Venlafaxine and User:Mr. Ibrahem/Venlafaxine: Difference between pages

| Verifiedfields = changed

| verifiedrevid = 419802400

| drug_name=Venlafaxine

| IUPAC_name = (''RS'')-1-[2-dimethylamino-1-(4-methoxyphenyl)-ethyl]cyclohexanol

| image = Venlafaxine.svg

| imagename = 1 : 1 mixture (racemate)

| width = 200

| image2 = Venlafaxine-3D-balls.png

| width2 = 200

| CASNo_Ref = {{cascite|correct|CAS}}

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = GRZ5RCB1QG

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 637

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C17H27NO2/c1-18(2)13-16(17(19)11-5-4-6-12-17)14-7-9-15(20-3)10-8-14/h7-10,16,19H,4-6,11-13H2,1-3H3

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = PNVNVHUZROJLTJ-UHFFFAOYSA-N

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 93413-69-5

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 5454

| ATC_prefix = N06

| ATC_suffix = AX16

| ATC_supplemental =

| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEBI = 9943

| PubChem = 5656

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB00285

| smiles = OC2(C(c1ccc(OC)cc1)CN(C)C)CCCCC2

| C=17 |H=27 |N=1 |O=2

| molecular_weight = 277.402 g/mol

| bioavailability = 10-45%<ref name="goodman-gilman">{{cite book | editor=Laurence L Brunton | title=Goodman & Gilman's The Pharmacological Basis of Therapeutics | edition=11th | year=2006 | publisher=McGraw-Hill Medical Publishing Division | location=New York | isbn=0-07-142280-3}}</ref>

| protein_bound = 27%

| metabolism = [[Hepatic]]

| elimination_half-life = 4.9 ± 2.4 h (parent compound);<ref name="goodman-gilman" /> 10.3 ± 4.3 h (active metabolite)<ref name="goodman-gilman" />

| pregnancy_category = C

| legal_US = Rx-only

| legal_UK = POM

| legal_AU = S4

| routes_of_administration = Oral

| excretion = Renal

}}

'''Venlafaxine''' ([[brand name]]: '''Effexor''' or '''Efexor''') is an [[antidepressant]] of the [[serotonin-norepinephrine reuptake inhibitor]] (SNRI) class.<ref name="pmid3790168">{{cite journal | author = Muth EA, Haskins JT, Moyer JA, Husbands GE, Nielsen ST, Sigg EB | title = Antidepressant biochemical profile of the novel bicyclic compound Wy-45,030, an ethyl cyclohexanol derivative | journal = Biochemical Pharmacology | volume = 35 | issue = 24 | pages = 4493–7 | year = 1986 | month = December | pmid = 3790168 | doi = 10.1016/0006-2952(86)90769-0| url = http://linkinghub.elsevier.com/retrieve/pii/0006-2952(86)90769-0}}</ref><ref name="pmid1976813">{{cite journal | author = Yardley JP, Husbands GE, Stack G, ''et al.'' | title = 2-Phenyl-2-(1-hydroxycycloalkyl)ethylamine derivatives: synthesis and antidepressant activity | journal = Journal of Medicinal Chemistry | volume = 33 | issue = 10 | pages = 2899–905 | year = 1990 | month = October | pmid = 1976813 | doi = 10.1021/jm00172a035| url = }}</ref><ref name="pmid11750180">{{cite journal | author = Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, ''et al.'' | title = Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors | journal = Neuropsychopharmacology | volume = 25 | issue = 6 | pages = 871–80 | year = 2001 | month = December | pmid = 11750180 | doi = 10.1016/S0893-133X(01)00298-6 | unused_data = DUPLICATE DATA: doi = 10.1016/S0893-133X(01)00298-6}}</ref> First introduced by [[Wyeth]] in 1993, now marketed by [[Pfizer]], it is [[licensed]] for the treatment of [[major depressive disorder]] (MDD), as a treatment for [[generalized anxiety disorder]], and [[comorbid]] [[Indication (medicine)|indications]] in certain [[anxiety disorders]] with depression. In 2007, venlafaxine was the sixth most commonly prescribed antidepressant on the U.S. retail market, with 17.2 million prescriptions.<ref>The number of prescriptions was calculated as the total of prescriptions for the corresponding generic and brand-name drugs using data from the charts for generic and brand-name drugs. {{cite web | title = Top 200 generic drugs by units in 2007. | work = Drug Topics, Feb 18, 2008 | url = http://drugtopics.modernmedicine.com/drugtopics/Top200Drugs/ArticleStandard/article/detail/491194 | accessdate = 2008-10-23}} {{cite web | title = Top 200 brand drugs by units in 2007. | work = Drug Topics, Feb 18, 2008 | url = http://drugtopics.modernmedicine.com/drugtopics/PharmacyFactsAndFigures/ArticleStandard/article/detail/491210 | accessdate = 2008-10-23}}</ref>

==Medical uses==

Venlafaxine is used primarily for the treatment of [[major depressive disorder|depression]], [[general anxiety disorder]], [[social phobia]], [[panic disorder]], and [[vasomotor symptoms]].<ref name=AHFS>{{cite web|title=venlafaxine-hydrochloride|url=http://www.drugs.com/monograph/venlafaxine-hydrochloride.html|work=The American Society of Health-System Pharmacists|accessdate=3 April 2011}}</ref>

===Depression===

Multiple double blind studies show venlafaxine's effectiveness in treating depression. Venlafaxine has similar efficacy to the [[tricyclic antidepressants]] [[amitriptyline]] (Elavil) and [[imipramine]], and is better tolerated than amitriptyline. Its efficacy is similar to or better than [[sertraline]] (Zoloft) and [[fluoxetine]] (Prozac), depending on the criteria and rating scales used. Higher doses of venlafaxine are more effective, and more patients achieved [[Remission (medicine)|remission]] or were "very much improved". The efficacy was similar if the number of patients who achieved "response" or were "improved" was considered. A [[meta-analysis]] comparing venlafaxine and combined groups of [[SSRI]] or tricyclic antidepressants showed venlafaxine's superiority.<ref name="pmid11098413">{{cite journal |author=Golden RN, Nicholas L |title=Antidepressant efficacy of venlafaxine |journal=Depression and anxiety |volume=12 Suppl 1 |issue= |pages=45–9 |year=2000 |pmid=11098413 |doi=10.1002/1520-6394(2000)12:1 |doi_brokendate=2010-07-26}}</ref> Judged by the same criteria, venlafaxine was similar in efficacy to the atypical antidepressant [[bupropion]] (Wellbutrin); however, the remission rate was significantly lower for venlafaxine.<ref name="pmid16974189">{{cite journal |author=Thase ME, Clayton AH, Haight BR, Thompson AH, Modell JG, Johnston JA |title=A double-blind comparison between bupropion XL and venlafaxine XR: sexual functioning, antidepressant efficacy, and tolerability |journal=Journal of clinical psychopharmacology |volume=26 |issue=5 |pages=482–8 |year=2006 |pmid=16974189 |doi=10.1097/01.jcp.0000239790.83707.ab}}</ref> In a double-blind study, patients who did not respond to an SSRI were switched to venlafaxine or [[citalopram]]. Similar improvement was observed in both groups.<ref name="pmid18408525">{{cite journal |author=Lenox-Smith AJ, Jiang Q |title=Venlafaxine extended release versus citalopram in patients with depression unresponsive to a selective serotonin reuptake inhibitor |journal=[[Int Clin Psychopharmacol]] |volume=23 |issue=3 |pages=113–9 |year=2008 |pmid=18408525 |doi=10.1097/YIC.0b013e3282f424c2 |url= }}</ref>

