Mitsukuni Murasaki

Demographic features of patients seeking cosmetic surgery.

The demographic features of 415 patients seeking cosmetic surgery were investigated from a psychiatric point of view. Of the 415 patients, 198 (47.7%) were found to have mental disorders according to ICD‐10 including: 17 with schizophrenia, 20 with other persistent delusional disorders, 33 with depressive episode, 47 with neurotic disorders, 42 with hypochondriacal disorder, five with paranoid personality disorder and 14 with histrionic personality disorder. The rate of subjects with poor social adjustment was 56.0%. It was noteworthy that such a considerable number of patients with mental disorders or with poor social adjustment had sought cosmetic surgery. Distinct gender differences were found: male subjects were characterized to have a greater number of mental disorders, especially dysmorphophobia (other persistent delusional disorders plus hypochondriacal disorder) and showed the narrow age range between teenage and young adult age when they were preoccupied with their ‘deformity’, and poor social function. A history of frequent operations was not considered to be an indicator for mental abnormality. The diagnostic issue in dysmorphophobia is briefly described.

Epidemiological study on sleep habits and insomnia of new outpatients visiting general hospitals in Japan

A large scale epidemiological survey of sleep habits, specifically for insominia, was conducted using 6277 new outpatients from 11 general hospitals in Japan. They were requested to answer a questionnaire newly designed for this study, which consisted of 34 questions concerning socio‐demographic characteristics, current medical conditions, sleep habits, current or past sleep complaints, symptoms of parasomnia, use of hypnotics/anxiolytics and other aspects of daily life. Insomnia was the focus of analysis using χ 2 statistics and, additionally, logistic regression to explore the predictors of insomnia. Bedtime was 23:30 and wake‐up time was 6:35 on average, with a mean sleep time of 6.77 h on weekdays. The number of subjects with current sleep complaints was 1276, of which 735 (11.7% of the total sample) had insomnia lasting for 1 month or more. Only 37.6% of those were taking hypnotics and/or anxiolytics. Old age, female sex, neurology, psychiatry, early bedtime, late wake‐up time, living alone and dissatisfication with the bedroom environment for sleep were found to be associated with long‐term insomnia. This study helps to provide a framework for further studies using the general population.

Paroxetine in the treatment of obsessive-compulsive disorder: randomized, double-blind, placebo-controlled study in Japanese patients

Abstract  The efficacy of paroxetine in the treatment of obsessive‐compulsive disorder in Western populations is well established. The present study compares the efficacy and safety of paroxetine with placebo in the treatment of obsessive‐compulsive disorder in Japanese patients. Patients aged 16 years or older who met Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM‐IV) criteria for obsessive‐compulsive disorder and had a Yale–Brown Obsessive‐Compulsive Scale (Y‐BOCS) score of ≥16 were randomized to receive 12 weeks’ therapy in a double‐blind manner. Paroxetine 20–50 mg/day or placebo was administered following a 1 week, placebo run‐in phase. One hundred and ninety‐one patients were randomized to either paroxetine or placebo, 188 patients were assessed as the full analysis set (FAS) and 144 patients completed the 12 week study. After adjustment for the Y‐BOCS total score at baseline, reductions in obsessive‐compulsive total score at week 6 and at the end of therapy were significantly greater in the paroxetine group than the placebo group. Most of the adverse events that occurred during the study were of mild to moderate intensity. Paroxetine is effective and well tolerated in Japanese adult patients with obsessive‐compulsive disorder.

Efficacy and safety of olanzapine, an atypical antipsychotic, in patients with schizophrenia : Results of an open-label multicenter study in Japan

