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Query: UMLS:C0012833 (dizziness)
 9,689 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

Drug development in psychiatry has evolved from a process dependent on chance discovery to one based on rationally targeting specific mechanisms of action believed to be important in the pathophysiology underlying psychiatric syndromes. Antidepressant pharmacotherapy is the first area to have substantially benefited from this evolution. Serotonin selective reuptake inhibitors (SSRIs) were the first class of psychiatric medications developed based on such molecular targeting. Nefazodone is a new antidepressant that combines blockade of the serotonin-2 receptor with serotonin uptake inhibition. Perhaps as a result of this dual action, nefazodone caused fewer complaints of nervousness (e.g., agitation, anxiety), insomnia, and tremors and a higher incidence of confusion, dizziness, and vision disturbance than do other advanced generation antidepressants based on several different ways of assessing the relative incidence of these adverse effects. Reports of sexual dysfunction on nefazodone and bupropion treatment were lower than on treatment with other recently released antidepressants.
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PMID:Comparison of the tolerability of bupropion, fluoxetine, imipramine, nefazodone, paroxetine, sertraline, and venlafaxine. 764 68

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 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

Toxicities and medical outcomes associated with nefazodone poisoning were characterized using national poisoning data from the American Association of Poison Control Centers and through prospective collection of additional data elements. Nefazodone exposures involving concomitant agents were excluded. There were 1,338 human exposures included in the final data analysis. Seventy-five percent of exposures were acute and 20% involved children < 13 years. Twenty-five percent of patients remained asymptomatic. There were no deaths. No dose response relationship was evident in the 45 cases where estimated doses were available. The most common manifestations were drowsiness (17.3% of all patients), nausea (9.7%), and dizziness (9.5%). The most common serious clinical effect was hypotension (1.6%). The median onset time for symptoms was 1.75 hours. Manifestations resolved within 8 to 24 hours. Most patients were treated with only gastrointestinal decontamination. No patients required intubation, mechanical ventilation, or vasopressors. Nefazodone appears to be of low toxicity during poisonings.
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PMID:Toxicities and outcomes associated with nefazodone poisoning: an analysis of 1,338 exposures. 1099 75

Nefazodone overdose has been reported infrequently. The commonest effects reported are drowsiness, nausea, dizziness, and vomiting, less commonly hypotension and bradycardia. We report a case of single-agent nefazodone poisoning. Serial drug concentrations were taken for quantification of parent drug and metabolites. Clinical findings were documented every 1 to 2 hours. We modeled both the toxicokinetics of nefazodone and correlated this with clinical effects and electrocardiograph (ECG) abnormalities. A 16-year-old female took 2.4 g of nefazodone. She had significant drowsiness in the first 6 hours, associated with hypotension (systolic BP < 90 mmHg; lowest BP 70/30 mmHg) for 18 hours, and mild bradycardia (slowest rate of 56 bpm). She had a prolonged QT/QTc which normalized over 24 hours. She was given charcoal and intravenous fluids and was observed carefully, recovering with no problems. The terminal elimination half-life for nefazodone was 8.3 hours, and its metabolite hydroxy(OH)-nefazodone was 14.6 hours. BP-time curves demonstrated an 18-hour period of hypotension. There was a significant correlation between systolic BPand OH-nefazodone (R2 = 0.602). HR remained between 56 and 66 bpm for 30 hours despite hypotension. QT was significantly correlated with nefazodone (R2 = 0.911) and OH-nefazodone (R2 = 0.797), but no significant relationship between QTc and drug concentrations. The case demonstrates that nefazodone may potentially cause cardiac toxicity, which appears to be concentration-dependent. Although QT was concentration-dependent, this would need confirmation with other cases. Bradycardia, hypotension, and drowsiness are the most significant effects and are maximal in the first 12 hours when parent and metabolite concentrations are high.
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PMID:Nefazodone poisoning: toxicokinetics and toxicodynamics using continuous data collection. 1273 55