===Other===

Many doctors are starting to prescribe venlafaxine "off label" for the treatment of [[diabetic neuropathy]] (in a similar manner to [[duloxetine]]) and [[migraine]] prophylaxis (in some people, however, venlafaxine can exacerbate or cause migraines). Studies have shown venlafaxine's effectiveness for these conditions.<ref>{{cite journal |author=Rowbotham M, Goli V, Kunz N, Lei D |title=Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study |journal=Pain |volume=110 |issue=3 |pages=697–706 |year=2004 |pmid=15288411 |doi=10.1016/j.pain.2004.05.010}}</ref><ref>{{cite journal |author=Ozyalcin S, Talu G, Kiziltan E, Yucel B, Ertas M, Disci R |title=The efficacy and safety of venlafaxine in the prophylaxis of migraine |journal=Headache |volume=45 |issue=2 |pages=144–52 |year=2005 |pmid=15705120 |doi=10.1111/j.1526-4610.2005.05029.x}}</ref>

It has also been found to reduce the severity of 'hot flashes' in [[menopause|menopausal]] women.<ref>{{cite web |author=Mayo Clinic staff |year=2005 |title=Beyond hormone therapy: Other medicines may help |work=Hot flashes: Ease the discomfort of menopause |publisher=Mayo Clinic |url=http://www.mayoclinic.com/invoke.cfm?id=HQ01409 |accessdate=19 August 2005}}</ref><ref>{{cite journal |author=Schober C, Ansani N |title=Venlafaxine hydrochloride for the treatment of hot flashes |journal=Ann Pharmacother |volume=37 |issue=11 |pages=1703–7 |year=2003 |pmid=14565812 |doi=10.1345/aph.1C483}}</ref>

Substantial weight loss in patients with major depression, generalized anxiety disorder, and [[social phobia]] has been noted, but the manufacturer does not recommend use as an [[anorectic]] either alone or in combination with [[phentermine]] or other amphetamine-like drugs.<ref name="Medicinedatasheet-Wyeth"/> Venlafaxine hydrochloride is in the phenethylamine class of modern chemicals, which includes amphetamine, methylenedioxymethamphetamine (MDMA), and methamphetamine. This chemical structure likely lends to its activating properties; however, some patients find venlafaxine highly sedating, despite its more common stimulatory effects.

Venlafaxine is not approved for the treatment of depressive phases of [[bipolar disorder]]; this has some potential danger as venlafaxine can induce [[mania]], [[mixed state (psychology)|mixed states]], rapid cycling and/or [[psychosis]] in some bipolar patients, particularly if they are not also being treated with a [[mood stabilizer]].<ref name="Medicinedatasheet-Wyeth"/>

Due to its action on both the serotoninergic and [[adrenergic]] systems, venlafaxine is also used as a treatment to reduce episodes of [[cataplexy]], a form of muscle weakness, in patients with the [[sleep disorder]] [[narcolepsy]].<ref>{{cite web |last= |first= |authorlink= |coauthors= |title=Medications |work= |publisher=Stanford University School of Medicine, Center for Narcolepsy |date=Revised 02/07/2003 |url=http://med.stanford.edu/school/Psychiatry/narcolepsy/medications.html |doi= |accessdate=2007-09-03}}</ref>

Venlafaxine was found in one study to be equal to [[anafranil]] (Clomipramine) in the treatment of [[OCD]] with fewer side effects.<ref name="pmid12444814">{{cite journal |author=Albert U, Aguglia E, Maina G, Bogetto F |title=Venlafaxine versus clomipramine in the treatment of obsessive-compulsive disorder: a preliminary single-blind, 12-week, controlled study |journal=J Clin Psychiatry |volume=63 |issue=11 |pages=1004–9 |year=2002 |month=November |pmid=12444814 |doi= |url=http://www.psychiatrist.com/privatepdf/2002/v63n11/v63n1108.pdf |format=PDF}}</ref>

Due to its tendency to increase blood pressure and its modulative effects on the [[Autonomic Nervous System|autonomic nervous system]], venlafaxine is often used to treat [[orthostatic intolerance]] and [[postural orthostatic tachycardia syndrome]].<ref>{{cite web |last=Hain T |title=Orthostatic Hypotension |work= |publisher=www.dizziness-and-balance.com |date=Revised 12/30/2007 |url=http://www.dizziness-and-balance.com/disorders/medical/orthostatic.html |doi= |accessdate=2008-03-29}}</ref>

==Contraindications==

Studies of venlafaxine in pediatric age groups have not established its efficacy.<ref>{{cite journal |author=Courtney D |title=Selective serotonin reuptake inhibitor and venlafaxine use in children and adolescents with major depressive disorder: a systematic review of published randomized controlled trials |journal=Can J Psychiatry |volume=49 |issue=8 |pages=557–63 |year=2004 |pmid=15453105}}</ref> Venlafaxine is not recommended in patients [[Hypersensitivity|hypersensitive]] to it, nor should it be taken by anyone who is allergic to the inactive ingredients, which include [[gelatin]], [[cellulose]], ethylcellulose, [[iron oxide]], [[titanium dioxide]] and [[hypromellose]]. It should never be used with a [[monoamine oxidase inhibitor]] (MAOI), as it can cause potentially fatal [[serotonin syndrome]]. Caution should also be used in those with a seizure disorder.

