Biomedical subjects
J Staedt
Publications and source records attributed to J Staedt.
[Evolution and function of sleep].
This paper presents a brief historical review of the beginning of scientific studies on sleep research and evaluation of the electrophysiological basics. Subsequently, hypotheses are presented and discussed on phylogenesis and function of NONREM- and REM-sleep as well as aspects of the regulation of energy conservation and temperature. Sleep may have first evolved out of rest/activity cycles. Later on, with the evolution of complex brains, sleep may also assume importance in development and maintenance of these structures. Hence, special emphasis is placed on the influence of NONREM and REM sleep on the reorganisation of neuronal networks.
Can chronic neuroleptic treatment promote sleep disturbances in elderly schizophrenic patients?
It has been proposed that sleep disturbances, especially reduced delta sleep, are related to a poor outcome in schizophrenia. To determine whether long-term treatment with neuroleptics can promote sleep disturbances by increasing the risk of a nocturnal myoclonus syndrome (NMS) (=periodic movements in sleep) related insomnia, we performed all-night polysomnography in 10 chronically ill schizophrenic patients who had been under neuroleptic therapy for a mean of 27 years. NMS-related insomnia was detected in all 10 patients. Potential pathophysiological relationships between long-term neuroleptic therapy and NMS occurrence are discussed. Our findings suggest that long-term administration of neuroleptics favours the appearance of insomnia.
Gender differences in the recognition of depression in old age.
OBJECTIVE: The study should answer the question of whether identical symptom presentations of depression in male and female patients leads to similar recognition rates in primary care. METHOD: We performed a survey in primary care. Two written case vignettes were presented to 170 family physicians in a face-to-face interview which took place in their practices. The case vignettes described either a mildly depressed otherwise healthy old patient (case 1) or a severely depressed patient with somatic comorbidity (case 2). For each case different versions with regard to patients' gender were used: in case 1 only the gender of the patient varied; in case 2 both the gender and the anamnesis (stroke/hypothyroidism) varied. Afterwards the interviewers asked standardised open questions. The physicians were not aware of the mental health focus and the gender focus of the study. RESULTS: The study is representative with a response rate of 77.6%. For primary diagnosis, the female versions were given the diagnosis of depression more often. There was a non-significant trend that female physicians considered depression more often. CONCLUSION: The results show that gender-related experience and stereotypes on the physicians' side influence the diagnosis of (old age) depression in primary care. Further studies should elucidate the influence of the physicians' gender on the management of psychiatric disorders.
[Psychopharmacotherapy of behavioral disorders in patients with dementia].
Behavioral disorders in dementia are common and are the most important symptoms with regard to socio-economic burden. Up to now there is no common international agreement of how to define and measure these disorders. Antidementia trials focus mainly on cognition. Investigations of neurobiological corrolaries of disturbed behavior in the dementias are rare. The same holds true for studies on the longitudinal course of behavioral disorders and their interrelation. Many symptoms may be the expression of variable conditions, e.g., agitation may be related to anxiety or akathisia. In primary care, hospitals and nursing homes, antipsychotics are most often chosen for their treatment. The available data demonstrate at least a modest efficacy. New neuroleptics (risperidone, clozapine, olanzapine) offer some advantages with regard to the risk benefit ratio. Benzodiazepines are frequently prescribed, but seem to be superior to neuroleptics only for the treatment of sleep disorders. Antidepressants, carbamazepine or valproic acid offer some benefits, but do not provide immediate effects, which may the reason why they are used much less. For long-term treatment of many behavioral symptoms, they may however be superior. Drugs should also be chosen with regard to dementia etiology. For example, physicians should consider the high neuroleptic sensitivity in dementia of Lewy body type and the anticholinergic sensitivity in dementia of Alzheimer type. Empirical evidence indicates overtreatment of the demented population with sedating psychotropic drugs. With regard to the instability of behavioral disorders in the time course the necessity of drug treatment should always be (re)evaluated.
Family physicians and the risk of suicide in the depressed elderly.
