Rokuro Mizukawa

Treatment of depression with clonazepam

ABSTRACT— The antidepressive effect of an anticonvulsant clonazepam was studied with maximum daily dose of 1.5 to 6.0 mg (mean 3.4 mg) in 27 patients with major depression (n= 18) or bipolar disorder (n= 9). Two of them dropped out at an early stage of the treatment, and the antidepressive effect of clonazepam was evaluated for the remaining 25 patients. A marked to moderate improvement was obtained for 21 patients (84%), and the onset of the antidepressive effect of clonzepam appeared within 1 week in most of the cases who responded to the therapy. The total scores on the Hamilton Depression Rating Scale and the Beck Self‐Rating Scale were significantly reduced after the clonazepam treatment. Side effects occurred in 14 patients, but most of them were not severe. From these results, it is thought that clonazepam might be useful as an antidepressant for patients in whom conventional antidepressant treatment are contraindicated.

Childhood parental loss and schizophrenia: evidence against pathogenic but for some pathoplastic effects

Childhood parental loss has been associated with a number of psychiatric disorders in adulthood. The present article aims to examine, firstly, the etiologic relationship between early parental loss and later development of schizophrenia and, secondly, the pathoplastic effect of the former on the symptomatology of the latter. We have administered semi-structured interviews inquiring into psychopathology and early separation experiences to a representative sample of first-visit patients to the 31 hospitals and clinics all over Japan (n=1963) and also to a community sample in a small city in Japan (n=218). When 225 patients diagnosed with schizophrenia according to DSM-III-R criteria were compared with 122 healthy control subjects without any lifetime psychiatric disorder, controlled for sex and age, there was no statistically significant difference in the rates of childhood parental loss (death or separation). As regards the pathoplastic effects, it was found that schizophrenic men were less likely to present with negative symptoms if they had experienced separation from the father, and were more likely to show panic attacks if they had experienced separation from the mother. Schizophrenic women were more likely to present with hallucinations if they had suffered any loss of the father. Childhood parental loss is not pathogenic of schizophrenia but appears to exert some pathoplastic influences on its presenting symptoms.

Age differences in effects on blood pressure, flicker fusion frequency, salivation and pharmacokinetics of single oral doses of dothiepin and amitriptyline

SummaryBlood pressure, critical flicker fusion frequency (CFF), salivary flow rate and pharmacokinetics were compared in 7 young healthy volunteers (average age: 22.7 years) and in 7 elderly healthy volunteers (average age: 70.6 years) after single oral doses of the antidepressants dothiepin (DP) 25 mg and amitriptyline (AMP) 25 mg. Systolic blood pressure fell further and the reduction lasted longer in the elderly than in the young after both drugs. The decrease in CFF after AMP 25 mg, and the reduction in salivary flow rate after either DP 25 mg or AMP 25 mg were larger in the elderly than in the young. Plasma levels, T1/2 and Cl of both drugs in the elderly were also higher, longer and smaller, respectively, in the elderly. Clearance was found to be reduced in the elderly. More cautions dosage regimens of these drug should be considered for elderly patients.

Comparative Study of the Effects of 9 Antidepressants on Several Physiological Parameters in Healthy Volunteers

Effects on physiological parameters were compared among 9 antidepressants (amitriptyline 50 mg, imipramine 50 mg, nortriptyline 50 mg, amoxapine 50 mg, maprotiline 50 mg, mianserin 20 mg, zimelidine 100 mg, nomifensine 50 mg, and Y-8894 50 mg) after a single oral administration in healthy volunteers. Critical fusion frequency of flicker, body sway distance, salivary flow rate, near blurred point, and pulse rate were employed as parameters. The degree of the drug effects on the physiological parameters could be roughly classified into two to four groups according to maximum percent deviation of each parameter.

