Pharmacological and medical considerations in hypnotic use.
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Anti-Anxiety Agents↗
Biomedical subjects
T Roth
Publications and source records attributed to T Roth.
Biological markers for depression in chronic pain.
Patients with chronic psychogenic pain appear to suffer from a specific depressive type of disease, with somatized pain as the prime expression of a concealed mental agony (pain-prone disorder). This view is supported by clinical, premorbid, and psychodynamic findings, as well as by the presence of biological markers including a family history of affective disorders and response to antidepressants. Additional biological markers of depression include shortened rapid eye movement (REM) latency in sleep and nonsuppression in the dexamethasone suppression test (DST). The study of both markers in 20 consecutive pain-prone patients with insomnia showed clearly abnormal REM latency and/or DST nonsuppression in one half of the otherwise homogeneous group. There was high correlation between DST cortisol level and REM latency. both biological markers tend to predict response to antidepressants. The findings confirm that the pain-prone disorder can be viewed as a variant of depressive disease.
Depressive Disorder↗
Disturbed sleep in patients complaining of chronic pain.
Polygraphic recordings of the sleep of patients complaining of insomnia has led to recognition of specific patterns of disturbed sleep corresponding to different etiologies of insomnia. This study presents results of polygraphic recordings of the sleep of 26 patients with chronic pain for which no physical cause can be found. All 26 also complained of insomnia. Sleep parameters of this group were compared with those to two other groups also complaining of insomnia: 12 patients whose disturbed sleep was judged secondary to psychiatric disorder, and 16 patients with the subjective complaint of insomnia in whom no objective evidence of sleep disturbance could be demonstrated. The three groups differed significantly in terms of their sleep parameters. The pain patients slept less than the subjective insomnia patients. The sleep disturbance of the psychiatric patients was more severe than that of the chronic patients. Several chronic pain patients showed evidence of nocturnal myoclonus; several also showed alpha rhythm intrusions into their sleeping electroencephalograms. The study verifies that chronic pain patients do experience significant sleep disturbance and raises several questions concerning relationships among chronic pain, sleep disturbance, and psychiatric illness, particularly depression.
Adult↗
Relationship of psychopathology to insomnia in the elderly.
Three groups of 18 volunteers each (nine men and nine women) were selected on the basis of age and the response to a sleep status questionnaire. Younger subjects (mean age, 43.8 years) who complained of difficulty in falling asleep or in staying asleep or of awakening too early were compared for evidence of psychopathologic signs with older subjects (mean age, 68.5 years) who had sleep-related complaints and with older subjects (mean age, 71.3 years) who did not have sleep-related complaints. Older subjects with insomnia complained more frequently of having trouble staying asleep and of awakening too early (P less than 0.05), whereas the younger subjects with insomnia complained primarily about difficulty in falling asleep (P less than 0.005). On a short form of the Minnesota Multiphasic Personality Inventory (MMPI-168), the number of elevated scores indicating pathologic disturbances (T score less than 70) was higher (p less than 0.05) for the younger subjects with insomnia (2.5 high scores) than for older subjects with insomnia (0.7 high scores) or for older normal sleepers (0.4 high scores). These results imply that although in younger persons psychopathologic disorders are associated with insomnia, psychopathic disorders usually are not the cause of insomnia in the elderly.
Age Factors↗
Protriptyline in the treatment of sleep apnoea.
Nine patients with obstructive sleep apnoea were treated with 5 to 20 mg of protriptyline each night for two to 18 months. In four patients, there was dramatic, sustained improvement in symptoms and measured sleep quality and apnoea frequency and duration. There was no improvement in two patients and three developed intolerable side-effects preventing adequate treatment. Apnoea frequency was the only apparent predictor of responsiveness. Those with fewer than 30 episodes of apnoea per hour consistently improved. Only two of four patients with more than 60 episodes per hour improved. These results provide additional evidence that a carefully monitored trial of protriptyline may benefit selected patients with mild to moderate obstructive sleep apnoea.
Adult↗
Sleep, arousals, and oxygen desaturation in chronic obstructive pulmonary disease. The effect of oxygen therapy.
In order to assess the role of hypoxemia in the sleep disruption of patients with COPD, we studied patients breathing air and oxygen during sleep. In 24 patients with COPD, we determined the 95% confidence bands for arterial O2 saturation (SaO2) in the various sleep stages. The lowest mean SaO2 was during REM sleep. Patients spent 22.4% of the night desaturated (SaO2 more than 5% below awake SaO2). Apneic episodes were uncommon and occurred in only 2 patients. When compared with established age-matched normal subjects from another center, poor sleep quality was indicated by reduced sleep time, increased sleep stage changes, and increased arousal frequency. Oxygen therapy had no apparent effect on sleep quality. Arousal frequency was independent of measurements of awake pulmonary function or chemical control of breathing. During room air breathing, arousals were strongly associated with periods of arterial oxygen desaturation. However, relief of the hypoxemia with supplemental oxygen had no effect on arousal frequency. This suggests that it is not hypoxemia per se, but an associated phenomenon such as hypercapnia that causes the arousals.
