:Venlafaxine

Venlafaxine is used primarily for the treatment of depression, general anxiety disorder, social phobia, panic disorder, and vasomotor symptoms.{{cite web |title=venlafaxine-hydrochloride |url=https://www.drugs.com/monograph/venlafaxine-hydrochloride.html |work=The American Society of Health-System Pharmacists |access-date=3 April 2011 |archive-date=27 November 2020 |archive-url=https://web.archive.org/web/20201127001402/https://www.drugs.com/monograph/venlafaxine-hydrochloride.html |url-status=live }}

Venlafaxine has been used off label for the treatment of diabetic neuropathy{{cite journal | vauthors = Grothe DR, Scheckner B, Albano D | title = Treatment of pain syndromes with venlafaxine | journal = Pharmacotherapy | volume = 24 | issue = 5 | pages = 621–629 | date = May 2004 | pmid = 15162896 | doi = 10.1592/phco.24.6.621.34748 | s2cid = 28187627 | doi-access = free }} and migraine prevention.{{cite book | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK535363 | pmid=30570984 | year=2022 | vauthors = Singh D, Saadabadi A | chapter = Venlafaxine | title = StatPearls | location = Treasure Island (FL) | publisher = StatPearls Publishing }} It may work on pain via effects on the opioid receptor.{{cite book |title=The Opioid System as the Interface between the Brain's Cognitive and Motivational Systems |date=2018 |publisher=Academic Press |isbn=978-0-444-64168-7 |page=73 |url=https://books.google.com/books?id=sEFyDwAAQBAJ&pg=PA73 |access-date=9 May 2020 |archive-date=27 August 2021 |archive-url=https://web.archive.org/web/20210827181238/https://books.google.com/books?id=sEFyDwAAQBAJ&pg=PA73 |url-status=live }} It has also been found to reduce the severity of 'hot flashes' in menopausal women and men on hormonal therapy for the treatment of prostate cancer.{{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 |access-date=19 August 2005 |archive-date=25 February 2005 |archive-url=https://web.archive.org/web/20050225032733/http://www.mayoclinic.com/invoke.cfm?id=HQ01409 |url-status=live }}{{cite journal | vauthors = Schober CE, Ansani NT | title = Venlafaxine hydrochloride for the treatment of hot flashes | journal = The Annals of Pharmacotherapy | volume = 37 | issue = 11 | pages = 1703–1707 | date = November 2003 | pmid = 14565812 | doi = 10.1345/aph.1C483 | s2cid = 45334784 }}

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.{{cite web |title=Medications |publisher=Stanford University School of Medicine, Center for Narcolepsy |date=7 February 2003 |url=http://med.stanford.edu/school/Psychiatry/narcolepsy/medications.html |access-date=3 September 2007 |archive-url=https://web.archive.org/web/20070821090305/http://med.stanford.edu/school/Psychiatry/narcolepsy/medications.html |archive-date=21 August 2007 |url-status=dead }} Some open-label and three double-blind studies have suggested the efficacy of venlafaxine in the treatment of attention deficit-hyperactivity disorder (ADHD).{{cite journal | vauthors = Ghanizadeh A, Freeman RD, Berk M | title = Efficacy and adverse effects of venlafaxine in children and adolescents with ADHD: a systematic review of non-controlled and controlled trials | journal = Reviews on Recent Clinical Trials | volume = 8 | issue = 1 | pages = 2–8 | date = March 2013 | pmid = 23157376 | doi = 10.2174/1574887111308010002 }} Clinical trials have found possible efficacy in those with post-traumatic stress disorder (PTSD).{{cite journal | vauthors = Pae CU, Lim HK, Ajwani N, Lee C, Patkar AA | title = Extended-release formulation of venlafaxine in the treatment of post-traumatic stress disorder | journal = Expert Review of Neurotherapeutics | volume = 7 | issue = 6 | pages = 603–615 | date = June 2007 | pmid = 17563244 | doi = 10.1586/14737175.7.6.603 | s2cid = 25215502 }} Case reports, open trials and blinded comparisons with established medications have suggested the efficacy of venlafaxine in the treatment of obsessive–compulsive disorder.{{cite journal | vauthors = Phelps NJ, Cates ME | title = The role of venlafaxine in the treatment of obsessive-compulsive disorder | journal = The Annals of Pharmacotherapy | volume = 39 | issue = 1 | pages = 136–140 | date = January 2005 | pmid = 15585743 | doi = 10.1345/aph.1E362 | s2cid = 30973410 }}

