Effects of the novel acetylcholinesterase inhibitor SDZ ENA 713 on sleep in man.

A novel brain-selective acetylcholinesterase inhibitor, SDZ ENA 713, is under development for the treatment of dementia of the Alzheimer type. To determine the threshold dose for central activity, single doses of the compound were administered to 20 young male volunteers in a double-blind cross-over design and the effects on the sleep electroencephalography studied. The first group of eight volunteers received in random order: placebo, 0.5 mg; and 1 mg SDZ ENA 713. The second group of 12 volunteers received: placebo, 1.3 mg; and 2 mg SDZ ENA 713. Sleep quality was not affected by the study medication, which was well tolerated by all subjects. A statistically significant increase in rapid-eye movement sleep density was observed after doses of 1 mg, 1.3 mg, and 2 mg. Rapid-eye movement latency and slow-wave sleep were not altered. The results demonstrate that SDZ ENA 713 is centrally active in man at well-tolerated doses.

The use of psychotropic drugs in the treatment of cancer pain.

Treatment of cancer pain with psychotropic drugs offers the following advantages: It helps patients who do not normally respond to the usual analgesics. The effect of analgesics is enhanced. There is reduction in the use of analgesics. The antidepressive and anxiolytic effects improve the psychological condition. The use of opiate analgesics may be avoided or delayed.

[EMG abnormalities in REM sleep of addicted patients]. / EMG-Störungen im REM-Schlaf bei Suchtpatienten.

EMG abnormalities such as short muscle twitches and marked increase of muscle tone can be identified during REM sleep. We compared the polysomnographic parameters of ten alcoholic patients who were sober and medication-free for at least four weeks, five methadone-substituted politoxicomanic patients (MSP) and ten healthy control patients. The alcoholics and the MSP showed significantly more twitches than the control patients, and the MSP had significantly more tonus increase than the alcoholics and the controlled. The polysomnographic measures differed significantly between the groups in sleep architecture. The alcoholics had significantly less slow-wave sleep (SWS) and more REM sleep, the MSP had a longer REM latency and more of stage 2. Dividing all subjects along the median of the two EMG abnormalities, the group which showed a high number of twitches had significantly less SWS with a compensatory increase of stage 2. The two EMG measures, which were scored additionally, may provide a useful additional information in the differentiation of sleep disturbances in alcoholic and methadone-substituted patients. The interaction between the occurrence of these EMG abnormalities and the other polysomnographic measures in our study needs further clarification.

[Psychopharmaceutic agents in pain treatment]. / Psychopharmaka in der Schmerzbehandlung.

The chronic pain state can be psychologically induced; on the other hand, pain lasting for months and years can lead to psychopathological alterations. In this context one speaks of the pain-sick patient or of the pain disease. Due to the introduction of psychopharmaca in the treatment of severe chronic pain states, significant progress has been made. Particularly the combination of antidepressants with neuroleptics leads to a substantial reduction of pain. Such a therapy allows substantial savings of analgesics. The indication, the dosage, the mechanism of action and the side-effects of neuroleptics and antidepressants as drugs in the service of pain reduction among patients suffering from chronic pain are covered in the paper.

[Convulsions caused by psychopharmaceutical agents]. / Konvulsion durch Psychopharmaka.

The convulsive effect of psychopharmaca depends on the 'epileptogenic' potency inherent to the substance, the sedation, the individual convulsion-threshold, epileptic disposition, paroxysmal EEG alterations, acute and chronic organic brain syndromes, alcoholism, high dosage, abrupt discontinuation of medication and forced onset of medication. The literature and the experience show convulsions to occur extremely rarely as a result of antidepressant and neuroleptic medication at standard doses. Caution is needed for patients at risk.

[Pain in society and in medicine]. / Schmerz in der Gesellschaft und in der Medizin.

Pain as a psychophysical experience and in particular its treatment have always been--and are particularly nowadays--an essential problem in medicine. Beyond that pain has a multitude of connections to human existence. The phenomenon of pain appears in almost all areas of art (painting, sculpture, music and poetry), philosophy and the religions. In the arts pain and its expression is often proof of the noblest esthetic-spiritual creativity; in medicine on the other hand it touches only the depth of human existence, then, when severe, chronic pain leads to disintegration of personality. From these propositions emerges that pain is not only sensed but is also a sentiment. Both belong together in an inseparable act of passive acceptance and active creative experience. Whereas the phenomenon of pain has earlier been seen in its alternative respective components such as physical or spiritual, it is in modern times, following the holistic perception of medicine, regarded as complementary. This complementary view is also the basis for the various forms of combined pain-treatment in use today.

[Acute sedative effect of a herbal relaxation tablet as compared to that of bromazepam]. / Die sedative Akutwirkung eines pflanzlichen Entspannungsdragées im Vergleich zu Bromazepam.

