Description

Simple

A medication used to treat depression.

Clinical

A selective serotonin and norepinephrine reuptake inhibitor (SNRI) used for the treatment of major depression.

Overview

Venlafaxine (Effexor) is an antidepressant within the serotonin-norepinephrine reuptake inhibitor (SNRI) class of medications. It exerts its effects primarily by blocking the transporters involved in the reuptake of the neurotransmitters serotonin and norepinephrine, therefore leaving more active neurotransmitter in the synapse. Venlafaxine is officially approved for use in the management of major depressive disorder (MDD), generalized anxiety disorder (GAD), social anxiety disorder, and panic disorder. As of 2014, Canadian clinical practice guidelines recommend venlafaxine as a first-line option for treatment of generalized anxiety, social anxiety, panic disorder, major depressive disorder (MDD), and consider it a second-line option for management of obsessive-compulsive disorder (OCD) [9,Read more

Pharmacology

Indication

Venlafaxine is indicated in the management of major depressive disorder (MDD), generalized anxiety disorder (GAD), social anxiety disorder (social phobia), and panic disorder with or without agoraphobia. Venlafaxine is also used off-label for prophylaxis of migraine headaches [ Read more

Pharmacodynamic

The mechanism of venlafaxine's (and its metabolite, O-desmethylvenlafaxine (ODV)) antidepressant effect is believed to be due to their potentiation of neurotransmitter activity in the central nervous system through the inhibition of the reuptake of serotonin and norepinephrine from within the synaps... Read more

Mechanism of action

The exact mechanism of action of venlafaxine is unknown, but appears to be associated with the potentiation of neurotransmitter activity in the CNS. Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), inhibit the reuptake of both serotonin and norepinephrine with a potency greater f... Read more

Absorption

Venlafaxine is well absorbed, with at least 92% of a single dose absorbed on the basis of mass balance studies [FDA Label]. Food does not affect the absorption of venlafaxine or its subsequent metabolism into ODV. Bioavailability is 45% following oral administration.
Time to steady state = 3 days.

Protein binding

The degree of binding of venlafaxine to human plasma is 27% ± 2% at concentrations ranging from 2.5 to 2215 ng/mL. The degree of ODV binding to human plasma is 30% ± 12% at concentrations ranging from 100 to 500 ng/mL. Protein-binding-induced drug interactions with venlafaxine are not expected.

Volume of distribution

7.5 ± 3.7 L/kg [venlafaxine]5.7 ± 1.8 L/kg [O-desmethylvenlafaxine(active metabolite)]

Clearance

Steady state plasma clearance, venlafaxine = 1.3 ± 0.6 L/h/kg;Steady state plasma clearance, ODV = 0.4 ± 0.2 L/h/kg.

Half life

5 hours

Route of elimination

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

Toxicity

Overdose of venlafaxine is typically associated with mild symptoms. However, severe toxicity is reported with the most common symptoms being CNS depression, serotonin toxicity, seizure, or cardiac conduction abnormalities. Venlafaxine's toxicity appears to be higher than other SSRIs, with a fatal to... Read more

Adverse Effects

Contraindications

  • Hypersensitivity:
    • true
  • Regions: US
  • Time Period: The use of MAOIs within 7 days of stopping treatment with venlafaxine, or the use of venlafaxine within 14 days of stopping and MAOI is contraindicated.
  • Regions: US
  • With Categories:
      • Name: Monoamine Oxidase Inhibitors
      • Drugbank Id: DBCAT001004
      • Mesh Id: D008996

Food Interactions

  • Avoid alcohol. Prescribing information recommends the avoidance of alcohol during therapy.
  • Avoid St. John's Wort. Co-administration of St. John's Wort may lead to additive serotonergic activity and an increased risk of serotonin syndrome.
  • Take with food. Co-administration with food helps to alleviate/mitigate GI upset.

