Venlafaxine

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This drug has a Black Box warning from the U.S. Food and Drug Administration.

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Venlafaxine quick reference

Venlafaxine
Venlafaxine general drug information
 Pronunciation ven la FAX een (.wav file)
 Trade Name(s) Effexor, Effexor XR
 How Supplied Effexor tablets 25mg, 37.5mg, 50mg, 75mg, 100mg
Effexor XR capsules 37.5mg, 75mg, 150mg
 Generic Availability Venlafaxine tablets 25mg, 37.5mg, 50mg, 75mg, 100mg
 Patent Expiry Date June 13, 2008
 Classification Selective serotonin and norepinephrine reuptake inhibitor (SSNRI)
 Schedule Rx
 Pregnancy Category C
 Breast-feeding Generally should not be used in breastfeeding (see comment below).
Venlafaxine chemical information
 IUPAC Name (R/S)-1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl] cyclohexanol hydrochloride
 Empirical Formula C17H27NO2•HCl
 Molecular Weight 313.87 g/mol
pharmacokinetic information  |  pharmacogenomic information
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Description

Venlafaxine is an antidepressant in the serotonin-norepinephrine reuptake inhibitor class, with a mechanism of action similar to that of duloxetine. Venlafaxine tablets were approved for major depression in December 1993, and the popular extended-release capsules were approved for this same indication in 1997. In 1999, it became the first antidepressant to gain an indication for generalized anxiety disorder (GAD). In 2003 it gained the social phobia indication, and subsequently in 2005 an indication for panic disorder. It has a tolerable side effect profile similar to the selective serotonin reuptake inhibitors (SSRIs). Venlafaxine carries a black box warning against the risk of increased suicidality in children and adolescents.[1]

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Mechanism of Action

The mechanism of the antidepressant action of venlafaxine in humans is believed to be associated with its potentiation of neurotransmitter activity in the CNS. Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), are potent inhibitors of neuronal serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake. Venlafaxine and ODV do not inhibit monoamine oxidase.[2]

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Time Required for Therapeutic Response

  • Initial: 1-4 weeks
  • Maximum: up to 4-6 weeks
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Pharmacokinetics

Absorption
Venlafaxine is extensively absorbed after oral administration. Absolute bioavailability is around 45%. Food has not been found to affect bioavailability of venlafaxine, or its active metabolite, O-desmethylvenlafaxine (ODV).[2][3]

Distribution
Venlafaxine's volume of distribution at steady state is 7.5 ± 3.7 L/kg, and the volume of distribution of ODV is 5.7 ± 1.8 L/Kg. Venlafaxine is 27% bound to human plasma protein, ODV is 30% bound.[3]

Metabolism
Venlafaxine undergoes extensive presystemic metabolism in the liver, primarily to ODV, but also to N-desmethylvenlafaxine, N,O didesmethylvenlafaxine, and other minor metabolites. In vitro studies indicate that the formation of ODV is catalyzed by CYP2D6; this has been confirmed in a clinical study showing that patients with low CYP2D6 levels ("poor metabolizers") had increased levels of venlafaxine and reduced levels of ODV compared to people with normal CYP2D6 ("extensive metabolizers"). The differences between the CYP2D6 poor and extensive metabolizers, however, are not expected to be clinically important because the sum of venlafaxine and ODV is similar in the two groups and venlafaxine and ODV are pharmacologically approximately equiactive and equipotent. [2][3]

Excretion
Approximately 87% of a venlafaxine dose is recovered in the urine within 48 hours as unchanged venlafaxine (5%), unconjugated ODV (29%), conjugated ODV (26%), or other minor inactive metabolites (27%). Renal elimination of venlafaxine and its metabolites is thus the primary route of excretion.[2][3]

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Special Population Pharmacokinetics