BACKGROUND: Depression is the most frequent psychiatric disorder in the elderly. It is the reason for most suicides in this age group. METHOD: We performed a representative survey in primary care. Two written case vignettes were presented to 170 family physicians in face-to-face interviews which took place in their practices. The case vignettes described either (Case 1) a mildly depressed otherwise healthy old patient or a severely depressed patient (Case 2) with somatic comorbidity. Afterwards the interviewers asked standardized open questions. The physicians were not let into the mental health focus of the study. RESULTS: The response rate was 77.6%. Depression was considered for primary or differential diagnosis by 91.2% of the physicians in Case 1 and by 70% in Case 2 (chi2-test; p < 0.01). For further anamnesis, only 2.4% of the physicians were interested in suicidal ideation of the patient. When directly asked at the end of the interview, 76.9% of the physicians said they would talk about suicide. Those who would not, thought that the patient would communicate suicidal intent himself/herself, or they feared to induce suicide by asking directly. CONCLUSION: Thinking of suicidality and its prevention is not uppermost in the physicians' mind. Therefore, and also with regard to the relatively high rate of depression recognition, we conclude that educational means should not only focus on the recognition and screening of depression, but also on the management--'how to talk about...'--of complex problems like suicide in the elderly, in order to change suicide rates.
[Gerontopsychiatric treatment in comparison between integrated management at a university and separated management at a district hospital. 1: Patient characteristics].
OBJECTIVE: We wanted to study differences between geriatric psychiatric patients and their management in an integrated (with other adult age groups) care in the University Psychiatric Hospital (PUK) compared to those in a separated (only according to age) care in the Psychiatric State Hospital (LKH), which together treat all psychiatric inpatients in Goettingen, Germany. METHOD: We performed standardized chart reviews of randomly selected groups of patients, who had been treated in the PUK (n = 151) and the LKH (n = 145) in the years 1991 and 1992. RESULTS: The LKH patients were significantly older (74.8 +/- 8.7 y versus 70.3 +/- 8.3 y), more often living alone and/or without children. 31.9% of them were living in a nursing home compared to 6.5% of the PUK patients. Psychic disorders had not shown up before old age in 55.7% of all cases. 50.4% of the patients were in a psychiatric hospital for the first time. The majority of the patients (65.6%) had not been investigated by a psychiatrist before admission. CONCLUSIONS: More socially handicapped patients were treated in the LKH. For most cases, the hospital treatment had been the first psychiatric treatment at all.
[Gerontopsychiatric treatment in comparison between integrated management at a university and separated management at a district hospital. 2: Diagnoses and treatment].
OBJECTIVE: We wanted to study differences between geriatric psychiatric patients and their management in an integrated (with other adult age groups) care in the University Psychiatric Hospital (PUK) compared to those in a separated (only according to age) care in the Psychiatric State Hospital (LKH), which together treat all psychiatric inpatients in Goettingen, Germany. METHOD: We performed standardized chart reviews of randomly selected groups of patients, who had been treated in the PUK (n = 151) and the LKH (n = 145) in the years 1991 and 1992. RESULTS: Most patients of the LKH suffered from organic brain diseases/dementia (63.4%; PUK: 29.1%). In the PUK, depression was the most frequent diagnosis (57.6%; LKH: 21.1%). A part of about 25% of the patients showed neurological deficits. Specialised diagnostics were performed mostly in the PUK. Both institutions treated the wide majority of patients with CNS drugs. Antidementia drugs were given significantly more often in the LKH. About one third of the patients were released into changed living environments. CONCLUSIONS: Patients with further progressed dementias were treated mainly in the LKH. This has consequences for diagnostics, treatment duration and side effect rate.
Pergolide: treatment of choice in Restless Legs Syndrome (RLS) and Nocturnal Myoclonus Syndrome (NMS). Longterm follow up on pergolide. Short communication.
Pergolide has proven significantly superior to L-dopa plus peripheral decarboxylase inhibitor in short-term therapy of RLS/NMS. We now first present long-term follow-up sleep data showing its lastingly good effects after averagely 517 treatment days.
