venlafaxine (Effexor)
Multiple complications and withdrawal syndrome associated with quetiapine/venlafaxine intoxication.

Precourt A, Dunewicz M, Gregoire G, Williamson DR.

Department of Pharmacy Services, Hopital Ste-Justine, Montreal, Quebec, Canada.

OBJECTIVE: To report a case of quetiapine/venlafaxine intoxication associated with multiple complications and to review their possible relationship with these 2 drugs. CASE SUMMARY: A 53-year-old white man was admitted to the hospital for loss of consciousness secondary to voluntary intoxication with venlafaxine and quetiapine. Several complications were attributable to this intoxication including seizures, prolonged coma, respiratory depression, neuroleptic malignant syndrome, prolonged QRS and QTc intervals, and a possible venlafaxine withdrawal syndrome. DISCUSSION: Quetiapine could be responsible for the neuroleptic malignant syndrome presented in this case. Moreover, venlafaxine intoxication, fever, autonomic instability, and myoclonus presented serotonin syndrome as a differential diagnosis. Potential causes of seizures and prolongation of the QRS and QTc intervals are reviewed. Finally, prolonged coma and late venlafaxine withdrawal are discussed with regard to the pharmacodynamics and pharmacokinetics of drug elimination in the context of intoxication. CONCLUSIONS: Clinicians should be aware of possible complications following intoxication with atypical antipsychotics and anti-depressants, including protracted altered mental status.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15562144&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
The effect of venlafaxine on behaviour, body weight and striatal monoamine levels on sleep-deprived female rats.

de Oliveira RA, Cunha GM, Borges KD, de Bruin GS, dos Santos-Filho EA, Viana GS, de Bruin VM.

Department of Clinical Medicine, Federal University of Ceara, Brazil, Prof Costa Mendes 1608 4o. Andar, CEP 60430140 Fortaleza, Ceara, Brazil.

Partial sleep deprivation is clinically associated with fatigue, depressive symptoms and reduced memory. Previously, it has been demonstrated that venlafaxine, an atypical antidepressant, increases the levels of noradrenaline and serotonin in rat hippocampus. The aim of this study was to evaluate the effects of venlafaxine on depression, anxiety, locomotor activity and memory in a model of REM sleep (REMs) deprivation in rats. We have also studied the influence of venlafaxine on monoamine levels in the striatum. Six groups of animals (N=20 each) were treated with saline or venlafaxine (1 or 10 mg/kg) during 10 days, submitted or not to REMs deprivation and studied with the forced swimming test of Porsolt (STP), plus-maze, passive avoidance and open-field tests right after sleep deprivation. Animals were also studied for passive avoidance 24 h later (rebound period). Brain samples for monoamine measurements were collected either immediately after REMs deprivation or after 24 h. Both REMs deprivation and venlafaxine showed an antidepressant effect. An anxiolytic effect was also observed after REMs deprivation. Previous treatment with venlafaxine blocked the antidepressant and anxiolytic effects of REMs deprivation. REMs deprivation alone and treatment with venlafaxine 10 mg/kg increased locomotor activity, and this effect was inhibited by venlafaxine in REMs deprived rats. Both venlafaxine treatment and REMs deprivation induced weight loss. Venlafaxine treatment, but not REMs deprivation, induced an increase in striatal dopamine (DA) levels. The combination of REMs deprivation and venlafaxine treatment was associated with an increase in serotonin turnover 24 h after rebound sleep. In this study, venlafaxine treatment hindered most behavioral effects of REMs deprivation and was associated with an interference on dopamine and serotonin systems in the striatum.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15582021&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
Combination therapy with venlafaxine and carbamazepine in depressive patients not responding to venlafaxine: pharmacokinetic and clinical aspects.

Ciusani E, Zullino DF, Eap CB, Brawand-Amey M, Brocard M, Baumann P.

Unite de Biochimie et Psychopharmacologie Clinique, Departement Universitaire de Psychiatrie Adulte, Prilly-Lausanne, Switzerland.

The chiral antidepressant venlafaxine (VEN) is both a serotonin and a norepinephrine uptake inhibitor. CYP2D6 and CYP3A4 contribute to its metabolism, which has been shown to be stereoselective. Ten CYP2D6 genotyped and depressive (F32x and F33x, ICD-10) patients participated in an open study on the pharmacokinetic and pharmacodynamic consequences of a carbamazepine augmentation in VEN non-responders. After an initial 4-week treatment with VEN (195 +/- 52 mg/day), the only poor metabolizer out of 10 depressive patients had the highest plasma concentrations of S-VEN and R-VEN, respectively, whereas those of R-O-demethyl-VEN were lowest. Five non-responders completed the second 4-week study period, during which they were submitted to a combined VEN-carbamazepine treatment. In the only non-responder to this combined treatment, there was a dramatic decrease of both enantiomers of VEN, O-demethylvenlafaxine, N-desmethylvenlafaxine and N, O-didesmethylvenlafaxine in plasma, which suggests non-compliance, although metabolic induction by carbamazepine cannot entirely be excluded. The administration of carbamazepine [mean +/- SD, range: 360 +/- 89 (200-400) mg/day] over 4 weeks did not result in a significant modification of the plasma concentrations of the enantiomers of VEN and its O- and N-demethylated metabolites in the other patients. In conclusion, these preliminary observations suggest that the combination of VEN and carbamazepine represents an interesting augmentation strategy by its efficacy, tolerance and absence of pharmacokinetic modifications. However, these findings should be verified in a more comprehensive study.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15582923&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

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

Xu H, He J, Richardson JS, Li XM.

Neuropsychiatry Research Unit, Department of Psychiatry, College of Medicine, University of Saskatchewan, Saskatoon, Canada.

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. 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 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 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 in the treatment of patients with major depression, a mental disease thought to be related to the mal-adaptation of subjects to environmental stressors.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15584914&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR

venlafaxine (Effexor)
The role of venlafaxine in the treatment of obsessive-compulsive disorder.

Phelps NJ, Cates ME.

Western Missouri Mental Health Center, Kansas City, MO, USA.

OBJECTIVE: To evaluate the published literature regarding the use of venlafaxine in the treatment of obsessive-compulsive disorder (OCD). DATA SOURCES: MEDLINE (1996-March 2004) and International Pharmaceutical Abstracts (1970-March 2004) were searched using the terms venlafaxine and obsessive-compulsive disorder. A bibliographic search was conducted as well. DATA SYNTHESIS: Successful treatment of OCD with venlafaxine has been reported in case reports, open trials, and blinded trials versus active comparators. The only placebo-controlled trial did not find statistically significant improvement with venlafaxine treatment; however, methodologic limitations may have influenced those results. Venlafaxine appears to be as efficacious as clomipramine, but is preferable to this agent in terms of safety and tolerability. Venlafaxine seems to be similar to paroxetine with respect to both therapeutic effects and adverse effects, but may be inferior to paroxetine when used for nonresponders to previous serotonin-reuptake inhibitor therapy. CONCLUSIONS: Although the relative scarcity of data precludes definitive conclusions, available evidence suggests that venlafaxine is effective and well tolerated in the treatment of OCD. Unfortunately, it has not shown any unique advantages relative to currently available medications.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15585743&dopt=Abstract venlafaxine Effexor refs
Effexor, Effexor XR