UMLS:C0011570 - FACTA Search

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

The selective serotonin reuptake inhibitors (SSRIs) have emerged as a major therapeutic advance in psychiatry. They have emphasized the pathophysiological role of serotonin (5-HT) in affective disorders. Indeed, SSRIs were developed for inhibition of the neuronal uptake for serotonin (5-HT), a property shared with the TCAs (tricyclic anti-depressants), but without affecting the other various central neuroreceptors (ie, histamine, acetylcholine and adrenergic receptors) that are responsible for many of the safety and tolerability problems with TCAs. In this way, fluoxetine and other SSRIs represent a major advance over tricyclics, because of their lower toxicity. While the position of fluoxetine relative to other selective serotoninergic antidepressants requires further investigation, fluoxetine has a more favorable tolerability profile for a similar efficacy in comparison to tricyclic antidepressants. The pharmacokinetic and pharmacodynamic properties of fluoxetine are well described. After oral administration, fluoxetine is almost completely absorbed. Due to hepatic first-pass metabolism, the oral bioavailability is < 90%. Fluoxetine has a half-life of 2-7 days, whereas the half-life of norfluoxetine ranges between 4 and 15 days. This long half-life of fluoxetine may be advantageous when the patient omits a dose since drug concentrations decrease slightly. On the other hand, in the case of fluoxetine non-response, long washout periods are necessary before switching the patient to a TCA or a MAO inhibitor to avoid drug interactions or the development of a 5-HT syndrome. As a class, SSRIs are considerably more selective in comparison to TCAs in terms of their central nervous system mechanisms, but differ in other clinically relevant aspects. This action affects several specific 5-HT receptors, which, in turn, effects a multitude of neural systems and signalization pathways. However, despite the facilitating serotoninergic neurotransmission, the direct mechanism by which a SSRI exerts its anti-depressant activity remains uncertain. The therapeutic response in major depression for SSRIs (ie 15-20 days) maybe due to a progressive desensitization of somatodendritic 5-HT autoreceptors in the midbrain raphe nucleus. On the other hand, it has also been postulated that 5-HT is a modulator of several neurophysiological pathways, including dopamine, noradrenaline, but also neurotrophic factors, intra-cytoplasmic phosphorylations and nuclear genes expression. Therapeutic activity of SSRIs may finally results in a complex modulation and homeostasis between monoaminergic neurotransmisson and neuronal plasticity. In term of health-care, the introduction of fluoxetine and other SSRIs in the 1980s has radically changed the treatment of depressive disorder worldwide and they have emerged as the first line of treatment for depressive disorders. The efficacy of fluoxetine is now well established in the treatment of major depressive disorder. Indeed, this efficacy has been assessed in numerous clinical controlled trials involving patients with major depressive disorders. Meta-analysis were carried out and confirmed that fluoxetine was as effective as the tricyclic antidepressants, and appeared more effective than placebo in improving the symptoms of depression. However, there is no scientific evidence to suggest that any one SSRI is more effective than another, but not all patients respond to the same agent. Looking to the future, we need further comparative studies of the SSRIs with the next generation of antidepressants such as 5-HT noradrenaline reuptake inhibitors (SNRIs, Venlafaxine). Actually, it is interesting to note that, whereas the emphasis with the SSRIs has been on their selectivity, recent developments have tended to move towards less selective agents, and now to other neurobiological pathways (ie neurotrophic factors). Finally, fluoxetine, in common with other SSRIs, remains today a first-line treatment option for major depressive disorder.
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PMID:[Fluoxetine: an update of its use in major depressive disorder in adults]. 1559 66

Antidepressants are often applied in the treatment of chronic pain. Analgesic action of tricyclic antidepressants (TCAs) has been extensively studied and proven. TCAs are associated with a number of adverse effects which are inconvenient for patients. The newer antidepressants have fewer side effects and equivalent efficacy on mood disorders. This article reviews the available publications (mainly placebo-controlled trials) concerning the efficacy of these medications in the treatment of chronic pain. The data regarding selective serotonin reuptake inhibitors (SSRI) are conflicting. Trazodone (a serotonin-reuptake inhibitor as well as a postsynaptic serotonin receptor antagonist) does not appear to be effective for the treatment of chronic pain. No placebo-controlled studies are available for noradrenergic and specific serotoninergic antidepressant (NaSSA)--mirtazapine and noradrenaline reuptake inhibitor (NaRI)--reboxetine. Bupropion, a noradrenaline and dopamine-reuptake inhibitor appears to be effective in the treatment of neuropathic pain. Venlafaxine--selective serotonin and noradrenergic reuptake inhibitors (SNRI) was shown to be effective in the treatment of different kinds of pain. Duloxetine (SNRI) is effective in relieving both the emotional and painful physical symptoms of depression. Additional randomized, controlled trials are necessary to fully evaluate the role of new antidepressants in the treatment of chronic pain.
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PMID:[The effectiveness of antidepressants in the treatment of chronic non-cancer pain--a review]. 1577 Nov 51

