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Biomedical subjects

E Holsboer-Trachsler

Publications and source records attributed to E Holsboer-Trachsler.

At least 19 recordsLinked to original sources

Polysomnographic effects of adjuvant ginkgo biloba therapy in patients with major depression medicated with trimipramine.

Sleep disturbance and cognitive impairment are frequent complaints of depressed patients under standard antidepressant medication. Therefore, additional therapies are required which specifically focus on the improvement of these deficits without exerting major side effects. Ginkgo biloba extract (EGb) has been shown to improve cognitive abilities in elderly subjects and in patients with disorders of the dementia spectrum. Animal studies surmise that EGb may reduce CRH activity, which is substantially related to depressive mood and behavior, predominantly cognition and sleep. An open non-randomized pilot study has been conducted to investigate the effects of ginkgo biloba extract (EGb Li 1370) on cognitive performance and sleep regulation in depressed inpatients. 16 patients were treated with a trimipramine (T)-monotherapy (200 mg) for six weeks. In eight of the 16 patients, an adjunct EGb therapy (240 mg/d) was applied for four weeks after a baseline week, the other eight patients remained on trimipramine monotherapy (200 mg) during the entire study. Polysomnography, cognitive psychomotor performance and psychopathology were assessed at baseline, after short-term and long-term adjunct EGb treatment, and after one week of ginkgo discontinuation (at the respective evaluation times in the eight patients on T-monotherapy). This report focuses on the results of EGb on sleep EEG pattern. EGb significantly improved sleep pattern by an increase of sleep efficiency and a reduction of awakenings. In addition, sleep stage 1 and REM-density were reduced, while stage 2 was increased. Non-REM sleep, predominantly slow wave sleep in the first sleep cycle, was significantly enhanced compared to trimipramine monotherapy. Discontinuation of EGb reversed most of these effects. Based on the animal data, these results suggest that EGb may improve sleep continuity and enhance Non-REM sleep due to a weakening of tonic CRH-activity. The compensation of the deficient Non-REM component in depression by the EGb application may provide a new additional treatment strategy, especially in the treatment of the depressive syndrome with sleep disturbance.

Adult↗

Antidepressive response to sleep deprivation in unipolar depression is not associated with dopamine D3 receptor genotype.

The psychostimulant theory of antidepressive sleep deprivation (SD) proposes a contribution of dopamine D3 receptors (DRD3) in the limbic system to the antidepressant effects of SD. Neuroendocrinological studies suggest a positive correlation of clinical response to SD and cortisol secretion. We hypothesized that the clinical response to SD and amount of cortisol secretion upon SD is associated with the 1-1 genotype of the Bal1 polymorphism of DRD3 on exon 1. In this study, aiming at evaluating the feasibility of screening large patient samples, 52 inpatients (19 males/33 females) with unipolar depression and a score of 18 or more on the 21-item Hamilton Depression Rating Scale were treated with 1 night of total SD. We found that 31% of our patients responded to SD. There was no association between response to SD and the genotype of the DRD3 Bal1 polymorphism (p < 0.879). There was also no association between increase in cortisol secretion after SD and DRD3 genotypes (p < 1.000) in a subgroup of patients. Statistical power analysis ruled out a major effect of the DRD3 Bal1 polymorphism on clinical response to SD. These results suggest that the DRD3 Bal1 polymorphism is not a promising lead to be followed up in larger patient samples.

Adult↗

[Phytotherapeutic drugs and sleep].

Most of the studies about phythotherapeutics and sleep confirmed only hypnotic effects on subjective sleep variables. For LI 160, a hypericum extract, an induction of slow wave sleep was demonstrated in older volunteers. In patients with major depression (MD) an increase of slow wave sleep was observed by our group after a six week therapy with hypericum extract (LI 160) and after an adjunct therapy with Ginkgo biloba LI 1370 extract. In MD sleep disturbances and hypersecretion of glucocorticoids are common features. For LI 160 beneficial effects on depressed mood and for LI 1370 effects on cognitive functioning are well documented. The potential relationship between influence on sleep structure and the hypothalamic-pituitary-adrenal axis will be discussed within the neurophysiological-neuroendocrine "extended two process model" of sleep regulation.

Ginkgo biloba↗

Effect of zopiclone and temazepam on sleep EEG parameters, psychomotor and memory functions in healthy elderly volunteers.

