A Placebo-controlled Study of the Antidepressant Activity of Moclobemide,A New MAO-A Inhibitor

Casacchia, M; Carolei, Antonio; Barba, Christophe; Frontoni, Marco; Rossi, Alessandro; Meco, Giuseppe; Zylberman, Marcelo

doi:10.1055/s-2007-1017421

Cited by 61 publications

(15 citation statements)

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“…Clinical studies have shown that moclobemide is superior to placebo (Casacchia et al, 1984) and is as effective as clomipramine (Larsen et al, 1984) and amitriptyline (Norman et al, 1985) in treating depressive patients. This indicates that the MAO inhibiting effect of moclobemide is sufficient to elicit clinical improvement at a dose used in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…Moclobemide is a new, reversible (Waldmeier, 1985) MAO-A selective (Koulu et al, 1989;Wiesel et al, 1985) MAOI with few adverse effects and clear antidepressant properties (Casacchia et al, 1984;Dajas et al, 1984;Larsen et al, 1984;Stabl et al, 1989). Moclobemide penetrates well the brain, maximal concentrations of moclobemide in CSF are reached 2 h after oral administration and high CSF/plasma ratio (0.5) can be obtained (Lauy et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

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Comparison of the monoamine oxidase inhibiting properties of two reversible and selective monoamine oxidase‐A inhibitors moclobemide and toloxatone, and assessment of their effect on psychometric performance in healthy subjects.

Berlin

Zimmer

et al. 1990

Brit J Clinical Pharma

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1 The effects of two reversible, predominantly monoamine oxidase-A (MAO-A) inhibitors, moclobemide (150 mg three times daily) and toloxatone (400-200-400 mg day-1) on monoamine metabolites and psychometric performance were compared in a double-blind placebo controlled crossover study in 12 healthy subjects. 2 After 7 days of moclobemide/toloxatone/placebo administration subjects were hospitalized for 24 h on day 8. Blood samples were drawn every 2 h for determination of plasma noradrenaline (NA), 3,4-dihydroxyphenylglycol (DHPG), homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA). Urine was collected for measurements of normetanephrine and 3-methoxytyramine excretion. Psychometric performance (short-and long-term memory, critical flicker fusion frequency, choice reaction time) and subjective feelings were assessed before each drug intake (in the morning, at noon, in the evening). 3 Compared with placebo, both reversible monoamine oxidase inhibitors decreased the plasma concentration of DHPG and HVA. The overall fall in DHPG (AUC from 0 to 24 h) was 44% during moclobemide and 12% during toloxatone (P < 0.001) and the overall decrease in HVA was 38% and 20% (P < 0.005) on moclobemide and toloxatone, respectively. 4 Before the next drug intake, MAO-A inhibition, as judged by the decrease of plasma DHPG concentration, was significantly different from placebo with moclobemide but not with toloxatone. 5 Moclobemide, but not toloxatone, exerted a moderate, but significant inhibition of the deamination of 5-hydroxytryptamine (5-HT) as judged by the fall in plasma 5-HIAA concentration. Neither drug influenced plasma NA concentration. 6 A significant rise in urinary excretion of normetanephrine was observed on moclobemide and to a lesser extent on toloxatone. The urinary excretion of 3-methoxytyramine was significantly raised by moclobemide but not by toloxatone. 7 Neither moclobemide nor toloxatone altered memory function, vigilance, subjective feelings or sleep characteristics of the subjects.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparison of the monoamine oxidase inhibiting properties of two reversible and selective monoamine oxidase‐A inhibitors moclobemide and toloxatone, and assessment of their effect on psychometric performance in healthy subjects.

Berlin

Zimmer

et al. 1990

Brit J Clinical Pharma

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“…Clinical phase III trials have shown that the drug possesses clear antidepressant therapeutic efficacy comparable with that of some classical tricyclic drugs (Larsen et al, 1984;Casacchia et al, 1984;Norman et al, 1985;Lensch et al, 1987). Compared with older irreversible and non-selective MAO inhibitors, the tyramine-potentiating effect of moclobemide is relatively slight (Korn et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of monoamine oxidase by moclobemide: effects on monoamine metabolism and secretion of anterior pituitary hormones and cortisol in healthy volunteers.

