venlafaxine (Effexor)
Treatment costs of venlafaxine and selective serotonin-reuptake inhibitors for depression and anxiety.

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

Wyeth Research, Philadelphia, USA. wang wyeth.com

In this article, health care expenditures are assessed for patients diagnosed with depression who are being treated with either venlafaxine (immediate or extended release) or a selective serotonin-reuptake inhibitor (SSRI). Patients beginning treatment for a new depressive episode were identified retrospectively from 1994 to 1998. Before beginning therapy, patients prescribed venlafaxine (N = 353) had more nonmental illnesses (0.84 vs. 0.75 clinical events/patient, respectively; P < .01) and hospitalizations for mental illness (0.56 vs. 0.30 hospitalizations/patient; P = .06) than patients prescribed SSRIs (N = 7,330). In the six months after initiating treatment, venlafaxine was associated with lower hospitalization expenditures for nonmental illness than were SSRIs ($206 vs. $472, respectively; P = .02), but total health care expenditures were not significantly different.

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Effexor, Effexor XR

venlafaxine (Effexor)
Dosage finding and outcome of venlafaxine treatment in psychiatric outpatients and inpatients: results of a drug utilization observation study.

Linden M, Ludewig K, Munz T, Dierkes W.

Research Group Psychosomatic Rehabilitation, UKBF, Free University of Berlin, Germany. linden zedat.fu-berlin.de

BACKGROUND: Venlafaxine is an antidepressive drug with the special characteristic of inhibiting both synaptic serotonin and norepinephrine reuptake. This double action is dosage dependent, with the relatively weaker inhibition of norepinephrine becoming clinically relevant only at higher dosages. This allows treatment to be tailored towards the needs of individual patients through differential dosing. It is unknown, however, how physicians use this unique feature in prescribing venlafaxine in routine treatment. METHOD: Data from a drug utilization observation (DUO) study, including 6706 patients, are used to investigate which patient and setting variables predict dosage of venlafaxine as prescribed by psychiatrists in inpatient and outpatient settings. Treatment outcome and adverse drug reactions (ADR) were analyzed for different dosage groups. RESULTS: Treatment setting is the most important factor in predicting high (> 75 mg/day) or low (up to 75 mg/day) dosage of venlafaxine, with inpatients receiving higher dosages. Severity of illness and a history of previous treatment with major antidepressives are also related to higher dosages. Although the total rate of ADR did not increase with increased dosage, the profile of drug reactions changed. Response to therapy was better in cases of non-chronic, major depression with no treatment history of antidepressives. Additionally, increased dosage increased the likelihood of response in outpatients. In both settings, very high dosages predicted better response to venlafaxine among severely ill patients. CONCLUSION: Venlafaxine at a dosage of 75 mg/day is sufficient for the majority of cases. In extremely ill patients, higher dosages are associated with additional benefits. Therefore, a stepwise dosage regimen is suggested, with an increase of dosage to upper limits in cases of non-response before discontinuation of treatment with venlafaxine.

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Effexor, Effexor XR

venlafaxine (Effexor)
Comparison of effects of dual transporter inhibitors on monoamine transporters and extracellular levels in rats.

Koch S, Hemrick-Luecke SK, Thompson LK, Evans DC, Threlkeld PG, Nelson DL, Perry KW, Bymaster FP.

Lilly Neuroscience Research Division, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA.

Compounds that block both serotonin (5-HT) and norepinephrine (NE) transporters have been proposed to have improved antidepressant efficacy. We compared the ability of four dual transporter inhibitors-chlorimipramine, duloxetine, milnacipran and venlafaxine-to block monoamine transporters in vitro and in vivo and increase extracellular monoamines in rat brain. Inhibition of radioligand binding to clonal human monoamine transporters in vitro and in vivo in rats was determined. Extracellular concentrations of 5-HT and NE in rat prefrontal cortex (PFC) were quantified using the microdialysis technique. All compounds blocked binding to human 5-HT and NE transporters, although chlorimipramine and venlafaxine had markedly greater affinity for 5-HT than NE transporters. In vivo, chlorimipramine and duloxetine potently blocked both transporters, milnacipran blocked both with lower potency and venlafaxine only blocked the 5-HT transporter. Chlorimipramine and duloxetine increased robustly and approximately equally monoamine extracellular concentrations. Milnacipran produced only small increases in NE, whereas venlafaxine increased 5-HT markedly at the lower doses and both monoamines at high doses. Thus, the dual transporter inhibitors blocked 5-HT and NE transporters in vitro and in vivo with varying potency. Chlorimipramine, duloxetine, and high dose venlafaxine acted as dual transporter inhibitors in rat PFC and increased extracellular concentrations of the monoamines, indicating functional dual transporter inhibition.

