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A Markov simulation model was constructed to assess the cost-utility of maintenance treatment for 2 years in recurrently depressed patients in Sweden. Risk of relapse and recurrence was based on a recent randomised clinical trial assessing the efficacy and tolerability of maintenance treatment with venlafaxine over 2 years. Costs and quality of life estimations were retrieved from a naturalistic longitudinal observational study conducted in Sweden. Health effects were quantified as quality-adjusted life-years (QALYs). Sensitivity analyses were conducted on key parameters employed in the model.
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Previous studies showed that the dual serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE) reuptake inhibitor, duloxetine, increases bladder capacity and urethral sphincter electromyographic (EMG) activity in a cat model of acetic acid-induced bladder irritation. The present study aimed to determine the relative importance of 5-HT versus NE reuptake inhibition for mediating these effects by examining drugs that are selective for either the 5-HT or NE system or both. Similar to duloxetine, venlafaxine (0.1 to 10 mg/kg), also a dual serotonin and norepinephrine reuptake inhibitor, produced marked increases in bladder capacity and EMG activity that were reversed by methiothepin (0.3 mg/kg). S-norfluoxetine (0.01 to 10 mg/kg), a serotonin selective reuptake inhibitor, produced small but significant increases in bladder capacity and EMG activity at doses of 3 and 10 mg/kg. Thionisoxetine (0.01 to 3.0 mg/kg), a NE selective reuptake inhibitor, produced no effects on bladder capacity or sphincter EMG activity. Surprisingly, co-administration of thionisoxetine and s-norfluoxetine up to doses of 1 mg/kg of each compound produced no effect on lower urinary tract function. These doses were the maximum that could be administered in combination due to drug-induced emergence of skeletal muscle activity in chloralose-anesthetized animals. These results indicate that there are unexplained pharmacological differences between the effects of single compounds that exhibit dual NE and 5-HT reuptake inhibition and a combination of compounds that exhibit selective NE and 5-HT reuptake inhibition on lower urinary tract function.
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Venlafaxine, oxydesmethylvenlafaxine and an internal standard (paroxetine) were extracted from plasma by a solid-phase extraction technique. Chromatography was performed using isocratic reversed-phase high-performance liquid chromatography (HPLC) with coulometric endpoint detection. The standard curves were linear over the range 0-200 ng/ml for both venlafaxine and oxydesmethylvenlafaxine in plasma. The mean inter- and intra-assay coefficients of variation over the range of the standard curves were less than 10%. The absolute recovery averaged 74% for venlafaxine and 67% for oxydesmethylvenlafaxine. The sensitivity was 0.5 ng for both the analytes. Plasma profiles of the analytes following oral administration of venlafaxine, are presented.
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Pathophysiological mechanisms implicated in the development of AEP in our patient seems to be associated with eotaxin and serotonin eosinophilic-specific chemoattracting action.
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Anesthetized guinea pigs were instrumented with jugular and carotid cannulae for drug infusion and blood pressure monitoring respectively; a thoracotomy was performed for placement of a monophasic action potential probe on the left ventricle and for placement of pacing wires on the left ventricular apex. Drugs were infused as a 5-min loading dose immediately followed by a 10-min maintenance dose to achieve clinically relevant plasma concentrations; blood samples were taken at the end of each maintenance dose. Ventricular pacing was performed twice at baseline and at each dose level as follows: 50 preconditioning-beats at S1=220 (or 240) ms immediately followed by 30 test-beats at S2=200 ms. This S1-S2 protocol was repeated for S2=190 to 140 ms. HERG and calcium current measurements were recorded in HEK-293 cells stably expressing hERG potassium currents and freshly isolated guinea pig cardiac myocytes using the whole-cell configuration of the patch clamp technique.
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The study enrolled 1008 adult patients with MDD (18-65 years old) from 18 primary and psychiatric care sites worldwide. Patients were randomly assigned to an 8-week course of escitalopram, sertraline, or venlafaxine-extended-release. We examined whether ADM is associated with changes in suppression, usually associated with maladaptive outcomes, and reappraisal, usually associated with adaptive outcomes. We also tested whether changes in emotion regulation predict changes in depressive symptoms following ADM.
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Results show that none of the tested variants were associated with treatment response to venlafaxine XR in GAD. Genotype and allele frequencies did not differ statistically significantly between responders and non-responders using either the Hamilton Anxiety or Clinical Global Impressions of Improvement Scale at 6 months.
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Platelet 5-HT uptake was inhibited by venlafaxine across the dose range and by sertraline but not maprotiline. Inhibition was competitive, related to increases in affinity and not related to capacity. Steady-state drug levels were associated with a 5-HT uptake inhibition of 87% or more in subjects taking venlafaxine or sertraline. The pressor response to tyramine differentially distinguished maprotiline from sertraline and the low dose of venlafaxine but not from the high dose of venlafaxine.
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The majority of the trials in the elderly are outpatient trials which excluded psychotic patients and patients with common comorbid physical disorders. Consequently information is lacking about the more complex cases of elderly depressed patients, as found in inpatient wards.
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Pharmacological effects of acute treatment with venlafaxine (VEN), a clinically active antidepressant [a noradrenaline (NA) and 5-hydroxytryptamine (5-HT) reuptake inhibitor without any affinity for neurotransmitter receptors] were studied in mice and rats. VEN inhibited the reserpine- or apomorphine-induced hypothermia and enhanced the L-5-HTP-induced head twitches in mice. It reduced the immobility time in Porsolt's test in mice and rats, but either did not change the locomotor activity (mice) or decreased it (rats). VEN reduced the locomotor hyperactivity induced by amphetamine (AMP), apomorphine (APO) and quinpirole (QUI), as well as the APO-induced stereotypy; the stereotypy induced by AMP in rats was prolonged. VEN neither changed the clonidine-induced aggressiveness in mice nor the behavioral syndrome induced by oxotremorine in rats. The obtained results indicate that VEN, given acutely, shows a pharmacological profile similar to that of tricyclic NA and 5-HT reuptake inhibitors. In contrast to the antidepressants mentioned above, VEN does not exhibit an alpha 1-adrenolytic or a cholinolytic activity (in vivo tests).
This study was undertaken to compare the antidepressant efficacy and short-term safety of venlafaxine with those of placebo in hospitalized patients with major depression and melancholia.
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we related medication choice and dosage range to outcomes of treatment as reflected by discharge rates and suicidality.
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Relevant articles on duloxetine and venlafaxine for the treatment of pediatric ADHD were reviewed; 5 studies on venlafaxine and 1 study on duloxetine were evaluated. Studies included open-label and randomized, double-blind trials. Case studies in pediatric populations and all studies in adult populations were excluded.
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Mitogen-stimulated cell proliferation was assessed in major depressive and dysthymic patients exhibiting either typical or atypical features. In a subset of patients, lymphocyte proliferation was also assessed before and after pharmacotherapy to determine whether alleviation of symptoms would be accompanied by normalization of immune functioning.
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Early graft function was satisfactory with anteroseptal dyskinesis and an ejection fraction of 75% on echocardiography. The cardiac allograft recipient suffered some postoperative complications including gastrointestinal problems. The following period was up to now uneventful. Discharge from the intensive care unit was after 4 days. In-hospital stay was prolonged at 26 days.
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Sixty-one percent of the patients treated with pharmacotherapy versus 32% of the patients treated with ECT plus pharmacotherapy relapsed within 1 year (P = 0.036). The Cox proportional hazard ratio was 2.32 (1.03-5.22).Cognitive function and memory measures were stable for patients without relapse in both groups.One suspected suicide and 3 suicide attempts by intoxication occurred, all in the pharmacotherapy-alone group.
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Totally, 184 Korean in-patients suffering from MD treated with either paroxetine or venlafaxine and 220 healthy control subjects were included in the present study. Depression severity was assessed by means of the Hamilton Rating Scale for Depression.
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Antidepressant/carnicetine combination therapy may be recommended for treatment of depression in elderly patients.
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Wheel-running activity rhythms were recorded in male Syrian hamsters. Drugs were administered systemically before a light stimulus that was used to advance the timing of the hamster running rhythms.
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Symptoms of anxiety and depression are common in a large proportion of alcohol-abusing/dependent individuals during alcohol detoxification. The aim of this study was to examine the impact of a combined psychotherapeutic-psychopharmacological (either with mirtazapine or venlafaxine) treatment of these symptoms during the early withdrawal phase of alcohol compared to a group treated only with psychotherapy. A total of 60 alcohol-dependent/abusing subjects randomly assigned to three groups (psychotherapy, psychotherapy plus mirtazapine, psychotherapy plus venlafaxine) were studied. Assessment of psychopathology and global functioning throughout a 4-5-week detoxification period was done by the Hamilton Anxiety Rating Scale (HARS), the Hamilton Depression Rating Scale (HDRS), and the Global Assessment Scale (GAS). At baseline, high scores of anxiety and depression were recorded (HARS: controls: 33.1+/-7.8, mirtazapine: 33.2+/-12.6, venlafaxine: 36.6+/-5.4; HDRS: controls: 39.5+/-7.4, mirtazapine: 37.9+/-7.8, venlafaxine: 41.9+/-4.5). A marked improvement (p<0.000) was evidenced in all groups by the end of the detoxification period. However, patients on mirtazapine improved significantly more compared to the other two groups (HARS: controls: 9.6+/-7.6, mirtazapine: 4.3+/-4.4*, venlafaxine: 7.2+/-4.1, *p=0.011; HDRS: controls: 8.6+/-7.9, mirtazapine: 3.8+/-3.2*, venlafaxine: 8.2+/-3.5, *p=0.017; GAS: controls: 79.5+/-9.4, mirtazapine: 87.5+/-5.5**, venlafaxine: 83.0+/-8.0, **p=0.006). It is concluded that addition of mirtazapine, but not venlafaxine, to a standard psychotherapy-oriented alcohol detoxification treatment may facilitate the detoxification process by minimizing psychological discomfort. Consequently, it may prove to be a facilitator for the long-term abstinence from alcohol.
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Patients showed a significant reduction in depressive symptoms with treatment. Group-by-time interactions in response to the negative versus neutral stimuli were found in the left insular cortex and the left anterior cingulate. At baseline, both groups showed bilateral activation in the visual cortices, lateral prefrontal cortex, and amygdala in response to the negative versus neutral stimuli, with patients showing greater activation in the visual cortex and less activation in the left lateral prefrontal cortex. Patients with greater relative anterior cingulate activation at baseline in response to the negative versus neutral stimuli showed the most robust treatment response.
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Of 64 patients achieving early improvement, 38 (59 %) became responders, whereas of 85 patients not achieving early improvement, only 23 (27 %) became responders. There was a significant difference in time to response between patients achieving early improvement and patients not achieving early improvement. Early improvement is a modest sensitive predictor for eventual response.
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6-month, double-blind, placebo-controlled trial.
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This systematic review evaluated Chinese trials examining the efficacy of venlafaxine in the treatment of depression. Chinese databases CNKI and VIP and western databases were searched for blinded randomized controlled trial publications comparing venlafaxine to other antidepressants or placebo (in English or Chinese). Trials had to establish diagnosis of depression according to the Chinese Classification of Mental Disorders, Diagnostic and Statistical Manual of Mental Disorders, or International Classification of Diseases. Studies were excluded if more than 20% of participants had a primary diagnosis of dysthymia or if more than 15% had a primary diagnosis of bipolar disorder. Effect sizes were calculated as Hedges' g for rating scale scores and Mantel-Haenszel risk ratios (MH RR) for response and remission data. Effect sizes were combined in a fixed-effects model. A total of 25 studies were included. Nine trials compared venlafaxine to selective serotonin reuptake inhibitor; placebo-controlled trials were lacking. Quality was at best modest, and all trials were underpowered. There were more responders (MH RR, 1.08; 95% confidence interval [CI], 1.02-1.15) and remitters (MH RR, 1.12; 95% CI, 1.02-1.24) in venlafaxine groups compared with those in tricyclic antidepressant group. Hamilton Depression Rating Scale end point scores in the venlafaxine groups were lower (Hedges' g = 0.16; 95% CI, 0.04-0.27), and venlafaxine was better tolerated than tricyclic antidepressant (Hedges' g = 0.56; 95% CI, 0.37-0.74). There were no significant differences between venlafaxine and selective serotonin reuptake inhibitor on any of these parameters. Analyses of publication bias were inconclusive. Chinese researchers have published a number of randomized controlled trials comparing venlafaxine to active comparators, but study quality was found to be low. To make optimal use of their research potential Chinese, researchers will have to improve trial reporting and the peer-review process.
