General considerations of sleep and sleep deprivation.

The state of affairs in the field of sleep deprivation has been discussed in this chapter. Special emphasis was placed on total sleep deprivation, a domain in which the most important work has been done since the dawning of this century, and especially during the 'golden years' between 1955 and 1975. After a discussion of the biorhythmical aspects, the general condition of sleep deprived subjects was pointed out. Psychological-psychiatric changes and impairment of performance were further topics of discussion, followed by sections on EEG, neurological, autonomic and metabolic changes. The relationship of SD to epileptic phenomena and endogenous depression has been considered. The characteristics of recovery sleep have also been presented. Most of the author's impressions are based on personal data, and especially on 2 subjects who underwent most elaborate testing. A discussion of partial sleep deprivation and selective sleep deprivation is also included.

[Sleep disorders. 2: Specific recommendations for ambulatory drug therapy]. / Schlafstörungen. Teil 2: Konkrete Vorschläge für die ambulante medikamentöse Therapie.

Most sleep disturbances (burring those occurring in the scope of acute psychoses) can be treated ambulatory. In chronic and syndromatic sleep disturbances it is recommended to carry out an intensive (cure type) therapy with i.v. infusions. After 10-20 infusions (antidepressants, neuroleptics, tranquilizers), slowly a transfer is made to peroral treatment where the preparations are incrementally lowered and withdrawn (to prevent rebound phenomena). An acceptable hypnoticum finalizers treatment. Numerous alternative therapy plans are explained.

[Sleep disorders. 1. Classification and incidence]. / Schlafstörungen. Teil 1: Klassifikation und Verbreitung.

Twenty years (1963-1983) of experience with polyhypnography (polygraphical all night recordings of sleep: EEG, EOG, ECG, EMG etc.) and ambulatory treatment of insomnia consequently resulted in the fact that sleep disturbances are not easy to classify. Procedure is to evade to framework-diagnosis, whereby only for practical purposes tab. 2 is provided. Approximately 25-32% of the population suffer from sleep disturbances resulting in lack of sleep.

Polygraphical sleep recordings in insomniac patients under zopiclone or nitrazepam.

Zopiclone, a new hypnotic with an original chemical structure, was compared in a sleep laboratory study with nitrazepam according to a double-blind, parallel group randomized design. Zopiclone (7.5 mg) and nitrazepam (5 mg) were each given for 14 nights to 5 insomniacs; a placebo washout period of 4 nights and a placebo withdrawal period of 10 nights were included in the design. Both drugs were found to be immediately and lastingly effective. Some slight insomnia rebound was found with nitrazepam, but not with zopiclone. Stage 2 was decreased, slow wave sleep (SWS) increased, and rapid eye movement unchanged by both drugs: however, only nitrazepam increased rapid eye movement latency. The differences between the effects of the drugs were quite limited. However, 3 out of 50 comparisons favoured zopiclone and none nitrazepam.

Polygraphical sleep recordings in insomniac patients under zopiclone or nitrazepam.

Zopiclone, a new hypnotic with an original chemical structure, was compared in a sleep laboratory study with nitrazepam according to a double-blind, parallel group randomized design. Zopiclone (7.5 mg) and nitrazepam (5 mg) were each given for 14 nights to 5 insomniacs; a placebo washout period of 4 nights and a placebo withdrawal period of 10 nights were included in the design. Both drugs were found to be immediately and lastingly effective. Some slight insomnia rebound was found with nitrazepam, but not with zopiclone. Stage 2 was decreased, slow wave sleep (SWS) increased, and rapid eye movement unchanged by both drugs: however, only nitrazepam increased rapid eye movement latency. The differences between the effects of the drugs were quite limited. However, 3 out of 50 comparisons favoured zopiclone and none nitrazepam.

Age-specific doses of lormetazepam as a night sedative in cases of chronic sleep disturbance.

Lormetazepam, a new benzodiazepine derivative, was tested under double blind conditions in order to find the optimal dosage for different age groups of out-patients. 120 patients suffering from chronic sleep disturbance were included in the study: a younger group (age 20 to 55) and an older group (age 56 to 85 years). Four different doses were given to each age group: 0.5, 1.0, 2.0, and 3.0 mg to the younger group and 0.5, 1.0, 1.5, and 2.0 mg to the older group. A pre-placebo week (i.e. when all patients received placebo) in which baseline data were recorded preceded the two verum weeks, and these were followed by a post-placebo or withdrawal week (again all patients receiving placebo). The level of significance accepted for statistical decisions was alpha = 0.05. No differences in effects between the different doses were observed with regard to sleep pattern variables (sleep latency, sleep duration, frequency of awakenings, sleep quality, occurrence of 'bad' dreams) with the exception of sleep quality which was better in the older group than in the younger group after 0.5 mg in week 2. Considerable differences with regard to hangover feelings the next morning and during the next day (morning feelings, tranquility, alertness, and concentration), comparison of the effects of discontinuing therapy upon the above-mentioned sleep pattern variables and small differences in side effects--which were few--led to the following conclusion: --0.5 mg stood out as the best dose for the older group. --None of the dosages given to the younger group emerged clearly as superior. However, it would seem that the 1 mg dose should be the dose recommended, since fewer unfavourable scores and side effects appeared after this dose.

Polygraphic sleep recordings before and after the administration of flunitrazepam.

