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Roman Amrein - One of the best experts on this subject based on the ideXlab platform.
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REVIEW PAPERS Efficacy and Tolerability of Moclobemide in Comparison with Placebo, Tricyclic Antidepressants, and Selective Serotonin Reuptake Inhibitors in Elderly Depressed Patients: A Clinical Overview
2015Co-Authors: Roman Amrein, Max Stabl, Stephan Henauer, Eva Affolter, Iris JonkanskiAbstract:Objective: To review the efficacy and safety of Moclobemide in comparison with TCAs (for our purposes, “TCAs ” will represent tricyclic and tetracyclic antidepressants, including maprotilin and mianserin) and selective serotonin reuptake inhibitors (SSRIs) in elderly depressed patients. Methods: The efficacy data reviewed were obtained from the following sources: 1) results of published studies in the elderly; 2) data on patients aged ≥ 60 years extracted from all available controlled trials in adults ( ≥ 18 years) in which Moclobemide was compared with TCAs or SSRIs; and 3) the adverse events were extracted for patients aged ≥ 60 years from the safety data base of all available comparative short-term studies with Moclobemide versus TCAs, SSRIs, or placebo and of long-term studies with Moclobemide. Results: The data show that Moclobemide is an effective antidepressant in depressed patients aged ≥ 60 years. The response rate to Moclobemide was 50 % to 55 % in this population. Moclobemide was more effective than placebo and was of similar efficacy to the TCAs and the more recently introduced SSRIs. The tolerability of Moclobemide was rated as “very good ” or “good ” in almost 90 % of these patients, which was better than the tolerability of TCAs and similar to that of SSRIs. Patients without any adverse events were more frequently found in the Moclobemide group than in those treated with TCAs (P < 0.01) or SSRIs (P < 0.01). Adverse events of the anticholinergic type were more frequent with TCAs than with Moclobemide (P < 0.001), and nausea was found 3 times more frequently with SSRIs than with Moclobemide (P < 0.01)
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clinical pharmacology of Moclobemide during chronic administration of high doses to healthy subjects
Psychopharmacology, 1998Co-Authors: J Dingemanse, Theodor W Guentert, N Wood, S Oie, M Ouwerkerk, Roman AmreinAbstract:The objectives of this study were to assess the tolerability, safety, pharmacodynamics and pharmacokinetics of high-dose Moclobemide in healthy subjects. Two sequential groups of six male and six female subjects (eight on active treatment, four on placebo) received for 8 days Moclobemide 450 mg b.i.d. and 600 mg b.i.d., respectively. Intravenous tyramine pressor tests were conducted at baseline, at the beginning of treatment and at steady state. Oral tyramine pressor tests with 50, 100 and 150 mg tyramine were conducted under steady-state conditions. Pharmacokinetic parameters of Moclobemide and two of its metabolites in plasma and urine were determined after the first and last dose of Moclobemide. The incidence and intensity of adverse events was dose-dependent. The most frequently reported adverse events were insomnia, headache, dizziness and dry mouth. The IV tyramine pressor sensitivity during both Moclobemide dosing regimens was enhanced 3 to 4-fold. Intake of tyramine 50 mg did not result in systolic blood pressure increases greater than 30 mmHg. With regard to blood pressure increases, tyramine 100 mg is still compatible with Moclobemide 450 mg b.i.d. but not with 600 mg b.i.d. The clearance of Moclobemide decreased by about 60% on multiple dosing, but no differences were found between both dosing regimens. The urinary excretion of the N-oxide metabolite doubled during multiple dosing. In conclusion, the maximum tolerated dose of Moclobemide in healthy subjects is 600 mg b.i.d. provided the tyramine content in a meal is not higher than 50 mg.