Aged↗
The effects of doxepin HCl on sleep and depression.
The effects of doxepin hydrochloride (Adapin) on sleep and depression were evaluated in nine depressed patients with documented sleep difficulties. All subjects were screened for depression on the Hamilton Psychiatric Rating Scale. Sleep disturbance was measured by all-night polysomnography. Doxepin in doses of 75 and 150 mg/day significantly improved sleep efficiency, as evidenced by decreased sleep latency and increased total sleep time. After 2 weeks of treatment, REM latency and percent REM time were dramatically changed. Maximal improvement in depression occurred after 2 weeks of doxepin therapy and at the 150 mg dose.
Adult↗
Waking and dreaming mentation: a test of their interrelationship.
The relationship of dream content to the immediate pre- and post-sleep mentation of the dreamer was studied using the electrophysiologically defined state of REM (rapid eye movement sleep) as dream collection time. The subjects were 20 male and 20 female volunteers, ages 18 to 25. Each slept for three non-consecutive nights in the laboratory and had REM awakenings and pre- and post-sleep verbal content collected. REM reports and waking verbal samples were scored on 18 Hall-Van de Castle content scales. The interscorer agreement of two judges was 0.90. Product moment correlations were performed on each of the 18 content categories between content of the REM reports and of the waking verbal samples. Across all 40 subjects, 9 out of 18 correlations were statistically significant and 14 of the 18 were positive. The zero-mu test indicated that the distribution of the 18 correlations was significantly different from zero. Thus it can be concluded that dream content is related to the psychological parameters of waking life, in a continuous rather than compensatory manner.
Adolescent↗
Dose-related effects of flurazepam on human sleep-walking patterns.
Two consecutive nights of flurazepam at each of 15, 26, and 45 mg were compared to placebo in a Latin-square double-blind crossover design using 24 healthy young-adult males. Flurazepam had significant hypnotic effects on objective and subjective measures of efficacy: shorter sleep latency, longer sleep time, and fewer awakenings. It also induced morning sedation along with decrements in cognitive performance. Flurazepam had dose-related impacts on both human and computer-scored EEG-EOG parameters: less stages 3 + 4 and decreased EEG delta, less stage 1 REM and decreased REM density, more stage 2 and increased EEG spindling. Also, EEG alpha and movement artifact were decreased and EEG beta was increased. Only a few of the EEG-EOG variables and none of the subjective indices had cumulative changes on the two drug nights. Stage shifting was unaffected at the two lower doses on the first night but decreased at all three dose levels on the second night; percent stages 3 + 4 was unaffected on the first night but decreased at all dose levels on the second night. The rate of delta waveform activity was also diminished by a greater amount on the second night. This study conclusively established that flurazepam affects the EEG-EOG architecture of sleep on each of the first two nights of administration.
Adult↗
A dose response study of the hypnotic effectiveness of alprazolam and diazepam in normal subjects.
One group of eight normal young males was administered three doses of alprazolam (0.25, 0.5 and 1.0 mg) and placebo, while a second group of eight normal young males was given three doses of diazepam (2, 5, and 10 mg) and placebo in the same design. All subjects slept in the sleep laboratory for 10 nights, 2 consecutive nights each week for 5 consecutive weeks. The first 2 nights served as adaptation. During the next 4 weeks subjects received a random dose of alprazolam (or placebo) or a random dose of diazepam (or placebo) each week. Similar dose-related benzodiazepine effects were found on sleep with both medications. Alprazolam reduced percent stage 4 and REM sleep and increased stage 2 sleep and latency to REM. Diazepam decreased percent stage 1 and increased percent stage 2 sleep. No drug by dose interactions were found. It was concluded that, while both drugs had similar effects on sleep, alprazolam showed significant effects on REM sleep parameters and might be evaluated for possible antidepressant effect.
Adolescent↗
Dose-related effects of phenobarbitone on human sleep-waking patterns.
1 Twenty-four healthy male subjects had two consecutive drug nights at 2-week intervals using placebo and 80, 140 and 240 mg doses of phenobarbitone in a double-blind cross-over design. 2 Phenobarbitone produced significant dose-related decreases in sleep latency and number of awakenings, along with increased total sleep time. 3 Both subjective and objective measures of sleep indicated the presence of cumulative (first v second night) effects of phenobarbitone, especially decreases in the number of awakenings and in delta waveform activity. 4 Measures of REM sleep were highly sensitive to phenobarbitone. The high dose decreased REM density to 30% of baseline on the first night and to 18% on the second night. 5 EEG alpha activity was decreased, beta activity was increased and sigma spindle activity was unaffected by phenobarbitone during sleep. 6 Subjects experienced some impairment of cognitive performance along with residual sedation the following morning.
Adult↗
Effects of benzodiazepines on sleep and wakefulness.
