A Double-blind Comparative Trial of Moclobemide v. Imipramine and Placebo in Major Depressive Episodes

Abstract

Patients (n = 490) suffering from a major depressive episode according to DSM-III criteria were randomly allocated to groups receiving either moclobemide, imipramine, or placebo treatment. Subjects were treated as out-patients for 6 weeks. On overall assessment of efficacy and on results of the Hamilton Rating Scale for Depression, both moclobemide and imipramine were superior to placebo, but the differences between moclobemide and imipramine were not significant. Premature termination due to insufficient efficacy was more frequent with placebo than with moclobemide or with imipramine, these differences being significant. The overall assessment of tolerance clearly favoured placebo and moclobemide over imipramine. This was also reflected in the frequency of premature terminations due to poor tolerance, as well as in the frequency of adverse events, which were highest in the imipramine group. The only cardiovascular finding was an increase of the mean heart rate with imipramine, maximum at the end of week 1, while placebo and moclobemide displayed no relevant changes. There were no other important drug-related changes.

Monoamine oxidase A inhibitor occupancy during treatment of major depressive episodes with moclobemide or St. John’s wort: an [11C]-harmine PET study

“…Although substances in St. John's wort have been reported to possess a similar in vitro affinity, no significant changes in MAO-A binding were detectable, indicating that St. John's wort should not be classified as an MAO-A inhibitor in vivo. Based on a dose of 300 mg of moclobemide twice daily being distinguished from placebo in clinical trials, [46][47][48] we infer that the occupancy associated with this dose reflects an optimal occupancy for the development of new MAO-A inhibitors. Since administration of 300 mg of moclobemide twice daily was associated with about 74% MAO-A occupancy, this occupancy level is preferred in future development of selective MAO-A inhibitor antidepressants for multiple-dose phase-1 studies.…”

Meta-Analysis of the Reversible Inhibitors of Monoamine Oxidase Type A Moclobemide and Brofaromine for the Treatment of Depression

“…Five studies compared MOC with imipramine (Lecrubier and Guelfi 1990;Pancheri et al 1994;Rimon et al 1993;Ucha Udabe et al 1990;Versiani et al 1989). Three studies used clomipramine (Anafranil) as the comparator (Kragh-Sorensen et al 1995;Larsen et al 1991;Lecrubier and Guelfi 1990), two studies each used amitriptyline (Elavil) (Bakish et al 1992c;Kusalic et al 1993) or maprotiline (Gachoud et al 1994;Steinmeyer et al 1993), and one each compared MOC with isocarboxazid (Marplan) (Larsen et al 1991), fluvoxamine (Luvox) (Bougerol et al 1992), amineptine (Macher and Mirabaud 1992), doxepin (Sinequan) (Philipp et al 1993), or dothiepin (Beaumont et al 1993).…”

Monoamine Oxidase Inhibitors—Revisiting a Therapeutic Principle

“…Unfortunately, moclobemide although successfully used in Europe was never registered for the US market. Data from clinical studies (Stabl, Biziére, Schmid-Burgk, & Amrein, 1989;Baumhackl et al, 1989;Versiani et al, 1989;Kok & Tsoi, 1995;Rimón et al, 1993;Silverstone et al, 1994) suggested that moclobemide treatment was superior to placebo and comparable, as judged by an improvement of the HAM-D rating score, to imipramine, a tricyclic antidepressant, in studies treating patients suffering from major depressive disorders. The doses applied ranged from 75 mg/d to 600 mg/d and the response rates reported from 50% to 70%.…”