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 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A meta-analysis of 20 short term comparative studies of 5 selective serotonin reuptake inhibitors (SSRIs; citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline) has shown no difference in efficacy between individual compounds but a slower onset of action of fluoxetine. There were suggestions that fluoxetine caused more agitation, weight loss and dermatological reactions than the other SSRIs. More patients discontinued fluvoxamine and fewer patients stopped sertraline because of adverse effects than their comparator SSRIs. The most common adverse reactions to the SSRIs were gastrointestinal (especially nausea) and neuropsychiatric (particularly headache and tremor). Data from the Committee on Safety of Medicines showed more reports of suspected reactions (including discontinuation reactions) to paroxetine, and of gastrointestinal reactions to fluvoxamine and paroxetine, than the other SSRIs during their first 2 years of marketing. Prescription-event monitoring revealed a higher incidence of adverse events related to fluvoxamine than its comparators. There were higher incidences of gastrointestinal symptoms, malaise, sedation and tremor during treatment with fluvoxamine and of sedation, tremor, sweating, sexual dysfunction and discontinuation reactions with paroxetine. Fluoxetine was not associated with a higher incidence of suicidal, aggressive and related events than the other SSRIs. Patients have survived large overdoses of each of the compounds, but concern has been expressed over 6 fatalities following overdoses of citalopram. Drug interactions mediated by cytochrome P450 enzymes are theoretically less likely to occur during treatment with citalopram and sertraline, but there is a sparsity of clinical data to support this. Methodological difficulties and price changes do not allow choice for recommendations on the choice of SSRI based on pharmacoeconomic data. Taking into account the strengths and weaknesses of the methods used to compare drugs, guidelines to the selection of individual SSRIs in clinical practice are proposed. Citalopram should be avoided in patients likely to take overdoses. Fluoxetine may not be the drug of first choice for patients in whom a rapid antidepressant effect is important or for those who are agitated, but it may have advantages over other SSRIs in patients who are poorly compliant with treatment and those who have previously had troublesome discontinuation symptoms. Fluvoxamine, and possibly paroxetine, should not be used as first choice in patients especially prone to SSRI-related adverse reactions, while paroxetine should be avoided if previous discontinuation of treatment was troublesome. When in doubt about the risks of drug interactions, citalopram or sertraline should be considered given the lower theoretical risk of interactions.
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PMID:Systematic review and guide to selection of selective serotonin reuptake inhibitors. 1065 95

Sexual dysfunction, a frequently reported side effect of many antidepressants, may result in patient dissatisfaction and noncompliance with treatment regimens. This paper describes the results of the first placebo-controlled comparison of the efficacy, safety, and effects on sexual functioning of sustained-release bupropion (bupropion SR) and the selective serotonin reuptake inhibitor sertraline. This randomized, double-masked, double-dummy, parallel-group, multicenter trial enrolled 360 patients with moderate-to-severe recurrent major depression. Patients were treated with bupropion SR 150 to 400 mg/d, sertraline 50 to 200 mg/d, or placebo for up to 8 weeks. Patients' depression and sexual functioning were assessed at weekly or biweekly clinic visits; safety was assessed by regular monitoring of adverse events, vital signs, and body weight. Treatment groups were similar at baseline in terms of age, sex, and race, and most patients had a diagnosis of moderate uncomplicated depression. Patients treated with bupropion SR or sertraline showed similar improvements on all efficacy measures; both active treatments were superior to placebo in improving scores on all rating scales for depression at various time points. Significantly more patients treated with sertraline experienced orgasmic dysfunction throughout the study than did patients treated with bupropion SR or placebo (P < 0.001). Headache was the most frequently reported adverse event in all 3 treatment groups and occurred with similar frequency in each group (30% to 40%). Nausea (31%), diarrhea (26%), insomnia (18%), and somnolence (17%) occurred in significantly more patients in the sertraline group than in the bupropion SR group (18%, 7%, 13%, and 3%, respectively) and the placebo group (10%, 11%, 4%, and 6%, respectively). Dry mouth occurred more frequently with bupropion SR (19%) than with sertraline (14%) or placebo (12%), although the differences were not significant. Changes in vital signs were similar in all groups. Similar (small, but not statistically significant) decreases in mean body weight were seen in both the bupropion SR (-1.06 kg) and sertraline (-0.79 kg) groups, whereas the placebo group experienced a minor increase (0.21 kg). Although bupropion SR and sertraline were similarly well tolerated and effective in the treatment of depression, sertraline treatment was more often associated with sexual dysfunction and certain other adverse events compared with bupropion SR and placebo. Therefore, bupropion SR may be an appropriate choice as an antidepressant for the treatment of sexually active patients.
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PMID:A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained-release bupropion and sertraline. 1036 31