A comparative meta-analysis of 21 major antidepressants found that venlafaxine, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, and vortioxetine were more effective than other antidepressants, although the quality of many comparisons was assessed as low or very low.{{cite journal | vauthors = Cipriani A, Furukawa TA, Salanti G, Geddes JR, Higgins JP, Churchill R, Watanabe N, Nakagawa A, Omori IM, McGuire H, Tansella M, Barbui C | title = Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis | journal = Lancet | volume = 373 | issue = 9665 | pages = 746–758 | date = February 2009 | pmid = 19185342 | doi = 10.1016/S0140-6736(09)60046-5 | s2cid = 35858125 }}{{cite journal | vauthors = Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, Leucht S, Ruhe HG, Turner EH, Higgins JP, Egger M, Takeshima N, Hayasaka Y, Imai H, Shinohara K, Tajika A, Ioannidis JP, Geddes JR | title = Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis | journal = Lancet | volume = 391 | issue = 10128 | pages = 1357–1366 | date = April 2018 | pmid = 29477251 | pmc = 5889788 | doi = 10.1016/S0140-6736(17)32802-7 }}

Venlafaxine was similar in efficacy to the atypical antidepressant bupropion; however, the remission rate was lower for venlafaxine.{{cite journal | vauthors = 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 = 482–488 | date = October 2006 | pmid = 16974189 | doi = 10.1097/01.jcp.0000239790.83707.ab | s2cid = 276619 }} In a double-blind study, patients who did not respond to an SSRI were switched to either venlafaxine or another SSRI (citalopram); similar improvement was observed in both groups.{{cite journal | vauthors = Lenox-Smith AJ, Jiang Q | title = Venlafaxine extended release versus citalopram in patients with depression unresponsive to a selective serotonin reuptake inhibitor | journal = International Clinical Psychopharmacology | volume = 23 | issue = 3 | pages = 113–119 | date = May 2008 | pmid = 18408525 | doi = 10.1097/YIC.0b013e3282f424c2 | s2cid = 34986490 }}

Studies have not established its efficacy for use in pediatric populations.{{cite journal | vauthors = Courtney DB | 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 = Canadian Journal of Psychiatry | volume = 49 | issue = 8 | pages = 557–563 | date = August 2004 | pmid = 15453105 | doi = 10.1177/070674370404900807 | doi-access = free }} In children and adolescents with depression, venlafaxine increases the risk of suicidal thoughts or attempts.{{cite journal |date=3 November 2022 |title=Antidepressants for children and teenagers: what works for anxiety and depression? |url=https://evidence.nihr.ac.uk/collection/antidepressants-for-children-and-teenagers-what-works-anxiety-depression/ |journal=NIHR Evidence |type=Plain English summary |language=en |publisher=National Institute for Health and Care Research |doi=10.3310/nihrevidence_53342|s2cid=253347210 |url-access=subscription }}{{cite journal | vauthors = Zhou X, Teng T, Zhang Y, Del Giovane C, Furukawa TA, Weisz JR, Li X, Cuijpers P, Coghill D, Xiang Y, Hetrick SE, Leucht S, Qin M, Barth J, Ravindran AV, Yang L, Curry J, Fan L, Silva SG, Cipriani A, Xie P | title = Comparative efficacy and acceptability of antidepressants, psychotherapies, and their combination for acute treatment of children and adolescents with depressive disorder: a systematic review and network meta-analysis | journal = The Lancet. Psychiatry | volume = 7 | issue = 7 | pages = 581–601 | date = July 2020 | pmid = 32563306 | pmc = 7303954 | doi = 10.1016/S2215-0366(20)30137-1 }}{{cite journal | vauthors = Hetrick SE, McKenzie JE, Bailey AP, Sharma V, Moller CI, Badcock PB, Cox GR, Merry SN, Meader N | title = New generation antidepressants for depression in children and adolescents: a network meta-analysis | journal = The Cochrane Database of Systematic Reviews | volume = 2021 | issue = 5 | pages = CD013674 | date = May 2021 | pmid = 34029378 | pmc = 8143444 | doi = 10.1002/14651858.CD013674.pub2 | collaboration = Cochrane Common Mental Disorders Group }}{{cite journal | vauthors = Solmi M, Fornaro M, Ostinelli EG, Zangani C, Croatto G, Monaco F, Krinitski D, Fusar-Poli P, Correll CU | title = Safety of 80 antidepressants, antipsychotics, anti-attention-deficit/hyperactivity medications and mood stabilizers in children and adolescents with psychiatric disorders: a large scale systematic meta-review of 78 adverse effects | journal = World Psychiatry | volume = 19 | issue = 2 | pages = 214–232 | date = June 2020 | pmid = 32394557 | pmc = 7215080 | doi = 10.1002/wps.20765 }}{{cite journal | vauthors = Boaden K, Tomlinson A, Cortese S, Cipriani A | title = Antidepressants in Children and Adolescents: Meta-Review of Efficacy, Tolerability and Suicidality in Acute Treatment | journal = Frontiers in Psychiatry | volume = 11 | pages = 717 | date = 2 September 2020 | pmid = 32982805 | pmc = 7493620 | doi = 10.3389/fpsyt.2020.00717 | doi-access = free }}{{cite journal | vauthors = Correll CU, Cortese S, Croatto G, Monaco F, Krinitski D, Arrondo G, Ostinelli EG, Zangani C, Fornaro M, Estradé A, Fusar-Poli P, Carvalho AF, Solmi M | title = Efficacy and acceptability of pharmacological, psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review | journal = World Psychiatry | volume = 20 | issue = 2 | pages = 244–275 | date = June 2021 | pmid = 34002501 | pmc = 8129843 | doi = 10.1002/wps.20881 }}

