Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004093 (asthenia)
 2,650 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Current antidepressants achieve similar efficacy, with 60% to 80% of patients responding adequately. Clinical response is gradual, and differential response factors are difficult to discern. However, side effect profiles and toxicity vary substantially, so the choice of medication depends primarily on tolerability and safety. Dry mouth is prevalent with tricyclic antidepressants (TCAs), whereas nausea occurs more frequently with a serotonin selective reuptake inhibitor (SSRI). Long-term unwanted effects tend not to be a major problem, with a dropout rate of approximately 5% due to side effects. The relationship between suicidality and antidepressants remains under debate. Many TCAs are highly toxic in overdose whereas the SSRIs appear much safer. Nefazodone is a unique antidepressant with demonstrated efficacy. It is different from other antidepressants because of its two actions in the serotonin system, moderate serotonin selective reuptake blocking properties and direct 5-HT2 antagonism, which also can enhance 5-HT1 neurotransmission. The 5-HT2 antagonist properties may limit serotonin-mediated effects and, as a result, nefazodone may be more anxiolytic than other antidepressants. Nefazodone also moderately inhibits norepinephrine reuptake and blocks alpha 1-adrenergic receptors. The data base on the safety of nefazodone currently comprises approximately 3,500 patients from all research trials, which include controlled trials that allow comparisons of nefazodone treatment with several hundred patients taking TCAs or SSRIs and nearly 900 patients receiving placebo. The most frequent adverse experiences with nefazodone as compared with placebo treatment are nausea (21% vs. 14%), somnolence (19% vs. 13%), dry mouth (19% vs. 13%), dizziness (12% vs. 6%), constipation (11% vs. 7%), asthenia (11% vs. 6%), light-headedness (10% vs. 4%), and amblyopia (blurred vision; 6% vs. 3%). Approximately 12% of nefazodone-treated patients dropped out because of adverse experiences, as compared with 7.4% on placebo, 10.4% on SSRIs, but 21.8% on imipramine after short-term exposure in placebo-controlled trials. Long-term safety data include nearly 1,300 patients; nefazodone was well tolerated. Nefazodone was evaluated in normal subjects by the author and was found to produce less impairment than imipramine and was less likely to interact with alcohol. In summary, nefazodone has a favorable adverse-event profile as compared with the TCAs and a rather different one from the SSRIs. It appears to be safe and well tolerated after both acute and long-term use.
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PMID:Tolerability and safety: essentials in antidepressant pharmacotherapy. 862 62

The therapeutic dose range of nefazodone for treatment of major depression was examined in a series of placebo-controlled efficacy studies carried out during phase 2 and 3 premarketing clinical evaluation. Nefazodone is a new antidepressant drug with pharmacologic effects on both serotonin and norepinephrine neurotransmitters. The usual starting dose of nefazodone for depressed patients, unless they are being switched from a serotonin selective reuptake inhibitor (SSRI), is 100 mg. b.i.d. A lower starting dose is recommended for elderly patients or patients being treated with an SSRI. Following assessment of the patient's clinical response after the first week of therapy, the daily dose should be adjusted upward for most patients. In the efficacy studies, the majority of patients were being maintained on a dose of 300 to 500 mg daily at the end of the acute treatment period. The side effects of nefazodone most often related to dosage were sedation, nausea, and visual symptoms. Imipramine-treated patients, on the other hand, had a high incidence of dry mouth, constipation, and asthenia. In these studies, nefazodone was found to be effective and well tolerated by patients, the majority of whom were being maintained at a 300- to 500-mg/day dose, following an initial starting dose of 100 mg b.i.d.
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PMID:Therapeutic dose range of nefazodone in the treatment of major depression. 862 65

