Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Social phobia is a common disorder which is associated with considerable suffering and impairment. Effective treatments have now been developed and they represent an important advance in the management of the disorder. Moclobemide is a reversible inhibitor of monoamine oxidase A (RIMA) which has an established place in the treatment of depression. The efficacy of moclobemide in social phobia has been demonstrated in short-term treatment for up to 12 weeks in three placebo-controlled studies. It has also proved to be effective in long-term treatment in a placebo-controlled study and in open treatment studies. This paper reviews the efficacy of moclobemide in social phobia.
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PMID:Moclobemide in the treatment of social phobia. 892 14

It is generally accepted that the clinical efficacy of monoamine oxidase inhibitors (MAOI) is related to inhibition of this enzyme. In order to evaluate the predictive ability of monoamine oxidase-A inhibition for therapeutic efficacy, the start of treatment effects of moclobemide, a selective, reversible monoamine oxidase-A inhibitor, on plasma concentrations of monoamines and monoamine metabolites were determined. The plasma levels of 3,4-dihydroxyphenylglycol (DHPG, deaminated metabolite of noradrenaline), 5-hydroxyindoleacetic acid (5-HIAA, deaminated metabolite of serotonin), 3,4-dihydroxyphenylacetic acid and homovanillic acid (DOPAC and HVA, deaminated metabolites of dopamine), L-dihydroxyphenylalanine (L-dopa) and noradrenaline were investigated and related to treatment outcome. This was a randomized double blind parallel group study in 47 patients with criteria of major depression according to DSM III R. Moclobemide 300 mg/day, 450 mg/day or 600 mg/day was administered continuously for 6 weeks. Plasma concentrations of monoamine metabolites and monoamines were determined just before treatment by moclobemide, 4 h after the first dose, 24 h after the first dose, before the first dose on day 7, and 4 h after the first dose, on day 7. Each moclobemide dose improved depression as measured by MADRS (Montgomery-Asberg Depression Rating scale) but there was no difference between the three doses. Moclobemide dose-dependently reduced plasma concentration of DHPG, L-dopa and HVA. No dose-dependent treatment effect was observed for plasma 5-HIAA, noradrenaline and DOPAC. The clinical outcome as defined by the final MADRS score was not related to any start of treatment changes in plasma monoamine metabolites reflecting inhibition of MAO-A. It is concluded that monoamine oxidase-A inhibition at the beginning of the treatment does not predict clinical outcome.
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PMID:Initial monoamine oxidase-A inhibition by moclobemide does not predict the therapeutic response in patients with major depression. A double blind, randomized study. 892 74

There is a strong association between the chronic fatigue syndrome and both depressive illness and sleep disturbance, but the efficacy of antidepressants is uncertain. We studied the efficacy and adverse effects of moclobemide in patients with chronic fatigue syndrome, stratifying the sample both by co-morbid major depressive illness and by sleep disturbance. Forty-nine patients with chronic fatigue syndrome were recruited. Patients were given moclobemide up to 600 mg a day for 6 weeks. Four (8%) patients dropped out, three because of adverse effects. Adverse effects wee otherwise mild and transient. On analysing the whole sample, there were significant but small reductions in fatigue, depression, anxiety and somatic amplification, as well as a modest overall improvement. The greatest improvement occurred in those individuals who had a co-morbid major depressive illness, with seven out of 14 (50%) of such individuals rating themselves as "much better" by 6 weeks, compared to six out of 31 (19%) of those who were not depressed (31% difference, 95% CI 1-60%, P = 0.04). Sleep disturbance had no effect on outcome. Moclobemide may be indicated in patients with chronic fatigue syndrome and a co-morbid major depressive disorder. A randomized, placebo-controlled trial is needed to confirm this. These results do not support moclobemide as an effective treatment of chronic fatigue syndrome in the absence of a major depressive disorder.
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PMID:An open study of the efficacy and adverse effects of moclobemide in patients with the chronic fatigue syndrome. 917 34

