Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nefazodone HCl (Serzone) is a new antidepressant with a chemical structure unrelated to selective serotonin reuptake inhibitors (SSRIs), tricyclics, tetracyclics, or monoamine oxidase inhibitors (MAOIs). Nefazodone is active in a number of preclinical tests for antidepressant activity and shows clinical efficacy in the treatment of depression with a more favorable side-effect profile than the structurally similar antidepressant trazodone. Previous studies have shown that nefazodone is a potent antagonist of 5-HT2A receptors and binds to the serotonin transporter in vitro and in vivo. Nefazodone also binds to the norepinephrine transporter in vitro and in acute ex vivo studies. To further investigate the ability of nefazodone to modify serotonergic transmission, the ability of systemically administered nefazodone to inhibit the serotonin transporter was assessed by investigating the ability of nefazodone to prevent p-chloroamphetamine- (PCA) induced depletions of cortical 5-HT concentrations. In addition, the ability of acute and subchronic nefazodone administration to inhibit ex vivo [3H]-5-HT uptake was assessed. Acute administration of nefazodone (30, 100, and 150 mg/kg) antagonized PCA-induced depletion of cortical 5-HT concentrations in a dose-dependent manner at 1, 2, and 3 hours post-treatment. This effect was directly correlated with serum nefazodone concentrations. Both 100 mg/kg and 150 mg/kg of nefazodone were equipotent with fluoxetine (10 mg/kg) over the course of the experiment with respect to sparing of 5-HT depletion. Acute administration of nefazodone (100 and 150 mg/kg s.c.) significantly increased the Km for [3H]-5-HT uptake in rat cortical synaptosomes from 60 nmol/L in controls to 230 and 242 nmol/L in nefazodone-treated rats, respectively. Subchronic administration of nefazodone (100 and 150 mg/kg, s.c., b.i.d. x 5.5 days) reduced [3H]-5-HT uptake by 24% and 29%, respectively. Sub-chronic dosing with fluoxetine (5 mg/kg, s.c., b.i.d. x 5.5 days) reduced [3H]-5-HT uptake by 65%. These experiments confirm and extend previous reports concerning the ability of nefazodone to inhibit the 5-HT transporter in vivo.
 ...
PMID:The serotonergic antidepressant nefazodone inhibits the serotonin transporter: in vivo and ex vivo studies. 747 71

Nefazodone is a new antidepressant drug with a pharmacologic profile distinct from that of the tricyclic, monoamine oxidase inhibitor, and serotonin selective reuptake inhibitor antidepressants. Nefazodone was initially discovered for its ability to block 5-HT2A receptors and its reduced potency as an alpha 1-adrenergic blocker. It was later shown to inhibit both serotonin and norepinephrine uptake in vitro, attributes which most likely impart its clinical efficacy and which differentiate nefazodone from its chemical predecessor trazodone. The combination of these two mechanisms may ultimately result in a facilitation of 5-HT1A-mediated neurotransmission, which may be beneficial for treating symptoms of depression as evidenced by recent clinical findings. In addition, the preclinical profile of nefazodone demonstrates that it has decreased anticholinergic and antihistaminic activity relative to traditional agents. Clinical findings to date are consistent with these observations.
 ...
PMID:Pharmacology and neurochemistry of nefazodone, a novel antidepressant drug. 1081 10