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pharmacokinetic and pharmacodynamic interactions between fluoxetine and Moclobemide in the investigation of development of the serotonin syndrome
Clinical Pharmacology & Therapeutics, 1998Co-Authors: J Dingemanse, Andreas Wallnofer, Ronald Gieschke, Theodor W Guentert, Roman AmreinAbstract:Objective To assess the tolerability, safety, pharmacokinetics, and pharmacodynamics of combined treatment with fluoxetine and Moclobemide in healthy subjects. Methods Fluoxetine (20 to 40 mg/day) was administered for 23 days to 18 subjects. At (nor)fluoxetine steady state, subjects were randomized in a 2:1 ratio to receive in addition either Moclobemide (ascending doses up to 600 mg/day) or placebo. A single 300 mg dose of Moclobemide was administered before and at the end of the fluoxetine regimen to assess the effects of the latter on the pharmacokinetics and pharmacodynamics of Moclobemide. Adverse events and vital signs were recorded and pharmacokinetic parameters of fluoxetine and Moclobemide were determined. Plasma concentrations of 3,4-dihydroxyphenylglycol, 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid, and serotonin uptake into platelets were assessed as pharmacodynamic measures. Results The number, intensity, or type of adverse events did not change when Moclobemide was added to fluoxetine. No clinically relevant changes in safety parameters occurred. Fluoxetine markedly inhibited the metabolism of Moclobemide. However, multiple dosing of Moclobemide did not lead to excessive accumulation. 3,4-Dihydroxyphenylglycol, 5-hydroxyindoleacetic acid, and 3,4-dihydroxyphenylacetic acid plasma levels and serotonin uptake did not reveal a pharmacodynamic interaction. Conclusions Combination treatment with fluoxetine and Moclobemide did not provide any indication of development of the “serotonin syndrome.” Clinical Pharmacology & Therapeutics (1998) 63, 403–413; doi:
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Moclobemide and imipramine in chronic depression dysthymia an international double blind placebo controlled trial international collaborative study group
International Clinical Psychopharmacology, 1997Co-Authors: Marcio Versiani, Roman Amrein, M StablAbstract:An international, multicenter, placebo-controlled study was undertaken to determine the safety and antidepressant efficacy of Moclobemide, a new reversible inhibitor of monoamine oxidase A, and imipramine in the treatment of dysthymia (DSM-III-R). A total of 315 patients were enrolled and randomly assigned to an 8-week treatment in one of three groups (Moclobemide, imipramine and placebo). Patients were male or female outpatients aged between 18 and 65 years meeting DSM-III-R criteria for dysthymia, primary type, with late or early onset. Of the patients in each group 85% completed the 8-week treatment period. The percentage of patients who no longer fulfilled DSM-III-R symptom criteria at treatment endpoint was significantly higher in the Moclobemide (60%) and imipramine (49%) treatment groups than in the placebo group (22%). Differences to placebo were also statistically significant both for Moclobemide and for imipramine on the other efficacy variables (i.e. Hamilton Rating Scale for Depression, final overall efficacy assessment, Clinical Global Impression and symptom check list self-rating). A significant superiority of Moclobemide and imipramine over placebo was found in pure dysthymia and in double-depression, as well as in early and late onset subgroups. In early onset cases, Moclobemide was significantly more effective than was imipramine on the Hamilton Rating Scale for Depression. Anticholinergic symptoms and sleepiness were significantly more frequent side effects on imipramine than on Moclobemide or on placebo, and the investigators' final overall assessment of tolerability significantly favoured Moclobemide over imipramine. This study demonstrates the efficacy of high dose Moclobemide (mean dose 675 mg/day) and high dose imipramine (220 mg/day) against placebo in the treatment of dysthymia. Moclobemide was better tolerated than was imipramine.