The experiments presented in this paper aimed to investigate whether estrogen level changes in oviariectomized rats (OVX) may lead to depression and memory disorders, and whether the effects of such changes may be reversible following administration of a new antidepressant, venlafaxine (CAS 9930-78-4, VEN, Efectin). The Porsolt forced swimming test and Morris water maze test were carried out on female Wistar rats after ovariectomy and in sham-ovariectomized rats. VEN 20 mg/kg was administered orally 30 min before the tests for the period of 14 days. Estradiol (17beta-estradiol benzoate, CAS 50-28-2, E2) administration (5 microg E2/0.2 ml sesame oil s.c.) was started 24 h after ovariectomy and was continued for 14 days--each dose was administered 180 min before the test. In the immobility test, which reflects antidepressant drug activity, it was found that VEN shortened immobility time (IT) after the 1st, 7th and 14th administration (days 1, 7, 14, respectively) in ovariectomized rats, whereas in the control group (sham-ovariectomized rats) VEN exerted antidepressant action only after single administration (day 1) and after 7 days of administration. E2 significantly reduced immobility behaviour both after single and chronic treatment in ovariectomized rats. After joint administration of VEN and E2 potentiation of the antidepressant activity of VEN could be observed in both groups except for concurrent administration of VEN and E2 after 14 days in sham-ovariectomized rats. VEN improved the spatial memory in the Morris water maze test, whereas E2 did not affect the memory of the tested animals. Joint administration of VEN and E2 maintained the memory improving effect induced by VEN. The regulatory role of the steroid hormone and the new antidepressant drug (VEN) in antidepressant activity and memory function could be related to the interactions between noradrenergic and serotoninergic systems.
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PMID:Antidepressant and memory affecting influence of estrogen and venlafaxine in ovariectomized rats. 1581 87

Generalized anxiety disorder is characterized by excessive chronic anxiety in association with many somatic symptoms. The disorder has pervasive effects on quality of life, including work, social and educational aspects and requires long-term therapy. Available studies in patients are the Diagnostic and Statistical Manual of Mental Disorders, third edition-revised and fourth edition, which have defined generalized anxiety disorder and demonstrate the efficacy of benzodiazepines, azapirones, some antidepressants and psychotherapy. Benzodiazepines are effective anxiolytics for short-term use but are accompanied by many adverse events. The antidepressants, paroxetine and venlafaxine (Efexor), have demonstrated efficacy in patients with generalized anxiety disorder with mild side-effect profiles. They have the additional benefit of efficacy in depression, which frequently occurs comorbidly in these patients. Long-term efficacy has been shown with venlafaxine in the treatment of this chronic condition, confirming that as in depression, the goal must not just be remission beyond simple symptom resolution but also on to improved functioning and quality of life. Psychotherapy with applied relaxation, cognitive therapy and cognitive behavioral therapy show the most promise in resolving and maintaining treatment gains in the long-term. These approaches may be useful alone or in combination with adjunctive pharmacotherapy to achieve remission. Based on current evidence, the recommended approach to achieving long-term benefits for patients with generalized anxiety disorder is antidepressant therapy with paroxetine or venlafaxine in combination with cognitive behavioral therapy.
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PMID:Treatments for generalized anxiety disorder. 1585 70

