Effects of fluvoxamine and paroxetine on sleep structure in normal subjects: a home-based Nightcap evaluation during drug administration and withdrawal.

BACKGROUND: Acute and chronic administration of the selective serotonin reuptake inhibitors (SSRIs) have been widely reported to disrupt sleep in laboratory studies. This study examines the naturalistic, longitudinal effects of paroxetine and fluvoxamine on sleep quality in the home setting. METHOD: Fourteen healthy volunteers free of medical and neuropsychiatric symptoms entered a 31-day protocol: 7 days of drug-free baseline (days 1-7), 19 days of drug treatment (steady state during days 18-26), and 5 days of acute withdrawal (days 27-31). On day 8, the subjects were randomly assigned to receive either 100 mg/day of fluvoxamine or 20 mg/day of paroxetine (half receiving each drug) in divided morning and evening oral doses. Investigators remained blinded to drug assignment until all sleep data had been analyzed. Sleep was monitored using the Nightcap ambulatory sleep monitor. Four standard and 3 novel measures were computed and compared using multivariate analysis of variance, analysis of variance, and Bonferroni-corrected comparison of means. RESULTS: Sleep disruption was most clearly demonstrated using the novel measures eyelid quiescence index, rhythmicity, and eyelid movements per minute in non-rapid eye movement sleep, but was also apparent as determined by standard measures of sleep efficiency, number of awakenings, and sleep onset latency. Paroxetine disrupted sleep more than fluvoxamine, and paroxetine-induced sleep disruption persisted into the withdrawal phase. Rapid eye movement sleep was suppressed during treatment (especially for fluvoxamine) and rebounded during withdrawal (especially for paroxetine). CONCLUSION: We confirm laboratory polysomnographic findings of SSRI-induced sleep quality changes and demonstrate the Nightcap's efficacy as an inexpensive longitudinal monitor for objective sleep changes induced by psychotropic medication.

SSRI treatment suppresses dream recall frequency but increases subjective dream intensity in normal subjects.

Clinical lore and a small number of published studies report that the selective serotonin reuptake inhibitors (SSRIs) intensify dreaming. This study examines the dream effects of paroxetine and fluvoxamine in order to both increase clinical knowledge of these agents and to test an important potential method for probing the relationship between REM sleep neurobiology and dreaming in humans. Fourteen normal, paid volunteers (4 males, 10 females; mean age 27.4 year, range 22--39) free of medical or neuropsychiatric symptoms as well as of psychotropic or sleep affecting drugs completed a 31-day home-based study consisting of: 7 days drug-free baseline; 19 days on either 100 mg fluvoxamine (7 Ss) or 20 mg paroxetine (7 Ss) in divided morning and evening doses; and 5 days acute discontinuation. Upon awakening, subjects wrote dream reports, self-scored specific emotions in their reports and rated seven general dream characteristics using 5-point Likert scales. Dream reports were independently scored for bizarreness, movement and number of visual nouns by three judges. REM sleep-related measures were obtained using the Nightcap ambulatory sleep monitor. Mean dream recall frequency decreased during treatment compared with baseline. Dream report length and judge-rated bizarreness were greater during acute discontinuation compared with both baseline and treatment and this effect was a result of the fluvoxamine-treated subjects. The subjective intensity of dreaming increased during both treatment and acute discontinuation compared with baseline. Propensity to enter REM sleep was decreased during treatment compared with baseline and acute discontinuation and the intensity of REM sleep increased during acute discontinuation compared with baseline and treatment. The decrease in dream frequency during SSRI treatment may reflect serotonergic REM suppression while the augmented report length and bizarreness during acute SSRI discontinuation may reflect cholinergic rebound from serotonergic suppression.

Dreaming and the brain: toward a cognitive neuroscience of conscious states.

Sleep researchers in different disciplines disagree about how fully dreaming can be explained in terms of brain physiology. Debate has focused on whether REM sleep dreaming is qualitatively different from nonREM (NREM) sleep and waking. A review of psychophysiological studies shows clear quantitative differences between REM and NREM mentation and between REM and waking mentation. Recent neuroimaging and neurophysiological studies also differentiate REM, NREM, and waking in features with phenomenological implications. Both evidence and theory suggest that there are isomorphisms between the phenomenology and the physiology of dreams. We present a three-dimensional model with specific examples from normally and abnormally changing conscious states.

Dreaming and waking consciousness: a character recognition study.

The formal features of dream characters were studied in a sample of 320 dream reports submitted by 33 adult subjects (13 male, 20 female) of varying ages in a university extension course. Subjects were queried by questionnaire about dream characters immediately after recording their dreams upon awakening in their normal home setting. It was found that 48% of characters represented a named personage known to the dreamer, 35% were generically identified by their social role (e.g., policeman) or abstract relation to the dreamer (e.g., a friend) while only 16% were wholly novel. Seventy-seven percent of characters were pseudosensorily present in the dream whereas 23% were present only by mention or thought. Subjects were allowed to endorse one or more of four bases of recognition and, among named characters, 32% were identified by 'appearance', 21% by 'behavior', 45% by 'face', and 44% by 'just knowing' (with the respective percentages for generic characters being 39%, 38%, 9% and 40%). Fourteen percent of named and generic characters had associated some element of bizarreness most frequently consisting of an incongruous feature. Comparing the 25 longest and 25 shortest reports, named subjects were significantly more common in the shortest reports whereas generic and unknown characters were more common in the longest reports. Results are interpreted in neurocognitive terms as possibly reflecting a decrease during dreaming relative to waking in the exchange of information between inferotemporal face identification areas and prefrontal areas subserving logic and working memory.