This study was conducted to assess long-term Quality of Life (QOL) in patients treated by radiotherapy with or without chemotherapy for anal carcinomas. Patients with a maximum age of 80 years, and who were alive at least 3 years following completion of treatment with a functioning anal sphincter and without active disease, were selected for this study. Of 52 such patients identified, 41 (79%) were evaluable. There were 35 females and six males with a median age of 71 years (55-80). The median follow-up interval was 116 months (range 37-218). QOL was assessed using two self-rating questionnaires developed by the European Organization for Research and Treatment of Cancer: one for cancer-specific QOL (EORTC QLQ-C30) and one for site-specific QOL (EORTC QLQ-CR38). For the function scales a higher score represents a higher level of functioning (100 being the best score), whereas for the symptom scales a higher score indicates a higher level of symptomatology/problems (0 being the best score). For the QLQ-C30, the functional scale scores ranged from 71 (global quality of life) to 85 (role function) and the symptom scale scores from 6 (nausea-vomiting) to 28 (diarrhoea). For the QLQ-CR38 module the functional scale scores ranged from 13 (sexual functioning) to 74 (body image) and for the symptom scale scores from 5 (weight loss) to 66 (sexual dysfunction in males). None of the functional and symptom scale scores seemed to be better in patients with longer follow-up. In patients treated with sphincter conservation for anal carcinomas, long-term QOL as measured by the EORTC QLQ-C30 and QLQ-CR38 appears to be acceptable, with the exception of diarrhoea and perhaps sexual function. Moreover, the subset of patients who presented with severe complications and/or anal dysfunction showed poorer scores in most scales.
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PMID:Assessment of long-term quality of life in patients with anal carcinomas treated by radiotherapy with or without chemotherapy. 1040 4

For the past decade, the role of noradrenaline in depression has been somewhat neglected in favour of serotonin. This is largely because of the advent of the selective serotonin reuptake inhibitors, which have facilitated clinical and experimental observation of the roles of serotonin. Until now, no such tools have been available to study the noradrenergic system. However, the recent development of reboxetine, the first selective noradrenaline reuptake inhibitor, has allowed clinical investigation of the role of the noradrenergic system in different aspects of depressive disorders. In clinical trials, the use of reboxetine has shown that selective noradrenaline reuptake inhibition is an effective approach to alleviating depression. It is more effective than placebo and at least as effective as desipramine, imipramine and fluoxetine in the short term. In addition, its efficacy is maintained in patients with severe depression and in those receiving long-term maintenance treatment. Reboxetine is very well tolerated, as predicted from its pharmacological profile, having fewer anticholinergic side-effects than imipramine or desipramine. Compared with fluoxetine, patients treated with reboxetine experienced less nausea and sexual dysfunction, adverse events that are common among those taking selective serotonin reuptake inhibitors. Adverse events predicted by the neuroanatomy of the noradrenergic system, such as tremor and cardiovascular effects, occurred less frequently than expected. Clinical experience with reboxetine challenges our current knowledge of the role of noradrenaline in depression and questions existing evidence based on studies with noradrenergic tricyclic antidepressants. Selective noradrenaline reuptake inhibition, as exemplified by reboxetine, therefore offers a significant improvement in antidepressant pharmacotherapy, and an opportunity to increase our understanding of the role of noradrenaline in depression.
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PMID:Predicting response: noradrenaline reuptake inhibition. 1046 25