The chemistry, pharmacology, pharmacokinetics, and clinical efficacy of nefazodone hydrochloride, a new antidepressant, are described. Nefazodone enhances serotonin (5-hydroxytryptamine [5-HT]) synaptic transmission by acting as an antagonist at 5-HT2 receptors and by inhibiting the reuptake of 5-HT. These two mechanisms combined may enhance 5-HT1A-mediated transmission. In addition, nefazodone weakly inhibits the reuptake of norepinephrine. Nefazodone is a structural analogue of trazodone but is pharmacologically distinct. In placebo-controlled trials, nefazodone was as effective as imipramine for the treatment of major depression and produced clinical benefits in patients with depression-related anxiety and sleep disturbances. More than 2000 patients have received nefazodone in clinical trials. The most commonly reported adverse drug reactions (ADRs) are asthenia, somnolence, dry mouth, nausea, constipation, dizziness, lightheadedness, confusion, abnormal vision, and blurred vision. The incidence of sexual-dysfunction ADRs may be less than that reported for other antidepressants. Nefazodone does not inhibit rapid-eye movement sleep. Nefazodone, an inhibitor of the hepatic P-450 isoenzyme CYP3A4, may increase concentrations of drugs metabolized by this isoenzyme, such as terfenadine, astemizole, triazolam, alprazolam, and midazolam. Caution should be exercised in administering nefazodone hydrochloride with triazolobenzodiazepines, and coadministration with terfenadine or astemizole is contra-indicated. The dosage should start at 100 mg twice daily and then be increased, depending on occurrence of ADRs and the patient's clinical response, to 300-600 mg daily. In elderly or debilitated patients, the initial dosage should be half the usual dosage. Nefazodone hydrochloride is as effective as other available antidepressants and may cause fewer ADRs.
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PMID:Nefazodone: a new antidepressant. 889 78

396 adult and adolescent patients with seasonal allergic rhinitis participated in this randomised double-blind parallel-group study in which the efficacy and tolerability of ebastine 10 or 20mg administered once daily in the morning or evening for 3 weeks were compared with those of placebo. Clinical efficacy was assessed by measuring improvement in rhinitis symptoms (nasal discharge, nasal stuffiness, sneezing, itchy nose and itchy/watery eyes) recorded by patients twice daily on diary cards. The improvement in individual and total symptom scores at the end of the 3-week treatment period in patients treated with ebastine 10mg in the morning or ebastine 20mg in the morning or evening was significantly greater than the improvement in placebo recipients. The 20mg dose of ebastine administered in the morning was associated with the greatest improvement in symptom scores. There was no significant effect with the 10mg evening dose compared with placebo. Ebastine was well tolerated by the majority of patients - the incidence of adverse events, including headache, dry mouth, somnolence and asthenia being similar to that reported in placebo recipients. Electrocardiograms showed no evidence of any clinically relevant changes in QTc intervals. In a subsequent nonblinded 4-month study that included 230 patients from the initial study, global evaluations at monthly intervals showed overall symptom improvement in > or = 72% of patients who received ebastine 10mg or 20mg once daily. The drug was well tolerated during prolonged therapy, with adverse events being similar in nature and incidence to those reported in the 3-week double-blind study. In conclusion, ebastine 10mg once daily in the morning is an appropriate starting dose for the treatment of rhinitis, and this can be increased to 20mg as required.
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PMID:Clinical studies of the efficacy and tolerability of ebastine 10 or 20 mg once daily in the treatment of seasonal allergic rhinitis in the US. 882 22