===Glaucoma===

Venlafaxine can increase eye pressure, so those with [[glaucoma]] may require more frequent eye checks.<ref name="Medicinedatasheet-Wyeth"/>

===Pregnant women===

There are few, well-controlled studies of venlafaxine in pregnant women. A study released in May 2010 by the Canadian Medical Association Journal suggests use of venlafaxine doubles the risk of [[miscarriage]].<ref>{{cite pmid|19863482}}</ref><ref>{{cite pmid|20513781}}</ref> Consequently, venlafaxine should only be used during pregnancy if clearly needed.<ref name="Medicinedatasheet-Wyeth"/> Prospective studies have not shown any statistically significant [[congenital malformation]]s.<ref>{{cite journal |author=Gentile S |title=The safety of newer antidepressants in pregnancy and breastfeeding |journal=Drug Saf |volume=28 |issue=2 |pages=137–52 |year=2005 |pmid=15691224 |doi=10.2165/00002018-200528020-00005}}</ref> There have, however, been some reports of self-limiting effects on newborn infants.<ref>{{cite journal |author=de Moor R, Mourad L, ter Haar J, Egberts A |title=[Withdrawal symptoms in a neonate following exposure to venlafaxine during pregnancy] |journal=Ned Tijdschr Geneeskd |volume=147 |issue=28 |pages=1370–2 |year=2003 |pmid=12892015}}</ref> As with other serotonin reuptake inhibitors, these effects are generally short-lived, lasting only 3 to 5 days,<ref>{{cite journal |author=Ferreira E, Carceller AM, Agogué C, Martin BZ, St-André M, Francoeur D, Bérard A |title=[Effects of selective serotonin reuptake inhibitors and venlafaxine during pregnancy in term and preterm neonates] |journal=Pediatrics |volume=119 |issue=1 |pages=52–9 |year=2007 |pmid=17200271 |doi=10.1542/peds.2006-2133}}</ref> and rarely resulting in severe complications.<ref name="pmid15900008">{{cite journal |author=Moses-Kolko EL, Bogen D, Perel J, Bregar A, Uhl K, Levin B, Wisner KL |title=[Neonatal signs after late in utero exposure to serotonin reuptake inhibitors: Literature review and implications for clinical applications] |journal=JAMA |volume=293 |issue=19 |pages=2372–83 |year=2005 |pmid=15900008 |doi=10.1001/jama.293.19.2372}}</ref>

===Heart disease and hypertension===

The FDA asked the manufacturers of all SNRIs to include the risk of persistent [[pulmonary hypertension]] (PPHN) in prescribing data as of July 19, 2006. Medications containing venlafaxine caused a mean heart rate increase of 4 bpm in clinical trials, along with a sustained increase in blood pressure in some.

==Adverse effects==

===Suicide===

The US Food and Drug Administration body (FDA) requires all antidepressants, including venlafaxine, to carry a [[black box warning]] with a generic warning about a possible suicide risk. In addition, the most recent research indicated that patients taking venlafaxine are at increased risk of suicide.

A study conducted in Finland followed more than 15,000 patients for 3.4 years. Venlafaxine increased suicide risk 1.6-fold (statistically significant), as compared to no treatment. At the same time, [[fluoxetine]] (Prozac) halved the suicide risk.<ref name="pmid17146010">{{cite journal |author=Tiihonen J, Lönnqvist J, Wahlbeck K, Klaukka T, Tanskanen A, Haukka J |title=Antidepressants and the risk of suicide, attempted suicide, and overall mortality in a nationwide cohort |journal=Arch. Gen. Psychiatry |volume=63 |issue=12 |pages=1358–67 |year=2006 |pmid=17146010 |doi=10.1001/archpsyc.63.12.1358}}</ref>

In another study, the data on more than 200,000 cases were obtained from the UK general practice research database. The patients taking venlafaxine had significantly higher risk of completed suicide than the ones on [[fluoxetine]] (Prozac) (2.8 times) or [[citalopram]] (Celexa) (2.4 times). Even after taking into consideration the fact that venlafaxine was generally prescribed for more severe depression, venlafaxine was associated with 1.6-1.7 times more suicides than fluoxetine or citalopram. This difference was no longer statistically significant due to the rarity of completed suicides. However, for the attempted suicides (more frequent event) the 1.2-1.3 times higher risk for venlafaxine still stayed statistically significant after the adjustment.<ref name="pmid17164297">{{cite journal |author=Rubino A, Roskell N, Tennis P, Mines D, Weich S, Andrews E |title=Risk of suicide during treatment with venlafaxine, citalopram, fluoxetine, and dothiepin: retrospective cohort study |journal=BMJ |volume=334 |issue=7587 |pages=242 |year=2007 |pmid=17164297 |doi=10.1136/bmj.39041.445104.BE |pmc=1790752}}</ref>

An analysis of clinical trials by the FDA statisticians showed the incidence of suicidal behaviour among the adults on venlafaxine to be not significantly different from fluoxetine or [[placebo]].<ref name=FDA>{{cite web |url=http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4272b1-01-FDA.pdf |title=Overview for December 13 Meeting of Psychopharmacologic Drugs Advisory Committee |accessdate=2007-06-20 |author= |authorlink= |coauthors= |date=November 16, 2006 |format=PDF |work= |publisher= |pages= |language= |archiveurl= |archivedate= |quote=}}</ref> A possible explanation for this discrepancy is that suicidal patients are generally excluded from clinical trials, and so clinical trials do not represent the real population of patients.{{Citation needed|date=March 2009}}

Venlafaxine is contraindicated in children, adolescents and young adults. According to the FDA analysis of clinical trials<ref name=FDA/> venlafaxine caused a statistically significant 5-fold increase in suicidal ideation and behavior in persons younger than 25. In another analysis, venlafaxine was no better than placebo among children (7–11 years old), but improved depression in adolescents (12–17 years old). However, in both groups, hostility and suicidal behavior increased in comparison to those receiving a placebo.<ref name="pmid17420682">{{cite journal |author=Emslie GJ, Findling RL, Yeung PP, Kunz NR, Li Y |title=Venlafaxine ER for the treatment of pediatric subjects with depression: results of two placebo-controlled trials |journal=Journal of the American Academy of Child and Adolescent Psychiatry |volume=46 |issue=4 |pages=479–88 |year=2007 |pmid=17420682 |doi=10.1097/chi.0b013e31802f5f03}}</ref> In a study involving antidepressants that had failed to produce results in depressed teenagers, teens whose [[SSRI]] treatment had failed who were randomly switched to either another SSRI or to venlafaxine showed an increased rate of suicide on venlafaxine. Among teenagers who were suicidal at the beginning of the study, the rate of suicidal attempts and self-harm was significantly higher, by about 60%, after the switch to venlafaxine than after the switch to an SSRI.<ref name="pmid19223438">{{cite journal |author=Brent DA, Emslie GJ, Clarke GN, ''et al.'' |title=Predictors of spontaneous and systematically assessed suicidal adverse events in the treatment of SSRI-resistant depression in adolescents (TORDIA) study |journal=Am J Psychiatry |volume=166 |issue=4 |pages=418–26 |year=2009 |month=April |pmid=19223438 |doi=10.1176/appi.ajp.2008.08070976 |url=}}</ref>