Although Black end-stage renal disease (ESRD) patients on dialysis report better functioning and well-being than do White patients, little is known about the association of race with disease symptoms and treatment side effects. Interviews were conducted with 183 older Black and 125 older White in-center hemodialysis (HD) patients in Georgia. Patients were identified in a stratified (by race and sex) random sample of patients aged 60+ years selected from the ESRD Network census of all patients in that age category. Self-assessed disease symptoms and/or side effects of treatment, disability days, and health satisfaction were measured. Data were analyzed via logistic or linear regression, controlling for the effects of patients' gender, age, months on dialysis, primary diagnosis of diabetes, cardiovascular co-morbidity, HD treatment time, and usual interdialytic weight gain. Older Whites, compared to older Blacks, were at increased risk for reporting nausea, sexual dysfunction, recent bed disability days, fatigue, greater HD recovery time, and health dissatisfaction. The relation of these complaints to dialysis adequacy and patients' nutritional status merits continued study.
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PMID:Black/white differences in symptoms and health satisfaction reported by older hemodialysis patients. 1111 Mar 48

We reviewed the side effects of antidepressants. Tricyclic antidepressants(TCAs) are associated with a higher frequency of adverse events than those of SSRIs and SNRIs, particularly with respect to anticholinergic-like effects(dry mouth, constipation, and blurred vision), delirium, and cardiovascular adverse events. On the other hand, SSRIs have some special side effects that include nausea, sexual dysfunction, and extrapyramidal symptoms. With regard to milnacipran, a member of the SNRI family, dysuria occurs at a higher frequency than with TCAs or SSRIs. When side effects occur, clinicians give patients symptomatic treatment or substitute the drugs that cause the adverse effects with other antidepressants that have different pharmacological effects.
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PMID:[Side effects and its countermeasures of antidepressant]. 1151 54

Paroxetine is a selective serotonin reuptake inhibitor (SSRI), with antidepressant and anxiolytic activity. In 6- to 24-week well designed trials, oral paroxetine 10 to 50 mg/day was significantly more effective than placebo, at least as effective as tricyclic antidepressants (TCAs) and as effective as other SSRIs and other antidepressants in the treatment of major depressive disorder. Relapse or recurrence over 1 year after the initial response was significantly lower with paroxetine 10 to 50 mg/day than with placebo and similar to that with imipramine 50 to 275 mg/day. The efficacy of paroxetine 10 to 40 mg/day was similar to that of TCAs and fluoxetine 20 to 60 mg/day in 6- to 12-week trials in patients aged > or =60 years with major depression. Paroxetine 10 to 40 mg/day improved depressive symptoms to an extent similar to that of TCAs in patients with comorbid illness, and was more effective than placebo in the treatment of dysthymia and minor depression. Paroxetine 20 to 60 mg/day was more effective than placebo after 8 to 12 weeks' treatment of obsessive-compulsive disorder (OCD), panic disorder, social anxiety disorder (social phobia), generalised anxiety disorder (GAD) and post-traumatic stress disorder (PTSD). Improvement was maintained or relapse was prevented for 24 weeks to 1 year in patients with OCD, panic disorder, social anxiety disorder or GAD. The efficacy of paroxetine was similar to that of other SSRIs in patients with OCD and panic disorder and similar to that of imipramine but greater than that of 2'chlordesmethyldiazepam in patients with GAD. Paroxetine is generally well tolerated in adults, elderly individuals and patients with comorbid illness, with a tolerability profile similar to that of other SSRIs. The most common adverse events with paroxetine were nausea, sexual dysfunction, somnolence, asthenia, headache, constipation, dizziness, sweating, tremor and decreased appetite. In conclusion, paroxetine, in common with other SSRIs, is generally better tolerated than TCAs and is a first-line treatment option for major depressive disorder, dysthymia or minor depression. Like other SSRIs, paroxetine is also an appropriate first-line therapy for OCD, panic disorder, social anxiety disorder, GAD and PTSD. Notably, paroxetine is the only SSRI currently approved for the treatment of social anxiety disorder and GAD, which makes it the only drug of its class indicated for all five anxiety disorders in addition to major depressive disorder. Thus, given the high degree of psychiatric comorbidity of depression and anxiety, paroxetine is an important first-line option for the treatment of major depressive disorder, OCD, panic disorder, social anxiety disorder, GAD and PTSD.
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PMID:Paroxetine: an update of its use in psychiatric disorders in adults. 1189 34

