Hiroshi Yamadera

Effects of trazodone hydrochloride and imipramine on polysomnography in healthy subjects

Polysomnography was performed on eight healthy men with trazodone hydrochloride, imipramine and placebo. Trazodone hydrochloride increased slow wave sleep significantly. Imipramine prolonged rapid eye movement (REM) latency and decreased the percentage of REM sleep significantly. Trazodone decreased stages 1 and 2 sleep, while imipramine increased it. These findings suggest that the antidepressive effect of trazodone might be different from that of imipramine with the suppression of REM sleep.

Association between Delta Waves during Sleep and Negative Symptoms in Schizophrenia

We examined the effects of benzodiazepine (BZD) hypnotics and zopiclone (ZPC), a nonbenzodiazepine hypnotic, on sleep and psychiatric symptoms in schizophrenia, as well as the clinical correlates of these variables. Seven male schizophrenic patients chronically taking neuroleptics together with BZD were studied. We replaced BZD with ZPC and performed polysomnography (PSG) and Brief Psychiatric Rating Scale (BRPS) scoring before and after an 8-week ZPC treatment. The replacement of BZD with ZPC increased the mean amplitude of high-amplitude low-frequency delta waves on the frontal derivation recognized by period-amplitude analysis, and it decreased the BPRS negative-symptom score. Under the BZD treatment, the negative-symptom score correlated inversely with the mean amplitude of high-amplitude low-frequency delta waves. This correlation was weak and not significant under the ZPC treatment. Therefore, delta waves during sleep have a close correlation to negative symptoms in schizophrenia, and such a correlation could be influenced by hypnotics. Although these are preliminary findings, it was suggested that, compared with BZD, ZPC might be a beneficial hypnotic in regard to both sleep and negative symptoms of chronic schizophrenic patients.

Effects of vitamin B12 on bright light on cognitive and sleep–wake rhythm in Alzheimer‐type dementia

The present study investigated the effects of vitamin B12 (VB12) on circadian rhythm in Alzheimer‐type dementia (ATD). Twenty‐eight ATD patients were treated with bright light therapy (BLT) for 8 weeks. For the latter 4 weeks, half were treated with VB12 with BLT (BLT + VB12). We evaluated the cognitive state with Mini‐Mental State Examination and the circadian rhythm with actigraphy after the fourth and eighth week. After the first 4 weeks BLT improved the circadian rhythm disturbances and cognitive state especially in the early stage of ATD. Although the latter 4 week‐BLT caused no significant effects on the circadian rhythm; BLT + VB12 improved the vigilance level during the daytime. These results suggest that VB12 has some efficiency to enhance vigilance for ATD patients.

Effects of trazodone on polysomnography, blood concentration and core body temperature in healthy volunteers

Polysomnography, blood concentration and core body temperature recordings were performed on 12 healthy volunteers with administration of trazodone and placebo. Trazodone increased slow wave sleep (SWS), and decreased the average, the highest and lowest core body temperature significantly compared to placebo. The blood concentration of trazodone correlated positively with amplitude (the difference between the highest and lowest temperature) and %SWS during the first period of a sleep phase divided into three periods, and negatively with the lowest temperature. The appearance time of the lowest temperature correlated negatively with %SWS.

Open study of effects of alprazolam on seasonal affective disorder

Abstract Seasonal affective disorder (SAD) differs from depression with melancholic features in atypical symptoms, such as hyperphagia, hypersomnia and weight gain. Moreover, SAD is confined to a certain season of the year. We examined the pharmacological efficacy of alprazolam for treatment of patients with SAD. Six patients with SAD were treated with alprazolam at doses of 1.2 mg/day or 1.2 mg/day first and then 2.4 mg/day for 2 weeks. The improvement was evaluated by the change of total score of the SIGH‐SAD (with both 21 items HAMD and eight items atypical symptoms) and the clinical global impression (CGI). Although only two patients showed a remarkable improvement by SIGH‐SAD, all patients showed a higher than moderate improvement with CGI. Our findings suggest that alprazolam might be efficacious for certain SAD patients.

A study of ring 20 chromosome karyotype with epilepsy

Abstract We reported a 24‐year‐old woman with moderate mental retardation and partial epilepsy. She developed complex partial seizures at 3 years of age and generalized tonic convulsions at 9 years. Chromosome analysis revealed that she had mosaicism (87%) of 46, XX, and r(20) (p13, q13.3). Her electroencephalogram showed bilateral 2–3 Hz sharp and wave complex over the bilateral frontopolar, and centro‐parieto‐occipital areas. Computed tomographic and magnetic resonance image examinations were normal. Twenty‐five cases of ring 20 chromosome karyotypes (including this case) have been reported in the literature; 19 showed epilepsy, and 18 showed moderate mental retardation. Many of the patients showed growth retardation and minor malformations. The ring 20 syndrome is associated with a high incidence of epilepsy, particularly partial epilepsy. Our findings indicate that the main features of the ring 20 syndrome are partial epilepsy and mental retardation.