Increased benzodiazepine receptor density in the prefrontal cortex in patients with panic disorder.
There are published studies concerning a regionally changed function of GABA-benzodiazepine-receptor-complexes in anxiety disorder. These studies implicate the limbic lobe, the brainstem and the prefrontal cortex. Using 123I-Iomazenil and single photon emission tomography (SPET) we investigated the benzodiazepine receptor density in twelve patients with panic disorder who had never been treated with benzodiazepines before. Nine age- and sex-matched volunteers who were free of mental illness served as controls. Patients with panic disorder showed a significant increase of benzodiazepine receptor binding in the right supraorbital cortex and a trend to an increased uptake in the right temporal cortex. There was no correlation between receptor density and scores on Spielberger's State Trait Anxiety Inventory in the patient group. Since the findings cannot be explained by benzodiazepine exposure we hypothesize an upregulation due to functional or neuroanatomic changes (at least) in the frontotemporal cortex.
Sleep cluster arousal analysis and treatment response to heterocyclic antidepressants in patients with major depression.
BACKGROUND: A close link between sleep normalisation and antidepressant response in depressed patients has been reported. We attempt to separate early antidepressant treatment responders from nonresponders by the use of sleep EEG recordings. METHODS: Sleep EEG recordings were performed in 20 inpatients with a unipolar major depressive disorder during the first and third week of treatment with heterocyclic antidepressants. Acute treatment polygraphic measures with microarousal analysis were used to predict response. Response was defined as a minimum reduction of > or = 30% in the v. Zerssen Depression Scale after 3 weeks. RESULTS: Compared to the 11 nonresponders, the 9 responders initially showed a highly significant increase of arousals during sleep quantified with the cluster disturbed sleep (CDS), whereas the classical sleep parameters (REM, stage I-IV) had no predictive value. CONCLUSIONS: The validity of our results is limited by the small number of patients and the lacking randomised assignment. Nevertheless the results are still interesting. Because the CDS clearly separated responders from nonresponders at treatment onset. This could be due to a different reagibility of the catecholaminergic system. The data indicate that the CDS can be helpful for the prediction of early antidepressant treatment response.
Pergolide: treatment of choice in restless legs syndrome (RLS) and nocturnal myoclonus syndrome (NMS). A double-blind randomized crossover trial of pergolide versus L-Dopa.
A double-blind randomized crossover study of 0.125 mg Pergolide (Lilly) at bedtime versus 250mg L-Dopa + Carbidopa (Roche) was conducted in 16-day phases in 11 patients with idiopathic restless legs syndrome. Two patients reported a partial and 9 patients a complete relieve of motor restlessness while receiving Pergolide. Only 1 patient experienced an improvement of restlessness after L-Dopa. The patients showed polysomnographically a mean decrease in NMS cluster disturbed time by 45% from control on L-Dopa (p < 0.025) and by 79% from control on Pergolide (p < 0.001). In addition, Pergolide increased the total sleep time compared to L-Dopa (p < 0.05). In conclusion, the dopamine agonist Pergolide is superior to L-Dopa in the treatment of RLS and NMS.
[123I]IBZM SPET analysis of dopamine D2 receptor occupancy in narcoleptic patients in the course of treatment.
Elevated levels of central D2 dopamine receptors were found on postmortem examination in cases of human narcolepsy. In vivo investigations using positron emission tomography (PET) and single photon emission tomography (SPET) found no changes of D2 binding in the striatal structures. To investigate whether the elevated D2 receptors in postmortem investigations are due to long-term treatment effects, we applied 123I-labeled (S)-2-hydroxy-3-iodo-6-methoxy-([1-ethyl-2-pyrrolidinyl]methyl) benzamide (IBZM) ([123I]IBZM, a highly selective CNS D2 dopamine receptor ligand) and SPET in narcoleptic patients in the course of treatment with stimulants and/or antidepressants. Before treatment we found no changes in D2 binding in 10 patients (in comparison to 10 normal controls). After treatment (performed in five patients for 3 months) we found changes in D2 binding in four of them, indicating that the results of the postmortem studies could have been influenced by long-term medications. Human narcolepsy seems not to be related to a striatal D2 dopaminergic disturbance.