===Common side effects===

[[Sexual dysfunction]] is often a side effect of drugs that inhibit serotonin reuptake. Specifically, common side effects include difficulty becoming aroused, lack of interest in sex, and [[anorgasmia]] (trouble achieving orgasm). Genital anesthesia,<ref>{{cite journal |author=Bolton JM, Sareen J, Reiss JP |title=Genital anaesthesia persisting six years after sertraline discontinuation |journal=J Sex Marital Ther |volume=32 |issue=4 |pages=327–30 |year=2006 |pmid=16709553 |doi=10.1080/00926230600666410 |url=http://www.informaworld.com/openurl?genre=article&doi=10.1080/00926230600666410&magic=pubmed |unused_data=1B69BA326FFE69C3F0A8F227DF8201D0}}</ref> loss of or decreased response to sexual stimuli, and ejaculatory [[anhedonia]] are also possible. Although usually reversible, these sexual side effects can last for years after the drug has been completely withdrawn.<ref>{{cite journal |author=Csoka AB, Bahrick AS, Mehtonen O-P |title=Persistent Sexual Dysfunction after Discontinuation of Selective Serotonin Reuptake Inhibitors (SSRIs) |journal=J Sex Med. |volume=5 |issue= 1|pages=227–33 |year=2008 |doi= 10.1111/j.1743-6109.2007.00630.x|url=http://www.blackwell-synergy.com/doi/abs/10.1111/j.1743-6109.2007.00630.x |pmid=18173768}}</ref> This is known as [[Post SSRI Sexual Dysfunction]].

NOTE: The percentage of occurrences for each side effect listed comes from clinical trial data provided by Wyeth Pharmaceuticals Inc. The percentage of people experiencing the side effect using Effexor should be compared to those using a [[placebo]], given in parentheses. The following list includes those side effects with a difference of 3% or more.<ref name="Medicinedatasheet-Wyeth"/>

* [[Nausea]] - 37% (placebo 11%)

* [[Somnolence]] - 23% (9%)

* [[Dry mouth]] - 22% (11%)

* [[Dizziness]] - 19% (7%)

* [[Insomnia]] - 18% (10%)

* [[Constipation]] - 15% (7%)

* [[Anxiety|Nervousness]] - 13% (6%)

* Abnormal ejaculation/orgasm - 12% (0%)

* [[Sweating]] - 12% (3%)

* [[Asthenia]] - 12% (6%)

* [[Anorexia (symptom)|Anorexia]] - 11% (2%)

* [[Impotence]] - 6% (0%)

* [[Anxiety]] - 6% (3%)

* [[Vomiting]] - 6% (2%)

* [[Blurred vision]] - 6% (2%)

* [[Tremor]] - 5% (1%)

* [[Chills]] - 3% (0%)

* [[Yawn]] - 3% (0%)

Difference of 1-2%: [[headache]], [[infection]], [[chest pain]], [[trauma]],{{disambiguation needed|date=April 2011}} [[vasodilation]], increased [[blood pressure]]/[[hypertension]], [[tachycardia]], [[postural hypotension]], [[rash]], [[itch]]ing, [[diarrhea]], upset stomach or indigestion ([[dyspepsia]]), [[flatulence]], [[weight loss]], abnormal dreams, [[hypertonia]], [[paresthesia]], decreased [[libido]], [[agitation]], [[confusion]], abnormal thinking, [[depersonalization]], [[major depressive disorder|depression]], [[urinary retention]], [[twitching]], [[taste]] perversion, [[tinnitus]] (ringing in the ears), [[mydriasis]].

Other possible side effects can be found on pp.&nbsp;26–27 of the report used for the above data.<ref name="Medicinedatasheet-Wyeth"/> Note that these are from a combination of studies, not all of which were controlled, and so it is possible the individuals reporting the effects may have experienced them even if they had not taken Effexor.

===Dose dependency of adverse events===

A comparison of adverse event rates in a fixed-dose study comparing venlafaxine 75, 225, and 375&nbsp;mg/day with [[placebo]] revealed a dose dependency for some of the more common adverse events associated with venlafaxine use. The rule for including events was to enumerate those that occurred at an incidence of 5% or more for at least one of the venlafaxine groups and for which the incidence was at least twice the placebo incidence for at least one venlafaxine group. Tests for potential dose relationships for these events (Cochran-Armitage test, with a criterion of exact 2-sided p-value <=0.05) suggested a dose-dependency for several adverse events in this list, including chills, hypertension, anorexia, nausea, agitation, dizziness, somnolence, tremor, yawning, sweating, and abnormal ejaculation.<ref name="Medicinedatasheet-Wyeth"/>

===Memory loss===

In a study of 70 patients that compared the tolerability of venlafaxine at standard doses, ranging from 75 to 300&nbsp;mg, against relatively high doses (rarely prescribed), ranging from 375 to 600&nbsp;mg per day, for treating DSM-IV major depressive disorder, "failing memory" was reported in 44% of cases. The severity of venlafaxine-induced memory loss was also noted to increase with dose and length of treatment.<ref name="pmid15260908">{{cite journal |author=Harrison CL, Ferrier N, Young AH |title=Tolerability of high-dose venlafaxine in depressed patients |journal=J. Psychopharmacol. (Oxford) |volume=18 |issue=2 |pages=200–4 |year=2004 |month=June |pmid=15260908 |doi=10.1177/0269881104042621 |url=}}</ref>

===Discontinuation syndrome===

{{Main|SSRI discontinuation syndrome}}

In vitro studies revealed venlafaxine has virtually no affinity for opiate, benzodiazepine, or N-methyl-D-aspartic acid ([[NMDA]]) receptors. It has no significant CNS stimulant activity in rodents. In primate drug discrimination studies, venlafaxine showed no significant stimulant or depressant abuse liability.<ref name="Medicinedatasheet-Wyeth"/>

Many patients stopping venlafaxine use experience [[SSRI discontinuation syndrome]], i.e. withdrawal symptoms. This is especially noted if a patient misses a dose, but can also occur when reduction of dosage is gradual. The high risk of discontinuation syndrome symptoms may reflect venlafaxine's short half-life.<ref name="pmid11347722">{{cite journal |author=Haddad PM |title=Antidepressant discontinuation syndromes |journal=Drug Saf |volume=24 |issue=3 |pages=183–97 |year=2001 |pmid=11347722 |doi=10.2165/00002018-200124030-00003 |url=}}</ref> Missing even a single dose can induce discontinuation effects in some patients.<ref name="ANZ JPsych1998-parker"/> Discontinuation is similar in nature to those of SSRIs such as [[paroxetine]] ([[Paxil]] or [[Seroxat]]). Sudden discontinuation of venlafaxine particularly seemed to cause discontinuation symptoms during the first 3 days in a study of 18 patients.<ref name="AmJPsych1997-fava">{{cite journal |author=Fava M, Mulroy R, Alpert J, Nierenberg A, Rosenbaum J |title=Emergence of adverse events following discontinuation of treatment with extended-release venlafaxine |journal=Am J Psychiatry |volume=154 |issue=12 |pages=1760–2 |year=1997 |pmid=9396960}}</ref> As reported in 2001 by Haddad in the journal ''Drug Safety'', "another strategy to consider is switching to fluoxetine, which may suppress the discontinuation symptoms, but which has little tendency to cause such symptoms itself," and then discontinuing that.<ref name="pmid11347722"/> Some psychiatrists actually prescribe the singular SSRIs to alleviate the symptoms of venlafaxine withdrawal.