  • Renal insufficiency: Halflife increases about 50% and clearance decreases about 24% in renally impaired patients. The halflife of ODV is increased 40% in renally impaired patients, however clearance appears to be unaffected.[4]
  • Hepatic insufficiency: In cirrhosis, elimination halflife is increased by 30% and clearance is decreased by 50%. The halflife of ODV is 60% longer and clearance is decreased 30% in patients with cirrhosis.
  • Hemodialysis: ODV elimination half-life was prolonged by about 142% and clearance was reduced by about 56% compared to normal subjects, with a large intersubject variability.
  • Geriatric: No differences found.[5]
  • Pediatric: Use of venlafaxine has not been approved in patients under the age of 18.
  • Gender: No differences found.[5][2]
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Indications and Dosages

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FDA Approved Indications

Major Depression

  • Starting dose:
    • (Regular-release tablets) 75mg po daily divided into 2-3 doses
    • (Extended-release capsules) 75mg po daily. Alternatively, 37.5mg po daily x 4-7 days to allow patient to adjust to medication before increasing to 75mg po daily.
  • Maintenance dose:
    • (Regular-release tablets) 75-225mg po daily for outpatient treatment, 75-375mg po daily for inpatient treatment.
    • (Extended-release capsules) 75-225mg po daily
  • Titration schedule:
    • (Regular-release tablets or extended-release capsules) If needed, dose may be increased by 75mg daily at increments of at least 4 days.[6][7][8]

General Anxiety Disorder

  • Starting dose (Extended-release capsules):
    • 75 mg po daily
    • Alternatively, 37.5mg po daily x 4-7 days to allow patient to adjust to medication before increasing to 75mg po daily.
  • Maintenance dose:
    • 75-225mg po daily
  • Titration schedule: Dose may be increased in increments of 75mg every 4 days up to a maximum daily dose of 225mg.[9][10]

Social Phobia (Social Anxiety Disorder)

  • Starting dose (Extended-release capsules):
    • 75mg po daily
    • Alternatively, 37.5mg po daily x 4-7 days to allow patient to adjust to medication before increasing to 75 mg po daily.
  • Maintenance dose:
    • 75-225mg po daily
  • Titration schedule: Dose may be increased in increments of 75mg every 4 days up to a maximum daily dose of 225mg.[11]

Panic Disorder (with or without agoraphobia)

  • Starting dose (Extended-release capsules):
    • 37.5mg po daily x 7 days
  • Maintenance dose:
    • 75-225mg po daily
  • Titration schedule: weekly titrations of 37.5mg-75mg daily with a maximum daily dose of 225mg. [12]
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Non-FDA Approved Indications

  • Hot Flashes[13]
  • Neuropathic Pain[14]
  • Diabetic Neuropathy[15]
  • Fibromyalgia[16]
  • Headache[17]
  • Premenstrual Dysphoric Disorder (PMDD)[18]
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Dosage Adjustment

Renal insufficiency:

  • CrCl 10—70 ml/min: reduce total daily dose by 25—50%
  • CrCl < 10 ml/min: reduce total daily dose by 50%[4]

Hepatic insufficiency:

  • For moderate hepatic impairment the initial daily dose should be reduced by 50%.
  • Clearance in cirrhotic patients shows considerable individual variability, and greater dosage reductions may be necessary.

Hemodialysis: Reduce total daily dose by 50%.[2]

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Dosage Limits

  • Adults: 375 mg/day PO for immediate-release tablets; 225 mg/day PO for Effexor XR
  • Elderly: 375 mg/day PO for immediate-release tablets; 225 mg/day PO for Effexor XR
  • Adolescents and children: Safe and effective use has not been established.[2]


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Administration

  • Route: oral
  • Method:
    • All Formulations - Administer with food to decrease GI upset.
    • Extended-Release Capsules - Take daily dose with a meal, with plenty of water. Alternatively, sprinkle contents of capsule in a spoonful of applesauce and consume immediately without chewing, followed by a glass of water.[2]


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Monitoring Parameters

  • Serum cholesterol
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Contraindications/Precautions

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Black box warning

Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of Effexor XR or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Effexor XR is not approved for use in pediatric patients.

