venlafaxine (Effexor)
Cost effectiveness of representatives of three classes of antidepressants used in major depression in the UK.

Lenox-Smith A, Conway P, Knight C.

Wyeth, Taplow, UK.

OBJECTIVE: To estimate the cost effectiveness of representatives of three different classes of antidepressants used in major depression in the UK NHS. DESIGN, PATIENTS AND INTERVENTIONS: A decision-tree model for the treatment of major depression was constructed by interviewing UK GPs and psychiatrists (as part of a Delphi panel). An important part of the tree was that patients in primary care were treated until remission (pre-morbid state). Three classes of antidepressants (serotonin and noradrenaline reuptake inhibitors [SNRIs; venlafaxine], selective serotonin reuptake inhibitors [SSRIs; fluoxetine, paroxetine and fluvoxamine] and tricyclic antidepressants [TCAs; amitriptyline]) were compared by populating the tree with clinical success rates determined by a meta-analysis and a clinical trial. Where there were insufficient data from clinical trials a Delphi panel was used. Costs within the tree were taken from UK data sources. Six-monthly costs and cost effectiveness were then calculated. MAIN OUTCOME MEASURES AND RESULTS: Treatment costs for 6 months were pound 1285 for venlafaxine, pound 1348 for SSRIs and pound 1385 for amitriptyline. Cost effectiveness as measured by cost per symptom-free day was pound 21 for venlafaxine, pound 26 for SSRIs and pound 32 for TCAs (2001 values). Incremental cost-effectiveness analyses showed a treatment strategy of using venlafaxine and switching if necessary to an SSRI was dominant over all other strategies considered. Sensitivity testing demonstrated that the cost of an SSRI could be reduced to 4 pence daily and amitriptyline to zero before the expected 6-monthly cost of venlafaxine ceased to be the lowest. CONCLUSION: The SNRI, venlafaxine, may be a cost-effective option compared with the SSRIs and TCAs when used as a first-line drug for depression in primary care in the UK. As this is a model, cost effectiveness can be suggested but not proven.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15061681&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
Are selective serotonin re-uptake inhibitors associated with an increased risk of self-harm by antidepressant overdose?

Bateman DN, Chick J, Good AM, Kelly CA, Masterton G.

Scottish Poisons Information Bureau (NPIS Edinburgh), Royal Infirmary of Edinburgh, 51 Little France Crescent, EH10 4SA Edinburgh, Scotland. spib luht.scot.nhs.uk

OBJECTIVE: To investigate likelihood of self-harm by overdose with antidepressant drugs of different types by examining hospital admission data and poisons inquiries and relating them to prescribing. DESIGN: Retrospective analysis of prospectively collected data on overdose admissions, poisons inquiries and prescribing of antidepressants in Edinburgh and Scotland. SETTING: Poisons treatment unit of the Royal Infirmary of Edinburgh and its surrounding catchment for overdose cases and Scotland for poisons inquiries. PARTICIPANTS: All patients admitted to the Royal Infirmary of Edinburgh between 1 January 2000 and 31 December 2002 with an overdose involving an antidepressant. MAIN OUTCOME MEASURES: Overdose admissions (patients) in relation to prescribing in Edinburgh and poisons inquiries in relation to prescription rates in Scotland. RESULTS: There were 1656 admissions involving 1343 patients. The likelihood of admission for an individual patient in relation to volume of prescribing (likelihood ratio: 95%CI) in the catchment was somewhat smaller for amitriptyline (0.83:0.74-0.92) and sertraline (0.79:0.63-0.99), and somewhat greater for mirtazapine (1.99:1.57-2.51), trazadone (1.30:1.09-1.54) and venlafaxine (1.33:1.13-1.55). For poisons inquiries in Scotland, the excess for venlafaxine and mirtazapine was confirmed and likelihood of an inquiry lowest for selective serotonin re-uptake inhibitors (SSRIs). CONCLUSIONS: There was no evidence of an excess likelihood of presentation with overdose with SSRIs, and the likelihood was reduced with sertraline. There was a small excess of both admissions and poisons inquiries for mirtazapine and venlafaxine. This is a concern in view of the increased toxicity of venlafaxine in overdose in comparison with SSRIs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15083251&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
Comparative toxicity of citalopram and the newer antidepressants after overdose.

Kelly CA, Dhaun N, Laing WJ, Strachan FE, Good AM, Bateman DN.