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Moclobemide a paradigm of research in clinical psychopharmacology
International Clinical Psychopharmacology, 1996Co-Authors: Jules Angst, Roman Amrein, M StablAbstract:The pre-clinical development of Moclobemide is an example of broad research combined with serendipity. Moclobemide was first hypothesized as being an antilipaemic or antibiotic, but the screenings were negative. The search for its antidepressant qualities, based on anticholinergic tests, also proved negative and Moclobemide was then suspected of being an antipsychotic before its specific and reversible monoamine oxidase (MAO)-A inhibition qualities were detected. After the establishment of its lack of relevant interference with tyramine pressure response, clinical trials were launched in 1977. In the first stage, multiple, small open and double-blind studies were carried out. Two decisive, large, multicentre, double-blind studies were later performed in Latin America and Austria. Further trials have confirmed the broad antidepressant activity of reversible monoamine oxidase inhibitors (RIMA), which is not confined to any one subtype of depression and which show good tolerability and low toxicity. Since Moclobemide has been available on the market, extensive meta-analyses of a large data set provided a series of methodological results : factor structure of the Hamilton Depression Scale (HAMD), optimal criteria of efficacy, predictors of response, onset of action for antidepressants and placebo.
M Stabl - One of the best experts on this subject based on the ideXlab platform.
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Moclobemide and imipramine in chronic depression dysthymia an international double blind placebo controlled trial international collaborative study group
International Clinical Psychopharmacology, 1997Co-Authors: Marcio Versiani, Roman Amrein, M StablAbstract:An international, multicenter, placebo-controlled study was undertaken to determine the safety and antidepressant efficacy of Moclobemide, a new reversible inhibitor of monoamine oxidase A, and imipramine in the treatment of dysthymia (DSM-III-R). A total of 315 patients were enrolled and randomly assigned to an 8-week treatment in one of three groups (Moclobemide, imipramine and placebo). Patients were male or female outpatients aged between 18 and 65 years meeting DSM-III-R criteria for dysthymia, primary type, with late or early onset. Of the patients in each group 85% completed the 8-week treatment period. The percentage of patients who no longer fulfilled DSM-III-R symptom criteria at treatment endpoint was significantly higher in the Moclobemide (60%) and imipramine (49%) treatment groups than in the placebo group (22%). Differences to placebo were also statistically significant both for Moclobemide and for imipramine on the other efficacy variables (i.e. Hamilton Rating Scale for Depression, final overall efficacy assessment, Clinical Global Impression and symptom check list self-rating). A significant superiority of Moclobemide and imipramine over placebo was found in pure dysthymia and in double-depression, as well as in early and late onset subgroups. In early onset cases, Moclobemide was significantly more effective than was imipramine on the Hamilton Rating Scale for Depression. Anticholinergic symptoms and sleepiness were significantly more frequent side effects on imipramine than on Moclobemide or on placebo, and the investigators' final overall assessment of tolerability significantly favoured Moclobemide over imipramine. This study demonstrates the efficacy of high dose Moclobemide (mean dose 675 mg/day) and high dose imipramine (220 mg/day) against placebo in the treatment of dysthymia. Moclobemide was better tolerated than was imipramine.
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Moclobemide a paradigm of research in clinical psychopharmacology
International Clinical Psychopharmacology, 1996Co-Authors: Jules Angst, Roman Amrein, M StablAbstract:The pre-clinical development of Moclobemide is an example of broad research combined with serendipity. Moclobemide was first hypothesized as being an antilipaemic or antibiotic, but the screenings were negative. The search for its antidepressant qualities, based on anticholinergic tests, also proved negative and Moclobemide was then suspected of being an antipsychotic before its specific and reversible monoamine oxidase (MAO)-A inhibition qualities were detected. After the establishment of its lack of relevant interference with tyramine pressure response, clinical trials were launched in 1977. In the first stage, multiple, small open and double-blind studies were carried out. Two decisive, large, multicentre, double-blind studies were later performed in Latin America and Austria. Further trials have confirmed the broad antidepressant activity of reversible monoamine oxidase inhibitors (RIMA), which is not confined to any one subtype of depression and which show good tolerability and low toxicity. Since Moclobemide has been available on the market, extensive meta-analyses of a large data set provided a series of methodological results : factor structure of the Hamilton Depression Scale (HAMD), optimal criteria of efficacy, predictors of response, onset of action for antidepressants and placebo.