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Contraindications

  • Venlafaxine or desvenlafaxine hypersensitivity
  • MAOI therapy
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Precautions

  • Venlafaxine should not be stopped abruptly.
  • Venlafaxine should not be used in patients in which bipolar disorder has not been ruled out.
  • Venlafaxine should not be used with weight loss agents such as phentermine.
  • Venlafaxine can cause hyponatremia.
  • Use caution in patients with existing seizure disorders.
  • Use caution in patients with impaired platelet aggregation.
  • Venlafaxine can cause increases in serum cholesterol.
  • Caution is advised in administering Effexor XR to patients with diseases or conditions that could affect hemodynamic responses or metabolism (eg. hyperthyroidism, recent myocardial infarction, or heart failure).
  • Discontinuation of venlafaxine therapy should be considered when interstitial lung disease or eosinophilic pneumonia are suspected, as these are rare adverse reactions to therapy that have been reported.[2]


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Pregnancy indications

Pregnancy Category C

Teratogenic effects were not observed in animal studies. Nonteratogenic effects including respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypo- or hypertonia, hyper-reflexia, jitteriness, irritability, constant crying, and tremor have been reported in the neonate immediately following delivery after exposure late in the third trimester. Exposure to SSRIs late in pregnancy has also been associated with persistent pulmonary hypertension of the newborn (PPHN). Adverse effects may be due to toxic effects of SNRI or drug discontinuation. In some cases, effects may present clinically as serotonin syndrome. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if the potential benefit to the mother outweighs the possible risk to the fetus. If treatment during pregnancy is required, consider tapering therapy during the third trimester.[2]

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Breast-feeding indications

Venlafaxine and its metabolite are found excreted in breast milk. Ingestion by infants has been found to be 9-10% of the maternal dose. Benefits and risks should be assessed, and if the decision to continue venlafaxine is made the infant should be closely monitored for toxicity.[2][19]

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Drug-Drug, -Food, -Herb Interactions

Click the link above to go to the drug interactions page.

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Adverse Reactions/Side Effects