Higher doses (e.g., 225 mg and 375 mg per day) of venlafaxine are more effective than lower doses (e.g., 75 mg per day) but also cause more side effects.{{cite journal | vauthors = Rudolph RL, Fabre LF, Feighner JP, Rickels K, Entsuah R, Derivan AT | title = A randomized, placebo-controlled, dose-response trial of venlafaxine hydrochloride in the treatment of major depression | journal = The Journal of Clinical Psychiatry | volume = 59 | issue = 3 | pages = 116–122 | date = March 1998 | pmid = 9541154 | doi = 10.4088/jcp.v59n0305 }}

Studies have shown that the extended-release is superior to the immediate-release form of venlafaxine.

A 2017 meta-analysis has shown that the efficacy of venlafaxine is not correlated with baseline severity of depression. In other words, regardless of how severe a person's depression is at treatment initiation, the efficacy of venlafaxine remains consistent and is not influenced by the severity of depression at the start of treatment.

Venlafaxine is not recommended in patients 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 not be used in conjunction with a monoamine oxidase inhibitor (MAOI), as it can cause potentially fatal serotonin syndrome.{{cite web | title=Efexor-XR (venlafaxine hydrochloride) | website=TGA eBS | url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-04889-3 | access-date=11 May 2021 | format=PDF | archive-date=12 May 2021 | archive-url=https://web.archive.org/web/20210512121509/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-04889-3 | url-status=live }}{{cite book |title=The Maudsley Prescribing Guidelines in Psychiatry | veditors = Taylor D, Paton C, Kapur S |edition=illustrated |publisher=John Wiley & Sons |year=2012 |isbn=978-0-470-97948-8}} Venlafaxine might interact with tramadol or other opioids, as well as trazodone, so caution is needed while mixing multiple serotonergic agents together.{{cite journal | vauthors = Ripple MG, Pestaner JP, Levine BS, Smialek JE | title = Lethal combination of tramadol and multiple drugs affecting serotonin | journal = The American Journal of Forensic Medicine and Pathology | volume = 21 | issue = 4 | pages = 370–374 | date = December 2000 | pmid = 11111800 | doi = 10.1097/00000433-200012000-00015 | url = https://pubmed.ncbi.nlm.nih.gov/11111800/ | access-date = 6 April 2022 | url-status = live | archive-url = https://web.archive.org/web/20220406120319/https://pubmed.ncbi.nlm.nih.gov/11111800/ | archive-date = 6 April 2022 }}

{{see also|List of adverse effects of venlafaxine}}

Venlafaxine can increase eye pressure, so those with glaucoma may require more frequent eye checks.

A 2017 meta-analysis estimated venlafaxine discontinuation rate due to adverse effects to be 9.4%.{{cite journal | vauthors = Thase M, Asami Y, Wajsbrot D, Dorries K, Boucher M, Pappadopulos E | title = A meta-analysis of the efficacy of venlafaxine extended release 75-225 mg/day for the treatment of major depressive disorder | journal = Current Medical Research and Opinion | volume = 33 | issue = 2 | pages = 317–326 | date = February 2017 | pmid = 27794623 | doi = 10.1080/03007995.2016.1255185 | publisher = Informa UK Limited | s2cid = 4394404 }}

The US Food and Drug Administration (FDA) requires all antidepressants, including venlafaxine, to carry a black box warning with a generic warning about a possible suicide risk.{{citation needed|date=May 2021}}