The relaxing effect and the systemic tolerance of a single oral dose of Valverde relaxation dragées have been examined double-blinded against 3 mg of bromazepam and placebo in groups of 20 healthy male volunteers each treatment. The systemic tolerance was assessed at the end of the examination, relying on spontaneous remarks or comments made on side effects upon questioning. As the four plants from which Valverde has been extracted (valerian, balm, passion-flower, and pestilence wort) have a reputation of being tranquilizing agents with spasmolytic effect, not only this effect needs to be demonstrated, but also sedative side effects and impairment of vigilance must be assessed to explore the risk for accident proneness. We expected that the relaxing-tranquilizing effect of bromazepam as well as of Valverde relaxation dragées compared with placebo is perceived subjectively. A potentially existing impairment of performance due to Valverde was assumed to be milder than impairment due to bromazepam. The study, however, inspite of a sophisticated test battery with extended testing, could not detect any effect for either of the two drugs; nor could it detect a side effect. The sedation and reduction of vigilance observed in a pre-study without placebo controls (Gerhard and Hobi, unpublished) was explained by natural fatigue which appeared in the course of the morning also under placebo. Therefore, sedative side effects, leading to an impairment in performance, can be excluded for both drugs at the studied dose level.

[Epilepsy in middle and older age]. / Epilepsien des mittleren und höheren Lebensalters.

Single fits and epileptic illness are more frequent in advanced age; their occurrence reaches the same frequency as in the neonatal period. Their origin and the possibilities of treatment are tightly connected to the process of ageing, a fact that requires special consideration. The main reasons for new epileptic attacks in the group of age 65 or more are structural changes, i.e. ischemic infarctions, tumors and atrophic involution. For certain patients, the use of antiepileptic drugs may be limited by unavoidable side effects. Complete cure of the attacks in advanced age is rare, but with a well selected treatment sufficient control is often possible.

[Dyskinesias in a clinical population. Results of a comparative follow-up]. / Dyskinesien in einer klinischen population. Ergebnisse einer Nachuntersuchung im Vergleich.

646 patients of a psychiatric clinic (272 m, 374 f) have been examined for tardive dyskinesia by two physicians, a neurologist and a psychiatrist. 192 patients exhibited some dyskinetic disturbances (32%). Thus the prevalence in this sample is rather high. The applied rating scale has proved successful (interrater reliability of .88). A year later the same sample of 192 patients (shrunk by 63 patients due to releases from the clinic and cases of death, non availability) was reexamined by the same physicians. The following results are noteworthy: Age exercises the strongest influence on the severity of tardive dyskinesia; women are more heavily affected than men; the clinical differential diagnosis has little influence on the degree of the disturbance; the same holds true for duration of therapy and dose. In the reexamination (computed as a dependent sample on the basis of 129 complete cases) a reduction of the intensity of dyskinesias has been observed. The results are discussed thoroughly from a clinical and methodological point of view.

[A new rating for the detection of dyskinesias. Clinical and metric problems]. / Ein Fremdrating zur Erfassung von Dyskinesien. Die klinische und metrische Problematik.

In context with a study on tardive dyskinesia in a psychiatric clinic, two ward psychiatrists rated patients with respect to extrapyramidal dyskinetic reactions. (Age, sex, type of neuroleptic treatment and diagnosis were taken into account.) Few multiple dyskinesias have been found. When they occur at all then predominantly in the area of head and limbs; dyskinesia of the eyes and joints of knee and elbow are rare. Although three factors can be extracted by a factor analysis (head, trunk, and limbs) the insufficient reliability of single subscales becomes evident. In spite of these metric problems the use of the rating in the existing version is justified for clinical and educational reasons. It is recommended to secure statistical reliability mainly with the total score which provides a good interrater reliability (.88 and .82) and a sufficient internal consistency (.70). For analyses of the course we suggest a data screening at the level of single items or subscales.

[The treatment of chronic pain with psychotropic drugs]. / Die Behandlung chronischer Schmerzen mit Psychopharmaka.

The results of long experience with psychotropic drugs in the treatment of chronic and severe pain resistant to ordinary therapy are reported. In 103 in-patients with chronic and severe pain caused by neurological conditions and treated with a combination of thymoleptics and neuroleptics, 82% showed a marked improvement. These encouraging results are compared with the results of other studies published in this field. The pharmacological basis of this good action is briefly discussed, together with the advantages of the use of psychotropic drugs and especially the combination of thymoleptics and neuroleptics. A clearcut dosage schedule for in- and out-patients using imipramine (Tofranil) or chlorimipramine (Anafranil) and haloperidol (Haldol) is established.

[Psychopharmaceuticals in chronic pain]. / Psychopharmaka bei chronischen Schmerzen.

Since the introduction of psychotropic drugs, especially carbamazepine (Tegretol), antidepressants and neuroleptics, the treatment of all chronic and severe pain has been decisively improved. Psychotropic drugs have an analgesic effect, and potentiate and economize analgesics. The essential advantage is the absence of dependence during long term treatment. The alleviation of pain is caused by "depersonalization of the pain" or by a "pain removing effect" through a favourable influence on central pain perception and sensation. They prevent the sometimes fatal vicious circles: pain leads to anxiety leads to depression leads to pain etc. or: pain leads to increased central nervous excitability leads to psychic reaction leads to pain etc. The antidepressants induce a change in the central metabolism of serotonin and noradrenaline. Serotoninergic and noradrenergic (pain)-inhibitory neurons are involved in the analgesic effect of exogenous and endogenous opiates. Some neuroleptics (e.g. haloperidol) have a stereospecific binding capacity to opiate receptors and have an opiate-agonistic effect.