Lamotrigine in the treatment of nocturnal myoclonus syndrome (NMS): two case reports.
In previous investigations we found an increase of D2 dopamine receptors in the striatum of patients with nocturnal myoclonus syndrome (NMS) after treatment with dopamimetics. Under the hypothesis, that, according to animal experiments, the glutamatergic system could be involved in this atypical dopaminergic up-regulation in NMS. The glutamate release inhibitor lamotrigine was tested in up to now two NMS patients. The results and the success of this approach and its implications are discussed.
Effects of chronic treatment with methadone and naltrexone on sleep in addicts.
Previous studies have described sleep disturbance secondary to chronic opiate use and abuse. Drug-dependency insomnia is of interest because chronic sleep disturbances can promote depressive symptoms which could lead to a drug relapse. For the first time we compared the polysomnographic parameters of 10 methadone-substituted outpatients and 10 naltrexone-treated outpatients. Methadone (mu-opioid agonist) produced a marked fragmentation of the sleep architecture with frequent awakenings and a decrease in EEG arousals. In comparison with methadone and controls, the naltrexone (mu-opioid antagonist) group showed the shortest sleep latency and the longest total sleep time. These data indicate that mu-agonists and mu-antagonists have different effects on sleep. The implications, especially the involvement of opioid-dopamine interactions on sleep and movements during sleep, are discussed.
Rebound insomnia after abrupt clozapine withdrawal.
Rebound insomnia has been reported upon discontinuation of benzodiazepines. We describe the first case of a sleep polygraphically documented rebound insomnia with an unusual somatic fatigue syndrome after long-term use of clozapine in a 30-year-old schizophrenic male. The withdrawal symptoms occurred the first day after drug discontinuation and could be stopped by readministering clozapine. In our opinion, the sudden occurrence of the withdrawal symptoms cannot be explained by a dopaminergic hypersensitivity or a cholinergic rebound, but indicates an involvement of GABAergic and perhaps antiglutamatergic properties of clozapine.
Prescribing practice with cognition enhancers in outpatient care: are there differences regarding type of dementia?--Results of a representative survey in lower Saxony, Germany.
Previous studies of cognition enhancers have mainly focused on insufficiently defined groups of cognition disorders, e.g., "cerebral insufficiency". With regard to the various biological changes in senile dementia of Alzheimer's type (SDAT) and in vascular dementia (VD), which together make up the great majority of senile dementias, many authors have encouraged different studies of these types of dementias, especially since both can be diagnosed clinically with satisfying certainty. Since primary care physicians treat the majority of elderly and demented patients, they have their own experience with cognition enhancers. We were therefore interested to know, how far these physicians differ in their treatment of SDAT and VD. We performed a representative survey (response rate 83.2%; 145 family physicians and 14 neuropsychiatrists) in the Goettingen area. A written case vignette described a 70-year-old widow with moderate dementia and vascular risk factors which are easily treated with drugs. Two versions were randomly assigned, in which (version A) either a "typical" VD history or a typical SDAT history (version B) were described. After perusal, the physician was asked whether and which drugs he would choose to treat the cognitive disorders in this patient. Most frequently, piracetam (A/B: 25.6%/30.9%), ginkgo biloba (24.4%/28.4%), and nimodipine (14.1%/25.9%) were considered. Aspirin was cited by 29.5%(A) and 17.3%(B) of the physicians respectively. As far as the type of dementia was concerned, significant differences were found only for co-dergocrine, which was preferred in SDAT. The following inter-group trends were observed: family physicians considered ginkgo biloba more often than nimodipine or co-dergocrine. The results show the apparent importance of cost-and safety aspects, while the type of dementia has hardly any impact. The latter impression corresponds to the results of drug trials demonstrating no different efficacy. In our opinion, aspirin was not sufficiently taken into consideration.