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.

[A controlled study of the prophylactic effect of mianserin and placebo in recurrent depression].

To examine the prophylactic effect of mianserin on depressive episode, 26 patients with recurrent depression were randomly allocated on a double-blind basis to treatment with either inactive placebo (PL group) or mianserin in daily dose of 20-60 mg (MIA group) for 18 months and the frequencies or durations of depressive episode during the treatment were compared between the two groups. Except for the 4 patients who dropped out, a comparison of the prophylactic effects of the two groups was performed on 9 patients of the MIA group and 13 patients of the PL group. As a result, recurrence of depressive episode occurred in 4 of 9 patients in the MIA group and in all 13 patients in the PL group during the study. The recurrence rate of the depressive episode during the period in the MIA group was always less than that in the PL group, and significant differences were observed between the two groups from the third to the 18th month of the study. Whereas the frequency and duration of the depressive episode in the MIA group during the period of the study were significantly less than those prior to the study, there was no such difference in the PL group. On the other hand, there was no significant difference in the safety between the two groups. From the result of this study, it was suggested that mianserin is effective in the prophylaxis of depressive episode in patients with recurrent depression.

Deviate N200 component of event-related potentials in shuchaku-seikaku, a premorbid personality of depression.

Twenty-one healthy subjects with Shuchaku-Seikaku (SS), a premorbid personality of depression, and 44 control subjects were tested for event-related potentials using the auditory odd ball paradigm. A higher percent of the N200 component was evoked by frequent task-irrelevant stimuli in the Shuchaku-Seikaku (81.0%) subjects than in the controls (45.5%). The mean amplitudes in the 50-100 ms latency range for task-relevant rare stimuli were smaller; whereas, the amplitudes in the 100-200 ms range for task-irrelevant frequent stimuli and the amplitudes in the 200-260 ms range for both stimuli were larger (shifted to negative direction) in the SS subjects than in the controls. The evidence suggests that the fully automatic detection process, which is assumed to be correlated with mismatch negativity, is hypoactivated and that a contrarily controlled or conscious mismatch process, which may be N2b, is hyperactivated in SS.

Treatment of depression with clonazepam.

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 clonazepam 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.

Clinical pharmacology of a new antidepressant, Y-8894 in healthy young and elderly volunteers.

In the first experiment the influences of a single oral administration of a new antidepressant, Y-8894 50 mg, nortriptyline 50 mg, and placebo on physiological and psychological parameters were evaluated by a double-blind, crossover method in 10 healthy male volunteers. As the second experiment eight elderly healthy men were also recruited to examine the clinical pharmacology of Y-8894. Y-8894 50 mg showed no significant anticholinergic, sedative, or cardiovascular effect on any of the measures used in young subjects. In the elderly Y-8894 50 mg increased pulse rate (P less than 0.05-0.01), lowered systolic blood pressure (P less than 0.05-0.005), and decreased salivary flow (P less than 0.05) compared with those of pre-drug baseline. C.f.f. was improved after Y-8894 50 mg, but not significantly. Neither psychomotor performance nor immediate memory was influenced after either treatment in young subjects. Furthermore, in the elderly Y-8894 50 mg did not affect these parameters. In the elderly both k21 and ke were smaller, t1/2,z was longer, and AUC was larger compared with young subjects (P less than 0.01). In conclusion, Y-8894 50 mg seemed to lack the anticholinergic, sedative and cardiovascular effects which were observed after nortriptyline 50 mg in young subjects. In the elderly some affects were recognized, in part, due to pharmacokinetic alteration.

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.

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.

Regional inhibition of monoamine oxidase activity by administration of clorgyline in rat brain.

The inhibiting effect of monoamine oxidase (MAO) activities towards 5-hydroxytryptamine, dopamine and beta-phenylethylamine by an acute and chronic administration of clorgyline was investigated in five locations of the rat brain. Inhibiting the percentage distributed unevenly in each hypothalamic nucleus and in the circumventricular areas, except the median eminence, the percentages were significantly low as compared with the hypothalamic lateral nucleus. A significant percentage of inhibition for type B MAO towards beta-phenylethylamine was noticed in the chronically administered group. In conclusion, the MAO-inhibiting effect of clorgyline administered intraperitoneally was unevenly distributed in the discrete brain nuclei and the regional difference depended upon the dose and the duration of the clorgyline administration.

The diurnal variations of glutamic acid decarboxylase activity in some discrete nuclei of rat brain.

The diurnal rhythmicity of glutamic acid decarboxylase (GAD) activity in the nucleus level of the rat brain was examined by the radiochemical micromethod in a light-dark condition. GAD activity showed a biphasic variation in globus pallidus and substantia nigra (zona reticulata and compacta), but a monophasic variation, i.e. high in the dark, in colliculus superior (stratum griseum superficiale and stratum opticum). As for hypothalamus GAD activity of some nuclei (N. arcuatus, N. periventricularis, N. preopticus, etc.) it indicated a monophasic variation, while that of some nuclei (N. suprachiasmaticus, N. ventromedialis, A. lateralis, etc.) it showed no significant variations despite their proved functional activity with rhythmicity.

Distribution of type A and type B monoamine oxidase activity in hypothalamic nuclei of the rat.

The regional distribution of type A, type A and B and type B activity of monoamine oxidase (MAO) in individual nuclei of the rat hypothalamus was studied according to quantitative micromethods with clorgyline as a specific inhibitor of type A MAO. As results, type A and type B MAO were distributed differently in the rat hypothalamus. It is suggested that type B MAO acts differently from type A MAO in regard to the function of the hypothalamus.

Distribution of monoamine oxidase in hippocampal region of the rat.

The distribution and development of type A and type B monoamine oxidase (MAO) activities in the hippocampal region of the rat was investigated with biochemical microdetermination. Type A MAO is absolutely dominant and unevenly distributed in the hippocampus. The development of type A MAO in the hippocampus seems to be delayed and reachs adult levels by the 30th day after birth.