Abstract This first clinical study of olanzapine in Japanese patients with schizophrenia was conducted to investigate the efficacy and safety of olanzapine. Eighty‐one patients were included in the analysis set. Mean modal dose for those patients were 9.4 ± 3.6 mg/day. For the primary efficacy measure (Final Global Improvement Rating score), 14.8% of patients had remarkable improvement, 59.3% of patients had moderate improvement or better, and 86.4% of patients had slight improvement or better. Results from the Brief Psychiatric Rating Scale showed improvement from baseline in all clusters including positive psychotic symptoms (thought disturbance) but also against negative symptoms (anergia). The most commonly reported treatment‐emergent signs and symptoms with ≥10% incidence, were insomnia, weight increase, excitement, sleepiness, and anxiety. There was a low incidence of extrapyramidal treatment‐emergent signs and symptoms, and events reported were tremor (6.2%), muscle rigidity (3.7%), and akathisia (2.5%). The most commonly reported treatment‐emergent laboratory changes, with ≥ 20% of incidence, were prolactin elevations (24.3%) followed by increases in triglycerides (20.4%). However, mean prolactin values tended to be normalized during the study. This study result suggests that olanzapine is an ‘atypical’ antipsychotic.

Abuse of bron : a Japanese OTC cough suppressant solution containing methylephedrine, codeine, caffeine and chlorpheniramine

Ishi OT’? ooka, Jun. Yoshiko Yoshida and Mitsukuni Murasaki: Abuse of “BRON”: a Japanese cough suppressant solution containing meth chlorpheniramine. Prog. Neuro-Psychopharmacol. L lephedrine, codeine, caffeine, and Biol. Psychiat. 1991,~(4):513-521_ 1. The paper describes the mental disturbances of 44 abusive cases of “BRON,” an overthe-counter (OTC) cough suppressant solution containing methylephedrine, codeine, caffeine, and chlorpheniramine. 2. Major psychiatric s affective disorder. T K mptoms observed included hallucinatory-paranoid state and ere also were groups which exhibited a combination of the two states and abuse only. 3. The hallucinatory-paranoid state grou short usa P had a relatively small BRON usage amount, 91 e term and few withdrawa symptoms. The affective disorder group, in contrast, ad large usage amount, longer usa autonomic nerve disorders during withdrawal. Q e term, and showed significant hese tendencies were seen more clearly in the mixed state group. 4. The hallucinatorywhile that of the af P. aranoid state group showed little or no physical de ectlve disorder group was thought to be firm1 in the former group, methylephedrine was considered the major drug, while in the latter, it was thought to be codeine. ehavior modifying

Comparison of Efficacy of Amoxapine and Imipramine in a Multi-Clinic Double-Blind Study Using the WHO Schedule for a Standard Assessment of Patients with Depressive Disorders

A multi-clinic double-blind controlled study on amoxapine in comparison with imipramine, using the WHO Schedule for a Standard Assessment of Patients with Depressive Disorders, was performed and the data were analyzed with 111 patients. The assessment of severity of illness and overall improvement indicated clearly the superiority of the antidepressive effect of amoxapine to that of imipramine. The onset of antidepressive effect of amoxapine was clearly more rapid than that of imipramine, and in more than half of the patients in the amoxapine group the improvement was seen within four days following the drug administration, Amoxapine was superior to imipramine in terms of safety and usefulness. The side-effects due to amoxapine appeared less frequently and were less serious than with imipramine. The difference between amoxapine and imipramine was especially remarkable for hypotensive effect. The antidepressive effect of amoxapine was superior to that of imipramine for almost all symptoms and signs. Amoxapine displayed an especially remarkable effect on psychomotor retardation, depressive feeling, anxiety and tension, somatic complaints and sleep disturbance.

A comparative study of the psychological effects of DN-2327, a partial benzodiazepine agonist, and alprazolam

The effects of single oral doses of DN-2327 (DN, 2 mg or 3 mg), a newly developed partial benzodiazepine receptor agonist, and alprazolam (APZ, 0.8 mg), a full receptor agonist, on psychomotor function and short-term memory were assessed using three psychometric tests: letter cancellation, visual vigilance and Sternbergs memory scanning task. Twelve healthy male volunteers participated in this study. Randomized, double-blind, cross-over test sessions were conducted at 2-week intervals. Both 3 mg DN and 0.8 mg APZ increased the time to completion of the letter cancellation task at 3 h after administration, but neither had any effect on accuracy of response. In the visual vigilance task, which required relatively intense concentration and continuous attention, both the number of errors and reaction times to correct responses significantly increased from 1.5 to 3.5 h after administration of 3 mg DN and at 3.5 h after administration with 0.8 mg APZ. DN at 2 mg also significantly increased the number of errors from 1.5 to 3.5 h after administration, but it did not affect reaction times. In the memory scanning task, 3 mg DN, but not 2 mg DN or APZ, significantly increased overall reaction times at 2 h after administration. These performance deficits paralleled the time-course changes in serum concentrations of both drugs and appeared to be associated with the hypnotic-sedative effects of the drugs tested. These findings did not support those of previous preclinical studies of DN, indicating superiority of DN over conventional full benzodiazepine agonists/anxiolytics in terms of adverse behavioral consequences.