Zolmitriptan (Zomig, formerly 311C90) at doses of 0.5-50 mg was administered to 316 unique volunteers in clinical pharmacology studies and 2,750 unique patients in eight clinical studies of acute migraine treatment. Overall, subjects received almost 50,000 doses; 97% of exposures were at doses > or = 2.5 mg. In the clinical pharmacology studies, the overall incidence of subject exposures experiencing at least one adverse event was 52% with zolmitriptan 2.5 mg (28% with placebo). In placebo-controlled studies, the overall incidence of patients with at least one adverse event was dose-dependent for zolmitriptan over the 1-15 mg dose range, e.g. 42% and 46% with 1 and 2.5 mg, respectively and 58% with 5 mg (29% with placebo). Only four serious adverse events attributable to zolmitriptan were reported. In a long-term study, during which 2,058 outpatients treated a total of 31,579 migraine attacks with either one or two zolmitriptan 5 mg doses over a period of up to 1 year, the number of attacks associated with at least one adverse event was similar after one (26%) and two (24%) doses. The majority (59%) of the adverse events reported in this study (59%) occurred within 2 h of dosing, were predominantly mild (59%) or moderate (35%) in intensity, of < or = 4 h duration (58%), required no further action (94%). In placebo-controlled studies, the percentage of patients who reported severe adverse events was similar with zolmitriptan 2.5 mg (4%) and placebo (5%). The most frequently reported adverse events with zolmitriptan in the placebo-controlled clinical studies were asthenia, heaviness (other than chest or neck), dry mouth, nausea, dizziness, somnolence, paresthesia and warm sensations. The type and severity of the adverse events was not influenced by gender (although the frequency of reported adverse events was higher in females, as was the case in the placebo group), age, presence of aura prior to the attack, association of migraine with menstruation, concurrent medication, or by the addition of a second zolmitriptan dose. Zolmitriptan showed a similar tolerability profile in the long-term study, in which a low withdrawal rate due to adverse events of 8% was observed. Zolmitriptan was not associated with an increased frequency of central nervous system-related adverse events in a comparative study of sumatriptan, despite pre-clinical and neurophysiological evidence of a dual peripheral and central action of zolmitriptan. Moreover, zolmitriptan doses of 5-20 mg produced no statistically significant effects on objective assessments of psychometric function. Zolmitriptan had no clinically significant effects on blood pressure (even in patients with controlled mild to moderate hypertension or impaired renal function), ECGs (e.g. there was no evidence of ischemic events) or clinical chemistry, hematological or urinalysis measurements. In summary, zolmitriptan is well tolerated, particularly at the recommended dose of 2.5 mg. Zolmitriptan has a well-defined dose-response with 2.5 mg proving highly effective and optimizing the benefit/risk ratio of treatment. Thus, zolmitriptan is well suited as an acute oral treatment for migraine in the outpatient setting.
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PMID:Tolerability profile of zolmitriptan (Zomig; 311C90), a novel dual central and peripherally acting 5HT1B/1D agonist. International clinical experience based on > 3000 subjects treated with zolmitriptan. 939 16

Palliative care is the management of patients with progressive, far-advanced disease for whom the prognosis is limited and the focus of care is quality of life. During the last days of life, it is important to redefine the goals, as previously present symptoms may increase and new symptoms may appear. To assess these symptoms, 176 patients were evaluated. A questionnaire evaluated symptoms during the last week of life and compared these prevalences with those at the first evaluation. The patients comprised 121 men and 55 women. The mean age was 67.7 years. Metastases were present in 66.5% and were multiple in 52%. The most frequent symptoms at the end of life (> 50%) were anorexia, asthenia, dry mouth, confusion, and constipation. The majority of patients died at home (64.2%). We observed good control of "reversible" symptoms, but many symptoms were difficult to control at the end of life. Symptom assessment is important in this population.
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PMID:Symptom prevalence in the last week of life. 940 97

This 12-week, double-blind, placebo-controlled study evaluated the efficacy and safety of venlafaxine as first-line therapy for the treatment of major depression and major depression associated with anxiety in 384 adult outpatients. Fixed total daily dosages of 75, 150, and 200 mg of venlafaxine were administered in a twice-a-day regimen. Primary efficacy parameters were the Hamilton Rating Scale for Depression (HAM-D) total score, the HAM-D Depressed Mood Item, the Montgomery-Asberg Depression Rating Scale total score, and the Clinical Global Impressions Scale. Overall, a higher percentage of patients responded to venlafaxine than to placebo. Efficacy data indicated a dose-related response, most evident in the onset of clinical improvement; statistically significant improvements in some primary parameters were seen as early as 1 to 2 weeks after initiation of treatment, especially in the 150-and 200-mg/day groups. These dose-related clinical improvements continued through week 12. Venlafaxine-treated patients who had depression associated with anxiety showed significant dose-related improvements compared with placebo-treated patients; improvement was noted by scores on the HAM-D Anxiety-Psychic Item and Anxiety-Somatization Factor. Few clinically significant changes were observed in laboratory values, vital signs, or electrocardiogram tracings. Venlafaxine was generally well tolerated at all dosages. The most common study events included nausea, dizziness, somnolence, insomnia, dry mouth, and asthenia, which are consistent with findings of previous studies. The current study demonstrated that 75 to 200 mg/day of venlafaxine twice daily produced a dose-related improvement in the primary efficacy parameters and in the onset of significant antidepressant effects, which was noted at weeks 1 to 2 with the highest dosage tested (200 mg/day). The study also demonstrated that these dosages of venlafaxine were safe and effective as first-line therapy for major depression and depression associated with anxiety.
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PMID:The use of venlafaxine in the treatment of major depression and major depression associated with anxiety: a dose-response study. Venlafaxine Investigator Study Group. 947 38

At present only two drugs are approved for long-term treatment of obesity. Sibutramine inhibits the reuptake of serotonin and norepinephrine. In clinical trials it produces a dose-dependent 5-10% decrease in body weight. Its side effects include dry mouth, insomnia, asthenia, and constipation. In addition, sibutramine produces a small increase in blood pressure and pulse that is a contraindication to the use of this drug in some individuals with heart disease. Xenical is the other drug approved for long-term use in the treatment of obesity. It works by blocking lipase and thus increasing the fecal loss of triglyceride. One valuable consequence of this mechanism of action is the reduction of serum cholesterol that averages about 5% more than can be accounted for by weight loss alone. In clinical trials it produces a 5-10% loss of weight. Its side effects are entirely due to undigested fat in the intestine that can lead to increased frequency and change in the character of stools. It can also lower fat-soluble vitamins. The ingestion of a vitamin supplement before bedtime is a reasonable treatment strategy. The effect on weight loss during long-term trials with these two drugs is shown in Figs 7 and 8 above. Also in this figure is data on phentermine used in trials of six months or more. Although there were differences in mean weight losses with these drugs, when the placebo effect was taken into account they all had a surprisingly similar magnitude of weight loss.
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PMID:Drug treatment of obesity. 1172 27

Cetirizine is the carboxylated metabolite of hydroxyzine, and has high specific affinity for histamine H(1) receptors. Pseudoephedrine is a sympathomimetic drug that acts directly on alpha-adrenergic receptors. black triangle Cetirizine/pseudoephedrine 5/120 mg twice daily was significantly more effective than intranasal budesonide 100 microg or placebo at improving nasal obstruction, nasal patency and reducing the volume of nasal secretion, and was significantly more effective than intranasal xylometazoline 0.1% with respect to nasal secretion, during house dust mite faeces challenge in three randomised, cross- over studies among volunteers with seasonal or perennial rhinitis. The onset of action of cetirizine/pseudoephedrine was reported to be approximately 30 minutes. black triangle The bioavailability of cetirizine and pseudoephedrine is similar after administration of cetirizine/pseudoephedrine 5/120 mg bilayer tablets or coadministration of cetirizine 5 mg tablets plus pseudoephedrine sustained-release (SR) 120 mg caplets. black triangle Cetirizine 5mg plus pseudoephedrine SR 120 mg twice daily for 2 to 3 weeks was significantly more effective than each drug given alone at reducing mean total symptom scores for seasonal or perennial allergic rhinitis in two randomised, double-blind, multicentre trials. In both studies, the mean proportion of days during which the five measured symptoms (nasal obstruction, sneezing, rhinorrhoea, nasal pruritus and ocular pruritus) were absent or mild was significantly greater in recipients of the cetirizine plus pseudoephedrine SR. black triangle In one study, cetirizine 5 mg plus pseudoephedrine SR 120 mg was significantly more effective at reducing nasal obstruction than either drug alone. black triangle Cetirizine 5mg plus pseudoephedrine SR 120 mg twice daily for 2 to 3 weeks was well tolerated in patients with seasonal or perennial allergic rhinitis. The most common adverse events were dry mouth, insomnia, headache, somnolence, asthenia and nervousness.
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PMID:Cetirizine/pseudoephedrine. 1177 35

This randomized, placebo-controlled, double-blind study was designed to evaluate the safety and efficacy of dexfenfluramine (Dfen). Dfen 15 mg BID, and placebo were administered for 12 weeks to 337 moderately obese patients on calorically restricted diets. Patients were monitored for an additional 4 weeks. Efficacy was evaluated in 321 patients who were an average of 52% in excess of ideal body weight. Dfen-treated patients lost significantly more weight than did those treated with placebo (p less-than-or-equal 0.001). Small nonsignificant fluctuations in body weight were observed during the 4-week posttreatment period in both groups. The most common drug-related side effects were diarrhea, asthenia, dry mouth, and thirst (p less-than-or-equal 0.05 compared with placebo). Dexfenfluramine may become a valuable addition to weight loss and weight management programs.
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PMID:Treatment of Obese Patients with Dexfenfluramine: A Multicenter, Placebo-Controlled Study. 1185 15


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