Proposed dose equivalence between clonazepam and pramipexole in patients with restless legs syndrome.

BACKGROUND: Dopamine agonists are accepted as the first-line medications for restless legs syndrome (RLS). In some Asian countries, clonazepam is one of the prevalent medications for RLS because of its effect on sleep disturbances. To date, there have not been any studies that examined equivalent doses of pramipexole and clonazepam. To evaluate equivalent doses of pramipexole and clonazepam in RLS, we investigated the efficacy and tolerability after conversion from clonazepam to pramipexole, and examined dose equivalence between the two prescriptions. METHODS: In a prospective, open-label, multicenter study, 26 RLS patients treated with clonazepam (mean age: 69.2+/-11.0years old) were enrolled and then rapidly switched to pramipexole using a conversion calculation of 4:1 for daily doses. Then the daily dose of pramipexole was up titrated or tapered by 0.125mg/day at each subsequent examination. RLS symptoms and daytime somnolence were evaluated using the International RLS Study Group rating scale (IRLS), Clinical Global Impressions - Severity of illness (CGI-S) and the Epworth Sleepiness Scale (ESS), respectively. RESULTS: Conversion from clonazepam to pramipexole resulted in significant reductions of IRLS (16.3+/-8.7 to 9.1+/-6.3) and ESS (6.5+/-4.2 to 4.4+/-3.2). CGI scores demonstrated improvement after conversion. In 4 patients (15%), adverse events such as somnolence, sensation of oppression in the lower limbs, diarrhea, or nausea were present. Correlation analysis demonstrated a significant relationship between these daily doses. Spearman's correlation coefficient was 0.662. Our study, however, has some limitations since it is an open-label trial and includes only 26 patients. Further studies using a double-blind design or a crossover design are recommended. CONCLUSIONS: Statistical analysis demonstrated a 4:1 conversion for clonazepam to pramipexole. When switchover from clonazepam to pramipexole is done, this conversion ratio may be helpful to determine the initial dose of pramipexole for treating RLS.

[Restless legs syndrome].

Restless legs syndrome has been recognized to be a common disorder as one of the sleep disturbances. The main symptom is an unpleasant and uncomfortable sensation frequently localized in the leg between the knee and the ankle. Patients find the nature of the discomfort difficult to describe and use words like creeping, pulling, stretching, restless sensations, aching and even pain. The authors report signs, symptoms, epidemiology, pathogenesis, treatment of the syndrome in this paper.

Factors disturbing treatment for cancer in patients with schizophrenia.

Patients with schizophrenia who develop cancer often have a variety of complicated medical and psychiatric problems. Problems associated with receiving a diagnosis of cancer and with understanding or cooperating with medical treatment may develop. Research in managing and treating schizophrenia patients with cancer is scarce. Presented herein is the experience of the authors' consultation-liaison psychiatry service in treating patients with schizophrenia who have cancer, and discussion of the medical management of such cases. Fourteen patients were treated between April 1999 and March 2003 and included patients receiving consultation psychiatric services at Shimane University Hospital as well as patients referred from other psychiatric hospitals. These patients were divided into two groups based on whether they were amenable to cancer treatment or not. The treated group consisted of patients who accepted cancer treatment, and the untreated group consisted of patients who refused or interrupted the cancer treatment. The clinical course, clinical psychiatric symptoms, problems in understanding cancer, cancer treatment course and convalescence were retrospectively assessed. Psychiatric symptoms and state were measured using the Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Syndrome Scale (PANSS). The mean of the duration of schizophrenia in these two groups was not significantly different. The mean scores on measures of psychiatric symptoms in each group (treated and untreated) were as follows: BPRS, 45.3+/-15.4 and 64.9+/-9.2 (P<0.05); positive symptoms scores on PANSS, 14.4+/-8.8 and 20.6+/-6.0 (NS); negative symptoms scores on PANSS, 20.6+/-4.7 and 33.6+/-4.4 (P<0.01); and total scores on PANSS, 31.7+/-7.0 and 48.6+/-7.4 (P<0.01). Patients with severe negative symptoms had greater difficulty understanding and cooperating with the cancer treatment. Regarding cancer stage, when cancer was discovered, the disease had already advanced and was no longer amenable to first-line treatment. Regarding notification of the diagnosis, it was rarely possible to give sufficiently early notice to patients in the untreated group. The important role of consultation-liaison psychiatrist in treating cancer patients is suggested. Some steps are proposed for managing schizophrenia patients with cancer who are not able to give informed consent.