Although many other drugs can cause withdrawal symptoms which are not associated with addiction or dependence, for example, [[anticonvulsants]], [[beta-blockers]], nitrates, [[diuretic]]s, centrally acting antihypertensives, [[sympathomimetic]]s, [[heparin]], [[tamoxifen]], dopaminergic agents, [[antipsychotics]], and [[Lithium pharmacology|lithium]],<ref name="pmid11347722"/> addiction or dependence is a more common effect described for drugs that (are thought to, or may) improve mental well-being.<ref

name="pmid9081020">{{cite journal |author=Double D |title=Prescribing antidepressants in general practice. People may become psychologically dependent on antidepressants |journal=BMJ |volume=314 |issue=7083 |pages=829 |year=1997 |pmid=9081020 |pmc=2126213}}</ref>

===Serotonin syndrome===

The development of a potentially life-threatening [[serotonin syndrome]] (also more recently classified as "serotonin toxicity")<ref name="Dunkley">{{cite journal |author=Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM |title=The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity |journal=QJM |volume=96 |issue=9 |pages=635–42 |year=2003 |month=September |pmid=12925718 |doi= 10.1093/qjmed/hcg109|url=http://www.qjmed.oxfordjournals.org/cgi/content/full/96/9/635}}</ref> may occur with venlafaxine treatment, particularly with concomitant use of serotonergic drugs, including but not limited to [[SSRI]] and [[Serotonin-norepinephrine reuptake inhibitor|SNRI]]s, many hallucinogens such as [[tryptamine]]s and [[phenethylamine]]s ([[LSD]]/[[Lysergic acid amide|LSA]], [[Dimethyltryptamine|DMT]], [[MDMA]], [[MDPV]], [[mescaline]] for example), [[dextromethorphan]] (DXM)/[[dextrorphan]] (DXO), [[tramadol]], [[tapentadol]], [[meperidine|meperidine/pethidine]] and [[triptan]]s and with drugs that impair metabolism of serotonin (including [[MAOI]]s). Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Venlafaxine-induced serotonin syndrome has also been reported when venlafaxine has been taken in isolation in overdose.<ref name="Kolecki">{{cite journal |author=Kolecki P |title=Isolated venlafaxine-induced serotonin syndrome |journal=J Emerg Med |volume=15 |issue=4 |pages=491–3 |year=1997 |pmid=9279702 |doi=10.1016/S0736-4679(97)00078-4 }}</ref> An abortive serotonin syndrome state, in which some but not all of the symptoms of the full serotonin syndrome are present, has been reported with venlafaxine at mid-range dosages (150&nbsp;mg per day)<ref>{{cite web |url=http://www.priory.com/psych/venhall.htm |title=Hallucinations as a side effect of venlafaxine treatment |accessdate=2008-06-17 |author=Ebert D. et al. |publisher=Psychiatry On-line}}</ref> A case of a patient with serotonin syndrome induced by low-dose venlafaxine (37.5&nbsp;mg per day) has also been reported.<ref name="pmid12549949">{{cite journal |author=Pan JJ, Shen WW |title=Serotonin syndrome induced by low-dose venlafaxine |journal=Ann Pharmacother |volume=37 |issue=2 |pages=209–11 |year=2003 |month=February |pmid=12549949 |doi= 10.1345/aph.1C021|url=}}</ref>

===Serotonin toxicity and discontinuation syndrome===

Venlafaxine may be particularly hazardous to those individuals who are susceptible to both venlafaxine-induced serotonin toxicity (also known as serotonin syndrome) and [[SSRI discontinuation syndrome]]. In such cases, individuals who have developed the potentially fatal serotonin toxicity and/or may be at risk of doing so, may find cessation or dose reduction unachievable, placing them at continuing risk. As it is not possible to determine which patients are likely to develop the most severe symptoms of the discontinuation syndrome before cessation or dose reduction is attempted, this dual risk requires that all patients be closely monitored during any increase in dosage (when the patient is most at risk of developing serotonin toxicity)<ref>Venlafaxine (marketed as Effexor) FDA Alert: SSRIs/SNRI/Triptan and Serotonin Syndrome [issued 7/2006]</ref> and that such increases be carried out in the smallest incremental steps possible. Additionally, patients who recommence venlafaxine or revert to a higher dosage following a failed attempt to discontinue the drug or reduce dosage are another group with an increased risk of developing serotonin toxicity.<ref name="pmid9081020"/>

===Drug interactions===

Venlafaxine should be taken with caution when using [[St John's wort]].<ref>{{cite book |title=2006 Lippincott's Nursing Drug Guide |last=Karch |first=Amy |year=2006 |publisher=Lippincott Williams & Wilkins |location=Philadelphia, Baltimore, New York, London, Buenos Aires, Hong Kong, Sydney, Tokyo |isbn=1-58255-436-6}}</ref> Venlafaxine may lower the seizure threshold, and coadministration with other drugs that lower the seizure threshold such as [[bupropion]] and [[tramadol]] should be done with caution and at low doses.<ref name="pmid18072153">{{cite journal |author=Thundiyil JG, Kearney TE, Olson KR |title=Evolving epidemiology of drug-induced seizures reported to a Poison Control Center System |journal=J Med Toxicol |volume=3 |issue=1 |pages=15–9 |year=2007 |month=March |pmid=18072153 |doi= 10.1007/BF03161033|url=}}</ref>

There have been false positive [[phencyclidine]] (PCP) results caused by venlafaxine, with certain on-site routine urine-based drug tests.<ref name="pmid17267806">{{cite journal |author=Santos PM, López-García P, Navarro JS, Fernández AS, Sádaba B, Vidal JP |title=False positive phencyclidine results caused by venlafaxine |journal=Am J Psychiatry |volume=164 |issue=2 |pages=349 |year=2007 |month=February |pmid=17267806 |doi=10.1176/appi.ajp.164.2.349 |url=http://ajp.psychiatryonline.org/cgi/content/full/164/2/349}}</ref><ref name="pmid11901076">{{cite journal |author=Sena SF, Kazimi S, Wu AH |title=False-positive phencyclidine immunoassay results caused by venlafaxine and O-desmethylvenlafaxine |journal=Clin. Chem. |volume=48 |issue=4 |pages=676–7 |year=2002 |pmid=11901076 |doi= |url=http://clinchem.org/cgi/content/full/48/4/676}}</ref>

Although the [[Synergy#Drug_synergy|synergistic effects]] may not be as bad as with other antidepressants, it is still not recommended to take venlafaxine with alcohol.<ref>http://www.nhs.uk/chq/Pages/863.aspx?CategoryID=73&SubCategoryID=103</ref>

