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Tricyclic antidepressants (TCAs) are notorious for a number of disadvantages, but particularly for an array of side-effects that leads to poor compliance, and also for a dangerous toxicity in overdose. Lofepramine is a new tricyclic that seems safer. Selective serotonin reuptake inhibitors (SSRIs) are more limited in their actions. Side-effects include nausea and insomnia, but on the whole the side-effect profile is an improvement on the TCAs. A miscellaneous group of novel antidepressants includes mianserin and trazodone (which both produce drowsiness) and viloxazine (which causes nausea). The reversible inhibitors of monoamine oxidase A (RIMAs) are a group of drugs that, by producing inhibition selectively of monoamine oxidase A (MOA-A), still allow metabolism of tyramine by MAO-B. Moclobemide is a RIMA that has proved itself to be very effective in severe depressive illness. It is remarkably safe and has an exceptionally low incidence of side-effects. It may be expected to be associated with a high acceptability in depressed patients.
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PMID:Recent advances in antidepressant drugs. 160 37

Seven hundred twelve patients meeting DSM-III-R criteria for major depression and recommended for antidepressant treatment were treated with moclobemide as outpatients (88%) or inpatients in ordinary psychiatric practices. These differ from the highly selected patients usually studied in antidepressant research, without comorbidity, or coprescription and treated in special clinics. Sixty-five percent were women, with a mean age of 45 (+/- 13.6) years, and 88% were outpatients. Eighty-eight percent had preexisting depression. Eight percent had prior manic episodes. Previous antidepressant treatment for this episode had been received by 69%, with the most common reasons for change to moclobemide being inadequate response (66%) and poor tolerability (20%). The modal final dose was 450 mg. Regarding tolerability, 52% did not report adverse events. The most common adverse events were insomnia or stimulation (13%), nausea (11%), headache or migraine (11%), dizziness or disorientation (6%), sedation or drowsiness (5%), agitation or nervousness (3%), and diarrhea (3%). Only 10% of adverse events were severe, and 83% lasted less than 2 weeks. There was no difference when moclobemide followed fluoxetine use. Most adverse events did not significantly differ from the frequencies reported in double-blind placebo-controlled studies. Concomitant medications from all major drug groups were taken by 520 patients (73%), with no adverse interactions. Moclobemide overdose resulted in an uneventful recovery, whereas mixed overdoses caused no problems other than those attributable to coprescribed medication. On physician clinical global impression, 65% were moderately improved or better after 8 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Moclobemide for depression: an Australian psychiatric practice study. 759 27

Moclobemide and fluoxetine were tested in a six-week trial involving 122 patients with major depressive illness. Patients initially received moclobemide, 150 mg three times daily, or fluoxetine 20 mg/day, but during weeks 3, 4, 5 and 6 the doses could be altered, giving a range of 300-600 mg/day for moclobemide or 20-40 mg/day for fluoxetine. No dietary restrictions were imposed on the patients. The trial was completed by 49 patients receiving moclobemide, and 43 patients receiving fluoxetine. The efficacies of these two agents, as determined on the Hamilton Depression Rating Scale and from Clinical Global Assessments, were found not to differ significantly. The frequencies of occurrence of adverse reactions were also similar, but sedation, nausea and vomiting were reported more frequently with fluoxetine, and insomnia was experienced with moclobemide. Tolerance of both drugs was judged to be high.
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PMID:A double-blind comparison of moclobemide and fluoxetine in the treatment of depressive disorders. 846 37

The primary objectives of this large multicenter study (n = 578) were to determine the efficacy and safety of moclobemide, 300 or 600 mg per day, for the treatment of social phobia. A double-blind fixed-dose parallel group study was conducted to compare the two different doses of moclobemide to placebo. After a 1-week placebo run-in period, patients were randomly assigned to one of the three treatment groups to receive the test compound for a 12-week period. Assessments were performed at screen, on baseline and on weeks 1, 2, 3, 4, 6, 8, 10, and 12. There were consistent, reliable and clinically meaningful drug effects and indications of a dose-response relationship. Statistical analysis of the results at both weeks 8 and 12 showed that 600 mg of moclobemide was effective and statistically significantly superior to placebo. The 300 mg dose also showed better efficacy than placebo on all measures of efficacy, and about half of them were statistically significantly different from placebo. Moclobemide was well tolerated. Adverse events, except for insomnia, were neither dose-related nor were there significant drug-placebo differences. The results indicate that 600 mg of moclobemide per day given b.i.d. is effective in social phobia, reducing the symptoms and the impairment associated with the disorder. The compound is well tolerated and safe.
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PMID:The International Multicenter Clinical Trial Group on Moclobemide in Social Phobia. Moclobemide in social phobia. A double-blind, placebo-controlled clinical study. 917 52