Prevalence of restless legs syndrome in non-institutionalized Japanese elderly.

The purpose of the present paper was to evaluate the prevalence of restless legs syndrome (RLS) in a non-institutionalized Japanese elderly population. The subjects consisted of 8900 elderly people >65 years of age belonging to the Seniors Association in Izumo City in November 2000. The present study was conducted in two parts. The phase 1 investigation was a screening by mailed questionnaire and the phase 2 investigation was diagnosis by face-to-face interview. Subjects with possible cases of RLS in phase 1 proceeded to phase 2 and definite cases of RLS were then detected. In phase 1, a total of 3287 subjects completely answering all questionnaire items, were defined as the subjects of the present study. A total of 150 were classified as having 'probable RLS', resulting in a prevalence of 4.6%. These subjects with probable RLS in phase 1 were detected as the subjects of phase 2. By face-to-face interview and various clinical examinations, a total of 35 subjects (nine male, 26 female) were diagnosed as having definite RLS, resulting in a prevalence of 1.06%. Furthermore, seven subjects (two male, five female) with symptomatic RLS were detected and finally 28 subjects (seven male, 21 female) were diagnosed as having idiopathic RLS. It was significantly higher in women for both the total and idiopathic RLS groups (0.60% male vs 1.46% female; 0.46% male vs. 1.18% female, respectively). The prevalence of RLS may be lower in the Japanese elderly than that in Caucasian subjects. These results could enhance understanding of the differences in predisposition between the races.

Urinary excretion of biopyrrins, oxidative metabolites of bilirubin, increases in patients with psychiatric disorders.

Several authors have suggested that psychological stress induces the production of reactive oxygen species (ROS). Several studies have supported the idea that bilirubin exerts antioxidative effects in vivo, and it was reported psychological stress provokes bilirubin oxidation in vivo [Yamaguchi T., Shioji I., Sugimoto A., Yamaoka M., 2002. Psychological stress increases bilirubin metabolites in human urine. Biochem. and Biophys. Res. Commun. 293, 517-520]. We investigated whether the concentration of bilirubin oxidative metabolites (biopyrrins) is increased in urine from patients with psychiatric disorders. The concentration of biopyrrins in urine of 25 patients with psychiatric disorders (schizophrenia, 15; depression, 10) was compared with 96 healthy volunteers. The concentrations of biopyrrins, as measured by enzyme-linked immunosorbent assay, were normalized to the urinary concentration of creatinine. The concentration of biopyrrins in patients with psychiatric disorders (schizophrenia and depression) was significantly higher than that of healthy volunteers. In schizophrenia, biopyrrins levels correlated with scores of the Brief Psychiatric Rating Scale (BPRS), and in depression, biopyrrins levels correlated with scores of the Hamilton Depression Rating Scale (HAM-D). These finding suggest that psychotic states are associated with an increase in the oxidative metabolites of bilirubin in human urine.

CSF iron, ferritin and transferrin levels in restless legs syndrome.

The aim of this study is evaluating iron, ferritin, and transferrin in both serum and CSF in patients of restless legs syndrome (RLS), based on the hypothesis that iron deficiency in the central nervous system (CNS) causes the symptoms as a result of the dysfunction of dopaminergic systems. These parameters, polysomnographic sleep measures, and subjective evaluation of the sleep quality were compared in 10 patients of idiopathic RLS (RLS group) and 10 age-matched patients of psychophysiological insomnia without RLS symptoms (non-RLS group). With sleep patterns, sleep latency was longer and sleep efficiency was lower in the RLS group than those in the non-RLS group. Periodic leg movement index in the RLS group was higher than that of the non-RLS group. With serum examination, there were no significant differences for the iron, ferritin, and transferrin values between the both groups. With CSF examination, the iron and ferritin values were lower and the transferrin values were higher in the RLS group than those in the non-RLS group. There was positive correlation between the serum and CSF ferritin levels in the both groups, but the slope of the regression lines for the RLS group was lower than that for the non-RLS group. These results indicate low brain iron concentration caused by the dysfunction of iron transportation from serum to CNS in patients with idiopathic RLS.