Depression is a significant problem in the elderly. Because of aging-related pharmacokinetic and pharmacodynamic changes, it is not possible to automatically extrapolate findings on the efficacy or tolerability of antidepressants from younger to older populations. Venlafaxine inhibits both noradrenaline (norepinephrine) and serotonin (5-hydroxytryptamine; 5-HT) reuptake. Analysis of data from phase II and III trials showed that venlafaxine was comparably effective in the young and in a subset of over 350 elderly patients. Venlafaxine dosage needs to be lowered in the elderly with renal impairment. As a weak cytochrome P450 (CYP) inhibitor, it is unlikely to have clinically significant drug interactions. Venlafaxine may be associated with some increase in supine diastolic blood pressure, especially at dosages above 150 mg/day. Nefazodone is a serotonin uptake inhibitor and serotonin 5-HT2A receptor antagonist. Pooled analysis of about 250 patients found nefazodone to be effective in elderly individuals with moderate or severe depressive symptoms, with or without melancholia, in both primary and recurrent episodes. Nefazodone clearance is reduced in patients with hepatic impairment, and plasma concentrations have been reported to be higher in the elderly. Nefazodone is an inhibitor of the CYP3A4 family. There does not appear to be any increase in the frequency or severity of adverse effects in the elderly. Moclobemide is a selective inhibitor of monoamine oxidase type A. Studies in the elderly have found it to be well tolerated and meta-analysis has shown it to be comparably effective in young and elderly populations, and comparable to other antidepressants in terms of efficacy. Neither age nor renal impairment necessitate dosage adjustment, but hepatic impairment does necessitate dosage reduction. Dietary restrictions are not required. Overall, there is a relative paucity of data on the tolerability and efficacy of newer antidepressants in the elderly, especially those with concomitant medical disorders. Data that are available indicate that venlafaxine, nefazodone and moclobemide have comparable efficacy in older and younger patients.
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PMID:Antidepressant use in the elderly. Current status of nefazodone, venlafaxine and moclobemide. 925 75

Tricyclic antidepressants have been used for a long time in migraine prophylaxis and in the treatment of chronic tension-type headache. Because of their relatively frequent and unpleasant side effects, however, their use cannot be recommended without reservation. The selective and reversible monoamine oxidase inhibitor type A (MAO-A inhibitor), moclobemide (Aurorix), is much better tolerated and safer to use. For this reason, we began to use this substance in the prophylactic treatment of migraine and chronic tension-type headache. The obviously good efficacy in many cases prompted us to conduct a retrospective analysis of 61 headache patients treated with moclobemide. The patients, classified according to the diagnostic criteria of the International Headache Society, were treated for about 8 months on average with moclobemide. While on this therapy, 35 of the 42 migraine patients and 16 of the 17 patients with tension-type headache experienced good or very good improvement in their symptoms. In the migraine patients, the average number of monthly headache days declined from 7.8 before treatment to 1.2 at the end of treatment. In tension-type headaches, the effect occurred at the earliest 3-6 weeks and in the case of migraines at the earliest 6-8 weeks after the start of treatment. The therapeutic result was independent of any concurrent depression. Nine patients ended their treatment prematurely, seven because of side effects and two because of compliance problems. Treatment compliance, essential for the success of any long term treatment of headache, is promoted by open and detailed explanation of the treatment concept, and by medical supervision with individual adjustment of treatment. The patient should be instructed regarding the time required until the onset of action, the intended length of treatment, treatment of further headache attacks, and an appropriate lifestyle. The highly promising results with moclobemide in the prophylactic treatment of migraines and chronic tension-type headaches should be verified in a controlled study.
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PMID:[Preventive treatment of migraine and chronic tension headache with moclobemide]. 932 19

Treatment data with moclobemide have been obtained from clinical practices of 91 Hungarian psychiatrists. Three hundred and twenty seven patients were included in the multicenter postmarketing surveillance study and observed during an 8 week treatment period. The mean age of the patients was 50 years, 71% were woman and 33% were outpatients. Sixty-five percent had preexisting depression. Previous antidepressant treatment for this episode had been received by 45%, with the most common reasons for change to moclobemide being inadequate response. Moclobemide was indicated in patients with mainly moderate to severe major depression and dysthymia. The frequency of comorbidity was 44%. The dosage of moclobemide was usually started at 300 or 450 mg/day and increased to 600 mg/day only in some patients. Three divided daily dosages were administered in 53% of the patients. Nine percent discontinued the treatment before the end of the observation period. 87% had no reported adverse events. The most common adverse events were sedation (3.7%), agitation (3%) and insomnia (3%). Concommitant medication from all major drug groups were taken by 250 (76.6%) patients, with no adverse interactions. The current therapeutic habits of the Hungarian psychiatrists in treatment of depression were also revealed. The findings in the normal clinical psychiatric practice suggest that moclobemide is a safe drug with excellent tolerability in the treatment of various subgroups of depressive disorders and especially useful in patients with coexisting physical illness. Moclobemide is a favourable alternative to the modern effective antidepressant agents in the Hungarian clinical practice.
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PMID:[Customary antidepressive treatment in Hungary: moclobemid therapy in everyday practice]. 934 May 82

