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.

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.

1 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. 2 Y-8894 50 mg showed no significant anticholinergic, sedative, or cardiovascular effect on any of the measures used in young subjects. 3 In the elderly Y-8894 50 mg increased pulse rate (P < 0.05-0.01), lowered systolic blood pressure (P < 0.05-0.005), and decreased salivary flow (P < 0.05) compared with those of pre-drug baseline. C.f.f. was improved after Y-8894 50 mg, but not significantly. 4 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.5 In the elderly both k21 and ke were smaller, t½,z was longer, and AUC was larger compared with young subjects (P < 0.01). 6 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.

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.

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.