Publications
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Wilson SJ, Bailey JE, Alford C, et al., 2002, Effects of 5 weeks of administration of fluoxetine and dothiepin in normal volunteers on sleep, daytime sedation, psychomotor performance and mood, J.Psychopharmacol., Vol: 16, Pages: 321-331
This was a placebo-controlled, double-blind randomized crossover study of long-term (5 weeks) administration of fluoxetine (20 mg/day) and dothiepin (75 mg/day for 1 week followed by 150 mg/day for 4 weeks) in 12 healthy male volunteers. Subjects were studied on day 10 and day 36 of treatment, with tests of nocturnal sleep, driving performance, continuous electroencephalogram (EEG), sleep during scheduled naps, computerized visual attention tasks, saccadic eye movement measurement and visual analogue ratings of mood. Both drugs had a marked suppressive effect on nocturnal rapid eye movement (REM) sleep; these effects were less at 36 days than at 10 days, and fluoxetine decreased and dothiepin increased REM in daytime naps. Sleep fragmentation after fluoxetine is similar to that reported in the literature. We found no sleep-promoting effects of dothiepin, in contrast to our previous single-dose study, and no subjective sleep effects of either drug. Subjects were less sleepy after both antidepressants than placebo at 5 weeks measured by sleep latencies and EEG. Saccadic eye movement measures were significantly faster after 5 weeks of fluoxetine than after 5 weeks of placebo. Reaction times to a peripheral stimulus during computerized tracking task were shorter after 10 days of dothiepin compared with placebo. Driving performance, visual attention and mood ratings showed no treatment effects. Subjective health reports during each 5 weeks of treatment were similar in number for the two drugs but showed a different profile of side-effects
Wilson S, Bailey J, Rich A, et al., 2002, Using sleep to measure relative 5HT uptake blockade, EUROPEAN NEUROPSYCHOPHARMACOLOGY, Vol: 12, Pages: S200-S200, ISSN: 0924-977X
Wilson SJ, Bailey JE, Nutt DJ, 2002, Probing serotonergic activity in the brain using sleep, Summer Meeting of the British-Association-for-Psychopharmacology, Publisher: SAGE PUBLICATIONS LTD, Pages: A41-A41, ISSN: 0269-8811
Bell C, Vanderlinden H, Hiersemenzel R, et al., 2002, The effects of levetiracetam on objective and subjective sleep parameters in healthy volunteers and patients with partial epilepsy, J.Sleep Res., Vol: 11, Pages: 255-263
Levetiracetam is a novel antiepileptic drug which has recently been released as an adjunctive treatment for partial epilepsy. In the two studies reported here we examined the objective and subjective effects of levetiracetam on sleep in 12 healthy volunteers and 17 patients [16 who could be evaluated for electroencephalogram (EEG) recordings] with a history of partial epilepsy on stable carbamazepine monotherapy. The studies were of a similar double-blind crossover placebo-controlled design with subjects' sleep being recorded in their own homes. The results from the two studies showed considerable similarities. In both, levetiracetam produced an increase in the time spent in stage 2 sleep, which in the patient study was accompanied by a decrease in the time spent in stage 4 sleep and in the volunteer study an increase in rapid eye movement (REM) latency. The subjective changes included reports that sleep was of a better quality with fewer awakenings and patients also reported that their sleep was more restful. Volunteers and patients did, however, feel less alert on waking in the morning. Therefore, both groups reported a decrease in awakenings after levetiracetam despite the finding from the EEG of no change in the actual number of awakenings. It may be concluded from both studies that levetiracetam does affect some indicators of subjective sleep perception, but does not influence objective sleep measures of sleep continuity. The results from the patient study during placebo add-on treatment also showed that patients on carbamazepine had a marked increase in SWS, an increase in stage 2 sleep and an increase in REM latency compared with healthy volunteers. Interestingly, levetiracetam also reduced bilateral epileptiform EEG activity, particularly in patients with more discharges
Wilson SJ, Bailey JE, Rich AS, et al., 2002, Using sleep to measure relative 5HT uptake blockade, Summer Meeting of the British-Association-for-Psychopharmacology, Publisher: SAGE PUBLICATIONS LTD, Pages: A41-A41, ISSN: 0269-8811