Venlafaxine Adverse Reactions Chart
Incidence Body System Adverse Reactions
>10% All Headache (25% to 34%), insomnia (15% to 23%), somnolence (12% to 23%), nervousness (6% to 21%), dizziness (11% to 20%), nausea (21% to 58%), xerostomia (12% to 22%), constipation (8% to 15%), anorexia (8% to 20%), abnormal ejaculation/orgasm (2% to 16%), weakness (8% to 17%), diaphoresis (10% to 14%).
1-10% CNS Abnormal dreams (3% to 7%), anxiety (5% to 6%), yawning (3% to 5%), agitation (2% to 4%), chills (3%), confusion (2%), abnormal thinking (2%), depersonalization (1%), depression (1% to 3%), fever, migraine, amnesia, hypoesthesia, trismus, vertigo
Cardiovascular Hypertension (dose related; 3% in patients receiving <100 mg/day, up to 13% in patients receiving >300 mg/day), vasodilation (3% to 4%), palpitation (3%), tachycardia (2%), chest pain (2%), postural hypotension (1%), edema
Dermatologic Rash (3%), pruritus (1%), bruising
GI Diarrhea (6% to 8%), vomiting (3% to 6%), dyspepsia (5%), abdominal pain (4%), flatulence (3% to 4%), taste perversion (2%), weight loss (1% to 4%), appetite increased, weight gain
Genitourinary Impotence (4% to 10%), urinary frequency (3%), urination impaired (2%), urinary retention (1%), prostatic disorder
Neuromuscular/skeletal Tremor (4% to 10%), hypertonia (3%), paresthesia (2% to 3%), twitching (1% to 2%), neck pain, arthralgia
Respiratory Pharyngitis (7%), sinusitis (2%), cough increased, dyspnea
Miscellaneous Infection (6%), flu-like syndrome (6%), trauma (2%), Tinnitus (2%), Abnormal or blurred vision (4% to 6%), mydriasis (2%), Libido decreased (3% to 9%)
<1% All Agranulocytosis, anaphylaxis, aplastic anemia, aneurysm, angina pectoris, anuria, arrhythmia (including atrial and ventricular tachycardia, fibrillation, and torsade de pointes), arteritis, asthma, ataxia, atelectasis, atrioventricular block, bacteremia, basophilia, bigeminy, biliary pain, bilirubinemia, bleeding time increased, bradycardia, bradykinesia, BUN increased, bundle branch block, carcinoma, cardiovascular disorder (mitral valve and circulatory disturbance), cataract, catatonia, cellulitis, cerebral ischemia, cholelithiasis, congestive heart failure, coronary artery disease, creatinine increased, crystalluria, cyanosis, deafness, DVT, dehydration, delusions, dementia, diabetes mellitus, dystonia, EKG abnormalities (including QT prolongation), electrolyte abnormalities, embolus, eosinophlia, erythema multiforme, exfoliative dermatitis, extrapyramidal symptoms, extrasystoles, facial paralysis, fasciitis, fatty liver, gastrointestinal ulcer, glaucoma, Guillain-Barré syndrome, heart arrest, hematemesis, hematoma, hemorrhage (eye, GI, mucocutaneous, rectal), hepatic necrosis, hepatic failure, hepatitis, homicidal ideation, hostility, hyperacusis, hypercalcinuria, hyperchlorhydria, hyper-/hypocholesteremia, hyper-/hypoglycemia, hyperlipemia, hyper-/hypothyroidism, hyperuricemia, hypokalemia, hyponatremia, hypophosphatemia, hypoproteinemia, hypotension, interstitial lung disease (including eosinophilic pneumonia), intestinal obstruction, jaundice, kidney function abnormal, larynx edema, leukocytosis, leukoderma, leukopenia, liver enzymes increased, loss of consciousness, lymphadenopathy, lymphocytosis, maculopapular rash, menstrual abnormalities, miliaria, moniliasis, multiple myeloma, myasthenia, myocardial infarct, myoclonus, myopathy, neck rigidity, neuroleptic malignant-like syndrome, neuropathy, neutropenia, osteoporosis, pancreatitis, pancytopenia, pleurisy, pneumonia, pyelonephritis, pyuria, renal failure, rhabdomyolysis, rheumatoid arthritis, seizure, serotonin syndrome, SIADH, skin atrophy, Stevens-Johnson syndrome, suicidal ideation (reported at a frequency up to 2% in children/adolescents with major depressive disorder), suicide attempt, syncope, tendon rupture, thrombocythemia, thrombocytopenia, thrombophlebitis, toxic epidermal necrolysis, withdrawal syndrome
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Overdosage Measures

Symptoms of overdose include altered consciousness (somnolence to coma), tachycardia, mydriasis, seizures, and vomiting. Predominantly occurs in combination with ethanol and/or other drug use. Most overdoses resolve with only supportive treatment, though ECG monitoring would be prudent considering the risk of arrhythmia. Postmarketing experience suggests that the risk of fatal outcome associated with overdose may be higher than that observed with SSRI-associated overdoses. [2]
Treatment:

  • Activated charcoal, induction of emesis, or gastric lavage for acute ingestion
  • Forced diuresis, dialysis, and hemoperfusion not effective due to large volume of distribution.[2]
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Product Information and Distribution

Note: appearance only available for brand-name product
Dose/form Drug color(s) Drug shape Markings or odor/flavor
37.5mg extended-release capsule grey/peach oblong W/Effexor XR/37.5
75mg extended-release capsule peach oblong W/Effexor XR/75
150mg extended-release capsule dark orange oblong W/Effexor XR/150
25mg tablet peach pentagonal, scored W 25/701
37.5mg tablet peach pentagonal, scored W 37.5/781
50mg tablet peach pentagonal, scored W 50/703
75mg tablet peach pentagonal, scored W 75/704
100mg tablet peach pentagonal, scored W 100/705
  • Inactive ingredients for extended-release capsules: cellulose, ethylcellulose, gelatin, hypromellose, iron oxide, titanium dioxide.
  • Inactive ingredients for regular release tablets: cellulose, iron oxide, lactose, magnesium stearate, sodium starch glycolate.
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Patient Information