The combined serotonin-norepinephrine reuptake inhibitor, venlafaxine XR, has demonstrated significant response and remission in patients diagnosed with depression when measured with the Hamilton Depression Rating Scale (HAM-D). This pooled analysis of data from five studies compared the sustained remission of depressive symptoms in patients treated with venlafaxine XR, the selective serotonin reuptake inhibitors (SSRIs) fluoxetine or paroxetine, or placebo. Data from 1391 subjects enrolled in five active and placebo-controlled studies who met the DSM-III-R or DSM-IV criteria for major depressive disorder were analysed. Three treatment groups were compared: venlafaxine XR (n = 560), fluoxetine/paroxetine (n = 298) and placebo (n = 496). Mean treatment duration was 8 weeks. Responders were defined as those patients whose HAM-D-21 score decreased by > or = 50% from baseline. Remission was defined as a HAM-D-17 score < or = 7. Sustained remission was defined as maintenance of remission through week 8 or the end of treatment (if before week 8) and for > or = 2 weeks. Between-group rate comparisons in outcome measures were carried out using Fisher's exact and log-rank tests. Venlafaxine XR produced significantly higher rates of sustained remission in depressed patients compared to fluoxetine/paroxetine or placebo over this 8-week treatment period. As early as week 2, a significantly greater proportion of patients treated with venlafaxine achieved improved depression scores (remission and response). A significantly greater rate of remission and sustained remission occurred with venlafaxine compared to placebo. Remission was achieved earlier with venlafaxine and lasted throughout the remainder of the study. These results demonstrate that venlafaxine XR is more effective than fluoxetine/paroxetine for sustaining remission of depressive symptoms.
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PMID:Venlafaxine XR demonstrates higher rates of sustained remission compared to fluoxetine, paroxetine or placebo. 1593 85

Worldwide, major depression is the leading cause of years lived with a disability, and the fourth cause of disability-adjusted life years. Depression is second only to hypertension as the most common chronic condition encountered in general medical practice. Unfortunately, despite the high prevalence of depression, under-recognition and under-treatment are common.Historically, clinicians have assessed the short-term effectiveness of antidepressants by response rates, often defined as a 50% reduction in depressive symptoms. However, this usually does not reflect true clinical remission, and residual symptoms are common. Persistence of residual symptoms appears to be a common link to relapse, chronic disability and suicide. The burden of not treating depression effectively to remission is significant, as the disease is an important contributor to the disability levels of the general population. Disability, in turn, has a profound impact on lost productivity and medical expenses. In 2000, depression cost the US more than US 83 billion dollars annually in lost productivity, medical expenses and premature death.Venlafaxine, a dual-acting serotonin norepinephrine (noradrenaline) reuptake inhibitor, may improve a patient's response to treatment and their chances of achieving complete remission compared with conventional antidepressant therapies, with the evidence for this being the strongest for comparisons with the selective serotonin receptor inhibitors (SSRIs). To date, there are only a small number of economic studies of venlafaxine, and most are cost or resource utilisation analyses with significant limitations. Nevertheless, two cost-effectiveness analyses of venlafaxine are available. They found venlafaxine had a lower average cost per patient achieving remission or per symptom-free day compared with SSRIs; one reported an incremental cost-effectiveness ratio for venlafaxine of US 586 dollars (year 2002 values) per additional patient achieving remission over 8 weeks, and the other found venlafaxine to be a dominant treatment choice over SSRIs over 6 months (year 2001 values). Although requiring further confirmation, these initial data suggest that venlafaxine is a cost-effective strategy for the treatment of depression. The availability of an effective armamentarium of antidepressant strategies, including venlafaxine, to achieve and sustain remission offers both clinical and economic value to all those touched by the burden of depression.
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PMID:Remission from depression : a review of venlafaxine clinical and economic evidence. 1596 May 53

Venlafaxine is a recently developed serotoninergic antidepressant whose reported toxicity at overdose levels includes central nervous system depression, seizures, and cardiovascular toxicity. The authors now present a case of venlafaxine overdose in a young woman complicated by a rise in plasma creatine kinase activity up to 52,600 U/L. Immediate therapy with intravenous fluids, bicarbonate, and furosemide was administered, and there were no further complications, notably no renal failure. This case supports the notion that venlafaxine can induce direct skeletal muscle toxicity leading to severe rhabdomyolysis. Therefore, clinicians should monitor muscle enzymes in patients with venlafaxine overdose to detect the development of rhabdomyolysis at an early stage and to initiate appropriate therapy rapidly.
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PMID:Severe rhabdomyolysis following venlafaxine overdose. 1617 26

Venlafaxine is an antidepressant drug with demonstrated serotonin (5-HT) and norepinephrine (NE) reuptake blockade properties in electrophysiological and microdialysis experiments in laboratory animals. In healthy volunteers, its 5-HT reuptake-inhibiting potential has also been clearly documented, but not its NE reuptake blockade action. This double-blind study compared the effects of a low dose (75 mg) and of a forced titration of high (up to 375 mg in 1 wk) daily doses of venlafaxine. Forty-four patients with major depression according to DSM-IV criteria were assessed bi-weekly for the first 2 wk and weekly for the next 2 wk. Inhibition of 5-HT reuptake was estimated using the depletion of whole-blood 5-HT, while that of NE was assessed using the attenuation of the systolic blood-pressure elevations produced by intravenous injections of tyramine. Forty-two patients completed the study. Both the low and the high doses of venlafaxine decreased the levels of 5-HT to the same extent: the reduction was of about 55% after 1 wk and of 75% after 4 wk. The 75 mg/d dose of venlafaxine did not alter the tyramine pressor response, whereas, in patients receiving the higher regimens of venlafaxine, there was a significant attenuation of the pressor effect of tyramine. There was no significant difference between the two treatment arms regarding the modifications of the depression scores. The present data showed that, at its minimal effective dose in depression (75 mg/d), venlafaxine acted as a selective 5-HT reuptake inhibitor, whereas when administered at higher doses (225 and 375 mg/d), it acted as a dual 5-HT and NE reuptake inhibitor.
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PMID:Differential physiological effects of a low dose and high doses of venlafaxine in major depression. 1669 6

Based on preliminary evidence of its usefulness in treatment-resistant depression (TRD), an olanzapine/fluoxetine combination (OFC) was examined in comparison with olanzapine, fluoxetine, and venlafaxine in a TRD population. In this 12-week double-blind study, 483 subjects with unipolar, nonpsychotic TRD, with historic failure on a selective serotonin reuptake inhibitor (SSRI) and prospective failure on open-label venlafaxine, were randomized to an OFC or to an olanzapine, fluoxetine, or venlafaxine monotherapy group. Venlafaxine was continued randomly in the double-blind acute phase to explore the benefits of continuation versus switching therapy. The Montgomery-Asberg Depression Rating Scale (MADRS) total change score at end point was the primary outcome measure. The OFC group had significantly greater improvement in depressive symptoms by week 1 of treatment (MADRS mean change =-7.2, baseline =29.6), in comparison to olanzapine (-4.8, P=.03), fluoxetine (-4.7, P=.03), or venlafaxine (-3.7, P=.002) groups and maintained its statistical separation from all three monotherapy groups through week 6. At end point, the OFC group was significantly different only from the olanzapine group (-14.1 vs. -7.7, P<.001). Analysis of a subgroup of subjects who had an SSRI failure in their current depressive episode (n=334) revealed statistical separation from both olanzapine and fluoxetine (but not venlafaxine) at end point: OFC (-14.6) versus olanzapine (-9.4, P<.001) versus fluoxetine (-10.7, P=.006) versus venlafaxine (-14.7, P=.98). The OFC had a safety profile comparable to its component monotherapies (i.e., olanzapine and fluoxetine), showed a rapid onset of antidepressant effect, and was effective in this TRD sample. At the study end point, OFC, fluoxetine, venlafaxine, and low-dose OFC all appeared to be similarly effective.
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PMID:A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, fluoxetine, and venlafaxine in treatment-resistant depression. 1671 Aug 53

To date, no large-scale, controlled trial comparing a serotonin-norepinephrine reuptake inhibitor and selective serotonin reuptake inhibitor with placebo for the treatment of panic disorder has been reported. This double-blind study compares the efficacy of venlafaxine extended-release (ER) and paroxetine with placebo. A total of 664 nondepressed adult outpatients who met DSM-IV criteria for panic disorder (with or without agoraphobia) were randomly assigned to 12 weeks of treatment with placebo or fixed-dose venlafaxine ER (75 mg/day or 150 mg/day), or paroxetine 40 mg/day. The primary measure was the percentage of patients free from full-symptom panic attacks, assessed with the Panic and Anticipatory Anxiety Scale (PAAS). Secondary measures included the Panic Disorder Severity Scale, Clinical Global Impressions--Severity (CGI-S) and--Improvement (CGI-I) scales; response (CGI-I rating of very much improved or much improved), remission (CGI-S rating of not at all ill or borderline ill and no PAAS full-symptom panic attacks); and measures of depression, anxiety, phobic fear and avoidance, anticipatory anxiety, functioning, and quality of life. Intent-to-treat, last observation carried forward analysis showed that mean improvement on most measures was greater with venlafaxine ER or paroxetine than with placebo. No significant differences were observed between active treatment groups. Panic-free rates at end point with active treatment ranged from 54% to 61%, compared with 35% for placebo. Approximately 75% of patients given active treatment were responders, and nearly 45% achieved remission. The placebo response rate was slightly above 55%, with remission near 25%. Adverse events were mild or moderate and similar between active treatment groups. Venlafaxine ER and paroxetine were effective and well tolerated in the treatment of panic disorder.
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PMID:A double-blind study of the efficacy of venlafaxine extended-release, paroxetine, and placebo in the treatment of panic disorder. 1689 19

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