Effects of donepezil on Alzheimer's disease: the relationship between cognitive function and rapid eye movement sleep.

The aim of this study was to observe the effects of donepezil on both the cognitive function and sleep patterns in patients of Alzheimer's Type Dementia (ATD), especially to determine the relationship between the improvement of cognitive function and the amount of rapid eye movement (REM) sleep. A total of 12 patients (7 females, 5 males; age, 73.0 +/- 6.8) meeting the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association) criteria of probable AD were studied. These patients presented with mild to moderate dementia, which was confirmed by a Clinical Dementia Rating score of 1 or 2. Following baseline examinations consisting of the Alzheimer's Disease Assessment Scale-cognitive component-Japanese version (ADAS-Jcog) and polysomnography (PSG), 5 mg of donepezil was administered to the patients at breakfast every day. All patients were reassessed 6 weeks later using the same examinations. With sleep patterns, the percentage of REM sleep to total sleep time increased after the administration of donepezil. In addition, it was also found that sleep efficiency was increased and sleep latency was shortened by this administration. Although the ADAS-Jcog score did not decrease significantly, there was significant positive correlation between the decrease of the ADAS-Jcog score and the increase in the percentage of REM sleep. These results indicate the increase action of REM sleep due to activate central cholinergic systems and the possibility to improve sleep conditions due to one-time administration after breakfast of donepezil in mild to moderate ATD. It is concluded that the increase in REM sleep may reflect the improvement of cognitive function in ATD patients.

Breath-holding spells in somatoform disorder.

Breath-holding spells (BHS) are commonly seen in childhood. However, there are no case reports of BHS occurring in adolescents or young adults. We report two young adult cases and discuss the pathogensis, both physically and psychologically. BHS occurred for 1-2 minutes after hyperventilation accompanied by cyanosis in both cases. Oxygen saturation was markedly decreased. Each patient had shown distress and a regressed state psychologically. These cyanotic BHS occurred after hyperventilation, and we considered that a complex interplay of hyperventilation followed by expiratory apnea increased intrathoracic pressure and respiratory spasm. Breath-holding spells can occur beyond childhood.

Korsakoff syndrome following chronic subdural hematoma.

We describe a patient who developed Korsakoff syndrome following a spontaneous chronic subdural hematoma. The present case demonstrates persistence of both amnesia and confabulation long after recovery from the acute phase of spontaneous chronic subdural hematoma. There are few reports describing persistent amnesia with confabulation following brain damage. We considered that chronic subdural hematoma in the bilateral frontal and temporal lobes caused amnesia and confabulations, and these conditions persisted as a result of organic atrophic changes of both the frontal and temporal lobes due to long-term compression by chronic subdural hematoma.

Sleep disturbances and depression in the elderly in Japan.

UNLABELLED: The purpose of the present study was to evaluate the relationship between sleep disturbances and depression in the Japanese elderly. METHODS: These investigations in the Japanese elderly were carried out with the Geriatric Depression Scale, the Pittsburgh Sleep Quality Index, and questions on restless legs syndrome and nocturnal eating disorder. A total of 2023 people (male: 1008; female: 1015; average age: 74.2 +/- 6.3 years) were analyzed by chi2 test and simple and multiple logistic regression. The prevalence of sleep disturbance was 37.3% and that of depression was 31.3%. Female gender and/or older (> or =75 years) age were significantly associated with depression. Characteristics in depressive elderly were poor sleep efficiency, sleep disturbances due to difficulty of initiating sleep (DIS), breathing discomfort, coldness and pain, poor subjective sleep quality and lack of enthusiasm for activities. Sleep disturbances due to using the bathroom, breathing discomfort and coldness and long sleep latency were associated with depression in younger (65-74 years) men. Sleep disturbance due to DIS was associated with depression in older (> or =75 years) men. Sleep disturbance due to pain was associated with depression in younger and older women. Poor sleep efficiency was associated with depression in older women. Poor subjective sleep quality was associated with depression in younger and older men and younger women. Lack of enthusiasm was associated with depression in younger and older men and older women. Restless legs syndrome was statistically significantly associated with depression in younger men. It is concluded that sleep disturbance and depression among the Japanese elderly are closely related symptoms. The features of sleep disturbance with depression differed with sex and age.