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efficacy of Moclobemide in different patient groups results of new subscales of the hamilton depression rating scale
Clinical Neuropharmacology, 1993Co-Authors: Jules Angst, P Scheidegger, M StablAbstract:Data from 38 double-blind and two single-blind studies with Moclobemide vs. placebo and/or standard antidepressants (10 drugs) were available for an intent-to-treat meta-analysis (n = 2,371). In all, 236 subjects received placebo and 1,107 Moclobemide. As a measure of efficacy, a > or = 50% decrease from the baseline on the Hamilton Rating Scale for Depression (HAM-D) and its new subscales was taken. Furthermore, the Global Assessment of Efficacy (GAE) was analyzed. New subscales of the HAM-D consist of a retarded depression and an agitation/anxiety scale. The two factors were obtained from factor analyses of 12 x 8 random subsamples resulting in a stable solution. The subjects were subclassified by severity (low, medium, high) prior to treatment. The response to placebo was consistently lower in high scorers. In contrast to that, high scorers on active drugs (Moclobemide, imipramine, and clomipramine) showed a tendency to higher response rates. Response rates were, in general, higher on the subscale retarded depression than on agitation/anxiety for both placebo and active drugs. Response rates to Moclobemide were highest in unipolar endogenous depressives (66%) followed by bipolars (57%), neurotic depressives (52%), and reactive depressives (43%).
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interactions of Moclobemide with concomitantly administered medication evidence from pharmacological and clinical studies
Psychopharmacology, 1992Co-Authors: Roman Amrein, J Dingemanse, M Stabl, T W Guntert, T Lorscheid, W SchmidburgkAbstract:Interactions may occur on pharmacological or pharmacokinetic grounds. Both types of interactions are discussed in relationship with the pharmacological and pharmacokinetic data of Moclobemide, a reversible MAO-inhibitor. A variety of interaction studies either designed more specifically as kinetic or as dynamic studies have been performed with Moclobemide. The results of these studies are presented. In view of these results as well as in view of data stemming from clinical trials it can be concluded that apart from interactions with cimetidine and pethidine, Moclobemide has been shown to be devoid of relevant interactions.
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efficacy of Moclobemide in different patient groups a meta analysis of studies
Psychopharmacology, 1992Co-Authors: J Angst, M StablAbstract:Whilst tricyclic antidepressants are efficacious in all depressive syndromes, classical MAO-inhibitors differ substantially from them in their action. They are considered less effective in general and not very effective in endogenous depression, but recommended for the treatment of 'atypical' depression. A new class of RIMA (Reversible Inhibitors of MAO-A) represented by Moclobemide requires a change in clinical thinking on antidepressants. Moclobemide shows the same efficacy in depression as tricyclics: its effects are similar in unipolar and bipolar affective disorders, and in patients with major depressive episode superimposed on dysthymia (double depression). As with classical antidepressants, the response rate tends to be lower, but is still present in psychotic depression. Agitated depressives do not respond less well than non-agitated patients to Moclobemide. Patients meeting DSM-III-R criteria for major depression with melancholia tend to respond better than non-melancholics, but this may be associated with the significantly higher baseline severity observed in melancholics. A slightly higher response rate in patients without concomitant benzodiazepine treatment, compared to those with benzodiazepine comedication, may also be related to baseline differences in the severity of depression. Elderly depressives respond less well than younger patients to classical antidepressants, but with Moclobemide, elderly patients do as well as younger ones.
Glen B. Baker - One of the best experts on this subject based on the ideXlab platform.
