venlafaxine (Effexor)
A pharmacoeconomic evaluation of escitalopram, a new selective serotonin reuptake inhibitor Comparison of cost-effectiveness between escitalopram, citalopram, fluoxetine,and venlafaxine for the treatment of depression in Norway.

Francois C, Toumi M, Aakhus AM, Hansen K.

International Department of Health-Economics, Epidemiology and Pricing, Lundbeck A/S,Paris, France.

This study compared the cost-effectiveness of escitalopram to that of citalopram,fluoxetine, and venlafaxine in the treatment of depression in Norway.A two-path decision analytic model with a 6-month horizon was used.Patients start at the primary path and are referred to specialist care in the secondary care path. Model inputs included drugspecific probabilities from comparative trial data, literature, and a panel of experts.The main outcome measure is success (remission), and costs of treatment (total and drug costs).Treatment with escitalopram yielded lower expected cost and greater effectiveness than citalopram,fluoxetine, and venlafaxine. The expected success rate was 64.2% with escitalopram,58.7% with citalopram, 58.7% with fluoxetine, and 62.1% with venlafaxine.Average expected total costs per patient were similar with escitalopram (19,661 Norwegian crowns) and venlafaxine (20,989) and somewhat higher with citalopram (22,379) and fluoxetine (22,558).Budgetary impact estimates a decrease in total health care budget of 72 million crowns.Escitalopram is therefore the most cost-effective alternative and its use would significantly reduce health care costs for the treatment of depression in Norway.

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Effexor, Effexor XR

venlafaxine (Effexor)
Quantification of venlafaxine and O-desmethylvenlafaxine in human serum using HPLC analysis.

Waschgler R, Moll W, Konig P, Conca A.

Medical Central Laboratory, Feldkirch, Austria. rwaschgler mzl.at

We describe an isocratic reversed-phase liquid chromatographic method for the determination of venlafaxine (VLX) and its main active metabolite O-desmethylvenlafaxine (ODV) in serum, using haloperidol as internal standard and liquid/liquid extraction for sample preparation. VLX and ODV were separated on a C18 column with a mobile phase of acetonitrile/buffer (30/70, v:v) at 60 degrees C and a flow rate of 1.5 ml/min. The measurement of the native fluorescence signals of the eluted compounds were carried out at 227/300 nm (excitation/emission) without interference from endogenous components in serum. High linearities for VLX and ODV for concentrations between 20 and 500 microg/l were obtained (r = 0.9997). A large spectrum of routinely prescribed drugs did not interfere in the assay. The coefficients of variation for repeatability varied between 5.40% and 5.99% and for reproducibility between 9.43% and 21.63%. Absolute recoveries were more than 52% for both substances.

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Effexor, Effexor XR

venlafaxine (Effexor)
Characterization of the longitudinal course of improvement in generalized anxiety disorder during long-term treatment with venlafaxine XR.

Montgomery SA, Sheehan DV, Meoni P, Haudiquet V, Hackett D.

Imperial College School of Medicine, PO Box 8751, London, UK. sam montgomery.demon.co.uk

OBJECTIVE: To characterize the response to the serotonin and norepinephrine reuptake inhibitor, venlafaxine extended release (XR), during the long-term treatment of generalized anxiety disorder. METHODS: Data from two double-blind, placebo-controlled, 6-month trials of venlafaxine XR for the treatment of generalised anxiety disorder were pooled. Criteria for response (> or = 50% improvement from baseline HAM-A score) and remission (HAM-A score < or = 7) and their temporal profile were used to characterize patient improvement over 6 months of treatment with venlafaxine XR and placebo. RESULTS: Venlafaxine XR was associated with significantly (P<0.001) higher response and remission rates (66 and 43%, respectively) compared with placebo (39 and 19%), regardless of the level of baseline anxiety. In the venlafaxine XR group, 61% of the patients who had responded but not remitted by week 8 showed remission by the end of 6 months. In comparison, only 39% of placebo responders who did not qualify for remission at the end of the first 8 weeks of therapy remitted by the end of the 6 months (P=0.007). Relapse occurred in 6% of venlafaxine XR-treated patients and 15% of placebo-treated patients (P<0.01). CONCLUSION: This analysis provides further insight into the outcome of long-term treatment of generalised anxiety disorder with venlafaxine XR and shows for the first time that long-term treatment might be necessary to achieve and maintain remission of symptoms. Copyright 2002 Elsevier Science Ltd.

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Effexor, Effexor XR

venlafaxine (Effexor)
NEURALGIAS AND NEUROPATHIES.

[No authors listed]