Koulu

Scheinin

Kaarttinen

et al. 1989

Brit J Clinical Pharma

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1. Single oral doses (100, 200 and 300 mg) of moclobemide, a reversible inhibitor of monoamine oxidase (MAO) with predominant effects on the A‐ type of the enzyme, were administered to eight young, healthy male volunteers in a double‐blind, random‐order, placebo‐controlled study. The investigation was thereafter continued in an open fashion by administering a single 10 mg dose of the MAO‐B inhibitor deprenyl to the same subjects. 2. Deamination of catecholamines was powerfully and dose‐dependently inhibited by moclobemide, as evidenced by up to 40% decreases in the urinary excretion of deaminated catecholamine metabolites, corresponding increases in the excretion of non‐ deaminated, methylated metabolites, and up to 79% average decreases in the plasma concentration of 3,4‐dihydroxyphenylglycol (DHPG), a deaminated metabolite of noradrenaline (NA), and up to 75% average decreases in the plasma concentrations of 3,4‐dihydroxyphenylacetic acid (DOPAC), a deaminated metabolite of dopamine. The urinary excretion of 5‐hydroxyindoleacetic acid (5‐HIAA) was only slightly reduced. In contrast, deprenyl, in a dose which almost totally inhibited MAO‐B activity in blood platelets, did not appreciably affect the plasma concentrations of DHPG or DOPAC. 3. Due to the rapid, reversible, dose‐dependent and MAO‐A specific effect of moclobemide on plasma concentrations of DHPG, it is suggested that DHPG in plasma may be a useful indicator of the magnitude and duration of MAO‐A inhibition in man. 4. Sympatho‐adrenal function at rest was not significantly altered by moclobemide, as judged by unchanged plasma catecholamine concentrations and stable blood pressure and heart rate recordings. 5. Monoamine oxidase type B activity in blood platelets was slightly (less than 30%) and transiently inhibited after moclobemide. 6. The secretion of prolactin was dose‐dependently stimulated by moclobemide, whereas the plasma concentrations of growth hormone (hGH) and cortisol remained unchanged.

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“…Subgroup analyses found no difference in efficacy between moclobemide and imipramine in patients with endogenous depression (ICD-9). Furthermore, three smaller studies revealed no difference in the antidepressant activity of the two drugs (41,127,199).…”

Section: Imipraminementioning

confidence: 98%

Moclobemide: Therapeutic Use and Clinical Studies

Bonnet¹

2003

CNS Drug Reviews

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100

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Moclobemide is a reversible inhibitor of monoamine-oxidase-A (RIMA) and has been extensively evaluated in the treatment of a wide spectrum of depressive disorders and less extensively studied in anxiety disorders. Nearly all meta-analyses and most comparative studies indicated that in the acute management of depression this drug is more efficacious than placebo and as efficacious as tricyclic (or some heterocyclic) antidepressants or selective serotonin reuptake inhibitors (SSRIs). There is a growing evidence that moclobemide is not inferior to other antidepressants in the treatment of subtypes of depression, such as dysthymia, endogenous (unipolar and bipolar), reactive, atypical, agitated, and retarded depression as with other antidepressants limited evidence suggests that moclobemide has consistent long-term efficacy. However, more controlled studies addressing this issue are needed. For patients with bipolar depression the risk of developing mania seems to be not higher with moclobemide than with other antidepressants. The effective therapeutic dose range for moclobemide in most acute phase trials was 300 to 600 mg, divided in 2 to 3 doses. While one controlled trial and one long-term open-label study found moclobemide to be efficacious in social phobia, three controlled trials subsequently revealed either no effect or less robust effects with the tendency of higher doses (600 -900 mg /d) to be more efficacious. Two comparative trials demonstrated moclobemide to be as efficacious as fluoxetine or clomipramine in patients suffering from panic disorder. Placebocontrolled trials in this indication are, however, still lacking.A relationship between the plasma concentration of moclobemide and its therapeutic efficacy is not apparent but a positive correlation with adverse events has been found. Dizziness, nausea and insomnia occurred more frequently on moclobemide than on placebo. Due to negligible anticholinergic and antihistaminic actions, moclobemide has been better tolerated than tri-or heterocyclic antidepressants. Gastrointestinal side effects and, espe-97

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A Placebo-controlled Study of the Antidepressant Activity of Moclobemide,A New MAO-A Inhibitor

Cited by 61 publications

References 1 publication

Comparison of the monoamine oxidase inhibiting properties of two reversible and selective monoamine oxidase‐A inhibitors moclobemide and toloxatone, and assessment of their effect on psychometric performance in healthy subjects.

Comparison of the monoamine oxidase inhibiting properties of two reversible and selective monoamine oxidase‐A inhibitors moclobemide and toloxatone, and assessment of their effect on psychometric performance in healthy subjects.

Inhibition of monoamine oxidase by moclobemide: effects on monoamine metabolism and secretion of anterior pituitary hormones and cortisol in healthy volunteers.

Moclobemide: Therapeutic Use and Clinical Studies

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