Paroxetine is a selective serotonin reuptake inhibitor (SSRI), with antidepressant and anxiolytic activity. In 6- to 24-week well designed trials, oral paroxetine 10 to 50 mg/day was significantly more effective than placebo, at least as effective as tricyclic antidepressants (TCAs) and as effective as other SSRIs and other antidepressants in the treatment of major depressive disorder. Relapse or recurrence over 1 year after the initial response was significantly lower with paroxetine 10 to 50 mg/day than with placebo and similar to that with imipramine 50 to 275 mg/day. The efficacy of paroxetine 10 to 40 mg/day was similar to that of TCAs and fluoxetine 20 to 60 mg/day in 6- to 12-week trials in patients aged > or = 60 years with major depression. Paroxetine 10 to 40 mg/day improved depressive symptoms to an extent similar to that of TCAs in patients with comorbid illness, and was more effective than placebo in the treatment of dysthymia and minor depression. Paroxetine 20 to 60 mg/day was more effective than placebo after 8 to 12 weeks' treatment of obsessive-compulsive disorder (OCD), panic disorder, social anxiety disorder (social phobia), generalised anxiety disorder (GAD) and post-traumatic stress disorder (PTSD). Improvement was maintained or relapse was prevented for 24 weeks to 1 year in patients with OCD, panic disorder, social anxiety disorder or GAD. The efficacy of paroxetine was similar to that of other SSRIs in patients with OCD and panic disorder and similar to that of imipramine but greater than that of 2'chlordesmethyldiazepam in patients with GAD. Paroxetine is generally well tolerated in adults, elderly individuals and patients with comorbid illness, with a tolerability profile similar to that of other SSRIs. The most common adverse events with paroxetine were nausea, sexual dysfunction, somnolence, asthenia, headache, constipation, dizziness, sweating, tremor and decreased appetite. In conclusion, paroxetine, in common with other SSRIs, is generally better tolerated than TCAs and is a first-line treatment option for major depressive disorder, dysthymia or minor depression. Like other SSRIs, paroxetine is also an appropriate first-line therapy for OCD, panic disorder, social anxiety disorder, GAD and PTSD. Notably, paroxetine is the only SSRI currently approved for the treatment of social anxiety disorder and GAD, which makes it the only drug of its class indicated for all five anxiety disorders in addition to major depressive disorder. Thus, given the high degree of psychiatric comorbidity of depression and anxiety, paroxetine is an important first-line option for the treatment of major depressive disorder, OCD, panic disorder, social anxiety disorder, GAD and PTSD.
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PMID:Spotlight on paroxetine in psychiatric disorders in adults. 1202 88

Newer antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs), selective noradrenaline reuptake inhibitors (NRIs) and drugs acting on both serotonin and noradrenaline, represent a clinically significant advance over the tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors. Nevertheless, all current pharmacological treatments for depression fall somewhat short of the 'ideal', and unmet needs remain in the pharmacological management of depression. In general, current antidepressants differ little in terms of efficacy. However, in terms of tolerability, SSRIs appear to offer clear advantages over older therapies. For example, the proportion of patients who discontinue treatment because of adverse events and the risk of fatal toxicity both appear to be lower with SSRIs, compared with TCAs. Some adverse events, however, such as sexual dysfunction and nausea (typical serotonergic side effects), tend to be more frequent with SSRIs. Also, individual SSRIs appear to differ in the likelihood that they will be associated with these side effects. However, no clear advantage emerges for any one SSRI over another, and the current recommendation is that the anticipated side-effect profile should be tailored to the patient. Current pharmacoeconomic data do not appear to favour any antidepressant over another, with no cost benefits associated with prescribing TCAs instead of SSRIs.The refinement of current drugs arising from the introduction of their active enantiomers may translate into clinical benefit, bringing closer the 'ideal' antidepressant. Potential benefits of a single enantiomer versus the racemate in the management of depression include: a reduction in the total dose, while maintaining desired outcomes, as well as a possible greater efficacy, dose for dose,simpler assessment of dose-response relationships,a reduction in pharmacokinetic and pharmacodynamic variability between patients, anda reduction in any toxicity arising from the inactive stereoisomer. However, these benefits remain to be proved in clinical trials and naturalistic studies. Further refinement of the benefit:risk ratio of current 'gold standard' drugs may go some way to addressing the shortfalls in existing antidepressant therapy. Copyright 2001 John Wiley & Sons, Ltd.
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PMID:Unmet needs in the pharmacological management of depression. 1240 14

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


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