  • A medication guide should be given with this medication to inform patients about potential risks of taking venlafaxine, such as increased risk of suicidality.
  • Do not operating hazardous machinery, including automobiles, until you know how venlafaxine therapy affects your ability to do this.
  • Do not take any prescription or over-the-counter drugs, including herbal preparations and nutritional supplements without first talking to a healthcare professional, since there is a potential for interactions.
  • There is an increased risk of serotonin syndrome with the concomitant use of venlafaxine and triptans, tramadol, tryptophan supplements or other serotonergic agents.
  • Do not drink alcohol while on venlafaxine.
  • Contact your doctor if rash, hives, or difficulty breathing occur, as these may be signs of a potentially serious allergic reaction.
  • Notify your doctor if you become or plan to become pregnant while on this medication, or if you are breast-feeding.
  • Notify your doctor if you have a history of glaucoma or increased ocular pressure.[2]
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References

  1. ↑ approved new drug bulletin: rocuronium bromide, venlafaxine hydrochloride. RN. 1994 Oct;57(10):47-8, 51-2.
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 Effexor XR [package insert]. Philadelphia,PA: Wyeth Inc.; September 2007.
  3. ↑ 3.0 3.1 3.2 3.3 Troy SM, Parker VD, Fruncillo RJ, Chiang ST. The pharmacokinetics of venlafaxine when given in a twice-daily regimen.J Clin Pharmacol. 1995 Apr;35(4):404-9.
  4. ↑ 4.0 4.1 Troy SM, Schultz RW, Parker VD, Chiang ST, Blum RA. The effect of renal disease on the disposition of venlafaxine.Clin Pharmacol Ther. 1994 Jul;56(1):14-21.
  5. ↑ 5.0 5.1 Klamerus KJ, Parker VD, Rudolph RL, Derivan AT, Chiang ST. Effects of age and gender on venlafaxine and O-desmethylvenlafaxine pharmacokinetics. Pharmacotherapy. 1996 Sep-Oct;16(5):915-23.
  6. ↑ Schweizer E, Feighner J, Mandos LA, Rickels K. Comparison of venlafaxine and imipramine in the acute treatment of major depression in outpatients. J Clin Psychiatry. 1994 Mar;55(3):104-8.
  7. ↑ Dierick M, Ravizza L, Realini R, Martin A. A double-blind comparison of venlafaxine and fluoxetine for treatment of major depression in outpatients. Prog Neuropsychopharmacol Biol Psychiatry. 1996 Jan;20(1):57-71.
  8. ↑ Cunningham LA. Once-daily venlafaxine extended release (XR) and venlafaxine immediate release (IR) in outpatients with major depression. Venlafaxine XR 208 Study Group.Ann Clin Psychiatry. 1997 Sep;9(3):157-64.
  9. ↑ Meoni P, Salinas E, Brault Y, Hackett D. Pattern of symptom improvement following treatment with venlafaxine XR in patients with generalized anxiety disorder. J Clin Psychiatry. 2001 Nov;62(11):888-93.
  10. ↑ Katz IR, Reynolds CF 3rd, Alexopoulos GS, Hackett D. Venlafaxine ER as a treatment for generalized anxiety disorder in older adults: pooled analysis of five randomized placebo-controlled clinical trials. J Am Geriatr Soc. 2002 Jan;50(1):18-25.
  11. ↑ Stein MB, Pollack MH, Bystritsky A, Kelsey JE, Mangano RM. Efficacy of low and higher dose extended-release venlafaxine in generalized social anxiety disorder: a 6-month randomized controlled trial.Psychopharmacology (Berl). 2005 Jan;177(3):280-8. Epub 2004 Jul 16.
  12. ↑ Pollack MH, Worthington JJ 3rd, Otto MW, Maki KM, Smoller JW, Manfro GG, Rudolph R, Rosenbaum JF. Venlafaxine for panic disorder: results from a double-blind, placebo-controlled study. Psychopharmacol Bull. 1996;32(4):667-70.
  13. ↑ Evans ML, Pritts E, Vittinghoff E, McClish K, Morgan KS, Jaffe RB. Management of postmenopausal hot flushes with venlafaxine hydrochloride: a randomized, controlled trial.Obstet Gynecol. 2005 Jan;105(1):161-6.
  14. ↑ Yucel A, Ozyalcin S, Koknel Talu G, Kiziltan E, Yucel B, Andersen OK, Arendt-Nielsen L, Disci R. The effect of venlafaxine on ongoing and experimentally induced pain in neuropathic pain patients: a double blind, placebo controlled study.Eur J Pain. 2005 Aug;9(4):407-16. Epub 2004 Nov 13.
  15. ↑ Rowbotham MC, Goli V, Kunz NR, Lei D. Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study.Pain. 2004 Aug;110(3):697-706. Erratum in: Pain. 2005 Jan;113(1-2):248.
  16. ↑ Dwight MM, Arnold LM, O'Brien H, Metzger R, Morris-Park E, Keck PE Jr. An open clinical trial of venlafaxine treatment of fibromyalgia. Psychosomatics. 1998 Jan-Feb;39(1):14-7.
  17. ↑ Zissis NP, Harmoussi S, Vlaikidis N, Mitsikostas D, Thomaidis T, Georgiadis G, Karageorgiou K. A randomized, double-blind, placebo-controlled study of venlafaxine XR in out-patients with tension-type headache.Cephalalgia. 2007 Apr;27(4):315-24. Epub 2007 Mar 7.
  18. ↑ Hsiao MC, Liu CY. Effective open-label treatment of premenstrual dysphoric disorder with venlafaxine.Psychiatry Clin Neurosci. 2003 Jun;57(3):317-21.
  19. ↑ Ilett KF, Hackett LP, Dusci LJ, Roberts MJ, Kristensen JH, Paech M, Groves A, Yapp P. Distribution and excretion of venlafaxine and O-desmethylvenlafaxine in human milk.Br J Clin Pharmacol. 1998 May;45(5):459-62.
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PUBMED References