Hicks JA, Argyropoulos SV, Rich AS, et al., 2002, Randomised controlled study of sleep after nefazodone or paroxetine treatment in out-patients with depression, Br.J.Psychiatry, Vol: 180, Pages: 528-535
BACKGROUND: Sleep effects of antidepressants are important clinically and for elucidating mechanism of action: selective serotonin reuptake inhibitors disturb sleep and 5-HT(2) receptor-blocking compounds may enhance sleep quality. AIMS: To compare the objective and subjective effects on sleep of paroxetine and nefazodone in patients with moderate to severe depression. METHOD: Forty patients with depression were randomised to take paroxetine 20-40 mg/day or nefazodone 400-600 mg/day for 8 weeks. Objective and subjective quality of sleep and depression measures were assessed throughout. RESULTS: Nefazodone significantly increased objective sleep efficiency and total sleep time, and improved subjective sleep on days 3 and 10. Paroxetine decreased sleep efficiency early in treatment and some sleep disruption remained at week 8. Paroxetine but not nefazodone produced marked suppression of rapid eye movement (REM) sleep. CONCLUSIONS: Nefazodone improves sleep in early treatment compared with paroxetine in patients with moderate to severe depression. These effects are seen within the first 2 weeks of treatment and diminish thereafter
Wilson SJ, Argyropoulos S, Nash J, et al., 2002, Exploring antidepressant mechanisms by acute and chronic sleep effects, EUROPEAN PSYCHIATRY, Vol: 17, Pages: 72S-72S, ISSN: 0924-9338
Daglish MR, Weinstein A, Malizia AL, et al., 2001, Changes in regional cerebral blood flow elicited by craving memories in abstinent opiate-dependent subjects, Am.J.Psychiatry, Vol: 158, Pages: 1680-1686
OBJECTIVE: The brain circuitry of opiate craving was investigated with positron emission tomography (PET) imaging of regional cerebral blood flow (rCBF). METHOD: Twelve abstinent opiate-dependent subjects listened to audiotaped autobiographical scripts of an episode of craving and a neutral episode while undergoing a PET scan with the tracer [(15)O]H(2)O. Statistical parametric mapping was used to analyze the PET images of rCBF changes. RESULTS: Comparison of the drug-related and neutral stimulus conditions revealed activation of rCBF in the left medial prefrontal and left anterior cingulate cortices and deactivation in the occipital cortex in response to the drug-related stimulus. A further statistical parametric mapping analysis with a subjective rating of craving as a covariate showed a positive association of between craving and rCBF in the left orbitofrontal cortex. CONCLUSIONS: The patterns of cerebral activation reflect the different brain regions mediating the salience of opiate-related stimuli and the subjective experience of craving for opiates
Hajak G, SINE Study Group Study of Insomnia in Europe, 2001, Epidemiology of severe insomnia and its consequences in Germany., Eur Arch Psychiatry Clin Neurosci, Vol: 251, Pages: 49-56, ISSN: 0940-1334
This is the first nation-wide face-to-face survey on the prevalence of well-defined severe insomnia and its impact on quality of life in the general population of Germany. The survey was part of an international epidemiological study, which was also conducted in Belgium, Great Britain, Ireland and Sweden. A representative sample of 1913 adults aged 18 years and over were interviewed in all parts of Germany according to the quota method. Subjects with symptomatic insomnia were identified using an algorithm compatible with the principal criteria for severe insomnia defined in the fourth revision of the Diagnostic and Statistical Manual of Mental Diseases (DSM-IV). Subjects provided data on quality of life using the Short Form 36 Health Survey (SF-36) questionnaire and on health care consumption. Prevalence of severe insomnia in Germany was found to be 4%, which was lower than in other European countries (6-22%). Severe insomnia was more prevalent among women, the unemployed, those living alone after divorce or separation, and those in large cities, but not more frequently in the elderly (aged 65 years and over). The majority of subjects had chronic complaints, with 74 % of them suffering from severe sleep problems for over a year's duration (average 56+/-23 months). Consultations with general physicians, medication usage, medical tests and hospitalisation were greater among severe insomniacs compared to subjects who had no sleep complaints. The question regarding overall appreciation of quality of life was rated as bad in 22% and good in 28% of severe insomniacs compared to 3% (bad) and 68 % (good) in subjects with no sleep complaints. Despite this, only 55% of severe insomniacs had ever discussed their sleep problem with a doctor and the proportion who consulted their doctor specifically regarding sleep problems in the previous 12 months was even lower (36%). The vast majority (73%) was not taking hypnotic or sedative medications. In conclusion, insomnia, even when s