Long-term observation of a manic-depressive patient with rapid cycles

For the past 35 years we have been treating a patient with regularly recurring MD episodes. Through longitudinal observations of this patient, we presented some characteristic findings in her biological rhythms, and the observed biological rhythm disturbances were speculated on

Prophylactic effect of mianserin on recurrent depression

The prophylactic effect of mianserin on recurrent depression was studied in a double‐blind comparison with an inactive placebo by analyzing the recurrence rate and the number of depressive episodes in 9 mianserin‐treated (daily dose 20–60 mg) and 13 placebo‐treated patients. The selected patients were those who had a higher incidence of recurrence (more than 2 depressive episodes during the 2 years preceding the study). During the 18‐month study period, 4 of 9 mianserin‐treated patients and all 13 placebo‐treated patients had recurrences. The ratio between patients with recurrence and total patients (recurrence ratio) was lower in the mianserin‐treated group throughout the study, and the intergroup difference from the 3rd to the 18th month was significant. In the mianserin‐treated group, the frequency of episode recurrence during the study period was significantly lower and the total duration of episodes was significantly shorter than those in the placebo‐treated group. The treatments did not differ significantly in safety. These results clearly indicate that mianserin is effective in the prophylaxis of recurrent depressive episodes.

Age-specific effects of noradrenergic alpha-2 agonist clonidine on the development of amygdaloid kindling in developing rats

The effects of clonidine on the development of amygdaloid kindling were studied in rats of various ages (14, 21, 28 and 70 postnatal days). Administration of clonidine (0.2, 0.5 mg/kg i.p.) caused a significant retardation of kindling development in the 28-day-old rats as well as in the adult rats, whereas, in the 14-day-old rats, the development of kindling was significantly facilitated by clonidine. No significant effect of clonidine was observed in the 21-day-old rats. These results indicate that in rats the effects of clonidine on the development of amygdaloid kindling vary during development.

Periodicity of episode occurrences in rapid cycling affective disorders

We analyzed the medical records of nine patients with severe rapid cycling affective disorders (RCAD), and determined the cycle of mania occurrences by calculating the period between two successive onsets of mania for each patient. Using the cycle as the index we devised a cycle-oriented diagram by dividing the observation period by the index cycle, and visually studied the mode of episode occurrences. In seven patients, the onset of mania generally followed the index cycle, but sometimes shifted from the day estimated by the index cycle. The shift seemed to be caused by a cycle other than the index cycle, which appeared temporarily in the course. The period between two successive onsets of mania was often several times longer than the index cycle length. In patients with RCAD, some sort of periodic rhythms may possibly control the course of episode occurrences on a continuing basis.

Influence of Single Doses of Dothiepin and Amitriptyline on Physiological Measures and Psychomotor Performance in Normal Young and Elderly Volunteers

The subjects were 14 (7 young and 7 elderly) men. Self-rating, and physiological and psychological measurements were applied, and experiments were performed 24 h after drug administrations. 25 mg dothiepin hydrochloride (DP) decreased critical flicker frequency less than 25 mg AMP in both age groups. 25 mg DP reduced whole mouth salivary rates less than 25 mg AMP, especially in the young subjects. 25 mg DP decreased diastolic blood pressure more than 25 mg AMP. Systolic blood pressure (after 25 mg DP and 25 mg AMP) and whole mouth salivary rates (after 25 mg AMP) were affected more intensely in the elderly than in the young volunteers.

Periodicity and prediction of mania onsets in biopolar I affective disorders

Abstract In studying the periodicity of mania onsets, cycle‐oriented diagrams were made of the clinical course from 257 manic episodes analyzed retrospectively in 34 bipolar I manic‐depressive patients for a period of about 5 years. Using these diagrams, the frequent period of mania onsets located in one‐quarter of the follow‐up period was pre‐estimated, and the accordance ratio during a 25 month follow‐up period was analyzed. The accordance ratio in all subjects was 39% (11/28) for the first episode and 35% (7/20) for the second episode. These ratios were not significantly different from the expected level (25%). The number of subjects was limited to 11 patients (10 rapid and 1 non‐rapid cyclers) whose number of episodes used for the determination of the index cycle was eight or more. The accordance ratio was 64% (7/11) and 60% (6/10) for the first and second episodes, respectively. Their levels were significantly higher than those expected. Periodicity of mania onsets existed at least in rapid cyclers with abundant past data.