The response of synaptophysin and microtubule-associated protein 1 to restraint stress in rat hippocampus and its modulation by Venlafaxine ( Effexor ).

As part of our continuing study of neural plasticity in rat hippocampus, we examined two structural proteins involved in neuronal plasticity, synaptophysin (SYP) and microtubule-associated protein 1 (MAP1) for their response to repeated restraint stress and modulation of such response by the antidepressant drug Venlafaxine ( Effexor ). This drug has the pharmacological action of inhibiting the reuptake of serotonin and norepinephrine in nerve terminals. We subjected the rats to restraint stress for 4 h per day for three days, and then injected the animals intraperitoneally (i.p.) with vehicle or 5 mg/kg/day of Venlafaxine ( Effexor ) for various time periods. In all, eight groups of 10 rats each were used. The expression of these two proteins in hippocampal tissue of the rats was examined by means of western blot and immunohistochemical staining techniques. We found that restraint stress decreased the expression of SYP in the rat hippocampus by 50% (p < 0.01), and increased the expression of MAP1 by 60% (p < 0.01). SYP returned to the pre-stress levels in three weeks and MAP1 in two weeks. In animals treated with Venlafaxine ( Effexor ) post-stress, SYP returned to pre-stress levels after 2 weeks and MAP1 after 1 week. These findings enhance our understanding of the compromise of the hippocampus by stressful assaults, and may be relevant to the action of Venlafaxine ( Effexor ) in the treatment of patients with major depression, a mental disease thought to be related to the mal-adaptation of subjects to environmental stressors.

Blockade of 5-hydroxytryptamine and noradrenaline uptake by Venlafaxine ( Effexor ): a comparative study with Paroxetine ( Paxil ) and desipramine.

1. Venlafaxine ( Effexor ) is an antidepressant agent which blocks in vitro the reuptake of both 5-HT and NA. The present in vivo electrophysiological studies were undertaken, in the rat, to compare the effects of Venlafaxine ( Effexor ) on 5-HT and NA reuptake to those of the selective 5-HT reuptake inhibitor Paroxetine ( Paxil ) and the selective NA reuptake inhibitor desipramine. 2. Administered acutely, Venlafaxine ( Effexor ) dose-dependently prolonged the time required for a 50% recovery (RT50) of the firing activity of dorsal hippocampus CA3 pyramidal neurons from the suppression induced by microiontophoretic applications of 5-HT and NA. Venlafaxine ( Effexor ) and Paroxetine ( Paxil ) increased with a similar potency the RT50 values for 5-HT, while desipramine was more potent than Venlafaxine ( Effexor ) at increasing the RT50 values for NA. Moreover, Venlafaxine ( Effexor ) demonstrated a greater potency at increasing the RT50 values for 5-HT compared to that of NA. 3. A two-day treatment with Venlafaxine ( Effexor ) (delivered s.c. by osmotic minipumps) increased the RT50 values for both 5-HT and NA applications. The RT50 values for 5-HT were significantly increased at a dose of 10 mg kg(-1) day(-1), whereas those for NA were increased at a dose of 20 mg kg(-1) day(-1), consistent with the data obtained following the acute administration of Venlafaxine ( Effexor ). 4. Taken together, these results indicate that, in vivo, Venlafaxine ( Effexor ) blocks both reuptake processes, with a potency greater for the 5-HT than for the NA reuptake process. This dual action, combined with the differential potency of Venlafaxine ( Effexor ), might constitute the biological substratum responsible for its apparent unique clinical efficacy in major depression.

Pharmacoeconomic analysis of antidepressants for major depressive disorder in the United Kingdom.

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 ( Effexor ) 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 ( Effexor ) use (73.7%), compared with 61.4% for SSRIs and 59.3% for TCAs. Treatment with Venlafaxine ( Effexor ) 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 ( Effexor ) appears to be a cost-effective treatment for outpatients with MDD in the UK.

Distribution of Venlafaxine ( Effexor ) and its O-desmethyl metabolite in human milk and their effects in breastfed infants.

AIMS: To characterize milk/plasma (M/P) ratio and infant dose, for Venlafaxine ( Effexor ) (V) and its O-desmethyl metabolite (ODV), in breastfeeding women taking Venlafaxine ( Effexor ) for the treatment of depression, and to determine the plasma concentration and effects of these drugs in their infants. METHODS: Six women (mean age 34.5 years, mean weight 84.3 kg) taking Venlafaxine ( Effexor ) (median dose 244 mg day(-1), range 225-300 mg day(-1)) and their seven infants (mean age 7.0 months, mean weight 7.3 kg) were studied. V and ODV in plasma and milk were measured by high-performance liquid chromatography over a 12 h dose interval at steady-state. Infant exposure was estimated as the product of estimated milk production rate (0.15 l kg(-1)day(-1)) and average drug concentration in milk, normalized to body weight and expressed as a percentage of the weight-adjusted maternal dose. RESULTS: Mean M/PAUC values of 2.5 (range 2.0-3.2) and 2.7 (range 2.3-3.2) were calculated for V and ODV, respectively. The mean maximum concentrations (95% CI) of V and ODV in milk were 1161 (95% CI, 588, 1734) microg l(-1) and 796 (362, 1230) microg l(-1). Mean infant exposure was 3.2% (1.7, 4.7%) for V and 3.2% (1.9, 4.9%) for ODV (as V equivalents). V was detected in the plasma of one out of seven infants studied (5 microg l(-1)), while ODV was detected in four of the infants, at concentrations ranging from 3 to 38 microg l(-1). All of the infants in the study were healthy, as reported by their mothers and/or by clinical examination on the study day. CONCLUSIONS: The concentrations of V and ODV in breast milk were 2.5 and 2.7 times those in maternal plasma. The mean total drug exposure (as Venlafaxine ( Effexor ) equivalents) of the breastfed infants was 6.4% (5.5-7.3%), which is below the 10% notional level of concern. There were no adverse effects in any of the infants. The data support the use of V in breastfeeding. Nevertheless, since low concentrations of ODV were detected in the plasma of four out of the seven infants studied, we recommend breastfed infants should be monitored closely. Each decision to breast feed should be made as an individual risk:benefit analysis.