venlafaxine (Effexor)
Cost and effectiveness of venlafaxine extended-release and selective serotonin reuptake inhibitors in the acute phase of outpatient treatment for major depressive disorder.

Trivedi MH, Wan GJ, Mallick R, Chen J, Casciano R, Geissler EC, Panish JM.

Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9119, USA. Madhukar.trivedi utsouthwestern.edu

OBJECTIVE: The purpose of this retrospective analysis was to estimate the cost and effectiveness of venlafaxine extended-release (VXR) compared with selective serotonin reuptake inhibitors in the outpatient treatment of major depressive disorder. METHODS: Pooled data from 8, 8-week, randomized, double-blind studies comparing treatment of major depressive disorder with venlafaxine/venlafaxine XR (n = 851), selective serotonin reuptake inhibitors (fluoxetine, paroxetine, fluvoxamine; n = 748), or placebo (4 studies; n = 446) were retrospectively analyzed to determine the economic implications of symptom remission from the perspective of a US third party payer and that of an employer. A decision modeling approach was used to determine cost and effectiveness ratios. RESULTS: Patients on VXR were associated with 22.8 depression-free days versus 18.6 depression-free days with the studied selective serotonin reuptake inhibitors, based on the decision model. Productive and quality-adjusted days were also expected to increase for VXR patients (22.06 vs. 19.34 and 4.56 to 9.36 vs. 3.72 to 7.63), as was the percentage of patients achieving full activity (25.9% vs. 19.6%). The expected cost per patient achieving remission of symptoms was US 1303.94 dollars and US 1514.96 dollars, and the cost per depression-free days was US 25.66 dollars and US 28.25 dollars, for the VXR and selective serotonin reuptake inhibitors groups, respectively. CONCLUSIONS: Treatment with VXR is not only expected to increase the rate of remission of symptoms but is also associated with achievement of full activity, higher number of depression-free days, productive days, and quality-adjusted days. VXR is a cost-effective treatment option for major depressive disorder.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15349005&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
Therapeutic drug monitoring of racemic venlafaxine and its main metabolites in an everyday clinical setting.

Reis M, Lundmark J, Bjork H, Bengtsson F.

Department of Psychiatry, Linkoping University, Linkoping, Sweden.

When Efexor (venlafaxine) became available in Sweden, a therapeutic drug monitoring (TDM) service was developed in the authors' laboratory. This analytical service was available to all physicians in the country. From March 1996, to November 1997, 797 serum concentration analyses of venlafaxine (VEN) and its main metabolites, O-desmethylvenlafaxine (ODV), N-desmethylvenlafaxine (NDV), and N,O-didesmethylvenlafaxine (DDV) were requested. These samples, each of which was accompanied by clinical information on a specially designed request form, represented 635 inpatients or outpatients, comprising all ages, treated in a naturalistic setting. The first sample per patient, drawn as a trough value in steady state and with documented concomitant medication, was further evaluated pharmacokinetically (n = 187). The doses prescribed were from 37.5 mg/d to 412.5 mg/d. There was a wide interindividual variability of serum concentrations on each dose level, and the mean coefficient of variation of the dose-corrected concentrations (C/D) was 166% for C/D VEN, 60% for C/D ODV, 151% for C/D NDV, and 59% for C/D DDV. The corresponding CV for the ratio ODV/VEN was 110%. However, within patients over time, the C/D VEN and ODV/VEN variation was low, indicating stability in individual metabolizing capacity. Patients over 65 years of age had significantly higher concentrations of C/D VEN and C/D ODV than the younger patients. Women had higher C/D NDV and C/D DDV, and a higher NDV/VEN ratio than men, and smokers showed lower C/D ODV and C/D DDV than nonsmokers. A number of polycombinations of drugs were assessed for interaction screening, and a trend for lowered ODV/VEN ratio was found, predominantly with concomitant medication with CNS-active drug(s) known to inhibit CYP2D6.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12142641&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
The role of alpha1- and alpha2-adrenoreceptors on venlafaxine-induced elevation of extracellular serotonin, noradrenaline and dopamine levels in the rat prefrontal cortex and hippocampus.

Weikop P, Kehr J, Scheel-Kruger J.

