[Sleep disorders in schizophrenia]. / Schlafstörungen bei schizophrenen Erkrankungen.

Difficulties initiating and maintaining sleep as well as circadian rhythm disorders are very common in schizophrenia. Sleeping disorders occur as early signs of the first manifestation of illness as well as early signs of relapse. They bear a relation to positive symptoms and disorganisation of thought. Polysomnographic investigations with schizophrenic patients typically demonstrate a prolonged sleep-onset latency and a decrease in sleep efficiency and slow wave sleep. In particular, distortions of deep sleep can affect neocortical plasticity and cognition negatively. The considerable sleeping disorders are often not sufficiently taken into account in clinical routine. Particularly older antipsychotic medication like Haloperidol can affect the circadian and sleep-wake rhythms negatively. Therefore, pathophysiological changes of sleep within the scope of schizophrenic disorders and their potential implications are discussed in this outline. Regarding therapy, psychoeducative approaches are discussed as well as the administration of antipsychotic medication in accordance with the recommendations of sleep medicine professionals.

[Restless legs syndrome in patients on dialysis for kidney insufficiency: effect of medication]. / Restless-Legs-Syndrom bei dialysepflichtiger Niereninsuffizienz: Einfluss der Medikation.

BACKGROUND AND OBJECTIVES: Many patients on dialysis have a restless legs syndrome (RLS). Drugs may cause as well as relieve RLS symptoms. It was the aim of this study to examine the effect of the prescribed drugs on the occurrence of RLS in patients on hemodialysis. PATIENTS AND METHODS: The cohort consisted of 82 out-patients undergoing dialysis (38 men and 44 women; mean age 65,4 [21 - 93] years) during 2002 and 2003. In addition to blood analysis the criteria of RLS were analysed, using the Johns Hopkins restless legs severity scale (JHRLSS) and the diagnostic criteria of the International Restless Legs Syndrome Study Group (IRLSSG). Periodic limb movements in sleep (PLMS) were measures by a special device. RESULTS: 25 of 82 patients had RLS symptoms, using the JHRLSS, in 23 this was confirmed by the IRLSSG criteria. PLMS occurred in 46 of 81 patients. The occurrence of RLS correlated significantly with the intake of drugs that could potentially increase RLS severity. But there was no strong correlation with drugs that could potentially decrease it. There was no association between medication and the occurrence of PLMS. There was also no correlation with laboratory parameters. CONCLUSION: In patients on dialysis those drugs which can potentially worsen RLS should be prescribed with care.

Sundowning and circadian rhythm disorders in dementia.

Sleep disorders and disruptive nocturnal behaviours are commonly reported in people with senile dementia and present both a significant clinical problem and a cause of increased stress for caregivers. Neuronal degeneration of cholinergic Nucleus basalis Meynert (NBM) neurons promote rest-activity disturbance and Sundowning in Alzheimer's disease. NBM neurons modulate the activity of the mainly cholinergic suprachiasmatic nucleus (SCN) and the induction of NONREM sleep. Sundowning might be explained as a syndrome occurring when arousal is to be processed while the neocortex is already turned "off" to (NONREM) sleep. The therapeutic measures should thus primarily be aimed at the stimulation of the circadian system and enforcing "external Zeitgebers". Pharmacologically, application of cholinergic enhancers i.e. cholinesterase inhibitors and melatonin supports and should stabilize the weakened structures.

[Evolution and function of sleep]. / Evolution und Funktion des Schlafes.

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]. / Psychopharmakotherapie von Verhaltensstörungen bei Demenzkranken.

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.

Behavioural problems associated with dementia: the role of newer antipsychotics.

