Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043352 (xerostomia)
 4,250 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An 8-week open-label study of nefazodone treatment of DSM-III-R major depressive episode (MDE) (n = 18) is reported. Nine of 15 individuals completing treatment also met DSM-III-R criteria for obsessive compulsive disorder (OCD). A significant reduction in depressive and anxiety symptoms was observed in treatment completers; no differences were found between those patients with and those without comorbid OCD. A trend toward an antiobsessional response was seen among those with OCD. The degree of anxiolytic response was found to be significantly correlated with the degree of antidepressant response. Nefazodone was well tolerated in most patients, with dizziness, joint pain, dry mouth, and sedation as the most commonly reported adverse events.
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PMID:An open-label study of nefazodone in the treatment of depression with and without comorbid obsessive compulsive disorder. 764 34

Nefazodone, a phenylpiperazine antidepressant, exhibits novel dual activity on serotonin (5-HT) neurons; it binds to 5-HT2 receptors and inhibits 5-HT reuptake. Flexible doses of nefazodone (100-400 mg/day) and amitriptyline (50-200 mg/day) were compared in 106 major depressive inpatients in a 6-week double-blind study. Results showed significant superiority of amitriptyline over nefazodone on all rating instruments: Montgomery and Asberg depression rating scale (P < 0.0001), Hamilton depression scale (P < 0.0006), Clinical Global Impressions (P < 0.0001) and Patient Global Assessment (P < 0.01). A total of 65% of patients under amitriptyline and 56% of patients under nefazodone reported adverse events during the study, with significantly more dry mouth in the amitriptyline group (39% versus 11%, P = 0.001). Modal daily doses within the last treatment week reached 242 mg with nefazodone and 124 mg with amitriptyline. The lower efficacy of nefazodone, which contradicts comparative trials with imipramine in US patients, is discussed with regard to the dose of nefazodone, probably below the optimal therapeutic range for melancholic patients, and to the clinical differences between the patient samples.
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PMID:Controlled comparison of nefazodone and amitriptyline in major depressive inpatients. 786 4

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

Nefazodone hydrochloride is a phenylpiperazine antidepressant with a mechanism of action that is distinct from those of other currently available drugs. It potently and selectively blocks postsynaptic serotonin (5-hydroxytryptamine; 5-HT) 5-HT2A receptors and moderately inhibits serotonin and noradrenaline (norepinephrine) reuptake. In short term clinical trials of 6 or 8 weeks' duration, nefazodone produced clinical improvements that were significantly greater than those with placebo and similar to those achieved with imipramine, and the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, paroxetine and sertraline. The optimum therapeutic dosage of nefazodone appears to be between 300 and 600 mg/day. Limited long term data suggest that nefazodone is effective in preventing relapse of depression in patients treated for up to 1 year. Analyses of pooled clinical trial results indicate that nefazodone and imipramine produces similar and significant improvements on anxiety- and agitation-related rating scales compared with placebo in patients with major depression. Short term tolerability data indicate that nefazodone has a lower incidence of adverse anticholinergic, antihistaminergic and adrenergic effects than imipramine. Compared with SSRIs, nefazodone causes fewer activating symptoms, adverse gastrointestinal effects (nausea, diarrhoea, anorexia) and adverse effects on sexual function, but is associated with more dizziness, dry mouth, constipation, visual disturbances and confusion. Available data also suggest that nefazodone is not associated with abnormal weight gain, seizures, priapism or significant sleep disruption, and appears to be relatively safe in overdosage. Nefazodone inhibits the cytochrome P450 3A4 isoenzyme and thus has the potential to interact with a number of drugs. Further long term and comparative studies will provide a more accurate assessment of the relative place of nefazodone in the management of major depression. Nonetheless, available data suggest that nefazodone is a worthwhile treatment alternative to tricyclic antidepressants and SSRIs in patients with major depression.
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PMID:Nefazodone. A review of its pharmacology and clinical efficacy in the management of major depression. 921 Oct 88