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monoamine oxidase a occupancy by Moclobemide and phenelzine implications for the development of monoamine oxidase inhibitors
The International Journal of Neuropsychopharmacology, 2016Co-Authors: Glen B. Baker, Lina Chiuccariello, Robert G Cooke, Laura Miler, Robert D LevitanAbstract:Background: Monoamine oxidase inhibitors (MAOIs) are being developed for major depressive disorder, Alzheimer’s, and Parkinson’s Disease. Newer MAOIs have minimal sensitivity to tyramine, but a key limitation for optimizing their development is that standards for in vivo monoamine oxidase-A (MAO-A) occupancy in humans are not well established. The objectives were to determine the dose-occupancy relationship of Moclobemide and the occupancy of phenelzine at typical clinical dosing. Methods: Major depressive episode (MDE) subjects underwent [11C]harmine positron emission tomography scanning prior to and following 6 weeks of treatment with Moclobemide or phenelzine. Results: Mean brain MAO-A occupancies were 74.23±8.32% for Moclobemide at 300–600mg daily (n = 11), 83.75±5.52% for Moclobemide at 900–1200mg daily (n = 9), and 86.82±6.89% for phenelzine at 45–60mg daily (n = 4). The regional dose-occupancy relationship of Moclobemide fit a hyperbolic function [F(x) = a(x/[b + x]); F(1,18) = 5.57 to 13.32, p = 0.002 to 0.03, mean ‘a’: 88.62±2.38%, mean ‘b’: 69.88±4.36 mg]. Multivariate analyses of variance showed significantly greater occupancy of phenelzine (45–60mg) and higher-dose Moclobemide (900–1200mg) compared to lower-dose Moclobemide [300–600mg; F(7,16) = 3.94, p = 0.01]. Conclusions: These findings suggest that for first-line MDE treatment, daily Moclobemide doses of 300–600mg correspond to a MAO-A occupancy of 74%, whereas for treatment-resistant MDE, either phenelzine or higher doses of Moclobemide correspond to a MAO-A occupancy of at least 84%. Therefore, novel MAO inhibitor development should aim for similar thresholds. The findings provide a rationale in treatment algorithm design to raise Moclobemide doses to inhibit more MAO-A sites, but suggest switching from high-dose Moclobemide to phenelzine is best justified by binding to additional targets.
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Comparison of neurochemical effects of the monoamine oxidase inhibitors phenelzine, Moclobemide and brofaromine in the rat after short- and long-term administration
Journal of affective disorders, 2000Co-Authors: Liana Urichuk, Karen Allison, Andrew Holt, Andrew J. Greenshaw, Glen B. BakerAbstract:Abstract Background : Chronic administration of several irreversible monoamine oxidase (MAO) inhibitors induces a down-regulation of tryptamine and 5-hydroxytryptamine 2 receptors in rat brain, but there is a paucity of information available on the effects of reversible MAO-A inhibitors on these receptors. Methods : Acute and chronic experiments were conducted in rats and the effects of the irreversible monoamine oxidase inhibitor, phenelzine and the reversible MAO type-A inhibitors, Moclobemide and brofaromine, on tryptamine and 5-hydroxytryptamine 2 receptors were analysed using radioligand binding techniques. In addition, activities of MAO-A and -B were determined radiochemically and brain and/or urine levels of tryptamine, 5-hydroxytryptamine, 3-methoxy-4-hydroxyphenylglycol (MHPG), β-phenylethylamine, brofaromine and Moclobemide were determined by chromatographic procedures. Results : After 30 days of administration, Moclobemide and brofaromine selectively inhibited brain MAO-A activity and phenelzine inhibited MAO-A and -B to equal extents. All three drugs caused a significant down-regulation of tryptamine receptors, whereas only phenelzine significantly down-regulated 5-hydroxytryptamine 2 receptors. In a comparison of phenelzine and brofaromine, both caused marked elevations of urinary tryptamine and decreases of urinary MHPG levels, while only phenelzine increased β-phenylethylamine levels. After 14 days of administration, phenelzine, but not Moclobemide or brofaromine, significantly increased levels of tryptamine in brain; all three drugs significantly increased 5-HT levels. Limitations : 24-h urine samples were not collected for Moclobemide-treated animals and brain levels of tryptamine were not measured after 30-day administration. Conclusions : These studies revealed marked neurochemical differences among phenelzine, Moclobemide and brofaromine which could contribute to their actions in the clinical setting.