Wilson SJ, Bell C, Coupland NJ, et al., 2000, Sleep changes during long-term treatment of depression with fluvoxamine--a home-based study, Psychopharmacology (Berl), Vol: 149, Pages: 360-365
RATIONALE: The effects of antidepressants on sleep in depression have been extensively investigated, although to date there have been relatively few studies of newer drug classes such as specific serotonin reuptake inhibitors (SSRIs). All reported studies on SSRIs have been conducted in patients admitted to sleep laboratories and very few longitudinal studies have continued to measure sleep beyond 5 weeks of treatment. The growing trend towards outpatient and community care has highlighted the need for studies of sleep in depression in a more naturalistic setting, and during longer periods of treatment in line with recommended clinical practice. OBJECTIVES: To establish if the changes in sleep architecture and continuity described during early treatment with SSRIs persist after 3 months, to relate these changes to clinical state, and to establish whether home recordings would yield similar results to previous laboratory studies. METHODS: We have recorded objective sleep parameters in 12 depressed patients before and during 12-week treatment with an SSRI, fluvoxamine. All the sleep recordings were performed in the patients' own homes, using the Oxford Medilog system. RESULTS: At 12 weeks, 7/12 patients had responded (HAM-D decreased by > 50%). REM latency showed the expected increase early in treatment; this change was less obvious at weeks 3 and 12. Amount of REM sleep was decreased at day 2 and week 3, but returned to baseline by week 12. Slow wave sleep was slightly increased at day 2 and decreased at week 12. Of the sleep continuity measures, the only significant change was in sleep onset latency, which was increased at week 3; the other measures showed non-significant worsening at night 2 and week 3, but most were better than baseline by 12 weeks. Subjective sleep (the three sleep items on the HAM-D) showed a progressive improvement over time, especially in the responders. CONCLUSIONS: The effects of the SSRI fluvoxamine on objective sleep measures are in the
Wilson SJ, Bailey JE, Alford C, et al., 2000, Sleep and daytime sleepiness the next day following single night-time dose of fluvoxamine, dothiepin and placebo in normal volunteers, J.Psychopharmacol., Vol: 14, Pages: 378-386
To explore the effects of sedating and non-sedating antidepressants, we conducted a placebo-controlled, double-blind cross-over study in 12 normal subjects of the effects of a single night-time dose of fluvoxamine 100 mg, dothiepin 100 mg or placebo on night-time sleep recorded at home, and sleepiness and performance the following day. Night-time sleep was altered significantly by both drugs, with main effects on rapid eye movement (REM) sleep and sleep continuity. Dothiepin increased total sleep time, REM latency and stage 2 sleep and decreased arousals, wake after sleep onset and stage 1, whereas fluvoxamine decreased total sleep time and REM time and increased wake after sleep onset. Sleep latencies in daytime naps were significantly shorter for dothiepin and longer for fluvoxamine, showing that subjects were more sleepy when taking dothiepin. Electroencephalograms (EEG) performed during performance tasks failed to distinguish significantly between drugs. There were no significant differences between groups on our measures of tracking performance or reaction time; however, these tasks were designed primarily to provide a standard setting in which to monitor continuous EEG, and were unsuitable to detect sleepiness effects themselves. Saccadic eye movement velocity, acceleration and deceleration showed small non-significant changes after both drugs. Mood self ratings showed no significant differences among the groups. Subjective measures of night-time sleep reflected the objective measures of sleep continuity, and the items for difficulty and speed of wakening in the morning were significantly higher (i.e. more difficulty and slower) in the dothiepin group. The home-recorded sleep findings after fluvoxamine in this study were very similar to sleep laboratory studies with other antidepressant drugs, thus providing more validation of the home recording method