Interactions

Type in a drug name to check for interaction with Venlafaxine
Type a drug name in the box above to get started
  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
Venlafaxine may increase the antiplatelet activities of (R)-warfarin.
(S)-Warfarin
Venlafaxine may increase the antiplatelet activities of (S)-Warfarin.
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine
The metabolism of Venlafaxine can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
2,4-thiazolidinedione
The risk or severity of hypoglycemia can be increased when Venlafaxine is combined with 2,4-thiazolidinedione.
2,5-Dimethoxy-4-ethylamphetamine
The risk or severity of serotonin syndrome can be increased when Venlafaxine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamine
The risk or severity of adverse effects can be increased when Venlafaxine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
4-Bromo-2,5-dimethoxyamphetamine
The risk or severity of adverse effects can be increased when Venlafaxine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-Bromo-2,5-dimethoxyphenethylamine
Venlafaxine may increase the tachycardic activities of 4-Bromo-2,5-dimethoxyphenethylamine.
4-hydroxycoumarin
Venlafaxine may increase the antiplatelet activities of 4-hydroxycoumarin.
4-Methoxyamphetamine
The metabolism of 4-Methoxyamphetamine can be decreased when combined with Venlafaxine.
5-methoxy-N,N-dimethyltryptamine
The metabolism of 5-methoxy-N,N-dimethyltryptamine can be decreased when combined with Venlafaxine.
7-Nitroindazole
The risk or severity of adverse effects can be increased when Venlafaxine is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the serotonergic activities of Venlafaxine.
Abacavir
Venlafaxine may decrease the excretion rate of Abacavir which could result in a higher serum level.
Abatacept
The metabolism of Venlafaxine can be increased when combined with Abatacept.
Abciximab
Venlafaxine may increase the antiplatelet activities of Abciximab.
Abediterol
Venlafaxine may increase the tachycardic activities of Abediterol.
Abemaciclib
Venlafaxine may increase the excretion rate of Abemaciclib which could result in a lower serum level and potentially a reduction in efficacy.
Abexinostat
The risk or severity of QTc prolongation can be increased when Venlafaxine is combined with Abexinostat.
Abiraterone
The metabolism of Venlafaxine can be decreased when combined with Abiraterone.
18 References
  1. 1 . Golden RN, Nicholas L: Antidepressant efficacy of venlafaxine. Depress Anxiety. 2000;12 Suppl 1:45-9.PubMed: 11098413
  2. 2 . Thase ME, Clayton AH, Haight BR, Thompson AH, Modell JG, Johnston JA: A double-blind comparison between bupropion XL and venlafaxine XR: sexual functioning, antidepressant efficacy, and tolerability. J Clin Psychopharmacol. 2006 Oct;26(5):482-8.PubMed: 16974189
  3. 3 . Bielski RJ, Ventura D, Chang CC: A double-blind comparison of escitalopram and venlafaxine extended release in the treatment of major depressive disorder. J Clin Psychiatry. 2004 Sep;65(9):1190-6.PubMed: 15367045
  4. 4 . 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.PubMed: 15288411
  5. 5 . Ozyalcin SN, Talu GK, Kiziltan E, Yucel B, Ertas M, Disci R: The efficacy and safety of venlafaxine in the prophylaxis of migraine. Headache. 2005 Feb;45(2):144-52.PubMed: 15705120
  6. 6 . Whirl-Carrillo M, McDonagh EM, Hebert JM, Gong L, Sangkuhl K, Thorn CF, Altman RB, Klein TE: Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther. 2012 Oct;92(4):414-7. doi: 10.1038/clpt.2012.96.PubMed: 22992668
  7. 7 . Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1.PubMed: 19515014
  8. 8 . Shelton RC: Serotonin and Norepinephrine Reuptake Inhibitors. Handb Exp Pharmacol. 2019 Mar 6. doi: 10.1007/164_2018_164.PubMed: 30838456
  9. 9 . Kennedy SH, Lam RW, McIntyre RS, Tourjman SV, Bhat V, Blier P, Hasnain M, Jollant F, Levitt AJ, MacQueen GM, McInerney SJ, McIntosh D, Milev RV, Muller DJ, Parikh SV, Pearson NL, Ravindran AV, Uher R: Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments. Can J Psychiatry. 2016 Sep;61(9):540-60. doi: 10.1177/0706743716659417. Epub 2016 Aug 2.PubMed: 27486148
  10. 10 . Pringsheim T, Davenport W, Mackie G, Worthington I, Aube M, Christie SN, Gladstone J, Becker WJ: Canadian Headache Society guideline for migraine prophylaxis. Can J Neurol Sci. 2012 Mar;39(2 Suppl 2):S1-59.PubMed: 22683887
  11. 11 . Gallagher HC, Gallagher RM, Butler M, Buggy DJ, Henman MC: Venlafaxine for neuropathic pain in adults. Cochrane Database Syst Rev. 2015 Aug 23;(8):CD011091. doi: 10.1002/14651858.CD011091.pub2.PubMed: 26298465
  12. 12 . Katzman MA, Bleau P, Blier P, Chokka P, Kjernisted K, Van Ameringen M, Antony MM, Bouchard S, Brunet A, Flament M, Grigoriadis S, Mendlowitz S, O'Connor K, Rabheru K, Richter PM, Robichaud M, Walker JR: Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry. 2014;14 Suppl 1:S1. doi: 10.1186/1471-244X-14-S1-S1. Epub 2014 Jul 2.PubMed: 25081580
  13. 13 . Handley AP, Williams M: The efficacy and tolerability of SSRI/SNRIs in the treatment of vasomotor symptoms in menopausal women: a systematic review. J Am Assoc Nurse Pract. 2015 Jan;27(1):54-61. doi: 10.1002/2327-6924.12137. Epub 2014 Jun 19.PubMed: 24944075
  14. 14 . Roxanas M, Hibbert E, Field M: Venlafaxine hyponatraemia: incidence, mechanism and management. Aust N Z J Psychiatry. 2007 May;41(5):411-8. doi: 10.1080/00048670701261202.PubMed: 17464733
  15. 15 . 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.PubMed: 9818630
  16. 16 . Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, Shaw JL, Thompson L, Nelson DL, Hemrick-Luecke SK, Wong DT: Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology. 2001 Dec;25(6):871-80.PubMed: 11750180
  17. 17 . FDA Approved Drug Products: Effexor XR® extended-release capsules Link
  18. 18 . FDA Approved Drug Products: Venlafaxine oral tablets Link