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metabolism of monoamine oxidase inhibitors
Cellular and Molecular Neurobiology, 1999Co-Authors: Glen B. Baker, Liana Urichuk, K F Mckenna, Sidney H. KennedyAbstract:1. The principal routes of metabolism of the following monoamine oxidase inhibitors (MAOIs) are described: phenelzine, tranylcypromine, pargyline, deprenyl, Moclobemide, and brofaromine.
Kurt Bjerregaard Stage - One of the best experts on this subject based on the ideXlab platform.
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the predictive validity of atypical neurovegetative depressive symptoms identified by the first principal component in the duag trial of Moclobemide versus clomipramine
Journal of Affective Disorders, 2012Co-Authors: Per Bech, Kurt Bjerregaard Stage, Jens Knud Larsen, Per Vestergaard, L F GramAbstract:Abstract Objective To investigate to what extent the primary depression subtype atypical depression can predict differential outcome of the mono-amino-oxidase inhibitor (MAO-I) Moclobemide and the tricyclic antidepressant clomipramine in the Danish University Antidepressant Group Study (DUAG). Methods In a randomised, double blind trial, a total of 117 patients with major depression were treated over 6 weeks with either 400 mg Moclobemide or 150 mg clomipramine. A baseline principal component analysis (PCA) was performed to identify atypical symptoms on the combined depression scales (Hamilton Depression Scale (HAM-D 17 ) and the Quantitative Scale for Atypical Depression (QSAD)). The primary outcome scale was the subscale HAM-D 6 which contains the pure items of depression. Results PCA identified two items with loadings opposite to the other depression items within HAM-D 17 and QSAD, namely increased duration of sleep and increased appetite (atypical neurovegetative symptoms). Patients with a positive score at baseline on these items were classified as having atypical depression. In total 13 patients were classified as having atypical depression. Within this group of patients 8 received clomipramine and 5 patients received Moclobemide. At endpoint the Moclobemide treated patients had a significantly better response than the clomipramine treated (P = 0.036), effect size 1.42, when using HAM-D 6 as outcome. However, in the 104 patients classified as having typical depression clomipramine was superior to Moclobemide (P = 0.034), effect size 0.47. Limitations The number of patients with atypical neurovegetative symptoms was very small and no placebo arm was included. Conclusions It is very important to screen for atypical depression (increased duration of sleep/increased appetite) in the acute therapy of patients with major depression. Our results add to the body of evidence that monoamine oxidase inhibitors are superior to tricyclic antidepressants in this sub-group of patients.
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the major depression rating scale mds inter rater reliability and validity across different settings in randomized Moclobemide trials
Journal of Affective Disorders, 1997Co-Authors: Per Bech, N P V Nair, Per Kraghsorensen, Kurt Bjerregaard Stage, J K Larsen, Annette GjerrisAbstract:The Major Depression Rating Scale (MDS) has been derived from the Hamilton Depression Scale and the Melancholia Scale. The MDS contains the nine DSM-IV items for major depression which all have anchoring scores from 0 to 4; hence, the theoretical score range is up to 36. The Major Depression Rating Scale has in this study been psychometrically analysed in randomized Moclobemide trials. The results showed that the MDS had higher internal validity than the Hamilton Depression Scale. Thus, the homogeneity of the items was higher; factor analysis identified only one general depression factor (after 4 weeks of treatment explaining more than 50% of the variance). The inter-rater reliability of the two scales was of the same high level. The ability to measure changes (external validity) was tested in randomized clinical trials with Moclobemide versus tricyclics (clomipramine and notriptyline) performed in Denmark in the psychiatric setting as well as in the general practice. The results showed that in the psychiatric setting tricyclics were superior to Moclobemide with effect sizes ranging between 0.43 and 0.53. The highest effect size was obtained with the Melancholia Scale and the Major Depression Rating Scale, while the Hamilton Depression Scale was below 0.50. In the general practice setting no difference was found between Moclobemide and clomipramine. In conclusion, the Major Depression Rating Scale has been found to have a more homogeneous factor structure than the Hamilton Depression Scale, but still with the same level of reliability and external validity. However, further studies are needed to standardize the scale, especially in the general practice setting.