To dream or not to dream? Relevant data from new neuroimaging and electrophysiological studies.

The study of sleep and dreams has enjoyed a major breakthrough with recent findings from brain imaging studies in humans. Several independent groups have shown global deactivation of the brain during non rapid eye movement sleep and a regionally selective reactivation during rapid eye movement sleep. These results are complemented by new brain lesion and electrophysiological recording data to give a detailed picture of the brain dynamics of changes in conscious state.

The neuropsychology of REM sleep dreaming.

Recent PET imaging and brain lesion studies in humans are integrated with new basic research findings at the cellular level in animals to explain how the formal cognitive features of dreaming may be the combined product of a shift in neuromodulatory balance of the brain and a related redistribution of regional blood flow. The human PET data indicate a preferential activation in REM of the pontine brain stem and of limbic and paralimbic cortical structures involved in mediating emotion and a corresponding deactivation of dorsolateral prefrontal cortical structures involved in the executive and mnemonic aspects of cognition. The pontine brainstem mechanisms controlling the neuromodulatory balance of the brain in rats and cats include noradrenergic and serotonergic influences which enhance waking and impede REM via anticholinergic mechanisms and cholinergic mechanisms which are essential to REM sleep and only come into full play when the serotonergic and noradrenergic systems are inhibited. In REM, the brain thus becomes activated but processes its internally generated data in a manner quite different from that of waking.

Sleep and vestibular adaptation: implications for function in microgravity.

Optimal human performance depends upon integrated sensorimotor and cognitive functions, both of which are known to be exquisitely sensitive to loss of sleep. Under the microgravity conditions of space flight, adaptation of both sensorimotor (especially vestibular) and cognitive functions (especially orientation) must occur quickly--and be maintained--despite any concurrent disruptions of sleep that may be caused by microgravity itself, or by the uncomfortable sleeping conditions of the spacecraft. It is the three-way interaction between sleep quality, general work efficiency, and sensorimotor integration that is the subject of this paper and the focus of new work in our laboratory. To record sleep under field conditions including microgravity, we utilize a novel system called the Nightcap that we have developed and extensively tested on normal and sleep-disordered subjects. To perturb the vestibular system in ground-based studies, we utilize a variety of experimental conditions including optokinetic stimulation and both minifying and reversing goggle paradigms that have been extensively studied in relation to plasticity of the vestibulo-ocular reflex. Using these techniques we will test the hypothesis that vestibular adaptation both provokes and is enhanced by REM sleep under both ground-based and space conditions. In this paper we describe preliminary results of some of our studies.

The neuropsychology of dreams: a clinico-anatomical study.

by Mark Solms, Lawrence Erlbaum Associates, 1997. $59.95 (292 pages) ISBN 0 8058 1585 6.

Consciousness in waking and dreaming: the roles of neuronal oscillation and neuromodulation in determining similarities and differences.

State-dependent aspects of consciousness are explored with particular attention to waking and dreaming. First, those phenomenological differences between waking and dreaming that have been established through subjective reports are reviewed. These differences are robustly expressed in most aspects of consciousness including perception, attention, memory, emotion, orientation, and thought. Next, the roles of high frequency neuronal oscillation and neuromodulation are explored in waking and rapid eye movement sleep, the stage of sleep with which the most intense dreaming is associated. The high frequency neuronal oscillations serve similar functions in the wake and rapid eye movement states sleep but neuromodulation is very different in the two states. The collective high frequency oscillatory activity gives coherence to spatially separate neurons but, because of the different neuromodulation, the binding of sensory input in the wake state is very different from the binding of internally perceived input during rapid eye movement sleep. An explanatory model is presented which states that neuromodulation, as well as input source and brain activation level differentiate states of the brain, while the self-organized collective neuronal oscillations unify consciousness via long range correlations.

Nightcap measurement of sleep quality in self-described good and poor sleepers.

The Nightcap is a home-based sleep monitoring device that reliably differentiates rapid eye movement sleep, nonrapid eye movement sleep and wake states using eyelid and body movement measurements. This study documents its capacity to measure differences in sleep latency and sleep efficiency between self-described good and poor sleepers drawn from a normal population. Ten self-described "good" sleepers and 11 self-described "poor" sleepers were selected from a pool of college students. These groups differed significantly on selection parameters and on subjective estimates of sleep quality obtained each morning during the study. Each subject wore the Nightcap at home for 12-17 nights. Statistically significant differences in Nightcap-measured sleep latency and sleep efficiency were obtained between groups using individual subject means. In individual subjects, Nightcap measurements of sleep latency were correlated with subjective estimates of sleep latency. Poor sleepers were less accurate in estimating their sleep onset latency than were good sleepers. The demonstrated sensitivity of the Nightcap to good and poor sleep in these normal subjects augurs well for its application in a clinical setting.