By means of polygraphic sleep recordings (EEG, EOG, EMG, ECG, EDG, Respirogram, Positogram), neurologic-psychologic investigation and questionnaires on subjective feeling, ten patients aged from 22 to 40 years (mean: 29 years), who suffered from irregular disturbances in falling asleep and in sleeping continuously, were examined over a period of ten consecutives nights. The first investigation night was reserved for adaptation of the patients and could therefore not be evaluated. On the following three evenings placebo (Placebo I) was given, then 2 mg of flunitrazepam for the ensuing three nights and placebo again (Placebo II) for the last three nights. Thus, 90 investigation nights could be evaluated. 1. Latency times until the patients fell asleep and up to the first deep sleep were reduced significantly by the active preparation. Latency times up to the first REM-phase were prolonged. 2. The frequency of nocturnal awakenings was lessened significantly. Thus, disturbances in sleeping continuously disappeared for the duration of the treatment. Duration of wakefulness after having woken during the night decreased considerably. 3. Duration of wakefulness during the total night was reduced considerably, deeper sleep stages, such as D (stage III) and E(stage IV) were prolonged. 4. Duration of the REM-phases was reduced slightly. This reduction was not significant according to the t-test. 5. According to these results, the preparation showed a clear effect. A placebo-effect can be excluded, since the improvements mentioned were not found when placebo was given before administration of the medication and afterwards (Placebo I and II). 6. When comparing our results to those of other authors, who described the effects of various preparations, we found that the substance flunitrazepam showed different effects.

[Polygraphic recording of sleep under the influence of Plantival plus]. / Polygraphische Registrierungen des Schlafes unter Wirkung von Plantival plus

10 patients with moderate non-psychotic sleep disturbances were investigated polygraphically for a total of 14 nights each. These 14 nights were subdivided into 4 test series: Placebo was given during the first, Plantival plus during the second and third and placebo again during the fourth series. The results showed that wakefulness decreased after the application of Plantival plus and that there was an increase in deep sleep. These effects could be observed mainly during the first hour of sleep and disappeared gradually during the later sleeping hours. REM-phases were not influenced by the medication. Due to these observations, Plantival plus should mainly be applicated when disturbances in falling asleep and problems in sleeping continuously occur. In case interrupted sleep in the early morning hours has been found, this preparation could be applicated only in combination with other kinds of treatment.

Statistical evaluation of polygraphic investigations of pentoxifylline.

Changes in the electro-encephalogram, and in the electro-oculogram electromyogram, ECG, blood supply, blood pressure, electrical skin activity and neurological/psychiatric findings, were investigated in 100 patients given single administrations of 200 mg of pentoxifylline (BL 191). It is concluded from the changes in the EEG wave patterns that pentoxifylline produces a beneficial effect on the cerebral processes contributing to bio-electrical brain activity. Pentoxifylline can be classed as a substance with microcirculatory/metabolic effects on the brain, which lead to stimulation of psychomotor behaviour.

[On the efficacy of a spleenic dialysate (M 40,412) in disturbed potency (author's transl)]. / Uber die Wirksamkeit eines Milzdialysates (M 40,412) bei Potenztörungen

By means of a combined phallographic-exploratory method and using statistical classification we were able to confirm clinically the potency enhancing action of a spleenic dialysate (M 40,412, Solcosplen). The remarkable alleviation of chronic and acute disturbances of potency can be explained not only by the elevated serum testosterone levels but likewise by biochemical mechanisms of action in the target organ, as was demonstrated by a research group. The treatment of potency disorders of different genetical origins yielded as the outstanding conclusions: 1. The interdependence of dream- and erection phases, usually injured in disturbed potency, could be restored by M 40,412. 2. The effect of 40,412 was the more striking the more pronounced were the initial values. 3. A particular type of experiencing (feeling of inferiority and disturbed contact) appears to respond prevailingly well to M 40,412. Further clinical studies are suggested.

[Polygraphic sleep recordings in patients with endogenous depression before and after treatment with amitriptyline-N-oxide (author's transl)]. / Polygraphische Registrierungen des Schlafes bei endogen depressiven Patienten vor und nach der Behandlung mit Amitriptylin-N-oxid

15 endogenous-depressive patients were treated with 3 X 20 mg amitriptyline-N-oxide for 20 days. Polygraphic sleep recordings were taken during the first seven and last six nights. In a single-blind study the patients were given placebo for the first four days, amitriptyline-N-oxide was applied during the following 13 days and on the last three days placebo was given again. The statistical evaluation showed the following results: a) Latency times up to the first deep sleep and to the first REM-phase decreased under the effect of the substance. b) Relative sleep duration (without wakefulness) increased. c) Actual sleep duration (without wakefulness and stage A) was similar. d) The frequency of awakenings during the night diminished under amitriptyline-N-oxide and increased somewhat when placebo was given again. The original values were not reached. The frequency of awakenings from REM-phases increased during the first three nights of medication and decreased in the last three nights the substance was administered. When placebo was given again, the original values were exceeded. e) Duration of wakefulness after waking up during the night decreased under amitriptyline-N-oxide and increased when the medication was discontinued. Here again the original values were not reached. After waking up during the night most waking time was spent in stage C. A placebo effect can be excluded. The effects of amitriptyline-N-oxide are compared to those of hypnotics, other antidepressants, antipsychotics and tranquilizers in the discussion.