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Anti-Anxiety Agents↗
Evaluation and diagnosis of persistent insomnia.
The authors placed 84 patients who complained of insomnia into 10 diagnostic categories on the basis of medical, psychiatric, and polysomnographic evaluations. Only half the patients had objectively defined difficulty inducing or maintaining sleep when compared with 20 normal control subjects. However, all but 16 patients showed polysomnographic evidence of some sleep disorder. Diagnostic categories within the insomnia groups could be distinguished from one another by polysomnography. Patients in only 3 of the 10 diagnostic categories showed evidence of psychological distress on the MMPI; patients in the other 7 categories displayed few psychological symptoms. These results have implications for the treatment of insomnia.
Conditioning, Psychological↗
The acute effect of quazepam on the sleep of chronic insomniacs. A dose-response study.
The present study investigated the effects of the benzodiazepine, 7-chloro-5-(2-fluorophenyl)-1,3-dihydro-1-(2,2,2-trifluoroethyl)-2H-1,4-benzodiazeepine-2-thione (quazepam), on hypnotic efficacy and sleep staging in chronic insomniacs. We evaluated the acute withdrawal effects of several doses (0, 7.5, 30 and 45 mg) of quazepam. The effects of the different doses were assessed using both objective (polysomnographic) and subjective sleep parameters in a double blind repeated measures design (n = 15). The results indicated that daily administration of quazepam over three nights produced increased effects on sleep which suggested drug accumulation. Lower doses (7.5 and 15 mg) only had significant effects on sleep (sleep induction and maintenance and sleep architecture) with three days of administration, while 45 mg of quazepam produced significant effects on the first night of drug administration. Contrary to previous research investigating longer periods of administration, acute administration of low doses of quazepam did not produce carryover effects on withdrawal, while higher doses did. The accumulation of the parent compound or its active metabolites thus seemed to mediate these effects on sleep in a dose related fashion.
Adolescent↗
Personality differences between insomniac and non-insomniac psychiatry outpatients.
The relationship between self-reported measures of sleep disturbance and psychopathology was investigated. Previous studies on this topic have failed to use appropriate control groups. The current study examined the relationship between sleep disturbance and personality using insomniac and non-insomniac outpatient counseling clients. The results confirm the significant and positive relation between emotional disturbance and insomnia. The insomniac group showed the expected pattern of MMPI abnormalities (elevated D, Hy, Pt and Sc). However, only the Pt scale of the MMPI and the Cornell Medical Index significantly differentiated the two groups. This suggests that characteristics such as obsessional worry which lead to elevated Pt scores play a more important and unique role in insomnia than previously hypothesized.
Adult↗
The effects of flurazepam, lorazepam, and triazolam on sleep and memory.
This study evaluated the effects of flurazepam 30 mg, lorazepam 4 mg, triazolam 0.5 mg, and placebo upon sleep and memory in eleven normal male subjects continuously monitored for nighttime EEG, EOG, and EMG recording. Subjects received each drug or placebo for two consecutive nights per week for 4 weeks in a repeated measures, double-blind, Latin Square design. Three hours post-administration, subjects were awakened and presented with a series of tasks. Recall was assessed immediately following task presentation and after the final morning awakening. The results showed that every drug significantly decreased stage 1, increased stage 2, and produced no change in stage 3--4 sleep in comparison to placebo. Only lorazepam significantly decreased REM percent. Post-drug recall was significantly decreased in comparison to placebo at night and was further decreased in the morning. Morning recall was significantly poorer when the return to sleep was 2.5 min or less than when the return to sleep was greater than 5 min following the nighttime awakening in all drug conditions. These results indicate that 1. failure of memory consolidation rather than failure of retrieval is the most likely explanation for the morning memory loss and 2. hypnotic drug properties, measured by latency to fall back asleep, affect memory consolidation.
Adult↗
The efficacy of triazolam and chloral hydrate in geriatric insomniacs.
A double-blind crossover study was performed to evaluate the efficacy of hypnotics in geriatric insomniacs. Twenty-seven patients with a mean age of 70 years (range 60-94 years) received each of five treatments on 5 consecutive nights. The treatment conditions, consisting of chloral hydrate 250 and 500 mg, triazolam 0.25 and 0.50 mg, and placebo, were administered using a Latin Square design. Subjective estimates of sleep were collected in the morning following each treatment night. The patients' global evaluation of effectiveness indicated that triazolam 0.25 mg and 0.50 mg improved sleep more than placebo, while chloral hydrate 250 and 500 mg were not better than placebo. Triazolam 0.50 mg was felt to be significantly better than either dose of chloral hydrate. In addition, triazolam 0.50 mg was found to significantly decrease the patients' estimates of their sleep latency. Patients estimated their total sleep time to be longer following the use of triazolam 0.25 mg as compared to choral hydrate 500 mg, and their estimates of the number of awakenings was significantly lower on triazolam 0.50 mg than it was on chloral hydrate 500 mg or placebo.
Aged↗