A meta-analysis of six randomized, placebo-controlled, double-blind trials was carried out to evaluate the effectiveness of the new antidepressant nefazodone in relieving symptoms of anxiety and agitation associated with major depression. Nefazodone blocks serotonin2 (5-HT2) receptors and selectively inhibits serotonin (5-HT) reuptake. This pharmacologic profile may confer clinical benefits that differ from those of other antidepressants, such as tricyclics (TCAs) and serotonin selective reuptake inhibitors (SSRIs). The data base included 817 patients with major depression and baseline 17-item Hamilton Rating Scale for Depression (HAM-D-17) scores > or = 18; 345 received placebo, 288 imipramine, and 184 nefazodone. Both nefazodone and imipramine exhibited antidepressant efficacy compared with that of placebo, irrespective of baseline anxiety levels. Statistically significant improvement in Hamilton Rating Scale for Anxiety (HAM-A), HAM-D anxiety factor, HAM-D psychic anxiety item, and HAM-D agitation item scores was observed with both active treatments. Nefazodone-treated patients showed significantly greater improvement in somatic anxiety (HAM-D item 11) ratings than placebo-treated patients from Week 4 through end of treatment (p < or = .01), while imipramine-treated patients did not differ from placebo patients on this item. Nefazodone-treated patients improved more rapidly (as early as Week 1) than imipramine- and placebo-treated patients on agitation (HAM-D item 9) (p < or = .01). Nefazodone was found to have an excellent safety profile and was well tolerated, with 5% of nefazodone patients prematurely discontinuing treatment for adverse experiences compared with 17% for imipramine and 5% for placebo treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Response of anxiety and agitation symptoms during nefazodone treatment of major depression. 764 72

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.
 ...
PMID:Controlled comparison of nefazodone and amitriptyline in major depressive inpatients. 786 4

Nefazodone is a phenylpiperazine antidepressant with 5-HT2 antagonism and 5-HT reuptake inhibition. Two hundred and eighty-three out-patients with a diagnosis of DSM-III-R major depression of at least one-month duration (65% ill for over 6 months), and a mean score of 24 on the 17-item Hamilton Rating Scale for Depression (HRSD), were randomised to treatment with nefazodone, imipramine, or placebo. The double-blind treatment period was 8 weeks in duration. Nefazodone's antidepressant efficacy was comparable with imipramine's, with both drug treatments significantly better than placebo in a variety of outcome measures. For example, after 8 weeks of therapy, 78% of nefazodone and 83% of imipramine but only 55% of placebo patients (P < 0.01) were globally much or very much improved. Nefazodone was better tolerated than imipramine, with fewer drop-outs and a lower incidence of side-effects during treatment.
 ...
PMID:Nefazodone and imipramine in major depression: a placebo-controlled trial. 795 87

A polysomnographic study was conducted on 10 outpatients with major depression at baseline and during 4 to 8 weeks of open-trial treatment with nefazodone (400 to 600 mg/day). All 10 patients were treatment responders as evidenced by at least 50% reduction from baseline scores on the Hamilton Depression Rating Scale. Nefazodone was associated with significantly decreased wake and movement time and increased minutes and percentage of stage 2 sleep at the expense of light stage 1 sleep. Nefazodone did not increase rapid-eye-movement (REM) latency and it did not suppress REM sleep. In fact, a trend toward increased REM in the second REM period was observed, although decreased REM in the third REM period was also noted. In summary, nefazodone, an effective antidepressant, decreases arousals and wakefulness during sleep and reduces light non-REM sleep. This agent does not appear to suppress REM sleep or prolong REM latency in patients who respond to treatment.
 ...
PMID:The effects of nefazodone on sleep architecture in depression. 802 73

Nefazodone, a new phenylpiperazine antidepressant agent with serotonin type 2 antagonism and serotonin reuptake inhibition, was evaluated in two patient groups to determine its effectiveness in reducing the symptoms of premenstrual syndrome (PMS). The two studied groups were PMS patients with no coexisting major depression or dysthymia (N = 23) and PMS patients with current major depression or dysthymia, termed the premenstrual exacerbation group (N = 24). The two patient groups received open-label nefazodone for 8 weeks, with optional maintenance at the same dose for up to 1 year. The initial dose was 100 mg, titrated to 600 mg/day, on a twice-daily dosing schedule. Symptoms were assessed by the Hamilton Rating Scale for Depression and by Daily Symptom Ratings. Premenstrual symptoms improved significantly from pretreatment baseline values, with similar improvement for the PMS and premenstrual exacerbation groups. Significantly improvement occurred by the end of the first treated cycle (4 weeks of therapy), at an average dose of 245 (range, 100 to 400) mg, and was maintained thereafter. Nefazodone was well tolerated, side effects were often transient, and the most common were nausea and headache. Forty-seven of 54 patients completed 2 months of therapy, with a mean daily nefazodone dose of 319 mg at the 2-month point. A placebo-controlled study should be conducted to confirm and extend these promising preliminary findings.
 ...
PMID:Nefazodone in the treatment of premenstrual syndrome: a preliminary study. 802 14