==Overdose==

Most patients overdosing with venlafaxine develop only mild symptoms. However, severe toxicity is reported, with the most common symptoms being [[CNS depression]], serotonin toxicity, [[seizure]], or [[Cardiac electrophysiology|cardiac conduction]] abnormalities.<ref>{{cite journal |author=Blythe D, Hackett L |title=Cardiovascular and neurological toxicity of venlafaxine |journal=Hum Exp Toxicol |volume=18 |issue=5 |pages=309–13 |year=1999 |pmid=10372752 |doi=10.1191/096032799678840165}}</ref> Venlafaxine's toxicity appears to be higher than other SSRIs, with a fatal toxic dose closer to that of the [[tricyclic antidepressant]]s than the SSRIs. Doses of 900&nbsp;mg or more are likely to cause moderate toxicity.<ref name="QJM2003-Whyte"/> Deaths have been reported following very large doses.<ref name="Pharmacotherapy2003-Mazur">{{cite journal |author=Mazur J, Doty J, Krygiel A |title=Fatality related to a 30-g venlafaxine overdose |journal=Pharmacotherapy |volume=23 |issue=12 |pages=1668–72 |year=2003 |pmid=14695048 |doi=10.1592/phco.23.15.1668.31951}}</ref><ref>{{cite journal |author=Banham N |title=Fatal venlafaxine overdose |journal=Med J Aust |volume=169 |issue=8 |pages=445, 448 |year=1998 |pmid=9830400}}</ref> Plasma venlafaxine concentrations in overdose survivors have ranged from 6 to 24&nbsp;mg/l, while postmortem blood levels in fatalities are often in the 10–90&nbsp;mg/l range.<ref>R. Baselt, ''Disposition of Toxic Drugs and Chemicals in Man'', 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1634–1637.</ref>

On May 31, 2006, the [[Medicines and Healthcare Products Regulatory Agency]] (MHRA) UK concluded its review of the latest safety evidence relating to venlafaxine, and particularly looked at the risks associated with overdose. The advice was: the need for specialist supervision in those severely depressed or hospitalized patients who need doses 300&nbsp;mg or more; cardiac contraindications are more targeted towards high risk groups; patients with uncontrolled hypertension should not take venlafaxine, and blood pressure monitoring is recommended for all patients; and updated advice on possible drug interactions.<ref>{{cite journal |author=MHRA UK |title=Updated product information for venlafaxine |journal=Safeguarding public health |volume= 120|issue= 8|pages= 778|year=2006 |month=31 May |doi=10.1016/j.puhe.2006.03.006}}</ref>

On 17 October 2006, Wyeth and the FDA notified healthcare professionals of revisions to the Overdosage/Human Experience section of the prescribing information for Effexor (venlafaxine) indicated for treatment of major depressive disorder. In post-marketing experience, there have been reports of overdose with venlafaxine, occurring predominantly in combination with alcohol and/or other drugs. Published retrospective studies report that venlafaxine overdosage may be associated with an increased risk of fatal outcome compared to that observed with SSRI antidepressant products, but lower than that for tricyclic antidepressants. Healthcare professionals are advised to prescribe Effexor and Effexor XR in the smallest quantity of capsules consistent with good patient management to reduce the risk of overdose.<ref>{{cite web |year=2006 |title=Wyeth Letter to Health Care Providers |publisher=Wyeth Pharmaceuticals Inc |url=http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm150546.htm |accessdate=2009-08-06}}</ref>

A report in the [[British Medical Journal]] in 2002 by Dr. Nicholas Buckley and colleagues at the Department of Clinical Pharmacology and Toxicology, [[Canberra]] Hospital, [[Australia]] studying fatal toxicity index (deaths per million prescriptions), found that venlafaxine's fatal toxicity is higher than that of other [[Selective serotonin reuptake inhibitor|serotoninergic antidepressants]], but it is similar to that of some of the less toxic [[tricyclic antidepressants]]. Overall, they found serious toxicity could occur following venlafaxine overdose with reports of deaths, arrythmias, and seizures. They did, however, state that this type of data is open to criticism, pointing out that mortality data may be influenced by previous literature and that "less toxic" drugs may be preferentially prescribed to patients at higher risk of poisoning and suicide, but they are also less likely to be listed as the sole cause of death from overdose. It also assumed that drugs are taken in overdose with similar frequency and in similar amounts. They suggested "clinicians need to consider whether factors in their patients reduce or compensate for this risk before prescribing venlafaxine."<ref>{{cite journal |author=Buckley N, McManus P |title=Fatal toxicity of serotoninergic and other antidepressant drugs: analysis of United Kingdom mortality data |journal=BMJ |volume=325 |issue=7376 |pages=1332–3 |year=2002 |pmid=12468481 |doi=10.1136/bmj.325.7376.1332 |pmc=137809}}</ref>

The 27 February 2007 Vancouver Sun reported that the BC Drug and Poison Information Centre had alerted doctors that the drug poses a significant risk of death from overdose, saying that venlafaxine "appears more toxic than it was originally hoped".<ref>{{cite web |last=Fayerman |first=Pamela |title=Warning issued over drug |publisher=Vancouver Sun |date=February 27, 2007 |url=http://www.canada.com/vancouversun/news/story.html?id=83f35b4e-ac13-4c09-b8de-44d16750b70b&k=58837 |accessdate=2007-06-02}}</ref> A doctor from the Department of Pharmacy Services College of Pharmacy, Medical University of South Carolina, Charleston, South Carolina, reported on the death of a 39-year-old patient with a 30 g overdose.<ref name="Pharmacotherapy2003-Mazur"/> To put this into perspective, a patient would have to take over 66 of the infrequently prescribed 450&nbsp;mg high dosage pills, or 400 of the commonly prescribed 75&nbsp;mg pills.