Department of Microdialysis, NeuroSearch A/S, Ballerup, Denmark. piw neurosearch.dk

The role of adrenergic alpha1- and alpha2-adrenoreceptors in augmentation of venlafaxine-induced elevation of extracellular serotonin (5-HT),noradrenaline (NA) and dopamine (DA) levels in the rat prefrontal cortex (PFC) and hippocampus (HIPP) was studied by in vivo microdialysis in anaesthetized rats. The alpha1-adrenoreceptor antagonist prazosin given alone (0.3 mg/kg, s.c.) induced only a moderate reduction of hippocampal 5-HT and NA levels. The alpha2-adrenoreceptor antagonist idazoxan (1.5 mg/kg, s.c.) causes moderate increases in the levels of 5-HT and DA in the PFC. The mixed 5-HT and NA reuptake inhibitor venlafaxine (10 mg/kg, i.p.) increased the efflux of 5-HT, NA and DA almost equally, to approximately 200% of the control levels in the PFC. The levels of 5-HT increased to 310%, an effect approximately twice the effect on NA in the HIPP. Venlafaxine also produced a moderate increase in DA levels in the PFC but had no effect in the HIPP. Pre-treatment with prazosin caused a significant attenuation of the venlafaxine induced 5-HT effect in the PFC, and a moderate increase in DA levels in the HIPP. Prazosin had no significant effect on the venlafaxine-induced increase of the NA levels in PFC or HIPP. A combined treatment of venlafaxine with idazoxan increased the venlafaxine NA and DA effects in PFC by a factor of two and resulted in a very robust five-fold augmentation of NA and DA concentrations in the HIPP. In summary, idazoxan was found to produce a potent enhancement of the venlafaxine effect to increase extracellular NA and DA levels in the PFC and, in particular, in the HIPP. Idazoxan had no effect on venlafaxine-induced elevation of extracellular 5-HT levels in either PFC or HIPP and prazosin induced a decrease of 5-HT in the PFC. The present data suggest that blockade of alpha2-adrenoreceptors may play an important role in augmentation of the effects of mixed monoamine reuptake inhibitors.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15358984&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
Antidepressant-like effect of tramadol and its enantiomers in reserpinized mice: comparative study with desipramine, fluvoxamine, venlafaxine and opiates.

Rojas-Corrales MO, Berrocoso E, Gibert-Rahola J, Mico JA.

Pharmacology and Neuroscience Research Group, Department of Neuroscience, Faculty of Medicine, University of Cadiz, Cadiz, Spain.

Tramadol is a centrally acting analgesic that demonstrates opioid and monoaminergic properties. Several studies have suggested that tramadol could play a role in mood improvement. Moreover, it has previously been shown that tramadol is effective in the forced swimming test in mice and the learned helplessness model in rats, two behavioural models predictive of antidepressant activity. The aim of the present study was to test tramadol and its enantiomers in the reserpine test in mice, a classical observational test widely used in the screening of antidepressant drugs. This test is a non-behavioural method where only objective parameters such as rectal temperature and palprebral ptosis are considered. Moreover, we compared the effects of tramadol and its enantiomers with those of antidepressants (desipramine, fluvoxamine and venlafaxine) and opiates [morphine (-)-methadone and levorphanol]. Racemic tramadol, (-)-tramadol, desipramine and venlafaxine reversed the reserpine syndrome (rectal temperature and ptosis), whereas(+)-tramadol and fluvoxamine only antagonized the reserpine-induced ptosis, without any effect on temperature. Opiates did not reverse reserpine-induced hypothermia. (-)-Methadone showed slight effects regarding reserpine-induced ptosis, morphine and levorphanol had no effect. These results show that tramadol has an effect comparable to clinically effective antidepressants in a test predictive of antidepressant activity, without behavioural implications. Together with other clinical and experimental data, this suggests that tramadol has an inherent antidepressant-like (mood improving) activity, and that this effect could have clinical repercussions on the affective component of pain.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15358985&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
Healthcare expenditure in patients treated with venlafaxine or selective serotonin reuptake inhibitors for depression and anxiety.

Wan GJ, Crown WH, Berndt ER, Finkelstein SN, Ling D.

Wyeth Research, Philadelphia, PA 19087, USA.

We compared healthcare expenditure over a six-month period following initiation of therapy with either venlafaxine (immediate and extended-release) or a selective serotonin reuptake inhibitor (SSRI) in depressed patients with or without anxiety. Patients beginning treatment for a new depressive episode were identified retrospectively using the administrative data of the MEDSTAT MarketScan database for the period 1994-1999. Before beginning therapy, patients prescribed venlafaxine had more non-mental illnesses (0.85 vs 0.76; p<0.01) and hospitalisations for mental illness (0.53 vs 0.29; p<0.05) than patients prescribed SSRIs. In the six months after initiating treatment, venlafaxine was associated with lower hospitalisation expenditure for non-mental illness ($177 vs $526; p<0.01) than SSRIs, although total healthcare expenditure was not significantly different. Venlafaxine was associated with a 50% decrease in the odds of hospitalisation for non-mental illness compared with SSRIs, with significantly lower inpatient expenditure.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12166541&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR