects , Serotonin Antagonists/pharmacology , Adult , Drug Interactions , Granisetron , Haloperidol/adverse effects , Humans , Indazoles/adverse effects , Male , Psychometrics , Random AllocationABSTRACT
The effects of granisetron (160 micrograms kg-1 body weight) and lorazepam (2.5 mg) on psychometric performance were investigated in a randomized, single-blind, crossover, placebo controlled study of twelve healthy male volunteers. There was strong evidence that lorazepam impaired psychometric performance. In contrast there was very little evidence to suggest that granisetron had any impact on performance or that there was any interaction between the two compounds. The findings from this study suggest that granisetron does not impair psychometric performance and that it can be co-administered with lorazepam without producing unwanted synergistic effects.
Subject(s)
Indazoles/pharmacology , Lorazepam/pharmacology , Psychomotor Performance/drug effects , Serotonin Antagonists/pharmacology , Adult , Drug Interactions , Flicker Fusion/drug effects , Granisetron , Humans , Indazoles/administration & dosage , Lorazepam/administration & dosage , Male , Mental Processes , Middle Aged , Psychometrics , Reaction Time/drug effects , Serotonin Antagonists/administration & dosage , Single-Blind Method , Time Perception/drug effectsABSTRACT
1. The EEG effects of granisetron, a potent and selective 5-HT3 receptor antagonist (160 micrograms kg-1), and lorazepam (2.5 mg) were examined in 12 healthy male volunteers. 2. The results indicated that lorazepam had a marked effect on the CNS, significantly increasing power in the slow (1-7 Hz) and fast (13-20 Hz; 21-30 Hz) wavebands whilst reducing power in the mid range (8-12 Hz). 3. In contrast there was no demonstrable effect of granisetron on the EEG at the dose tested, and no evidence of a pharmacodynamic interaction between the two compounds.
Subject(s)
Indazoles/pharmacology , Lorazepam/pharmacology , Serotonin Antagonists/pharmacology , Adult , Double-Blind Method , Drug Interactions , Electroencephalography , Granisetron , Humans , Male , Middle Aged , Random AllocationABSTRACT
The effects of a nocturnal nonsteroidal anti-inflammatory drug (tenoxicam) on twelve male osteoarthritic patients were investigated in a randomised, double-blind, placebo-controlled, cross-over study. Tenoxicam produced no significant changes in any of the areas evaluated which included electroencephalographic (EEG) sleep, subjective sleep, pain and early morning stiffness. The selection of patients may have contributed to this unexpected result. There was no evidence to suggest that tenoxicam caused any unwanted side-effects or affected early morning psychomotor performance. The use of the sleep EEG as an objective pain measure is discussed.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Osteoarthritis/physiopathology , Piroxicam/analogs & derivatives , Sleep Stages/drug effects , Aged , Double-Blind Method , Drug Administration Schedule , Electroencephalography , Humans , Male , Middle Aged , Pain Measurement , Piroxicam/administration & dosage , Psychomotor Performance/drug effects , Psychomotor Performance/physiology , Randomized Controlled Trials as Topic , Sleep Stages/physiologyABSTRACT
The St. Mary's Hospital Sleep Questionnaire was designed to evaluate the sleep of hospital patients. To gain an understanding of possible underlying factors, the questionnaire was factor analysed using data collected from 222 hospitalised rheumatic patients. The analysis did not produce a completely clear factor structure. Two factors relating to "sleep latency" and "sleep quality" emerged more clearly than the other factors produced. These factors correspond with two sleeping state factors (ease of getting to sleep; quality of sleep) that were extracted by a previous factor analysis of the Leeds Sleep Evaluation Questionnaire. This suggests that the two most important aspects of subjectively perceived sleep are the process of going to sleep and the quality of sleep.
Subject(s)
Hospitalization , Psychological Tests , Sleep Stages , Arthritis, Rheumatoid/psychology , Female , Humans , Male , Middle Aged , WakefulnessABSTRACT
A sleep laboratory comparison of the sleep of 14 osteoarthritic patients with that of 16 age and sex matched healthy controls was undertaken. After three nights of adaptation continuous recordings of electroencephalographic (EEG), electro-oculographic (EOG), and electromyographic (EMG) activity were obtained for the next two nights. A comparison of EEG sleep variables during this baseline period showed that osteoarthritic patients had a significantly greater percentage of stage 1 and significantly smaller percentage of stage 2 sleep than control subjects. These findings indicate sleep disturbance in osteoarthritic patients. The limited degree of disturbance observed in these patients may be due to the fact that they were allowed to continue with their normal anti-inflammatory and analgesic medication for the course of the study.
Subject(s)
Osteoarthritis/physiopathology , Sleep/physiology , Aged , Electrocardiography , Electromyography , Electrooculography , Humans , Male , Middle AgedABSTRACT
Nocturnal body motility has been compared in a sleep laboratory between patients with osteoarthritis and healthy age-, sex- and weight-matched controls using a Bio-medical timer and bedleg force transducers connected to a Disa polygraph. Four motility variables were derived (duration of movement; duration adjusted for sensitivity; number of movements; number of 30-s epochs containing movements) enabling an assessment of nocturnal body motility in the two groups. There was a trend for osteoarthritic patients to move more than controls during sleep on all variables measured, although this did not reach statistical significance. Temazepam elixir (0.4 mg/kg body weight/night) reduced all four motility variables in both osteoarthritic patients and controls, although only the reduction of the number of 30-s epochs containing movements (P less than 0.05) in the control group attained statistical significance.
Subject(s)
Circadian Rhythm , Movement , Osteoarthritis/physiopathology , Aged , Humans , Male , Middle Aged , Movement/drug effects , Osteoarthritis/drug therapy , Reference Values , Sleep/drug effects , Sleep Stages/drug effects , Temazepam/therapeutic useABSTRACT
The St. Mary's Hospital Sleep Questionnaire was used to investigate sleep in 439 hospitalized rheumatic and non-rheumatic patients. This questionnaire enabled an evaluation of both the level of sleep disturbance and the causes of such disturbance. The findings from this study indicated that there was little difference in the level of sleep disturbance between rheumatic and non-rheumatic patients. The sleep problem most frequently cited by rheumatic patients was pain. Noise appeared to be the worst environmental sleep problem in these patients. The only significant difference in the sleep problems reported by rheumatic and non-rheumatic patients, was that pain was cited more frequently in the rheumatic group. In order to determine whether sleep varied according to type of rheumatic disease, the rheumatic patients were divided into four diagnostic groups (rheumatoid arthritis; seronegative spondarthritis; osteoarthritis; other conditions). There were no significant differences between these groups in sleep disturbance or reported sleep problems.
