venlafaxine (Effexor)
1-[2-(1-Hydroxycyclohexyl)-2-(4-methoxyphenyl)ethyl]dimethylammonium chloride (venlafaxine hydrochloride).

Vega D, Fernandez D, Echeverria G.

Departamento de Fisica, Comision Nacional de Energia Atomica, Buenos Aires, Argentina. vega cnea.gov.ar

The crystal structure of racemic Venlafaxine hydrochloride, C(17)H(28)NO(2)(+).Cl(-), consists of two types of parallel chains formed by translated Venlafaxine(+) cations, hydrogen bonded by Cl(-) anions, and characterized by the opposite chirality of their constituent molecules. These chains organize in two different types of broad layers of opposite handedness, related by a glide plane.

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Effexor, Effexor XR

venlafaxine (Effexor)
Venlafaxine and its interaction with WAY 100635: effects on serotonergic unit activity and behavior in cats.

Bjorvatn B, Fornal CA, Martin FJ, Metzler CW, Jacobs BL.

Program in Neuroscience, Department of Psychology, Princeton University, Princeton, NJ, USA. bjron.bjorvatn isf.uib.no

The therapeutic efficacy of antidepressant drugs that inhibit the reuptake of serotonin (5-hydroxytryptamine, 5-HT) may be enhanced by blocking their indirect activation of 5-HT(1A) autoreceptors, which mediate feedback inhibition of serotonergic neuronal activity. In this study, we examined the effects of venlafaxine, a dual 5-HT/noradrenaline reuptake inhibitor, alone and in combination with the selective 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide (WAY 100635), on the single-unit activity of serotonergic dorsal raphe neurons and concurrent behavior in freely moving cats. Systemic administration of venlafaxine (0.05-1.0 mg/kg, i.v.) produced a dose-dependent decrease in firing rate (ED(50)=0.19 mg/kg), with virtually complete inhibition of neuronal discharge at the highest dose tested. The subsequent administration of WAY 100635 (0.1 mg/kg, i.v.) rapidly reversed the neuronal suppression produced by venlafaxine and significantly elevated the firing rate above baseline levels. The overshoot in neuronal activity was associated with the onset of an adverse behavioral reaction resembling the 5-HT syndrome resulting from excessive levels of brain 5-HT. The intensity of this reaction paralleled the degree of neuronal restoration induced by WAY 100635, suggesting a causal relationship. Such behavioral responses were either not observed previously, or of a low intensity, when WAY 100635 was combined with selective 5-HT reuptake inhibitors. Overall, these results suggest that the risk of inducing adverse effects, such as the 5-HT syndrome, may be higher with dual 5-HT/noradrenaline reuptake inhibitors than with selective 5-HT reuptake inhibitors, when these agents are combined with a potent 5-HT(1A) autoreceptor antagonist. Possible mechanisms that might account for these differences in drug interaction are discussed.

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Effexor, Effexor XR

venlafaxine (Effexor)
Pharmacoeconomic analysis of antidepressants for major depressive disorder in the United Kingdom.

Freeman H, Arikian S, Lenox-Smith A.

Green College, Oxford, England.

OBJECTIVE: To estimate the cost effectiveness of different classes of antidepressants in the UK National Health Service. DESIGN, PATIENTS AND INTERVENTIONS: The use of the serotonin (5-hydroxytryptamine; 5-HT) and noradrenaline (norepinephrine) reuptake inhibitor (SNRI) venlafaxine was compared with that of selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) in patients with major depressive disorder (MDD). A meta-analysis determined the clinical success rate, and a decision tree was constructed by interviewing general practitioners and psychiatrists. Adding pharmacological and nonpharmacological treatment costs, meta-analytic rates were applied to the decision tree to calculate the expected cost and outcome for each drug. Cost effectiveness was determined using a composite measure of outcome [symptom-free days (SFD)]. MAIN OUTCOME MEASURES AND RESULTS: The meta-analysis included data from 44 studies on 4033 patients. The highest overall efficacy rate for outpatients with MDD was with venlafaxine use (73.7%), compared with 61.4% for SSRIs and 59.3% for TCAs. Treatment with venlafaxine yielded the lowest outpatient cost for a SFD (10.53 Pounds), compared with 13.23 Pounds for SSRIs and 15.52 Pounds for TCAs (1998 values). CONCLUSIONS: Using this economic model, venlafaxine appears to be a cost-effective treatment for outpatients with MDD in the UK.

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Effexor, Effexor XR

venlafaxine (Effexor)
Efficacy, safety, and tolerability of venlafaxine XR in generalized anxiety disorder.

Kelsey JE.

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia 30329, USA. jkels01 emory.edu

Generalized anxiety disorder (GAD) is a common and chronic disorder with a low rate of spontaneous remission. A complication in treatment selection is the high rates of co-morbid major depressive disorder in this population. A number of treatments exist to treat GAD. The most recent medication to gain an indication for GAD is venlafaxine XR, a serotonin/norepinephrine reuptake inhibitor that is also approved for the treatment of major depressive disorder. More than 2,000 patients with GAD have been studied in outpatient trials of venlafaxine XR with demonstrated efficacy, tolerability and safety of this compound. This article reviews these studies, both short term and longer (6 month) continuation trials. The response to venlafaxine XR in this population, combined with good tolerability, makes this agent an appropriate first-line medication for GAD. In general, treatment with antidepressants, though associated with a longer onset of action than benzodiazepines, does not produce physiological dependency, and is useful in a patient population with a high prevalence of mood disorders.

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Effexor, Effexor XR

venlafaxine (Effexor)
[Sexual dysfunctions induced by serotonin reuptake inhibitors]

[Article in Spanish]

Arias F, Padin JJ, Rivas MT, Sanchez A.

Unidad de Psiqiatria, Fundacion Hospital de Alcorcon, Madrid. farias fhalcorcon.es

OBJECTIVE: To assess the incidence of serotonin reuptake inhibitor (SRI) antidepressant-induced sexual dysfunction (SD) and to compare the sexual side effects of SRI. DESIGN: Naturalistic, prospective, observational study. SETTING: Two urban health centers. PATIENTS: 235 outpatients (164 women, 71 males) who began treatment with some of the following SRI: fluoxetine, sertraline, paroxetine, citalopram and venlafaxine, who had engaged in regular sexual practices with stable partner, who were suffering from different mental disorders who were being treated with SRI. The assignment to each group was according to clinical criteria. INTERVENTIONS: Patients completed questionnaires that allowed reporting of both SD induced by the illness and the treatment, evaluating changes in libido, arousal, and orgasm. The patients were observed over 6 months of treatment. RESULTS: 147 patients (62.6%) reported one or more SD related to SRI treatment. There were differences in the incidence between the different SRI: 39% with fluoxetine, 75.5% with paroxetine, 78.8% with sertraline, 28.9% with citalopram and 80% with venlafaxine. In 78.2% of patients the SD showed no improvement by the end of this period. In a predictive logistical regression model of the presence of SD induced by the SRI, the female category and the presence of previous sexual problems were favourable predictors and the treatment with paroxetine, sertraline or venlafaxine were increased the risk of SD. CONCLUSIONS: SD is one of the most frequent and persistent SRI adverse effect. We recommended to inquiry about SD in patients who were treated with SRI. Significant differences were found in the occurrence of SD between the different SRI. Such data would be particularly valuable to physicians when choosing a specific antidepressant from this therapeutic group.

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Effexor, Effexor XR