Subjects meeting DSM-IV-TR criteria for a major depressive episode and a diagnosis of a major depressive disorder received a fluorine-18-fluorodeoxyglucose PET scan before randomization and after 16 weeks of antidepressant treatment with either CBT (N=12) or venlafaxine (N=12). Modality-specific and modality-independent regional brain metabolic changes associated with response status were analyzed.
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The majority of the patients in the study were part of a larger double-blind trial using desipramine. This subgroup consisted of people who had failed to respond to desipramine or could not tolerate its side effects. Thirteen patients were enrolled, 10 men and 3 women. Of the patients, 11 completed the 12-week study. All of the patients had a Hamilton Depression (HAM-D) score greater than 14 at baseline, and each had used at least $20 worth of cocaine per week in the 4 weeks prior to entering the study. In addition, all of the patients received weekly relapse prevention therapy throughout the study. The median dose of venlafaxine was 150 mg/day.
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The published literature is reviewed to find grounds for these concerns.
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The median (inter-quartile range) SFDs were 19 (2-36) for venlafaxine XR and 10 (0-27) for placebo in the 8-week studies (p < 0.0001). In the 6-month extension studies the SFDs were 102 (27-139) for venlafaxine XR and 36 (0-94) for placebo (p < 0.0001).
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Serotonin transporters (SERT) are a major target for antidepressant medication, although there have been limited in vivo studies of SERT availability in patients being treated with antidepressants. It is not known whether SERT availability differs in treatment-responsive and -nonresponsive patients receiving long-term treatment. In this study, we used single photon emission computed tomography (SPECT) to compare SERT residual availability in unipolar responders and nonresponders during long-term antidepressant treatment. Dopamine transporter (DAT) availability was also assessed in the same patients to examine the relationship between the two transporter systems.
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High doses of antidepressants are often used for treatment-resistant depression. Venlafaxine, a dual serotonin and noradrenaline reuptake inhibitor, has been shown to have a tolerable side-effect profile in previous studies using doses of up to 375 mg/day. We investigated the tolerability of higher than currently recommended doses of venlafaxine using the UKU side-effect rating scale. Seventy outpatients fulfilling DSM-IV criteria for major depressive disorder were recruited into two demographically matched groups according to their daily dosage of venlafaxine: high dose n = 35 (> or = 375 mg/day, range 375-600 mg, average 437 mg/day) or standard dose n = 35 (< 375 mg/day, range 75-300 mg, average 195 mg/day. Clinical characteristics were noted and the UKU side-effect rating scale was administered to a subsample of patients. The most frequently reported complaints in both groups were increased fatigue (48%), concentration difficulties (48%), sleepiness/sedation (37%), failing memory (44.4%) and weight gain (29.6%). Apart from weight gain, the complaints were found to be experienced significantly more severely by the high-dose group. Six patients discontinued venlafaxine due to intolerable side-effects but only two of these patients were on a high dose. There was a tendency for mildly raised blood pressure in 10% of patients on an average dose of 342 mg/day. However, no difference between the two groups was found. This preliminary open study demonstrates that venlafaxine is tolerated at higher than British National Formulary recommended doses (i.e. up to 600 mg daily). However, increased frequency and severity of reported side-effects in the high-dose group are not associated with increased rates of discontinuation.