Potokar J, Lawson C, Wilson S, et al., 1999, Behavioral, neuroendocrine, and cardiovascular response to flumazenil: no evidence for an altered benzodiazepine receptor sensitivity in panic disorder, Biol.Psychiatry, Vol: 46, Pages: 1709-1711
Potokar J, Coupland N, Wilson S, et al., 1999, Assessment of GABA(A)benzodiazepine receptor (GBzR) sensitivity in patients on benzodiazepines, Psychopharmacology (Berl), Vol: 146, Pages: 180-184
OBJECTIVES: To measure GABA(A) benzodiazepine receptor sensitivity in patients taking benzodiazepines and compare with matched controls. METHODS: Seven patients who were on prescribed benzodiazepines for an anxiety disorder or insomnia were recruited from general practice and an adult mental health service outpatient clinic. They were matched with seven volunteers. All subjects received an intravenous injection of midazolam 50 microgram/kg in 10 ml normal saline over 10 min. Objective responses to midazolam were assessed using saccadic eye movement velocity slowing and subjective assessments using visual analogue scales. Measurements were recorded for 120 min and plasma midazolam concentrations obtained at 15-min intervals post-infusion to 120 min. Ratios of pharmacodynamic/pharmacokinetic effects were obtained for each individual to estimate GABA(A) benzodiazepine receptor sensitivity. RESULTS: Patients had an attenuated response to midazolam on both subjective and objective measures. GABA(A) benzodiazepine receptor sensitivity was significantly reduced in the patient group. CONCLUSIONS: Chronic treatment with benzodiazepines was associated with reduced effects of midazolam. Saccadic eye movement velocity was especially sensitive as a measure of attenuated response
Nutt DJ, Wilson S, 1999, Evaluation of severe insomnia in the general population - Implications for the management of insomnia: The UK perspective, Journal of Psychopharmacology, Vol: 13, ISSN: 0269-8811
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Nutt DJ, Wilson S, 1999, Evaluation of severe insomnia in the general population--implications for the management of insomnia: the UK perspective, J.Psychopharmacol., Vol: 13, Pages: S33-S34
Coupland NJ, Melichar J, Bailey JE, et al., 1998, Effects of α<sub>2</sub>-adrenoceptor agonists and antagonists on saccades, BIOLOGICAL PSYCHIATRY, Vol: 43, Pages: 44S-45S, ISSN: 0006-3223
Weinstein A, Feldtkeller B, Malizia A, et al., 1998, Integrating the cognitive and physiological aspects of craving, J.Psychopharmacol., Vol: 12, Pages: 31-38
'Craving is generally considered a significant factor in opiate addiction that is associated with drug-dependence and in relapse to drug use after treatment'-ARC expert consensus (Pickens and Johanson, Drug and Alcohol Dependence 30: 127-131). There are however difficulties in defining craving and urges to use drugs and in associating craving with drug use and relapse. Tiffany [Psychological Review 97(2): 147-168] has reviewed a considerable number of studies that associated reports of craving with consumption measures of drugs and revealed only an overall modest correlation of 0.4. These findings call into question the general assumption that subjective cravings are invariably associated with drug use. Furthermore, it led to Tiffany's provocative argument that cravings are not necessary for drug use. We have addressed these issues by using a range of complementary techniques derived from research in related fields such as the cognitive psychology of anxiety and depression, physiological response measurements and positron emission tomography (PET) neuro-imaging. Initially we developed computerized assessments to probe cognitive dysfunction in addiction that related to biased processing of automatic thoughts and beliefs about craving and drug use in opiate-dependent subjects and alcoholics. Subsequently in an attempt to develop a reliable method of inducing craving we explored an imagery-based technique that relied on the memory of craving experiences. These experiments were conducted both in opiate addicts who had achieved abstinence and in those undergoing detoxification. Finally, we have begun a study to understand the neural mechanisms of craving using imagery-based procedures at the same time as performing PET studies of regional blood flow using the O15-labelled water technique