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Moclobemide and nortriptyline in elderly depressed patients a randomized multicentre trial against placebo
Journal of Affective Disorders, 1995Co-Authors: N P V Nair, M Amin, P Holm, Cornelius Katona, N A Klitgaard, N Ng Ying M K Kin, Per Kraghsorensen, H Kuhn, C Leek, Kurt Bjerregaard StageAbstract:Moclobemide and nortriptyline were compared with placebo in a double-blind randomized multinational (Canada, Denmark and UK) trial comprising 109 patients of > 60 years of age with major depression (DSM-III-R). Patients were randomized to 7 weeks of treatment with doses of 400 mg/day Moclobemide, 75 mg/day nortriptyline or placebo. It was necessary to adjust nortriptyline dosage in < 20% of patients to maintain serum levels within the postulated therapeutic window of 50-170 ng/ml. At end of treatment, the remission rates were 23% for Moclobemide, 33% for nortriptyline and 11% for placebo. Anticholinergic and orthostatic events occurred more often with patients on nortriptyline than either Moclobemide or placebo.
N P V Nair - One of the best experts on this subject based on the ideXlab platform.
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the major depression rating scale mds inter rater reliability and validity across different settings in randomized Moclobemide trials
Journal of Affective Disorders, 1997Co-Authors: Per Bech, N P V Nair, Per Kraghsorensen, Kurt Bjerregaard Stage, J K Larsen, Annette GjerrisAbstract:The Major Depression Rating Scale (MDS) has been derived from the Hamilton Depression Scale and the Melancholia Scale. The MDS contains the nine DSM-IV items for major depression which all have anchoring scores from 0 to 4; hence, the theoretical score range is up to 36. The Major Depression Rating Scale has in this study been psychometrically analysed in randomized Moclobemide trials. The results showed that the MDS had higher internal validity than the Hamilton Depression Scale. Thus, the homogeneity of the items was higher; factor analysis identified only one general depression factor (after 4 weeks of treatment explaining more than 50% of the variance). The inter-rater reliability of the two scales was of the same high level. The ability to measure changes (external validity) was tested in randomized clinical trials with Moclobemide versus tricyclics (clomipramine and notriptyline) performed in Denmark in the psychiatric setting as well as in the general practice. The results showed that in the psychiatric setting tricyclics were superior to Moclobemide with effect sizes ranging between 0.43 and 0.53. The highest effect size was obtained with the Melancholia Scale and the Major Depression Rating Scale, while the Hamilton Depression Scale was below 0.50. In the general practice setting no difference was found between Moclobemide and clomipramine. In conclusion, the Major Depression Rating Scale has been found to have a more homogeneous factor structure than the Hamilton Depression Scale, but still with the same level of reliability and external validity. However, further studies are needed to standardize the scale, especially in the general practice setting.