===Gastrointestinal effects===

Two cases are known of patients who deliberately overdosed on a huge quantity of venlafaxine, resulting in their stomach or intestines respectively being blocked by a mass of tablets (pharmaco-[[bezoar]]). The first patient died; the second recovered after the blocked part of her colon was surgically removed. The second patient's physicians speculate that the vasoconstrictive effects of venlafaxine contributed to tissue [[ischaemia]] (lack of blood supply) in the affected part of the intestine.<ref>{{Cite journal

| last = Lung

| first = Derrick

| coauthors = Cristina Cuevas, Uwais Zaid and Benedict Ancock

| title = Venlafaxine Pharmacobezoar Causing Intestinal Ischemia Requiring Emergent Hemicolectomy

| journal = Journal of Medical Toxicology

| volume =

| issue =

| pages =

| publisher =

| location =

| date = 4 March 2011

| url = http://www.springerlink.com/content/dx22wn16732u4628/fulltext.html

| doi = 10.1007/s13181-011-0144-8

| accessdate = 14 March 2011}}</ref>

===Management of overdose===

There is no specific [[antidote]] for venlafaxine, and management is generally supportive, providing treatment for the immediate symptoms. Administration of [[activated charcoal]] can prevent absorption of the drug. Monitoring of cardiac rhythm and vital signs is indicated. Seizures are managed with [[benzodiazepine]]s or other anticonvulsants. [[Forced diuresis]], [[hemodialysis]], [[exchange transfusion]], or [[hemoperfusion]] are unlikely to be of benefit in hastening the removal of venlafaxine, due to the drug's high [[volume of distribution]].<ref>{{cite journal |author=Hanekamp B, Zijlstra J, Tulleken J, Ligtenberg J, van der Werf T, Hofstra L |title=Serotonin syndrome and rhabdomyolysis in venlafaxine poisoning: a case report |journal=Neth J Med |volume=63 |issue=8 |pages=316–8 |year=2005 |pmid=16186642}}</ref>

==Mechanism of action==

Venlafaxine is a [[bicyclic]] antidepressant, and is usually categorized as a [[serotonin-norepinephrine reuptake inhibitor]] (SNRI), but it has been referred to as a [[serotonin-norepinephrine-dopamine reuptake inhibitor]] (SNDRI).<ref>{{cite web |author=[No Authors listed] |year= |title=Acute Effectiveness of Additional Drugs to the Standard Treatment of Depression |publisher=ClinicalTrials.gov |url=http://www.clinicaltrials.gov/ct/show/NCT00001483 |accessdate=23 June 2005}}</ref><ref>{{cite journal |author=Goeringer K, McIntyre I, Drummer O |title=Postmortem tissue concentrations of venlafaxine |journal=Forensic Sci Int |volume=121 |issue=1–2 |pages=70–5 |year=2001 |pmid=11516890 |doi=10.1016/S0379-0738(01)00455-8}}</ref> It works by blocking the [[Monoamine transporter|transporter "reuptake" proteins]] for key [[neurotransmitter]]s affecting mood, thereby leaving more active neurotransmitters in the [[synapse]]. The neurotransmitters affected are [[serotonin]] and [[norepinephrine]]. Additionally, in high doses it weakly inhibits the reuptake of [[dopamine]],<ref name="CNSDrugs2001-Wellington">{{cite journal |author=Wellington K, Perry C |title=Venlafaxine extended-release: a review of its use in the management of major depression |journal=CNS Drugs |volume=15 |issue=8 |pages=643–69 |year=2001 |pmid=11524036 |doi=10.2165/00023210-200115080-00007}}</ref> with recent evidence showing that the [[norepinephrine transporter]] also transports some [[dopamine]] as well, since dopamine is inactivated by norepinephrine reuptake in the [[frontal cortex]], which largely lacks dopamine transporters, therefore venlafaxine can increase dopamine neurotransmission in this part of the brain.<ref>http://stahlonline.cambridge.org/prescribers_drug.jsf?page=0521683505c95_p539-544.html.therapeutics&name=Venlafaxine&title=Therapeutics</ref><ref>{{cite journal | last1 = Delgado | first1 = P.L. | last2 = Moreno | first2 = F.A. | year = 2000 | title = Role of norepinephrine in depression | url = | journal = Journal of Clinical Psychiatry | volume = 61 | issue = | pages = 5–12 | pmid = 10703757 }}</ref>

Venlafaxine interacts with opioid receptors (mu-, kappa1- kappa3- and delta-opioid receptor subtypes) as well as alpha2-adrenergic receptor, and was shown to increase pain threshold in mice. When mice were tested with a hotplate analgesia meter, both venlafaxine and mirtazapine induced a dose-dependent, naloxone-reversible antinociceptive effect following ip administration. These findings suggest venlafaxine's seemingly superior efficacy in severe depression.<ref>http://www.opioids.com/depression/antidepressants.html</ref>

===Pharmacokinetics===

Venlafaxine is well absorbed, with at least 92% of an oral dose being absorbed into systemic circulation. It is extensively metabolized in the liver via the [[CYP2D6]] [[isoenzyme]] to [[desvenlafaxine]] (''O-desmethylvenlafaxine''), which is just as potent a serotonin-norepinephrine reuptake inhibitor as the parent compound, meaning that the differences in metabolism between extensive and [[poor metabolizer]]s are not clinically important in terms of efficacy. Side effects, however, are reported to be more severe in [[CYP2D6]] poor metabolizers.<ref name="JCPT JClinPharmTher2006-shams">{{cite journal |author=Shams ME et al. |title=CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine |journal=J Clin Pharm Ther |volume=31 |issue=5 |pages=493–502 |year=2006 |pmid=16958828 |doi=10.1111/j.1365-2710.2006.00763.x}}</ref> Steady-state concentrations of venlafaxine and its [[metabolite]] are attained in the [[blood]] within 3 days. Therapeutic effects are usually achieved within 3 to 4 weeks. No accumulation of venlafaxine has been observed during chronic administration in healthy subjects. The primary route of excretion of venlafaxine and its metabolites is via the [[kidneys]].<ref name="Medicinedatasheet-Wyeth">{{cite web |year=2006 |title=Effexor Medicines Data Sheet |publisher=Wyeth Pharmaceuticals Inc |url=http://www.wyeth.com/content/showlabeling.asp?id=99 |accessdate=17 September 2006}}</ref> The [[half-life]] of venlafaxine is relatively short, and, therefore, patients are directed to adhere to a strict medication routine, avoiding missing a dose. Even a single missed dose can result in the withdrawal symptoms.<ref name="ANZ JPsych1998-parker">{{cite journal |author=Parker G, Blennerhassett J |title=Withdrawal reactions associated with venlafaxine |journal=Aust N Z J Psychiatry |volume=32 |issue=2 |pages=291–4 |year=1998 |pmid=9588310 |doi=10.3109/00048679809062742}}</ref>

Venlafaxine is a substrate of [[P-glycoprotein]] (P-gp), which pumps it out of the brain. ABCB1, the gene encoding P-gp, has the [[single-nucleotide polymorphism|SNP]] rs2032583, with [[allele]]s C and T. The majority of people (about 70% of Europeans and 90% of East Asians) have the TT variant.<ref name="snpedia '583">{{cite web |url=http://www.snpedia.com/index.php/Rs2032583 |title=Rs2032583 - SNPedia}}</ref> A 2007 study<ref name="Neuron: ABCB1">{{cite doi|10.1016/j.neuron.2007.11.017}}</ref> found that carriers of at least one C allele (variant CC or CT) are 7.72 times more likely than non-carriers to achieve [[Cure#Remission|remission]] after 4 weeks of treatment with [[amitriptyline]], [[citalopram]], [[paroxetine]] or venlafaxine (all P-gp substrates). The study included patients with [[mood disorder]]s other than [[major depressive disorder|major depression]], such as [[bipolar II disorder|bipolar II]]; the ratio is 9.4 if these other disorders are excluded. At the 6-week mark, 75% of C-carriers had remitted, compared to only 38% of non-carriers.

