Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A review of the clinical efficacy of four structurally distinct antidepressant drugs is presented. Their antidepressant activity can be rationalised within current pharmacological hypotheses of drug action, despite markedly different effects on "in vitro" testing. Fluoxetine, a specific serotonin re-uptake inhibitor, has proven safe, effective treatment for depressive illness and may have a role to play in the treatment of obsessive-compulsive disorder and panic attacks. While it has few of the anticholinergic side effects of the tricyclic antidepressants, nausea, tremor, headache, weight loss, nervousness and sweating are side effects most frequently reported. Minaprine, a compound with weak MAO inhibiting properties and effects on serotonergic receptors, has clinical efficacy in the treatment of depression based on several comparative studies. It is claimed that minaprine lacks anticholinergic and sedative properties. Moclobemide, a specific, reversible inhibitor of MAO-A, has been extensively evaluated in depressive illness. The major advantage of this agent over other irreversible, non-specific MAO inhibitors, is the significant attenuation of the so-called "cheese effect" with doses of tyramine likely to be encountered in foodstuffs. Rolipram, a phosphodiesterase inhibitor, represents a new approach to antidepressant treatment. Limited clinical data suggest that the drug may be an effective antidepressant with few side effects. The place of these agents in therapy is yet to be established.
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PMID:New pharmacological approaches to the management of depression: from theory to clinical practice. 158 Aug 88

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

Moclobemide, a new selective and reversible inhibitor of monoamine oxidase A (RIMA), has been compared with various tricyclic antidepressants (TCAs) in numerous controlled studies. Pooled data from these studies, comprising 1656 patients, as well as the consideration of individual trials, show that moclobemide is far better tolerated than the TCAs. Its side effects mainly comprise mild degrees of nausea and dizziness at the beginning of treatment in a small proportion of patients. Age and sex do not affect the tolerability of moclobemide: it is equally well tolerated by elderly patients. In 2300 patients treated with moclobemide in doses up to 600 mg/day, without dietary restrictions, there was no tyramine-related hypertensive reaction. It is concluded that moclobemide may be the second-generation antidepressant doctors were waiting for--equally effective as the classical antidepressants but far better tolerated.
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PMID:Tolerability of moclobemide, a new reversible inhibitor of monoamine oxidase-A, compared with other antidepressants and placebo. 212 66

Moclobemide is a reversible monoamine oxidase inhibitor (MAOI) which preferentially inhibits type-A MAO. In the present communication the results obtained with moclobemide in various clinical trials are reviewed. To this day, the antidepressant efficacy of moclobemide has been compared to that of placebo in four trials. The antidepressant efficacy of moclobemide (300-600 mg/d; N = 164) was found to be superior to that of placebo (N = 162) and comparable to that of imipramine (100-200 mg/d; N = 164) in a 6-w., double-blind, multicentre study, in patients suffering from a Major Depressive Episode (DSM-III). Two smaller trials, strongly suggest that moclobemide is more efficacious than placebo for the treatment of endogenous depression (ICD-9) and for the treatment of Dysthymic Disorders (DSM-III). The antidepressant efficacy of moclobemide was compared to that of imipramine, desipramine, clomipramine and amitriptyline. The antidepressant efficacy of moclobemide (300-600 mg/d; N = 189) was found to be comparable to that of imipramine (100-200 mg/d; N = 192) in a 4-w., double-blind, multicentre study, in patients suffering from a Major Depressive Episode. This finding is supported by the results obtained in 12 other smaller studies, using either imipramine, desipramine, clomipramine or amitriptyline as comparator drug. When the tolerability of moclobemide, as judged by reported and observed adverse events, is compared to that of placebo, it appears that only nausea is reported significantly more frequently with moclobemide than with placebo (9.5% vs 4.8%). In the trials comparing moclobemide to tricyclic antidepressant drugs (TCAs), the tolerability of moclobemide was constantly found to be superior to that of the TCAs; in particular the incidence of anticholinergic side effects was low with moclobemide and was significantly higher with the TCAs. The cardiovascular tolerability of moclobemide tended to be superior to that of the TCAs. Physical examination, hematology and clinical chemistry did not seem to be affected by treatment in any of the studies summarized in this review.
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PMID:Review of comparative clinical trials. Moclobemide vs tricyclic antidepressants and vs placebo in depressive states. 267 44

Moclobemide, a benzamidederivate, is a reversible, selective MAOI with a predominant effect upon MAO-A. In clinical trials with moclobemide so far no clearcut tyramine interaction leading to a hypertensive crisis has been reported and no case of hepatotoxicity has been observed. Open and double-blind studies have shown moclobemide to be an activating antidepressant whose efficacy is superior to placebo and comparable to standard tricyclics. The global tolerance has been shown to be better than in tricyclics, frequency of (anticholinergic) side effects has been lower compared to tricyclics. Our data confirmed the antidepressant efficacy of moclobemide with a rapid onset of action and activating properties devoid of clinically relevant tyramine interactions. As side-effects restlessness, paraesthesias, nausea and sleep disturbances were noted; sleep disturbances could not be improved in most cases. In the light of existing clinical data moclobemide may become an exponent of the "renaissance" of MAOI in the treatment of retarded depression.
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PMID:[Moclobemide in the treatment of depression--an overview]. 268 55

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 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