Scottish Poisons Information Bureau, Royal Infirmary, Little France Crescent, Edinburgh, Scotland, UK. cathy.kelly luht.scot.nhs.uk

OBJECTIVE: To compare the toxicity of citalopram, venlafaxine, mirtazapine, and nefazadone after overdose. METHODS: Two-year retrospective review of consecutive patients admitted to the toxicology unit of Edinburgh Royal Infirmary. Outcome measure included physiological variables, ECG recordings, peak creatine kinase, development of arrhythmias, seizure, tremor or agitation, and the need for admission to a critical care facility. RESULTS: A total of 225 patients were studied. Venlafaxine was associated with a significantly higher pulse rate (p < 0.0001) and tremor (p = 0.007) than other antidepressants. Citalopram was associated with a significantly longer QT interval on ECG recording (p < 0.0001) but mean QTc durations were not significantly different between all drugs studied. No arrhythmias were recorded. Only venlafaxine and citalopram caused seizures and were associated with the need for admission to Intensive Care, but there was no significant difference between them. CONCLUSIONS: Mirtazapine and nefazadone appear safe in overdose and were associated with minimal features of neurological or cardiovascular toxicity. Citalopram is more likely to cause QT prolongation but other features of cardiovascular toxicity were uncommon. Both citalopram and venlafaxine are proconvulsants. Venlafaxine also causes more frequent features of the serotonin syndrome.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15083939&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
Effects on drug disposition, brain monoamines and behavior after chronic treatment with the antidepressant venlafaxine in rats with experimental hepatic encephalopathy.

Wikell C, Apelqvist G, Hjorth S, Kullingsjo J, Bergqvist PB, Bengtsson F.

Department of Clinical Pharmacology, Lund University, Lund, Sweden.

Patients with chronic hepatic encephalopathy (HE) may present affective symptoms and antidepressant drug treatment in this condition is not uncommon. The present microdialysis study investigated treatment with the chronic antidepressant venlafaxine (VEN) in experimental HE with regard to tentative changes in pharmacokinetic and/or pharmacodynamic parameters. Three weeks after portacaval shunt (PCS) or sham operation in rats, VEN (10 mg/kg daily) was administered by implanted osmotic minipumps. VEN treatment for 14 days resulted in higher concentrations of VEN in PCS rats than in sham controls in serum and brain compartments, and the VEN levels in serum and brain were strongly inter-correlated. The serum N-desmethylvenlafaxine concentration did not differ between the groups, but correlated with the serum VEN levels. The other VEN metabolites were below the quantification limits. VEN treatment for 9-12 days significantly stimulated locomotion and rearing in the open field in sham controls, but failed to do so in the PCS rats. The concentrations of noradrenaline, dopamine, 5-HT, and 5-HIAA in neocortical dialysates were higher in PCS than in sham rats after 14 days of VEN treatment, but the elevations reached statistical significance only in the case of dopamine and 5-HIAA. In summary, there were significant pharmacokinetic and pharmacodynamic alterations in rats with experimental HE as compared to controls. The described experimental HE model may be useful for continued pharmacokinetic/pharmacodynamic interaction studies to unravel the pathophysiological consequences of HE on the CNS.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12126872&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
Blockade of supraspinal 5-HT1A receptors potentiates the inhibitory effect of venlafaxine on wind-up activity in mononeuropathic rats.

Marchand F, Pelissier T, Eschalier A, Ardid D, Alloui A, Soto-Moyano R, Mondaca M, Laurido C, Constandil L, Hernandez A.

E 9904 INSERM/UdA, Laboratory of Medical Pharmacology, Faculty of Medicine, University of Auvergne-1, Clermont-Ferrand, France.

In mononeuropathic rats submitted to a C-fiber reflex responses paradigm, repeated administration (five successive injections every half-life) of 10 mg/kg, s.c. of venlafaxine, but not of 2.5 mg/kg, s.c., a mixed monoamine reuptake inhibitor with preferential inhibitory activity in 5-HT reuptake, induced a progressive reduction of spinal wind-up. Repeated co-administration of the selective 5-HT1A receptor antagonist WAY 100,635 i.c.v. (50 microg/injection) significantly increased the effect of venlafaxine s.c., indicating that venlafaxine-induced inhibition of spinal wind-up in mononeuropathic rats is potentiated by blockade of central 5-HT1A receptors. Copyright 2004 Elsevier B.V.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15145768&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR