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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effectiveness of the newer antidepressants in comparison to that of the more established agents is frequently questioned. Although selective serotonin reuptake inhibitors (SSRIs) show a high degree of pharmacologic selectivity, this does not seem to translate into improved clinical efficacy. Instead, the clinical effectiveness of the tricyclic agents may be attributable to their dual inhibitory effects on both noradrenergic and serotonergic systems. Accordingly, newer antidepressants with multiple modes of action may prove more effective than serotonin-selective compounds. To assess the relative merits of older and newer antidepressant drugs in severe depression, efficacy findings from the limited number of comparative clinical trials conducted in this patient population were reviewed. A systematic approach was taken, with studies being grouped according to the various characteristics that, in conjunction with standard DSM-IV and International Classification of Diseases, 10th revision, diagnostic criteria, define severe depression, viz. a 17-item Hamilton Rating Scale for Depression score > or = 25, hospitalization, and the presence of psychotic (delusional), melancholic, and endogenous features. The contention that tricyclic antidepressants offer superior efficacy to the SSRIs and the reversible monoamine oxidase inhibitors in the treatment of severe depression is supported by several comparisons of clomipramine with fluoxetine, paroxetine, citalopram, and moclobemide. Venlafaxine also seems to be more effective than fluoxetine in hospitalized patients with melancholic depression. Mirtazapine, a noradrenergic and specific serotonergic antidepressant, displays comparable antidepressant efficacy to clomipramine and amitriptyline in severe depression and seems to be a useful option in this patient population.
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PMID:Efficacy of antidepressants in the treatment of severe depression: the place of mirtazapine. 909 May 74

Major depression is commonly found in the child and adolescent population. Venlafaxine, a new antidepressant, has been used successfully in adults; however, its use in children and adolescents has been very limited. This study evaluated the efficacy and side effect profile of venlafaxine in the treatment of depression in children and adolescents. In a double-blind, placebo-controlled, 6-week study, 33 subjects between the ages of 8 and 17, who met DSM-IV criteria for major depression, were treated with either venlafaxine and therapy or placebo and therapy. Patient progress data were obtained by weekly rating assessments. Data on side effects were also obtained weekly. The statistical analysis indicated a significant improvement over time, but it could not be attributed to venlafaxine drug therapy. These findings are consistent with other studies where the efficacy of antidepressants in the treatment of major depression in this age population remains unproven. Low dosage and short length of treatment may account for the lack of efficacy. The findings did, however, suggest a low side-effect profile. Further studies are recommended to assess efficacy and to corroborate its safety in children and adolescents.
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PMID:Venlafaxine in the treatment of children and adolescents with major depression. 913 67

Major depressive disorder (MDD) is a common affective disorder that is associated with a range of psychiatric disturbances. The pathophysiology of MDD is commonly believed to involve the reduced availability of the monoamines, serotonin (5-HT) and norepinephrine (NE), the enhancement of which is also believed to mediate, at least in part, the therapeutic effects of antidepressants. The first-generation antidepressants, the tricyclic antidepressants (TCAs), provide considerable efficacy but have several limitations, including (1) delayed onset of action, (2) intolerable or distressing side effects, (3) low therapeutic index, and (4) a significant proportion of nonresponders. The second-generation antidepressants, the selective-serotonin-reuptake inhibitors (SSRIs), mitigate some of the side effects associated with the TCAs by selectively inhibiting the reuptake of 5-HT. Venlafaxine is a new antidepressant that blocks reuptake of both 5-HT and NE. It, like the SSRIs, has a relatively benign side-effect profile. In addition, it may exert a rapid onset of action, and it appears to be particularly effective in moderate-to-severe depression and in patients who have treatment-refractory depression.
Depression 1996
PMID:Venlafaxine: a novel antidepressant that has a dual mechanism of action. 916 Jun 40

A double-blind, placebo-controlled study of 229 patients with a Research Diagnostic Criteria diagnosis of major, minor or intermittent depression was used to compare the clinical profiles of venlafaxine and imipramine in general practice. Venlafaxine produced a significant improvement compared to placebo in symptoms of depression and anxiety as rated by the total MADRS and percentage of responders, the CGI improvement, the CGI severity of illness, the BSA psychic anxiety item and the HSCL. On a number of these measures, venlafaxine was also significantly more effective than imipramine. Venlafaxine was significantly superior to both imipramine and placebo for the SARS total score and the items 'social/leisure' and 'extended family.' A similar proportion of patients discontinued treatment in each group, but fewer patients on venlafaxine discontinued treatment because of an unsatisfactory response.
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PMID:Efficacy of venlafaxine in depressive illness in general practice. 924 43

Depression is a significant problem in the elderly. Because of aging-related pharmacokinetic and pharmacodynamic changes, it is not possible to automatically extrapolate findings on the efficacy or tolerability of antidepressants from younger to older populations. Venlafaxine inhibits both noradrenaline (norepinephrine) and serotonin (5-hydroxytryptamine; 5-HT) reuptake. Analysis of data from phase II and III trials showed that venlafaxine was comparably effective in the young and in a subset of over 350 elderly patients. Venlafaxine dosage needs to be lowered in the elderly with renal impairment. As a weak cytochrome P450 (CYP) inhibitor, it is unlikely to have clinically significant drug interactions. Venlafaxine may be associated with some increase in supine diastolic blood pressure, especially at dosages above 150 mg/day. Nefazodone is a serotonin uptake inhibitor and serotonin 5-HT2A receptor antagonist. Pooled analysis of about 250 patients found nefazodone to be effective in elderly individuals with moderate or severe depressive symptoms, with or without melancholia, in both primary and recurrent episodes. Nefazodone clearance is reduced in patients with hepatic impairment, and plasma concentrations have been reported to be higher in the elderly. Nefazodone is an inhibitor of the CYP3A4 family. There does not appear to be any increase in the frequency or severity of adverse effects in the elderly. Moclobemide is a selective inhibitor of monoamine oxidase type A. Studies in the elderly have found it to be well tolerated and meta-analysis has shown it to be comparably effective in young and elderly populations, and comparable to other antidepressants in terms of efficacy. Neither age nor renal impairment necessitate dosage adjustment, but hepatic impairment does necessitate dosage reduction. Dietary restrictions are not required. Overall, there is a relative paucity of data on the tolerability and efficacy of newer antidepressants in the elderly, especially those with concomitant medical disorders. Data that are available indicate that venlafaxine, nefazodone and moclobemide have comparable efficacy in older and younger patients.
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PMID:Antidepressant use in the elderly. Current status of nefazodone, venlafaxine and moclobemide. 925 75

Venlafaxine (VEN), a drug used in the treatment of depression, undergoes significant first-pass metabolism after oral dosing to O-desmethylvenlafaxine (ODV), a metabolite with comparable therapeutic activity to that of parent drug. The pharmacokinetic disposition of VEN was characterized using a "first-pass" model that incorporates a presystemic compartment (liver) to account for the first-pass metabolism of VEN to ODV. A series of differential equations were simultaneously fitted to plasma concentrations of parent and metabolite. A good fit of the model to observed data was demonstrated, generating estimates for the following parameters: ka (1.31 +/- 0.009 hr-1), VVEN (252 +/- 87.6 liters), CLint (65.8 +/- 39.7 liters/hr), RL (liver:plasma partition coefficient, 29.6 +/- 18. 3), VODV (181 +/- 84.1 liters), and CLODV (23.5 +/- 12.5 liters/hr). Parameter estimates correlated closely with those obtained through noncompartmental methods. These results indicate that the time-course disposition of a compound undergoing first-pass hepatic metabolism after oral dosing can be successfully modeled.
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PMID:Application of a first-pass effect model to characterize the pharmacokinetic disposition of venlafaxine after oral administration to human subjects. 932 27

This was a randomized, double-blind, placebo-controlled comparison of the efficacy and safety of once-daily venlafaxine extended release (XR) and venlafaxine immediate release (IR). Outpatients with DSM-III-R major depression were randomly assigned to venlafaxine XR, 75 mg once daily, venlafaxine IR, 37.5 mg twice daily, or placebo for a maximum of 12 weeks. If the response was inadequate after 2 weeks of treatment, the dosage of venlafaxine XR or IR could be increased to 150 mg daily. The primary efficacy variables were the 21-item Hamilton Depression (HAM-D) Rating Scale total score and depressed mood item, the Montgomery-Asberg Rating Scale (MADRS) total scores, and the Clinical Global Impressions (CGI) severity scale. Two hundred seventy-eight patients were evaluated for efficacy. Venlafaxine XR was significantly superior (p < 0.05) to placebo beginning at week 2 for the HAM-D, week 3 for the MADRS, and week 4 for the CGI severity. Similarly, venlafaxine IR was significantly superior (p < 0.05) to placebo beginning at week 2 on the HAM-D total and depressed mood item, week 3 on the MADRS total, and week 6 on the CGI severity scales. Venlafaxine XR exhibited superiority (p < 0.05) over venlafaxine IR at week 12 for all efficacy variables. The most common treatment-emergent adverse event with venlafaxine XR was nausea. The incidence of nausea was highest during the first 2 weeks with a low likelihood of developing nausea thereafter. The results of this study indicate that venlafaxine XR is safe, effective, and well tolerated for the treatment of major depression at once-daily doses ranging from 75 to 150 mg.
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PMID:Once-daily venlafaxine extended release (XR) and venlafaxine immediate release (IR) in outpatients with major depression. Venlafaxine XR 208 Study Group. 933 81

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

Venlafaxine is the first member of a novel class of antidepressants that inhibits the reuptake of both serotonin and norepinephrine. Clinical trials of venlafaxine have demonstrated its efficacy and safety in the treatment of patients diagnosed with major depression. Because patients who have depression also often have anxiety, recent investigations have focused on determining whether venlafaxine can relieve symptoms of anxiety in depressed patients. We performed a pooled analysis of six short-term trials of venlafaxine, retrospectively measuring anxiety in anxious depressed patients using the Hamilton Rating Scale for Depression (HAM-D), Anxiety/Somatization factor and Anxiety Psychic item scores. Three studies were placebo-controlled, and three were placebo- and active-drug-controlled; active controls were imipramine in two trials and trazodone in the third trial. Patients were categorized as having anxiety accompanying depression if baseline HAM-D Anxiety Psychic item scores were 2 or greater. Anxious depressed patients treated with venlafaxine showed greater improvement than those treated with placebo beginning at week 3, according to the HAM-D Anxiety/Somatization factor score, and beginning at week 1, according to the Anxiety Psychic item score. Both effects were maintained at week 6 of treatment (and at week 12 in the one study of longer duration). Finally, treatment with venlafaxine resulted in a highly significant (p < or = 0.001) improvement in depression scores in patients who were anxious at baseline, compared with placebo-treated patients. The results of this analysis demonstrate that venlafaxine is more effective than placebo in reducing symptoms of anxiety in depressed patients and suggest that venlafaxine may afford a monotherapy option for treating patients who have a comorbid diagnosis of depression with anxiety.
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PMID:A meta-analysis of the effects of venlafaxine on anxiety associated with depression. 955 99

Venlafaxine (Efexor) is the first representative of a new class of antidepressants: serotonin noradrenaline reuptake inhibitors. Its usual dose is 75 mg/d in two intakes but can be progressively increased until a maximal daily dose of 375 mg/d in severe or resistant depression, particularly among inpatients. The efficacy of venlafaxine is at least equivalent to reference antidepressants. At high doses, venlafaxine could even exhibit a better efficacy and a shorter latency than current compounds. Its profile of side-effects is quite similar to selective serotonin reuptake inhibitors with mainly nausea, with the exception if an increase in blood pressure which can appear at high doses. In total, venlafaxine represents an interesting innovation in the pharmacological treatment of depression.
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PMID:[Pharma-Clinics. The drug of the month. Venlafaxine (Efexor)]. 956 31


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