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Efficacy Trial Articles

  1. Schweizer E, Feighner J, Mandos LA, Rickels K. Comparison of venlafaxine and imipramine in the acute treatment of major depression in outpatients. J Clin Psychiatry. 1994 Mar;55(3):104-8.
  2. Dierick M, Ravizza L, Realini R, Martin A. A double-blind comparison of venlafaxine and fluoxetine for treatment of major depression in outpatients. Prog Neuropsychopharmacol Biol Psychiatry. 1996 Jan;20(1):57-71.
  3. Cunningham LA. Once-daily venlafaxine extended release (XR) and venlafaxine immediate release (IR) in outpatients with major depression. Venlafaxine XR 208 Study Group.Ann Clin Psychiatry. 1997 Sep;9(3):157-64.
  4. Meoni P, Salinas E, Brault Y, Hackett D. Pattern of symptom improvement following treatment with venlafaxine XR in patients with generalized anxiety disorder. J Clin Psychiatry. 2001 Nov;62(11):888-93.
  5. Katz IR, Reynolds CF 3rd, Alexopoulos GS, Hackett D. Venlafaxine ER as a treatment for generalized anxiety disorder in older adults: pooled analysis of five randomized placebo-controlled clinical trials. J Am Geriatr Soc. 2002 Jan;50(1):18-25.
  6. Stein MB, Pollack MH, Bystritsky A, Kelsey JE, Mangano RM. Efficacy of low and higher dose extended-release venlafaxine in generalized social anxiety disorder: a 6-month randomized controlled trial.Psychopharmacology (Berl). 2005 Jan;177(3):280-8. Epub 2004 Jul 16.
  7. Pollack MH, Worthington JJ 3rd, Otto MW, Maki KM, Smoller JW, Manfro GG, Rudolph R, Rosenbaum JF. Venlafaxine for panic disorder: results from a double-blind, placebo-controlled study. Psychopharmacol Bull. 1996;32(4):667-70.
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Therapeutic Class Comparison Articles