Behavioural disorders are a common feature in dementia, especially in the later stages of the disease. The most frequent disorders are agitation, aggression, paranoid delusions, hallucinations, sleep disorders, including nocturnal wandering, incontinence and (stereotyped) vocalisations or screaming. Behavioural disorders, rather than cognitive disorders, are the main reason why caregivers place patients with dementia in a nursing home. However, although behavioural disorders are important, there is still no international agreement with respect to the description and definition of symptoms and syndromes. This also holds true for the wide variety of scales for quantification and measurement of behavioural disorders. Drug therapy should be considered after possible underlying causes such as physical illness, drug adverse effects and environmental stressors have been ruled out, or specifically addressed, and a behavioural approach has also failed. This article briefly reviews the evidence for non-antipsychotic drug therapies, which include a variety of substances. However, antipsychotics are the group of drugs which have been most frequently studied for the treatment of behavioural syndromes in dementia. Drug responsive symptoms include anxiety, verbal and physical agitation, hallucinations, delusions, uncooperativeness and hostility, whereas wandering, hoarding, unsociability, poor self-care, screaming and other stereotyped behaviour seem to be unresponsive to all drugs. Although the use of classical antipsychotics is limited by extrapyramidal symptoms, anticholinergic adverse effects, sedation and postural hypotension, the newer antipsychotics offer the chance of a better risk:benefit ratio. This article reviews the small amount of data published on the use of the newer antipsychotics, and concludes that risperidone at low dosages (0.5 to 2 mg/day) seems to be especially useful for the treatment of behavioural symptoms in dementia because of its negligible anticholinergic adverse effects. The use of clozapine is limited by its anticholinergic activity, at least in dementia of the Alzheimer and Lewy body types. However, in patients with psychosis arising from Parkinson's disease it seems to be the drug of choice, and similar activity is likely for olanzapine. There are no published data on other newer drugs, such as sertindole, quetiapine or ziprasidone. Future studies should also address questions of dementia heterogeneity and should compare different drug treatments and treatment combinations.

[Gerontopsychiatric treatment in comparison between integrated management at a university and separated management at a district hospital. 1: Patient characteristics]. / Gerontopsychiatrische Behandlung im Vergleich zwischen integrierter Versorgung an einer Universität und separierter Versorgung an einem Landeskrankenhaus. Teil 1: Patientencharakteristik.

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]. / Gerontopsychiatrische Behandlung im Vergleich zwischen integrierter Versorgung an einer Universität und separierter Versorgung an einem Landeskrankenhaus. Teil 2: Diagnosen und Behandlung.

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.

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.

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.

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.

Nocturnal melatonin secretion and sleep after doxepin administration in chronic primary insomnia.

Nocturnal melatonin secretion and polysomnographic sleep patterns were investigated in ten patients with chronic primary insomnia (age 41.3 +/- 9.5 years) and in five healthy subject, (age 27.2 +/- 0.7 years) after either a single intravenous administration of 25 mg doxepin or placebo in a randomized, double blind, and cross-over setting. In the patient group a third session was performed after a three-week open oral treatment with 25 mg doxepin daily. The single-dose administration of doxepin did not affect plasma melatonin concentrations in either the patients on the healthy subjects. After three weeks of oral doxepin intake by the patients, the area under the curve of total nocturnal plasma melatonin concentration was significantly increased by 26% and the peak values were increased by 30%. Both after the single i.v. treatment as well as after long-term oral administration, doxepin also significantly improved sleep latency, total sleep time, and sleep efficiency in the insomniacs as well as the healthy subjects, whereas the nocturnal wake time was decreased. These findings indicate that this tricyclic antidepressant not only improves sleep and but also preserves the secretion of a hormone which is believed to play a special role in the circadian sleep-wake rhythm. Long-term doxepin treatment of chronic insomniac patients not only improves sleep but also restores nocturnal melatonin secretion in these patients.

[Cerebral cognitive deficits in the aged. Diagnostic and therapeutic standards: organization of strategies for problem detection and solution]. / Hirnleistungsstörungen im Alter. Diagnostische und therapeutische Standards: Erarbeitung von Strategien zur Problemerkennung und Lösung.

This paper reports the results of a representative survey which was performed in cooperation with 145 family physicians and 14 primary care neuropsychiatrists (response rate 83.2%) in the area of Göttingen, Germany. With the use of a standardised interview referring to written sample case histories, we investigated the diagnostic and therapeutic management of memory disturbances in old age. The results showed, that dementia and depression are underdiagnosed in primary care, and that memory disturbances are mainly regarded as consequences of disturbed cerebrovascular perfusion. About 70% of all physicians would prescribe a cognition enhancer, however about a third of them would do it in spite of major doubts about their efficacy. The results underline the necessity of continuing education especially with regard to early diagnosis of dementive and affective disorders in later life. The development of therapeutic standards in this area should take "irrational" motives into account. Appropriate exemplary case histories seem to be a potentially useful tool for the measurement of physicians' competence and its changes.