Bell C, Wilson S, Nutt DJ, 1998, Pindolol augmentation of sertraline in resistant depression and its effect on sleep, J.Psychopharmacol., Vol: 12, Pages: 105-107
A case is reported of a 34-year-old lady with a 2-year history of resistant depression who responded to pindolol augmentation of sertraline. It also illustrates the use of sleep electroencephalogram measures as a way of assessing changes in brain 5-hydroxytryptamine function
Weinstein A, Wilson S, Bailey J, et al., 1997, Imagery of craving in opiate addicts undergoing detoxification, DRUG AND ALCOHOL DEPENDENCE, Vol: 48, Pages: 25-31, ISSN: 0376-8716
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- Citations: 24
Potokar J, Coupland N, Glue P, et al., 1997, Flumazenil in alcohol withdrawal: a double-blind placebo-controlled study, Alcohol Alcohol, Vol: 32, Pages: 605-611
The purpose of the present study was to study gamma-aminobutyric acid (GABA)-A receptor function in alcohol-dependent subjects during withdrawal, using the benzodiazepine antagonist flumazenil. In particular, we wanted to examine the hypotheses that an endogenous inverse agonist ligand at the GABA-A benzodiazepine receptor (GBzR) is active during withdrawal (in which case flumazenil should be anxiolytic), or whether chronic alcohol intake results in a shift in sensitivity of the receptor in the inverse agonist direction (in which case flumazenil should be anxiogenic). Results from 15 alcohol-dependent subjects in a double-blind placebo-controlled cross-over study showed that flumazenil was neither anxiolytic nor anxiogenic, although withdrawal scores were reduced during the course of the study. The fact that flumazenil was not anxiogenic, as it is in panic disorder, suggests that the GBzR is functioning differently in these two clinically similar conditions
Wilson SJ, Lillywhite AR, Potokar JP, et al., 1997, Adult night terrors and paroxetine, Lancet, Vol: 350
Friston KJ, Malizia AL, Wilson SJ, et al., 1996, The analysis of dynamic radioligand displacement or "activation" studies
Malizia AL, Gunn RN, Wilson SJ, et al., 1996, Benzodiazepine site pharmacokinetic/pharmacodynamic quantification in man: direct measurement of drug occupancy and effects on the human brain in vivo, Neuropharmacology, Vol: 35, Pages: 1483-1491, ISSN: 0028-3908
To date, the study of the relationship between drug occupancy and action in the brain has had to rely on the use of either animal models or of indirect kinetic measures in man, e.g. serum concentrations of unbound drug (as a measure of "free" drug in brain). We describe the first set of experiments which directly measure agonist-induced changes in both pharmacodynamic effects and pharmacokinetic parameters simultaneously and which demonstrate the feasibility of these studies in man. Five healthy volunteers each had two PET scans using [11C]flumazenil (a radiolabelled benzodiazepine site antagonist) as part of a study investigating kinetic models and the relationship between occupancy and effect of benzodiazepine site ligands. In both studies the [11C]flumazenil was displaced from the brain by infusion of midazolam administered i.v. 30 min into the scan. In one study a higher dose of midazolam was administered than in the other (range 12.5-50 micrograms/kg). Time-activity curves of the concentration of radioligand were derived in 17 different brain regions using a stereotactic automatic method of region selection. We demonstrated that there are significant differences in an index of occupancy, induced by the two different doses of midazolam, both across brain regions and within subjects. There was a significant correlation between measured occupancy index change and pharmacodynamic effects as measured by the peak change in beta 1 spectral power on EEG. There was no significant correlation between dose administered and EEG changes; plasma concentrations of midazolam were correlated with the occupancy index and with the EEG measures. In addition, we have demonstrated that a non-regional total index of brain occupancy can be obtained by analysing the non-tomographic data obtained with the PET scanner (total radioactivity counts head curve) and that this index shows significant correlations both with the dose administered and with the pharmacodynamic measure. T
Weinstein AM, Malizia AL, Wilson SJ, et al., 1996, Imagery and PET imaging of craving experiences in abstinent opiate addicts, BAP summer meeting
Weinstein AM, Wilson SJ, Bailey JE, et al., 1996, Sedative antidepressants impair visual detection mechanisms in humans, J.Psychopharmacol., Vol: 10, Pages: 141-145
Coupland NJ, Wilson SJ, Nutt DJ, 1996, alpha(2)-Adrenoceptors in panic and anxiety disorders, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 10, Pages: 26-34, ISSN: 0269-8811
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- Citations: 4
Coupland NJ, Wilson SJ, Potokar JP, et al., 1995, A comparison of the effects of phenelzine treatment with moclobemide treatment on cardiovascular reflexes, Int.Clin.Psychopharmacol., Vol: 10, Pages: 229-238
The effects of treatment with phenelzine (n = 15) and moclobemide (n = 20) on heart rate variability and cardiovascular responses to standing were examined using non-invasive beat-to-beat blood pressure (BP) monitoring in an open cross-sectional study. Phenelzine markedly impaired the BP response compared with moclobemide, with 83% vs 15% of patients lacking the normal initial BP overshoot (p < 0.01). BP recovery to supine levels was delayed (median time for diastolic BP 14.5 s after phenelzine vs 4.9 s after moclobemide; p < 0.002). Standing BP at 1 min and its change from supine levels were also significantly lower in the phenelzine group (delta diastolic BP 4 mmHg vs 15 mmHg; p < 0.001). Heart rate responses and variability were preserved and did not differ between treatments. These findings are consistent with impairment of sympathetic function but preservation of parasympathetic responses after phenelzine treatment
Coupland NJ, Bailey JE, Wilson SJ, et al., 1995, The effects of clonidine on cardiovascular responses to standing in healthy volunteers, Clin.Auton.Res., Vol: 5, Pages: 171-177
This study assessed the effects of clonidine on blood pressure (BP) and heart rate responses to active standing, recorded continuously using a Finapres monitor. Ten subjects were given a placebo infusion over 1 h, followed by clonidine hydrochloride 1.5 micrograms/kg over 2 h. During placebo and at 1, 3 and 19 h following the clonidine infusion, heart rate and blood pressure were recorded during the second half of supine rest for 10 min, active standing and quiet standing for 7 min. Clonidine did not alter the size of immediate drop in BP on standing, although the nadir was lower. BP recovery was impaired, with a loss of the usual BP overshoot in most subjects and with delays in reaching supine levels of diastolic BP (6.1 versus 9.6 s; p < 0.01) and systolic BP (8.1 versus 12.3 s; p < 0.05). The compensatory initial heart rate rise was significantly increased from 47 to 53 beats/min (p < 0.05), although the peak rate reached was reduced from 114 to 104 beats/min (p < 0.05). These results demonstrate that impairment of central sympathetic vasomotor drive leads to a delay in BP recovery and loss of initial BP overshoot immediately after standing, together with impaired maintenance of early steady-state BP
Nutt DJ, Wilson SJ, Coupland NJ, 1995, Use of selective serotonin reuptake inhibitors and other serotonergic drugs in the biological dissection of affective disorders, Int.Clin.Psychopharmacol., Vol: 9 Suppl 4, Pages: 53-59
The need to subtype patients with affective disorders on the basis of biological characteristics is well recognized, and much of the research in this area has focused on the serotonergic system. Biological subtyping can be approached using both peripheral and central markers. Peripheral markers include platelet serotonin concentrations, the density and affinity of platelet serotonin reuptake and platelet 5-HT2 receptors, and plasma serotonin concentrations. Central markers include cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) concentrations, and endocrine, psychological and body temperature responses to challenge tests with a number of serotonergic drugs. More recently, the role of selective serotonin reuptake inhibitors (SSRIs) and other serotonergic drugs in sleep, and in the control of cardiovascular homeostasis, has been studied. This may provide a greater understanding of the mechanisms of serotonin dysregulation in affective disorders, and may ultimately improve treatment of these conditions
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