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Moclobemide and nortriptyline in elderly depressed patients a randomized multicentre trial against placebo
Journal of Affective Disorders, 1995Co-Authors: N P V Nair, M Amin, P Holm, Cornelius Katona, N A Klitgaard, N Ng Ying M K Kin, Per Kraghsorensen, H Kuhn, C Leek, Kurt Bjerregaard StageAbstract:Moclobemide and nortriptyline were compared with placebo in a double-blind randomized multinational (Canada, Denmark and UK) trial comprising 109 patients of > 60 years of age with major depression (DSM-III-R). Patients were randomized to 7 weeks of treatment with doses of 400 mg/day Moclobemide, 75 mg/day nortriptyline or placebo. It was necessary to adjust nortriptyline dosage in < 20% of patients to maintain serum levels within the postulated therapeutic window of 50-170 ng/ml. At end of treatment, the remission rates were 23% for Moclobemide, 33% for nortriptyline and 11% for placebo. Anticholinergic and orthostatic events occurred more often with patients on nortriptyline than either Moclobemide or placebo.
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biochemistry and pharmacology of reversible inhibitors of mao a agents focus on Moclobemide
Journal of Psychiatry & Neuroscience, 1993Co-Authors: N P V Nair, Shehab Ahmed, N Ng Ying M K KinAbstract:Abstract Moclobemide, p-chloro-N-[morpholinoethyl]benzamide, is a prototype of RIMA (reversible inhibitor of MAO-A) agents. The compound possesses antidepressant efficacy that is comparable to that of tricyclic and polycyclic antidepressants. In humans, Moclobemide is rapidly absorbed after a single oral administration and maximum concentration in plasma is reached within an hour. It is moderately to markedly bound to plasma proteins. MAO-A inhibition rises to 80% within two hours; the duration of MAO inhibition is usually between eight and ten hours. The activity of MAO is completely reestablished within 24 hours of the last dose, so that a quick switch to another antidepressant can be safely undertaken if clinical circumstances demand. RIMAs are potent inhibitors of MAO-A in the brain; they increase the free cytosolic concentrations of norepinephrine, serotonin and dopamine in neuronal cells and in synaptic vesicles. Extracellular concentrations of these monoamines also increase. In the case of Moclobemide, increase in the level of serotonin is the most pronounced. Moclobemide administration also leads to increased monoamine receptor stimulation, reversal of reserpine induced behavioral effects, selective depression of REM sleep, down regulation of beta-adrenoceptors and increases in plasma prolactin and growth hormone levels. It reduces scopolamine-induced performance decrement and alcohol induced performance deficit which suggest a neuroprotective role. Tyramine potentiation with Moclobemide and most other RIMA agents is negligible.
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a comparison of Moclobemide amitriptyline and placebo in depression a canadian multicentre study
Psychopharmacology, 1992Co-Authors: David Bakish, J Bradwejn, N P V Nair, Jennifer B Mcclure, Ronald A Remick, L BulgerAbstract:In a 7-week prospective multicentre study, the efficacy, tolerability and safety of Moclobemide were compared to those of amitriptyline and placebo in parallel groups of out-patients (n=173) fulfilling the DSM III-R criteria for a major depressive episode. Participants were required to have a minimum baseline total score of 18 on the 17-item Hamilton Depression Rating Scale (HAMD). After a 1-week placebo washout, patients were randomly allocated to the three treatment groups. Assessment of efficacy, as judged by the number of responders achieving a 50% reduction in HAMD score by the end of treatment, showed that both Moclobemide and amitriptyline were significantly superior to placebo, but that they were not significantly different from each other. Both treatments differed significantly from placebo with respect to the Physician's Global Assessment of Efficacy (‘very good’ or ‘good’ response: Moclobemide 57%, amitriptyline 60% and placebo 35%). Assessment of tolerance as judged by the spontaneous reporting of adverse events showed a significant superiority of Moclobemide over amitriptyline, but there was no significant difference between Moclobemide and placebo. At termination of the study, amitriptyline patients showed a significant elevation of heart rate both supine (10.8 beats/min) and standing (15.5 beats/min), as well as significant weight gain (1.7 kg), but no changes were seen in the Moclobemide or placebo groups. In conclusion, both Moclobemide and amitriptyline were found to be more effective than placebo in the treatment of depression, while Moclobemide had fewer side effects.