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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PMID:Moclobemide and imipramine in chronic depression (dysthymia): an international double-blind, placebo-controlled trial. International Collaborative Study Group. 934 78

This review deals with the new generation of selective and partly reversible monoamine oxidase (MAO) inhibitors. In contrast to the non selective inhibitors, used in the year 1957-1970, the selective inhibitors bind to and block only one of the two isoenzymes, MAO-A or MAO-B. The MAO-A inhibitors and part of the MAO-B inhibitors differ also from the classic drugs by their reversibility. The inhibition of MAO-A cause the rise of norepinephrine, dopamine and serotonin in the synaptic cleft, of MAO-B only of dopamine. The new inhibitors diminish also to some extent the reuptake of monoamines. The molecular action mechanism of the new drug generation is the same as in the non-selective drugs: increase of monoamines, near to the receptor, leads, after a number of intermediate steps, to activation of functional proteins in the cell. The selective block of one of the isoenzymes does not stop the metabolism of tyramine (from cheese, red wine), because this toxic compound is metabolised by both isoenzymes. The control of therapy with MAO-A inhibitors is easier, because of their reversibility. Selective inhibitors of MAO have found a secure place in therapy of depression (inh. of MAO-A, esp. Moclobemide) and Parkinson's disease (inh. of MAO-B, at this time mainly selegiline). Discussed is possible use of selective MAO-inhibitors for achieving an increase in cognitive function and protections of neurone cells from biochemical lesions.
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PMID:[Inhibitory monoamine oxidases of the new generation]. 943 89

Moclobemide is a reversible selective inhibitor of monoamine oxidase A. It has proven efficacy in a wide range of depressive disorders, including agitated anxious depression. In an international, multicentre, double-blind parallel-group study, the tolerability and efficacy of moclobemide were compared with that of the selective serotonin reuptake inhibitor fluoxetine. The target dose of moclobemide was 450 mg/day in the dose range of 300-600 mg/day, while the target dose for fluoxetine was 20 mg/day in the dose range of 10-30 mg/day. There were two consecutive studies. The first was an 8-week short-term study of acute adverse events, tolerability and efficacy. The efficacy data showed no significant difference between moclobemide and fluoxetine. Evaluation of the tolerability in a long-term study of up to 1 year is still in progress. A review of the moclobemide safety database for panic disorder with 624 patients showed a marginal increase in events with moclobemide compared with placebo for insomnia (11.2%), dizziness (4.5%) and dry mouth (3.7%), with rates for headaches and nausea lower for moclobemide than placebo. These data suggest moclobemide is a well tolerated and effective treatment for panic disorder.
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PMID:Moclobemide for anxiety disorders: a focus on moclobemide for panic disorder. 946 72

The efficiency of moclobemide (selective reversible inhibitor of monoamine oxidase) in therapy of "hyperestetic" depressions and the relation of the drug's efficiency with both psychopathologic structure and severity of the disease were assessed. 20 patients with prolonged (more than 2 years duration) anxious-somatisized depressions resistant to the treatment with tricyclic antidepressants were treated. Moclobemide was quite effective in 14 (70%) patients. Psychopathologic structure of depression in the group of the responders was characterized by hypothymia, somatopsychic catesthesia and vitalized anxiety. There was a correlation between the therapeutic response, and the severity of depression. It is possible to use positive changes in HAM-D, HAM-A and SCL-90 rating scales as the predictors of the efficiency. It is necessary to use high daily doses (450-750 mg) to overcome resistance. Any side effects are practically absent.
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PMID:[Effectiveness of moclobemide in therapy-resistant depression]. 981 86


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