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Effexor, Effexor XR

venlafaxine (Effexor)
Anxiolytic-like effects of escitalopram, citalopram, and R-citalopram in maternally separated mouse pups.

Fish EW, Faccidomo S, Gupta S, Miczek KA.

Department of Psychology, Tufts University, Medford, Massachusetts 02155, USA.

The S-enantiomer of citalopram, escitalopram, is a selective serotonin reuptake inhibitor (SSRI) that appears to be responsible for citalopram's antidepressant and anxiolytic effects. Clinically, escitalopram is reported to have fewer adverse side effects than do other SSRIs. This study compared escitalopram to other antidepressants in a preclinical procedure predicting anxiolytic-like effects of drugs. Carworth Farms Webster (CFW) mouse pups (7 days old) were separated from the dam and maintained at a temperature of 34 degrees C. Forty-five minutes after administering citalopram (0.56-10 mg/kg), escitalopram (0.0056-3 mg/kg), R-citalopram (1-10 mg/kg), paroxetine (0.3-3 mg/kg), fluoxetine (1-30 mg/kg), or venlafaxine (3-56 mg/kg) subcutaneously, the pups were placed individually on a 19.5 degrees C surface for 4 min. Ultrasonic vocalizations (USVs) (30-80 kHz), grid crossing, rolling (i.e., the pup turned on one side or its back), and colonic temperature were recorded. All the drugs reduced USV emission; escitalopram was the most potent (ED(50) 0.05 mg/kg), followed by paroxetine (0.17 mg/kg), citalopram (1.2 mg/kg), fluoxetine (4.3 mg/kg), R-citalopram (6 mg/kg), and venlafaxine (7 mg/kg). The doses that decreased USVs differed from those that increased motor activity. Increased grid crossing occurred after low doses of paroxetine (0.03 or 0.1 mg/kg) and fluoxetine (1 mg/kg), but only after the highest doses of the citalopram enantiomers and venlafaxine (0.3, 10, and 56 mg/kg, respectively). Except for escitalopram and venlafaxine, high doses of the treatments increased rolling. R-Citalopram caused a 10-fold rightward shift in escitalopram's dose-effect curve, suggesting that R-citalopram inhibits escitalopram's anxiolytic-like effects. These data support clinical findings that escitalopram is a potent, well tolerated SSRI with anxiolytic-like effects.

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Effexor, Effexor XR

venlafaxine (Effexor)
Economic evaluation of citalopram use and expenditures among recipients in the Texas Medicaid program.

Johnsrud MT, Crismon ML.

Center for Pharmacoeconomic Studies, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA.

OBJECTIVE: To describe the trends in the utilization and expenditures of selective serotonin reuptake inhibitors (SSRIs) and venlafaxine within the Texas Medicaid program in 1999 and 2000; more specifically, to compare the use of citalopram with other SSRI agents and venlafaxine. METHODS: A retrospective analysis of Texas Medicaid paid prescription claims data involving Texas Medicaid clients aged 18 to 64. The main outcome measures were allowed, discounted cost per day; dose per day; treatment days (persistence); adherence rates; and switching rates. RESULTS: Citalopram had a significantly lower calculated cost per day than all other comparator agents. There were no statistically significant differences between study agent groups when comparing treatment days and adherence days for newly started patients, except for lower rates with venlafaxine IR. CONCLUSIONS: Within the Texas Medicaid Program, citalopram had a positive economic impact on prescription drug costs compared to other comparator agents, while showing similar outcomes in utilization measures such as treatment days and adherence rates.

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Effexor, Effexor XR