Org 3770 versus amitriptyline: A 6‐week randomized double‐blind multicentre trial in hospitalized depressed patients

Abstract

Following a placebo washout period of 3-7 days, 251 hospitalized patients with a major depressive episode (DSM I11 and RDC criteria) were treated with either Org 3770 (20-60 mg/day) or amitnptyline (75-225 mg/day) for six consecutive weeks in this randomized, double-blind, multicentre study. Forty-one patients (19 Org 3770,22 amitriptyline) withdrew before completion of the 6-week active treatment period. In both groups, the main reason for withdrawal was lack of efficacy. However, fewer patients in the Org 3770 group than in the amitriptyline group withdrew as a result of adverse events (one and three patients, respectively). The severity of depressive symptoms and general psychopathology, as assessed by HPRSD (total and factors) and BPRS scales, improved to the same extent after 6 weeks' treatment with Org 3770 and amitriptyline. Similar improvement in global functioning, as assessed by GAS scale, was observed in both treatment groups. There were no statistically significant differences between the two treatments on all scales used. Dry mouth and sweating were reported significantly more often in the amitriptyline group. Other adverse events, such as constipation, dizziness, tremor and muscle weakness, occurred more frequently in the amitriptyline-treated patients as well. The results of this study indicate that Org 3770 has similar antidepressant efficacy to amitriptyline and a more favourable tolerability profile in patients with major depression.

A double-blind, fixed blood-level study comparing mirtazapine with imipramine in depressed in-patients

“…Such a difference has not been reported in previous studies (Smith et al 1990;Claghorn and Lesem 1995;Marttila et al 1995;Richou et al 1995;Van Moffaert et al 1995;Zivkov and De Jong 1995). A possible explanation may be found in differences between the present and other trials with mirtazapine.…”

“…Previous studies on mirtazapine (Smith et al 1990;Claghorn and Lesem 1995;Marttila et al 1995;Richou et al 1995;Van Moffaert et al 1995;Zivkov and De Jong 1995) used a flexible dose design. This may lead to inappropriate dosing especially with tricyclic antidepressants because side effects preventing dose increments may occur at subtherapeutic doses / blood levels (Dawling 1982;DUAG 1990).…”

“…Mirtazapine has recently been registered as an antidepressant. Efficacy and safety have been explored in controlled clinical trials (Smith et al 1990;Claghorn and Lesem 1995;Marttila et al 1995;Richou et al 1995;Van Moffaert et al 1995;Zivkov and De Jong 1995). In all trials tolerance and safety of mirtazapine were satisfactory.…”

“…In all trials tolerance and safety of mirtazapine were satisfactory. In out-patients efficacy of mirtazapine was reported to be significantly superior to placebo (Smith et al 1990;Claghorn and Lesem 1995) and to trazodon (Van Moffaert et al 1995); no significant differences between mirtazapine and amitriptyline (Smith et al 1990;Zivkov and De Jong 1995), clomipramine (Richou et al 1995) and doxepin (Marttila et al 1995), respectively, have been found.…”

New classes of antidepressant drugs

“…The starting dose recommended by the manufacturer is 30 mg daily because the prevalence of adverse effects attributable to mirtazapine's affinity for histamine receptors (somnolence and increased appetite) is less with this dose than with lower doses. Five flexible dosing trials compared the antidepressant effect of mirtazapine with amitriptyline in psychiatric practice, and this included one in 251 patients suffering endogenous depression and requiring hospital admission (Zivkov & de Jongh, 1995). A meta-analysis concluded that there was no significant difference in the reductions in depression rating scores over six weeks (Zivkov et ai, 1995).…”