  1. Eckert L, Lancon C. Duloxetine compared with fluoxetine and venlafaxine: use of meta-regression analysis for indirect comparisons. BMC psychiatry. 2006;6:30.
  2. Vis PM, van Baardewijk M, Einarson TR. Duloxetine and venlafaxine-XR in the treatment of major depressive disorder: a meta-analysis of randomized clinical trials. The Annals of pharmacotherapy. 2005 Nov;39(11):1798-807.
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Pharmacokinetics Articles

  1. Howell SR, Hicks DR, Scatina JA, Sisenwine SF. Pharmacokinetics of venlafaxine and O-desmethylvenlafaxine in laboratory animals. Xenobiotica. 1994 Apr;24(4):315-27.
  2. Troy SM, Parker VD, Fruncillo RJ, Chiang ST. The pharmacokinetics of venlafaxine when given in a twice-daily regimen. J Clin Pharmacol. 1995 Apr;35(4):404-9.
  3. Klamerus KJ, Parker VD, Rudolph RL, Derivan AT, Chiang ST. Effects of age and gender on venlafaxine and O-desmethylvenlafaxine pharmacokinetics. Pharmacotherapy. 1996 Sep-Oct;16(5):915-23.


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Drug Interaction Articles

  1. Ereshefsky L, Dugan D. Review of the pharmacokinetics, pharmacogenetics, and drug interaction potential of antidepressants: focus on venlafaxine. Depress Anxiety. 2000;12 Suppl 1:30-44.
  2. Troy SM, Lucki I, Peirgies AA, Parker VD, Klockowski PM, Chiang ST. Pharmacokinetic and pharmacodynamic evaluation of the potential drug interaction between venlafaxine and diazepam. J Clin Pharmacol. 1995 Apr;35(4):410-9.
  3. Phillips SD, Ringo P. Phenelzine and venlafaxine interaction. Am J Psychiatry. 1995 Sep;152(9):1400-1.
  4. Klysner R, Larsen JK, Sørensen P, Hyllested M, Pedersen BD. Toxic interaction of venlafaxine and isocarboxazide. Lancet. 1995 Nov 11;346(8985):1298-9.
  5. Brubacher JR, Hoffman RS, Lurin MJ. Serotonin syndrome from venlafaxine-tranylcypromine interaction. Vet Hum Toxicol. 1996 Oct;38(5):358-61.
  6. Troy SM, Turner MB, Unruh M, Parker VD, Chiang ST. Pharmacokinetic and pharmacodynamic evaluation of the potential drug interaction between venlafaxine and ethanol. J Clin Pharmacol. 1997 Nov;37(11):1073-81.
  7. Bhatara VS, Magnus RD, Paul KL, Preskorn SH. Serotonin syndrome induced by venlafaxine and fluoxetine: a case study in polypharmacy and potential pharmacodynamic and pharmacokinetic mechanisms. Ann Pharmacother. 1998 Apr;32(4):432-6
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Adverse Effects Articles

  1. Thase ME. Effects of venlafaxine on blood pressure: a meta-analysis of original data from 3744 depressed patients. J Clin Psychiatry. 1998 Oct;59(10):502-8.
  2. Harrison CL, Ferrier N, Young AH. Tolerability of high-dose venlafaxine in depressed patients. J Psychopharmacol. 2004 Jun;18(2):200-4.
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Compliance Articles

  1. Gartlehner G, Hansen RA, Carey TS, Lohr KN, Gaynes BN, Randolph LC. Discontinuation rates for selective serotonin reuptake inhibitors and other second-generation antidepressants in outpatients with major depressive disorder: a systematic review and meta-analysis. Int Clin Psychopharmacol. 2005 Mar;20(2):59-69.
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Pharmacoeconomic Articles

  1. Morrow TJ. The pharmacoeconomics of venlafaxine in depression. Am J Manag Care. 2001 Sep;7(11 Suppl):S386-92.
  2. van Baardewijk M, Vis PM, Einarson TR. Cost effectiveness of duloxetine compared with venlafaxine-XR in the treatment of major depressive disorder. Curr Med Res Opin. 2005 Aug;21(8):1271-9.
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External Links

Clinical treatment guidelines

Patient information pages


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