RATIONALE: The increased prevalence of sleep disturbance in old age is accompanied by a higher prescription rate of hypnotics, predominantly benzodiazepines in the elderly. In young volunteers zopiclone exerts a beneficial effect on sleep continuity without suppression of SWS and REM sleep; psychomotor performance and vigilance seemed to be less impaired than under classical benzoediazepines. OBJECTIVE: The present study investigates the effects of zopiclone on sleep EEG and cognitive performance in comparison to temazepam and placebo in the elderly population. METHODS: Single oral doses of zopiclone (7.5 mg), temazepam (20 mg) and placebo were administered in a randomized double-blind, completely counterbalanced cross-over design to 12 healthy elderly men and women (65.9 +/- 3.6 years, range 60-70 years). On each of the 3 study nights a sleep EEG was registered from 10 p.m. to 6.30 a.m. and cognitive performance tests were applied at 8 p.m., 2 a.m. (when subjects were awake for 30 min), 7 a.m. and 9 a.m. RESULTS: After zopiclone treatment, sleep continuity had significantly improved and sleep stage 4 was increased compared to temazepam and placebo. In addition, both active substances significantly reduced REM density. Neither active compound substantially altered psychomotor and memory performance. CONCLUSIONS: Zopiclone and temazepam can be considered as effective hypnotics in elderly subjects when administered in that dosage. The superiority of zopiclone on sleep architecture may be related to a more specific action of zopiclone at the GABA-A benzodiazepine receptor complex. The suppression of REM density by both compounds and their subtle effects on cognition may reflect a GABAergic mediated reduction of cholinergic neuro-transmission.

Aged↗

Depression and sleep disorders: clinical relevance, economic burden and pharmacological treatment.

A wide range of studies have been published over the past two decades that involve the intersection of sleep EEG, insomnia, psychiatric illness (especially depressive disorders) and psychopharmacology. Much of value has been discovered, but there have also been false starts and contradictory results. There is in fact strong evidence that insomnia is associated with medical and psychiatric illness and that the sleepiness associated with insomnia is the cause of many accidents. Thus, the direct (visits to doctors, cost of sleeping medication, complications from use of these medications) and indirect (accidents, quality of life) costs of insomnia are enormous and constitute a major public health problem in the industrialized countries. Believing that it is now timely to assess the state of this important research area, a consensus conference was convened on June 26-28, 1998, in Porto Cervo (Italy) to attempt to clarify the important issues and findings on the clinical effect of the different classes of antidepressant drugs on sleep quality in depression. The participants' consensus on some of the main topics is presented with the hope that this discussion and analysis will contribute to productive research in this important field.

Antidepressive Agents↗

Sleep in depression and sleep deprivation: a brief conceptual review.

Risk factors for somnipathies are psychological stress or psychiatric illness. More severe sleep difficulties have been found to be clearly related to psychiatric illness such as depression and phobias, as well as to addiction. Somnipathies can objectively be identified by means of polygraphy. Overall, polysomnographic measures in patients with affective disorders differ most frequently and significantly from those in normal control subjects. Persistent sleep disturbances are associated with significant risk of both relapse and recurrence in mood disorders and an increased risk of suicide. In addition to changes in sleep architecture, patients with major depression show profoundly altered patterns of nocturnal hormone secretion, possibly through mechanisms that link regulation of sleep with neuroendocrine activity. Basic and clinical approaches of sleep research established neurobiological models into the underlying pathophysiology associated with psychiatric disorders.

Major Depressive Disorder↗

[Clinical efficacy and tolerance of the hypericum special extract LI 160 in depressive disorders--a drug monitoring study].

PATIENTS AND METHODS: 647 patients suffering from mild to moderate depression treated for 6 weeks with hypericum extract LI 160 (Jarsin 300), 1 tablet t.i.d. RESULTS: The condition of the patients improved in 75% (primary endpoint). The von Zerssen depression score decreased from 19.8-21.2 (95%-CI) at base-line to 8.1-9.3 at week 6 (p < 0.001). All symptoms were improved at week 3 and further at week 6. The condition improved somewhat slower in patients older than 65 years. The severity of the depression did not appear to have an effect on the outcome. Adverse events were reported by 17% of the patients (gastrointestinal 10%). These were mostly mild or moderate. Tolerance was rated in 89% as satisfactory or better.

Adolescent↗

Contingent negative variation and attention in schizophrenic and depressed patients.

Contingent negative variation (CNV) is supposed to be a psychophysiological indicator of attention and arousal. Both have been reported to be deteriorated in schizophrenic and depressed patients. Thirty-four patients with major depression, 43 patients with schizophrenia and 49 healthy subjects were investigated during acute illness with a complex three-stimulus go/no-go task which requires different states of attention: trials consisted of three complex figures that were tachistoscopically presented. Three identical figures had to be confirmed by pressing a button (target condition). CNV was measured: (1) after the first figure waiting for the second (baseline condition), (2) after two identical figures waiting for the third (response-relevant condition), (3) after two different figures waiting for the third (response-irrelevant condition). The response-relevant condition compared to baseline significantly intensified CNV in healthy controls and to a minor extent in depressed patients but not in schizophrenics. In the response-relevant conditions in healthy controls, CNV was significantly reduced compared to the response-relevant condition. This clear discrimination between response-relevant and response-irrelevant conditions was not observed in either group of patients. Thus, the applied CNV paradigm was able to discriminate schizophrenic and depressed patients from healthy controls. Furthermore, subtle differences between schizophrenic and depressed patients were detected, reflected by the different CNV development across experimental conditions.

Adult↗

[Therapy refractory depression].

Patients who fail in an adequate trial of a standard antidepressant drug (corresponding to 150 mg/d imipramine over a minimal period of 4 weeks) are defined as treatment resistant. According to these guidelines a substantial number of patients is not sufficiently treated and, thus, should be reassessed for dosage and length of antidepressant medications. If patients fail to a sufficient treatment a response may be achieved if they are switched to an alternative drug and/or if biochemically differently acting antidepressants are combined. Furthermore, an increasingly popular approach to handle treatment resistance is the use of augmentation strategies. Among these, lithium and thyroid T3 are the most well studied with the most consistently positive results. As non-pharmacological augmentation approach partial sleep deprivation has proved to be effective in combination with antidepressant medication. Finally, patients who had no or only a partial response to several treatments with antidepressants may benefit from electroconvulsive therapy.

Antidepressive Agents↗

Microsleep during partial sleep deprivation in depression.

BACKGROUND: Sleep deprivation (SD) exerts a beneficial effect on mood and sleep in about 60% of depressed patients usually followed by a relapse into depression after the recovery night. Short phases of sleepiness, especially naps in the early morning, may be responsible for this phenomenon. METHODS: To evaluate the effect of short, even ultrashort phases of sleep-microsleep (MS) during partial sleep deprivation (PSD) on mood, cognitive psychomotor performance (CPP), and sleep, an electroencephalograph (EEG) was continuously recorded over 60 hours in 12 patients with major depression. Subjective mood was assessed by a visual analogue scale and CPP by a letter cancellation test. RESULTS: The results illustrate that in depressed patients during PSD the amount of MS is increased, predominantly in the early morning, which was subjectively unrecognized and not observed by nursing staff. Patients with a low cumulative amount of MS during PSD improved significantly in mood, CPP, and sleep pattern compared to the patients with a high amount of MS who showed only slight changes. CONCLUSION: Therefore, accumulated MS may influence the SD-induced positive effects in depressed patients.

Adult↗

Side effects of adjunct light therapy in patients with major depression.

Adjunct bright-light therapy has been suggested to augment antidepressant drug treatment in patients with non-seasonal major depression. Side effects of the combined therapy have not been investigated thus far. Therefore, somatic complaints and side effects of combined therapy were evaluated in 28 patients with major depression (DSM-III-R) randomly assigned to either trimipramine or trimipramine and serially applied adjunct bright-light therapy. Response rates were comparable in both treatment groups and rates of newly emergent side effects during treatment were generally low. The most prominent unfavourable side effects of adjunct bright-light therapy as compared with trimipramine monotherapy were aggravated sedation, persisting restlessness, emerging sleep disturbance and decreased appetite as well as the worsening of vertigo. Discriminant analysis revealed that the combination of trimipramine with bright light results in a different side effect profile compared with drug monotherapy.

Antidepressive Agents, Tricyclic↗

[Diagnosis and treatment of affective disorders].