Although the monoamine oxidase inhibitor phenelzine has proven efficacious in social phobia, the risk of hypertensive crises has reduced its acceptability. The reversible monoamine oxidase inhibitor moclobemide has less potential for such reactions, but its efficacy in this disorder remains unproven. A double-blind, placebo-controlled study was undertaken to assess the efficacy and safety of fixed doses of moclobemide. After a 1-week placebo run-in, subjects with social phobia were randomly assigned to placebo or one of five doses (75 mg, 150 mg, 300 mg, 600 mg, or 900 mg daily) of moclobemide for 12 weeks. Although a trend toward greater efficacy of higher doses of moclobemide was observed at 8 weeks, no differences in response to various doses of the drug and placebo were observed at 12 weeks. At 12 weeks, 35% of subjects on 900 mg of moclobemide and 33% of those on placebo were at least much improved. Moclobemide was well tolerated, insomnia being the only dose-related adverse event observed with the drug. In this dose-response trial, moclobemide did not demonstrate efficacy at 12 weeks. Some other controlled studies have found moclobemide and brofaromine, another reversible monoamine oxidase inhibitor, efficacious in social phobia. Possible reasons for inconsistent findings are discussed.
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PMID:Moclobemide in social phobia: a controlled dose-response trial. 969 Jul 4

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

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

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. Placebo-controlled 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, especially, sexual dysfunction were much less frequent with moclobemide than with SSRIs. Unlike irreversible MAO-inhibitors, moclobemide has a negligible propensity to induce hypertensive crisis after ingestion of tyramine-rich food ("cheese-reaction"). Therefore, dietary restrictions are not as strict. However, with moclobemide doses above 900 mg/d the risk of interaction with ingested tyramine might become clinically relevant. After multiple dosing the oral bioavailability of moclobemide reaches almost 100%. At therapeutic doses, moclobemide lacks significant negative effects on psychomotor performance, cognitive function or cardiovascular system. Due to the relative freedom from these side effects, moclobemide is particularly attractive in the treatment of elderly patients. Moclobemide is a substrate of CYP2C19. Although it acts as an inhibitor of CYP1A2, CYP2C19, and CYP2D6, relatively few clinically important drug interactions involving moclobemide have been reported. It is relatively safe even in overdose. The drug has a short plasma elimination half-life that allows switching to an alternative agent within 24 h. Since it is well tolerated, therapeutic doses can often be reached rapidly upon onset of treatment. Steady-state plasma levels are reached approximately at one week following dose adjustment. Patients with renal dysfunction require no dose reduction in contrast to patients with severe hepatic impairment. Cases of refractory depression might improve with a combination of moclobemide with other antidepressants, such as clomipramine or a SSRI. Since this combination has rarely been associated with a potentially lethal serotonin syndrome, it requires lower entry doses, a slower dose titration and a more careful monitoring of patients. Combination therapy with moclobemide and other serotonergic agents, or opioids, should be undertaken with caution, although no serious adverse events have been published with therapeutic doses of moclobemide to date. On the basis of animal data the combined use of moclobemide with pethidine or dextropropoxyphene should be avoided. There is no evidence that moclobemide would increase body weight or produce seizures. Some preclinical data suggest that moclobemide may have anticonvulsant property.
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PMID:Moclobemide: therapeutic use and clinical studies. 1504 13

Moclobemide, a potent reversible monoamine-oxidase A (MAO-A) inhibitor, is an effective antidepressant that does not cause impairment of cognitive function in elderly patients and might be beneficial to motor deficits in Parkinson's disease (PD). In a 12-week open-label prospective study, we administered moclobemide (300-600 mg day(-1)) as an add-on medication to twelve PD patients who met DSM-III-R criteria for depressive illness. There were two early drop-outs due to subjective worsening of Parkinsonism associated with insomnia and anorexia, respectively. The Beck Depression Inventory score decreased significantly in the ten patients who completed the study, and clinical global assessment of efficacy recorded 'good' or 'excellent' responses or in nine of the ten patients. Mean parkinsonian disability, as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) and Schwab-England Daily Life Activities scales, remained unchanged throughout the study in the group as a whole. However, worsening or onset of resting tremor occurred in five patients and the UPDRS tremor subscore in the group overall was significantly higher by week 8 (p = 0.03) when dose titration was optimal. There was a trend toward improvement in UPDRS bradykinesia subscores that did not attain statistical significance. Compared to baseline, patients complained more often of insomnia, anorexia, increased perspiration, and restlessness. Though these preliminary results need to be replicated in a large controlled trial, we suggest that moclobemide may be an effective alternative in the treatment of PD associated depression.
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PMID:Treatment of depression in Parkinson's disease with moclobemide: A pilot open-label study. 1859 Oct 80