Phase I study of a new antianxiety drug, buspirone

1. A phase I study of buspirone was conducted in 7 healthy male volunteers. 2. Diazepam was selected as the control drug and administered in equipotent doses to buspirone. Dosage was initiated at 2.5mg and doubled until a maximum dosage of 20mg was attained. Subsequently, 10mg was administered once a day for three consecutive days. 3. Clinico-pharmacologically both drugs produced sleepiness/drowsiness, but dizziness, light-headed feeling and feeling of drunkenness were marked only in the diazepam group. 4. No drug-related abnormalities were observed in clinical laboratory test values, endocrinological tests and ECG. 5. On the Uchida-Kraepelin test, no change with the control values was observed under buspirone but subjects administered diazepam exhibited marked deterioration during the latter half of the test. Moreover, in the tapping test, significant impairment was observed in the diazepam group whereas buspirone had no effect. 6. On the EEG some fast waves were observed with diazepam whereas buspirone exhibited slow waves.

Olanzapine optimal dose: Results of an open‐label multicenter study in schizophrenic patients

Abstract This open‐label clinical study was conducted for patients with schizophrenia in order to investigate the efficacy, safety and optimal dose of olanzapine. One hundred and fifty‐six of the 159 enrolled patients were included in the analysis set. For the primary efficacy measure, the Final Global Improvement Rating (FGIR) score, 15.4% of patients had remarkable improvement, 58.3% of patients had moderate improvement or more, 79.5% of patients had slight improvement or more, and 10.3% of patients had increase in disease symptomatology (worsening). Results from the Brief Psychiatric Rating Scale (BPRS) in all individual items were improved from baseline. Olanzapine was effective not only against positive psychotic symptoms but also against negative symptoms. This was consistent with results from the Positive and Negative Syndrome Scale (PANSS). For the majority of patients, a dose range of 7.5–10.0 mg/day, as a lower bound on the minimally effective dose, was suggested by the results of the dose to first response based on improvement in Global Improvement Rating (GIR) analyses. The ratio of olanzapine dose to equivalent haloperidol dose was estimated at 1.2 : 1. The most commonly reported treatment‐emergent signs and symptoms (TESS) occurring at a frequency of 10% or more were insomnia, weight increase, excitement, sleepiness, anxiety, malaise and dull headaches. There was a low incidence of extrapyramidal treatment‐emergent signs and symptoms; the most commonly reported were akathisia (6.4%), tremor (5.8%) and muscle rigidity (2.6%).

Survival analytic approach to long-term prescription of benzodiazepine hypnotics.

Eight hundred and sixty‐two patients who visited the department of neuropsychiatry and who were prescribed benzodiazepine (BZ) hypnotics were investigated to evaluate the actual state of their use, in terms of age, gender, diagnostic categories according to ICD‐9, duration of prescription and dose equivalent to diazepam prescribed. The frequency of prescriptions in subjects were surveyed using Kaplan–Meier survival analysis at every 3 months. Mean survival time to discontinuation was 8.5 months. A total of 60% of the subjects did not receive BZ hypnotics at the end of the third month, but 20% remained to be prescribed after 1 year. Moreover, 7.9% of the subjects were prescribed BZ hypnotics even after 3 years. The results indicated that 20% of patients who had started prescriptions for BZ hypnotics had the potential to induce dependence. The following variables were found in the long‐term prescription: male patients; aged patients over 60; and affective psychoses (which mainly consisted of depression) including neurotic depression, in the present study. A low dose was considered to be associated with an ability to be free from BZ hypnotics in an early period.