The rates of major depression (5-12%) are considerably higher than for bipolar disorder (ca. 1%). Depressive disorder is most frequent in general practice. Although general practitioners recognise and manage efficiently a large number of depressed patients, at any consultation about half the patients are not diagnosed. Recognising depression is made difficult by the frequency in general practice of presentations with somatic symptoms (masked depression) and of depression related to physical disorder. The best method for the general practitioner to overcome these problems is by using a relatively direct interview for the main specific symptoms of depression. The general practitioner has a key role in the management of depression and as a gatekeeper with a prime responsibility to make appropriate referrals to specialists. Counselling members of the family or friends and recommending self-help groups are important to improve the therapeutic compliance of the patients.

Antidepressive Agents↗

[Epidemiological study of sleep disorders in patients in Swiss general practice].

The aim of the study was to assess the prevalence, severity, associated factors and diagnosis of sleep disorders in general practice. Over 700 patients were investigated with a multiple choice questionnaire in 24 general practices in Switzerland. To assess sleep disorders, criterion A for insomnia according DSM-III-R was applied. The prevalence of sleep disorders was 44%, 64% of these were classified as mild, 31% as moderate and 5% as severe. 50% of the female patients complained about insomnia compared to 36% in males. Retrospectively, 74% of the patients stated having suffered from sleep disorders for more than one year (mild 76%, moderate 69%, severe 75%). 70% of patients with mild, 42% with moderate and 30% of patients with severe insomnia didn't inform their physicians about their sleep difficulties on the occasion of an earlier consultations. Patients with moderate or severe insomnia felt moderately or markedly disabled in their quality of life (71%) and work (58%). To estimate general anxiety and depressive state, self-rating scales were used (STAI, D-S). In comparison to reference values for healthy volunteers, insomniac patients had significantly higher scores on both scales, which were associated with the severity of sleep disorders, corroborating the association of sleep disorders with anxiety disorders and depressions. The physicians diagnosed in 18% of insomniacs a psychiatric disease, in 52% a psychoreactive disorder and in 26% a somatic etiology. The study shows that sleep disorders are a frequent syndrome in general practice and often not reported to the physician; therefore, the patients should routinely be questioned about sleep problems, and associated psychiatric diseases should be considered.

Adult↗

Neuroendocrine effects of a 20-mg citalopram infusion in healthy males. A placebo-controlled evaluation of citalopram as 5-HT function probe.

Pharmacokinetic measurements, neuroendocrine responses, and side effects profiles of intravenous infusions of 20 mg citalopram over 30 minutes during the early afternoon have been studied. Eight healthy male volunteers were enrolled in a placebo- (saline) controlled, single-blind, cross-over protocol. Plasma concentrations of the parent compound showed a double exponential decay. Demethyl and didemethyl metabolites were not detectable, but low concentrations of the propionic acid derivative of citalopram were found. Determination of the citalopram enantiomers yielded a balanced S(+)/R(-) ratio of 0.9 to 1.2. The endocrine response to the drug was characterized by significant increases in plasma prolactin and cortisol. Except for one subject, who developed pronounced side effects, human growth hormone showed a surge following saline that was inhibited following citalopram. Rectal temperature and heart rate were not affected and tolerability was favorable. Because of citalopram's extremely high selectivity for the presynaptic 5-hydroxytryptamine nerve terminals, the present data suggest that it might be a promising tool for the investigation of serotonergic function in the human brain in vivo.

Citalopram↗

[Sleep disorders in chronic pain and generalized tendomyopathy].

Patients with a chronic pain syndrome often suffer from sleep disturbance. As both symptoms are frequent in the fibromyalgia syndrome, these patients in particular have been examined in this regard. No clear polysomnographic evaluation of the subjectively experienced sleep disturbance in these patients has been done so far. Therefore, we recorded the sleep EEG of 13 patients with a fibromyalgia syndrome in order to objectively characterize their sleep. Furthermore, we were interested in the relationship between the sleep alterations and pain intensity. In a subsequent placebo-controlled study based on pathophysiological considerations, we attempted to beneficially influence the sleep disturbance and the pain syndrome with the 5-HT2-receptor antagonist ketanserine, as this system has been proved to play a major role in the regulation of both sleep and pain. The results of our studies in patients with fibromyalgia show that the alteration of sleep is mainly characterized by a disturbance of sleep continuity associated with the experience of pain intensity. The application of 5-HT-receptor-antagonists may be a new strategy for the common treatment of sleep disturbance and the pain syndrome which needs to be evaluated in further studies. Duration of the patients' illness seems to be a predictive value in relation to intensity of the symptoms and the therapeutic outcome.

Adult↗