Neuropsychobiology
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It has been suggested that delirium in the elderly is caused by abnormally high levels of circulating glucocorticoids or by an increased vulnerability to their effects. We performed a dexamethasone suppression test (DST) in 16 consecutive patients without depression or dementia admitted to an acute-care geriatric unit with a clinical diagnosis of lower respiratory tract infection. Seven of 9 (78%) patients who developed delirium were non-suppressors on the DST compared with 1 of 7 (14%) patients without delirium (p = 0.04). ⋯ On re-examination 8 weeks later, after resolution of the delirium and of the chest infection, 5 of 6 non-suppressors still had an abnormal DST. It is known that some non-demented and non-depressed elderly patients fail to suppress cortisol in response to 1 mg of dexamethasone. Our results suggest that such patients may be at increased risk for developing delirium during acute illness.
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Randomized Controlled Trial Clinical Trial
Effect of morphine on the electroencephalogram and other physiological and other physiological and behavioral parameters.
A double-blind, crossover, placebo-controlled study was carried out in 10 healthy male volunteers to investigate the effects of subcutaneously administered single doses of 4 and 8 mg morphine and 2.5 and 5 mg of a new centrally acting analgesic with a benzomorphane structure. After an adaptation session, each subject received all five treatments in a random sequence at intervals of 1 week. Quantified EEG, cardiovascular and behavioral parameters, quantitative respiratory measurements, body temperature, symptom reports, pain threshold estimates, and blood drug assays were used to assess the effects of the drugs. ⋯ The pain threshold increased. All these effects had a maximum between min 120 and 240, although the highest blood levels of the parent drug were measured 10-25 min after drug administration. An explanation for this delay might be that the pharmacological effects are due not to free morphine but to one of its metabolites.
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Treatment-refractory depressed patients who objected to electroconvulsive therapy (ECT) were given a series of anesthesias with isoflurane (Forane), a modern and established inhalation anesthetic. According to our hypothesis to be tested, the brief period of electrocerebral silence (ES), which can be observed shortly after the grand mal seizure in ECT, may be in itself a crucial biological determinant for the therapeutic effects of ECT. Isoflurane is the only drug known to effect an ES in the EEG in nontoxic concentrations, which does not result in adverse effects on any body organ including the brain; no seizure activity can be observed. ⋯ Rapid antidepressant effects were observed in 9 patients (p less than 0.0001). Effects were reproducible and lasted up to several weeks. No adverse effects of anesthesia were noticed.
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Analysis of the mechanisms underlying the clinical effects of different drugs is a vital part of psychopharmacology. It is fair to say, however, that such analyses have thus far met with little success. This lack of success can be traced to a variety of sources that have flawed the analytical process itself. Detailed examination of these sources not only illuminates the nature of the flaws they engender, but suggests ways in which the analytic process can be modified so as to be a more fruitful one.
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Clinical Trial
Traffic noise-induced sleep disturbances and their correction by an anxiolytic sedative, OX-373.
In a double-blind, placebo-controlled study the effect of nocturnal traffic noise and bedtime medication of a new benzodiazepine, OX-373, on objective and subjective sleep variables as well as on the quality of morning awakenings was investigated. 10 healthy subjects spent 17 nights in the sleep laboratory: 2 adaptation nights, 1 baseline night, 4 drug nights (20, 30, and 40 mg OX-373 and placebo) and 4 subsequent wash-out nights as well as 3 nights under traffic noise with placebo, 30 and 40 mg OX-373 and 3 subsequent wash-out nights. Nocturnal traffic noise with an intensity of 45-65 dB(A) induced sleep disturbances characterized by an increase in intermittent wakefulness and stage 1 and the number of nocturnal awakenings as well as by a decrease of spindle and REM sleep stages. Subjectively, a decrease of deep sleep and increase of light sleep and middle insomnia was reported. ⋯ In the morning, there were no signs of 'hangover', which was confirmed also by psychometry. Nor were there any clinically relevant alterations in blood pressure and pulse. Thus, our studies confirmed earlier pharmaco-EEG and psychometric investigations predicting OX-373 as well-tolerated anxiolytic sedative, and suggested further that traffic noise could eventually be utilized as an experimental provocative technique in order to induce a standardized sleep disturbance for early clinical drug evaluation of potentially hypnotic substances.