Rosenstock J, Tuchman M, LaMoreaux L, Sharma U. Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial. Pain. 2004;110:628-638. A randomized, double-blind, placebo-controlled, parallel-group, multicenter, 8-week trial (with subsequent open-label phase) evaluated the effectiveness of pregabalin in alleviating pain associated with diabetic peripheral neuropathy (DPN). For enrollment, patients must have had at baseline: 1- to 5-year history of DPN pain; pain score >/= 40 mm (Short-Form McGill Pain Questionnaire [SF-MPQ] visual analogue scale); average daily pain score of >/= 4 (11-point numerical pain rating scale [0 = no pain, 10 = worst possible pain]). One hundred forty-six (146) patients were randomized to receive placebo (Formula: see text) or pregabalin 300 mg/day (Formula: see text). Primary efficacy measure was endpoint mean pain score from daily patient diaries (11-point numerical pain rating scale). Secondary measures included SF-MPQ scores; sleep interference scores; Patient and Clinical Global Impression of Change (PGIC and CGIC); Short Form-36 (SF-36) Health Survey scores; and Profile of Mood States (POMS) scores. Safety assessment included incidence and intensity of adverse events, physical and neurological examinations, and laboratory evaluations. Pregabalin produced significant improvements versus placebo for mean pain scores [Formula: see text], mean sleep interference scores [Formula: see text], total SF-MPQ score [Formula: see text], SF-36 Bodily Pain subscale [Formula: see text], PGIC [Formula: see text], and Total Mood Disturbance and Tension-Anxiety components of POMS [Formula: see text]. Pain relief and improved sleep began during week 1 and remained significant throughout the study [Formula: see text]. Pregabalin was well tolerated despite a greater incidence of dizziness and somnolence than placebo. Most adverse events were mild to moderate and did not result in withdrawal. Pregabalin was safe and effective in decreasing pain associated with DPN, and also improved mood, sleep disturbance, and quality of life. Comment: Pregabalin is a new compound related to gabapentin, but long acting, so presumably QD in dosing. Because gabapentin works in migraine prevention (Mathew NT, Rapoport A, Saper J, Magnus L, Bernstein P, Klapper J, Ramadan N, Stacey B, Tepper S. Efficacy of gabapentin in migraine prophylaxis. Headache. 2001;41:119-128.), and because we use gabapentin for neuralgias, the unfolding of the utility of pregabalin is quite important.-Stewart J. Tepper, MD Rowbotham MC, Goli V, Kunz NR, Lei D. Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study. Pain. 2004;110:697-706. To evaluate the efficacy and safety of 6 weeks of venlafaxine extended-release (ER) (75 mg and 150-225 mg) treatment in patients with painful diabetic neuropathy. This multicenter, double-blind, randomized, placebo-controlled study included 244 adult outpatients with metabolically stable type 1 or 2 diabetes with painful diabetic neuropathy. Primary efficacy measures were scores on the daily 100 mm Visual Analog Pain Intensity (VAS-PI) and Pain Relief (VAS-PR) scales. Secondary efficacy measures included the Clinical Global Impressions-Severity of Illness and the Clinical Global Impressions Improvement, Patient Global Rating of Pain Relief, and percentage of patients achieving 50% reduction in pain intensity. Baseline pain intensity was 68.7 mm (moderately severe). At week 6, the percentage reduction from baseline in VAS-PI was 27% (placebo), 32% (75 mg), and 50% (150-225 mg [Formula: see text] vs placebo). Mean VAS-PR scores in the 150-225 mg group were significantly greater than placebo at week 6 (44 vs 60 mm [Formula: see text]). The number needed to treat (NNT) for 50% pain intensity reduction with venlafaxine ER 150-225 mg was 4.5 at week 6. Nausea and somnolence were the most common treatment-emergent adverse events. Seven patients on venlafaxine had clinically important ECG changes during treatment. Venlafaxine ER appears effective and safe in relieving pain associated with diabetic neuropathy. NNT values for higher dose venlafaxine ER are comparable to those of tricyclic antidepressants and the anticonvulsant gabapentin. Comment: I found this a remarkable and unexpected study, first because venlafaxine was comparable to TCAs and gabapentin for diabetic neuropathic pain, and second, because of the phrase "Seven patients... had clinically important ECG changes during treatment."-Stewart J. Tepper, MD.

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Effexor, Effexor XR

venlafaxine (Effexor)
The four-plates test-retest paradigm to discriminate anxiolytic effects.

Ripoll N, Nic Dhonnchadha BA, Sebille V, Bourin M, Hascoet M.

Neurobiologie de l'anxiete et de la depression, Faculte de Medecine, EA 3256, 1 rue Gaston Veil, BP 53508, 44035, Nantes cedex 01, France, Michel.Bourin univ-nantes.fr.

RATIONALE: Animal models of anxiety such as the four-plates test (FPT) enable the detection of an anxiolytic effect not only of benzodiazepines (BZDs) but also of other non-BZD anxiolytic compounds such as the antidepressants paroxetine and venlafaxine. Retesting mice in animal models of anxiety markedly alters the behavioural profile of various drugs. OBJECTIVES: The aim of this study was first to investigate the function of GABA(A)/BZD receptor and passive avoidance acquisition in the FPT "test-retest". The second aim of this study was to evaluate the capacity of the FPT to discriminate BZDs from other non-BZD anxiolytics in experienced mice. METHODS: The FPT was performed in naive and experienced mice (submitted to the test 24 h previously). The drugs studied were two BZDs, diazepam (1 mg/kg) and alprazolam (0.25 mg/kg); flumazenil, a GABA(A) receptor antagonist (8 mg/kg); atropine sulphate, a muscarinic cholinergic receptor antagonist (4 mg/kg) known for its amnesic properties; paroxetine, a selective serotonin reuptake inhibitor (4 and 8 mg/kg); venlafaxine, a serotonin and noradrenalin reuptake inhibitor (4 and 16 mg/kg); and DOI, a 5-HT(2A) agonist (1 mg/kg). RESULTS: Our results reveal an increase of anxiety (decrease of punished passages) in saline-experienced mice. Diazepam, alprazolam, paroxetine and venlafaxine did not prevent the increase in anxiety during retest, revealing a passive avoidance acquisition. Flumazenil did not modify the anxiogenic-like behaviour of experienced mice. In contrast, atropine seems to oppose the increase of anxiety; however, its effect is weak and disputable. DOI was the only anxiolytic compound able to oppose the decrease of punished passages of experienced mice. CONCLUSION: Anxiogenic behaviour on retesting indicates aversive learning. The protocol test-retest is unable to discriminate between the anxiolytic effect of BZDs from that of paroxetine or venlafaxine. However, this modified model may constitute a new tool to investigate other neural pathways implicated in anxiety.

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Effexor, Effexor XR