Study of Nocturnal Sleep and the Carryover Effects of Triazolam and Brotizolam Using Neurophysiological and Subjective Methods

In the present study, the effects of short-acting benzodiazepines on nocturnal sleep and the carryover effects of these drugs were studied. The study involved 10 young, healthy male subjects who had given their written informed consent to participate. Either a placebo (PLA), 0.125 mg triazolam (TRZ), 0.25 mg TRZ or 0.25 mg brotizolam (BRZ) was administered to the subjects in a double-blind crossover design by randomized allocation with a single oral administration at 23.00 h. A polysomnography (PSG) was recorded for each subject from 23.00 to 07.00 h the following day. Then, the Stanford Sleepiness Scale (SSS) and Kwansei Gakuin Sleepiness Scale (KSS) were checked between 07.55 and 08.00 h, and the sleep latency test (SLT) was performed between 08.00 and 08.20 h. Event-related potentials (ERPs) were then recorded with an oddball paradigm; the reaction time (RT) was measured simultaneously. According to the PSG, treatment with 0.25 mg TRZ resulted in a statistically significant increase in the percentage of stage 2 sleep (p < 0.05) and a reduction in the percentage of rapid eye movement sleep (p < 0.05) compared with PLA. None of the drugs had any effect on the percentage of slow-wave sleep compared with PLA. With regard to carryover effects, although none of the drugs had any effect on SSS, KSS, RT or ERPs, BRZ did cause a statistically significant decrease in sleep latency (p < 0.05) compared with PLA. TRZ (0.125 and 0.25 mg) and 0.25 mg BRZ exerted different effects on SLT. We suggest that these different effects are attributable to differences in the half-life of these hypnotics.

Relationship between the Effects of a Hypnotic Drug, Zopiclone, on Polysomnography and on Daytime EEGs

The correlation between the effects of zopiclone (ZPC), a nonbenzodiazepine hypnotic drug, on sleep polysomnograms and on daytime EEGs was examined in 12 healthy adult male volunteers. Sleep polysomnograms were recorded after a single oral administration of ZPC 10 mg or placebo according to the double-blind crossover method. Daytime EEGs were recorded after the administration of ZPC, 7.5 mg, or placebo in the same manner, and recorded for 3 min with closed eyes at rest. Then, square roots of the absolute power (amplitude) of the delta-, theta-, alpha-, and beta-activities were calculated from the power spectrum obtained by the fast Fourier transform method. As a result, ZPC decreased the percentage of stage 1 sleep in total sleep time, while it increased the percentage of stage 2, total sleep time, and time of slow wave sleep in the first and second sleep cycles (SWS 1 and 2). Changes in SWS 1 and 2 correlated positively with the amplitude changes in daytime resting delta-activity. This indicates that the increase of SWS due to ZPC could be related to the change of delta-activity in the daytime resting EEG.

The REM rhythm of depression in daytime and sleep EEG.

Y.O. Major depression. A 47-year-old female. Family history: n.p. Past history: n.p. Present history: Three months before admission, she suffered from insomnia, felt loss of energy, gradually became pessimistic and started to lose weight. She was given medication of amitriptyline 75 mg and bromazepam 6 mg during the day, and amitriptyline 25 mg and haloxiazolam 10 mg before sleep until her discharge. She recovered from the depressive state in two months from admission. Experimental Design

The study of sleep effect in the night and the next morning of triazolam and brotizolam on the polysomnography and subjective sleep rating scale

Abstract We studied the sleep effect, the carry over effect (sleepiness) on polysomnography (PSG), the sleep propensity test (SPT), the subjective sleep rating scale for the ultra short acting hypnotics triazolam and short acting hypnotics brotizolam. Ten healthy male volunteers were used for double blind crossover design by randomized allocation with a single oral administration. Informed consent was obtained from all subjects. Placebo (PL), triazolam (TL, 0.125 mg), triazolam (TH, 0.25 mg) and brotizolam (BR, 0.25 mg) were administered at 11 p.m. PSG was recorded from 11 p.m. to 7 a.m. in the next morning. Then, Stanford Sleepiness Scale (SSS) and Kwansei Gakuin Sleepiness Scale (KSS) were checked before 8 a.m., and SPT was recorded at 8:00–8:20 a.m. In PSG of total sleep, TH decreased the frequency of stage shifts significantly ( p p p p