Nefazodone (2-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-5-ethyl- 2,4-dihydro-4-(2-phenoxyethyl)-3H-1,2,4-triazol-3-one) has been reported to be effective in the treatment of depression. Antagonism of serotonin type 2A (5HT2A) receptors, as well as inhibition of the serotonin (5HT) uptake carrier, has been suggested to contribute to the antidepressant action of nefazodone in vivo (Eison et al., 1990). Nefazodone weakly antagonized the quipazine-induced rise in rat serum corticosterone levels and the quipazine-induced increase in rat hypothalamic 3-methoxy-4-hydroxy-phenylglycol sulfate, suggesting blockade of 5HT2A receptors in vivo. Nefazodone, however, failed to antagonize the p-chloroamphetamine-induced depletion of mouse or rat brain 5HT, displaying a lack of effect on the 5HT uptake carrier. These data extend previous in vitro and in vivo data (Eison, et al. 1990) reporting nefazodone to be an antagonist at 5HT2A receptors, but fail to show inhibition of the 5HT uptake carrier in the same dose range.
 ...
PMID:Evaluation of nefazodone as a serotonin uptake inhibitor and a serotonin antagonist in vivo. 804 Dec 27

Retrospective analysis of two randomized, placebo-controlled trials evaluated the effectiveness of nefazodone in relieving depression-associated anxiety symptoms of patients with major depression in two practice settings. One study involved depressed patients (N = 138) treated in a family practice setting, the other, psychiatric clinic outpatients (N = 180). Nefazodone treatment was broadly effective across several measures of anxiety symptoms (HAM-D, HAM-A and SCL rating scales) in relieving depression-associated anxiety. The comparison drug, imipramine, was also found to be more effective than placebo treatment, although the treatment effect on depression-associated anxiety, as measured by several factors, was less than that seen with nefazodone. A subgroup of psychiatric clinic outpatients with comorbid major depression and panic disorder (N = 55) was identified by blinded record review. During nefazodone treatment, patients with panic disorder experienced marked global improvement compared with placebo-treated patients, including relief of panic and phobic anxiety symptoms. Imipramine treatment was not significantly better than placebo for improvement in depression and anxiety ratings in this patient group. These results extend previous findings indicating that the new antidepressant nefazodone effectively relieves anxiety and depressive symptoms of patients with major depression.
 ...
PMID:The effect of nefazodone on comorbid anxiety symptoms associated with depression: experience in family practice and psychiatric outpatient settings. 862 57

The development of a new antidepressant medication is usually accompanied by a concern as to whether or not the compound will be sufficiently effective in clinically important subgroups of patients (e.g., depressed patients with increased severity of symptomatology, patients with melancholic features, and patients whose illness is recurrent). This paper describes results of a pooled analysis of four placebo-controlled studies included in the development program of the antidepressant nefazodone. These studies involved a total of 247 patients receiving nefazodone in a dose of up to 600 mg/day, 251 patients on placebo, and 166 patients receiving imipramine. For purposes of the analysis, patients were defined as being more severely depressed (Clinical Global Impressions scale [CGI] psychopathology score of at least markedly ill), having melancholia using DSM-III-R criteria, or having recurrent major depression (using DSM-III-R criteria). Efficacy was assessed by improvement in the Hamilton Rating Scale for Depression (17 items; HAM-D-17) Total score and CGI scale. Nefazodone (mean dose at endpoint = 379 mg/day) was effective in the management of depressed patients with moderate or severe symptomatology, depressed patients with or without melancholic features, and patients with single or recurrent episodes of depression.
 ...
PMID:Nefazodone in the treatment of severe, melancholic, and recurrent depression. 862 59


1 2 3 4 Next >>