==Physical/chemical properties==

The [[chemical structure]] of venlafaxine is designated (R/S)-1-[2-(dimethylamino)-1-(4 methoxyphenyl)ethyl] cyclohexanol hydrochloride or (±)-1-[a [a- (dimethylamino)methyl] p-methoxybenzyl] cyclohexanol hydrochloride, and it has the [[empirical formula]] of C₁₇H₂₇NO₂. It is a white to off-white crystalline solid. Venlafaxine is structurally and pharmacologically related to the atypical opioid [[analgesic]] [[tramadol]], and more distantly the newly-released opioid [[tapentadol]], but not to any of the conventional antidepressant drugs, including [[tricyclic antidepressant]]s, SSRIs, MAOIs, or [[Reversible inhibitor of monoamine oxidase A|RIMAs]].<ref name="QJM2003-Whyte">{{cite journal |author=Whyte I, Dawson A, Buckley N |title=Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants |journal=QJM |volume=96 |issue=5 |pages=369–74 |year=2003 |pmid=12702786 |doi=10.1093/qjmed/hcg062}}</ref>

==Available forms==

[[Image:EffexorXR 75and150mg.png|thumbnail |right |150px |Effexor XR 75 mg and 150 mg capsules]]

[[Image:Venlafaxin Krka.jpg|thumbnail |right |150px |Generic 75mg (top) and 150mg (bottom) venlafaxine capsules by Krka]]

Effexor is distributed in pentagon-shaped, peach-colored tablets of 25&nbsp;mg, 37.5&nbsp;mg, 50&nbsp;mg, 75&nbsp;mg, and 100&nbsp;mg. There is also an extended-release version distributed in capsules of 37.5&nbsp;mg (gray/peach), 75&nbsp;mg (peach), and 150&nbsp;mg (brownish red).

===Extended release===

Venlafaxine extended release is chemically the same as normal venlafaxine. The extended release (controlled release) version distributes the release of the drug into the [[gastrointestinal tract]] over a longer period than normal venlafaxine. This results in a lower peak plasma concentration. Studies have shown that the extended release formula has a lower incidence of patients suffering from [[nausea]] as a side effect, resulting in a lower number of patients stopping their treatment due to [[nausea]].<ref>{{cite journal |author=DeVane CL. |title=Immediate-release versus controlled-release formulations: pharmacokinetics of newer antidepressants in relation to nausea |journal=J Clin Psychiatry |volume=64 |issue=Suppl 18 |pages=14–9 |year=2003 |pmid=14700450}}</ref> In Australia, New Zealand and Switzerland, [[Wyeth]] sells their venlafaxine XR tablets under the name "Efexor-XR" (note the spelling with one 'f', rather than "Effexor-XR"). In Brazil, Medley sells a venlafaxine XR capsule under the brand name Alenthus XR. In September 2008, Osmotica Pharmaceuticals began marketing venlafaxine extended release tablets in the United States to compete with Wyeth's capsule-form, Effexor-XR. Sales of branded Efexor XR have remained strong, at US$2.7bn.<ref>[http://drugpatentwatch.com/ultimate/preview/tradename/index.php?query=EFFEXOR+XR Details for Effexor XR]</ref> Teva may begin to offer generic Effexor XR in the US on July 1, 2010, per a settlement agreement with Wyeth, but will have to pay Wyeth a portion of the sale price, driving up the cost.<ref>http://www.wyeth.com/irj/servlet/prt/portal/prtroot/com.sap.km.cm.docs//wyeth_xml/home/news/announcements/1153395074748.pdf (Archived by WebCite at http://www.webcitation.org/5pXQuFykU) p. 3, 4</ref>

Impax may begin to offer generic Effexor XR in the US on July 1, 2011, per a settlement agreement with Wyeth, but, like Teva, will have to pay Wyeth a portion of the sale price.<ref>http://www.wyeth.com/irj/portal/news/archive?nav=display&navTo=/wyeth_html/home/news/pressreleases/2008/1216240549738.html</ref>

===Generic===

Generic venlafaxine is available in the [[United States]] as of August 2006 and in Canada as of December 2006 due to patent expiry. Generic forms of the extended-release version have been available in Canada as of January 2007 and currently include Co Venlafaxine XR (Cobalt Pharmaceuticals Inc.), Gen-Venlafaxine XR (Genpharm), Riva-Venlafaxine XR (Laboratoire Riva Inc.), Novo Venlafaxine XR (Novopharm Limited), PMS-Venlafaxine XR (Pharmascience Inc.), Ratio-Venlafaxine XR (ratiopharm), Viepax (in Israel) and Sandoz Venlafaxine XR (Sandoz Canada Inc.). Generic versions of both drug forms are available now in India. Generic versions are also available in the UK such as Vaxalin manufactured by RatioPharm GmbH.<ref>http://www.mhra.gov.uk/home/groups/l-reg/documents/licensing/con025694.pdf</ref> On May 7, 2010 the Canadian pharmaceutical company [[IntelliPharmaCeutics|IntelliPharmaCeutics Inc.]] announced that the FDA had accepted its filing for a generic version of Venlafaxine XR utilizing its own proprietary technologies.<ref>http://www.intellipharmaceutics.com/releasedetail.cfm?ReleaseID=467633</ref>

;Notes

{{Reflist|2}}

==External links==

;Drug information

* [http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm106481.htm U.S. Food and Drug Administration information on Effexor]

* [http://www.medicines.org.uk/EMC/medicine/8609/XPIL/Efexor+XL/ Efexor patient information leaflet (UK)]

* [http://www.wyeth.com/content/ShowLabeling.asp?id=100 Effexor XR prescribing information for healthcare professionals (pdf) (USA only)]

* [http://www.rxlist.com/cgi/generic/venlafax_pi.htm Detailed Patient/Parent Information on Effexor]

* [http://www.merck.com/mmpe/lexicomp/venlafaxine.html#N18219E List of international brand names for Venlafaxine]

* [http://druginfo.nlm.nih.gov/drugportal/dpdirect.jsp?name=Venlafaxine U.S. National Library of Medicine: Drug Information Portal - Venlafaxine]

;Diagnostic tools

* [http://www.qjmed.oxfordjournals.org/cgi/content/full/96/9/635 The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity]

===Patient experiences===

*[http://www.nytimes.com/2007/05/06/magazine/06antidepressant-t.html?_r=1&ei=5087%0A&em=&en=cdeb03773a3deee0&ex=1178596800&pagewanted=all&oref=slogin Stutz, Bruce "Self-Nonmedication" New York Times Magazine May 6, 2007]

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