A 2014 meta-analysis of 21 clinical trials of venlafaxine for the treatment of depression in adults found that compared to placebo, venlafaxine reduced the risk of suicidal thoughts and behavior.{{cite journal | vauthors = Gibbons RD, Brown CH, Hur K, Davis J, Mann JJ | title = Suicidal thoughts and behavior with antidepressant treatment: reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine | journal = Archives of General Psychiatry | volume = 69 | issue = 6 | pages = 580–587 | date = June 2012 | pmid = 22309973 | pmc = 3367101 | doi = 10.1001/archgenpsychiatry.2011.2048 }}

A study conducted in Finland followed more than 15,000 patients for 3.4 years. Venlafaxine increased suicide risk by 60% (statistically significant), as compared to no treatment. At the same time, fluoxetine (Prozac) halved the suicide risk.{{cite journal | vauthors = 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 = Archives of General Psychiatry | volume = 63 | issue = 12 | pages = 1358–1367 | date = December 2006 | pmid = 17146010 | doi = 10.1001/archpsyc.63.12.1358 | doi-access = free }}

In a study sponsored by Wyeth, which produces and markets venlafaxine, the data on more than 200,000 cases were obtained from the UK general practice research database. At baseline, patients prescribed venlafaxine had a greater number of risk factors for suicide (such as prior suicide attempts) than patients treated with other anti-depressants. The patients taking venlafaxine had a significantly higher risk of suicide than the ones on fluoxetine or citalopram (Celexa). After adjusting for known risk factors, venlafaxine was associated with an increased risk of suicide relative to fluoxetine and dothiepin which was not statistically significant. A statistically significant greater risk for attempted suicide remained after adjustment, but the authors concluded that it could be due to residual confounding.{{cite journal | vauthors = 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 | date = February 2007 | pmid = 17164297 | pmc = 1790752 | doi = 10.1136/bmj.39041.445104.BE }}

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.{{cite web |url=https://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4272b1-01-FDA.pdf |title=Overview for December 13 Meeting of Psychopharmacologic Drugs Advisory Committee |access-date=20 June 2007 |date=16 November 2006 |publisher=Food and Drug Administration: Center for Drug Evaluation and Research |archive-url=https://web.archive.org/web/20070316092329/https://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4272b1-01-FDA.pdf |archive-date=16 March 2007 |url-status=dead}}

Venlafaxine is contraindicated in children, adolescents, and young adults. In children and adolescents with depression, venlafaxine increases the risk of suicidal thoughts or attempts.

The development of a potentially life-threatening serotonin syndrome (also classified as "serotonin toxicity"){{cite journal | vauthors = 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 = 635–642 | date = September 2003 | pmid = 12925718 | doi = 10.1093/qjmed/hcg109 | doi-access = free }} may occur with venlafaxine treatment, particularly with concomitant use of serotonergic drugs, including but not limited to SSRIs and SNRIs, many hallucinogens such as tryptamines and phenethylamines (e.g., LSD/LSA, DMT, MDMA, mescaline), dextromethorphan (DXM), tramadol, tapentadol, pethidine (meperidine) and triptans and with drugs that impair metabolism of serotonin (including MAOIs).{{Citation needed|date=January 2021}} 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), 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.{{cite journal | vauthors = Kolecki P | title = Isolated venlafaxine-induced serotonin syndrome | journal = The Journal of Emergency Medicine | volume = 15 | issue = 4 | pages = 491–493 | date = July–August 1997 | pmid = 9279702 | doi = 10.1016/S0736-4679(97)00078-4 }} 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 mg per day).{{cite web |url=http://www.priory.com/psych/venhall.htm |title=Hallucinations as a side effect of venlafaxine treatment |access-date=17 June 2008 |vauthors=Ebert D, etal |publisher=Psychiatry On-line |archive-date=21 May 2008 |archive-url=https://web.archive.org/web/20080521183032/http://www.priory.com/psych/venhall.htm |url-status=live }} A case of a patient with serotonin syndrome induced by low-dose venlafaxine (37.5 mg per day) has also been reported.{{cite journal | vauthors = Pan JJ, Shen WW | title = Serotonin syndrome induced by low-dose venlafaxine | journal = The Annals of Pharmacotherapy | volume = 37 | issue = 2 | pages = 209–211 | date = February 2003 | pmid = 12549949 | doi = 10.1345/aph.1C021 }}

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.{{cite journal | vauthors = Broy P, Bérard A | title = Gestational exposure to antidepressants and the risk of spontaneous abortion: a review | journal = Current Drug Delivery | volume = 7 | issue = 1 | pages = 76–92 | date = January 2010 | pmid = 19863482 | doi = 10.2174/156720110790396508 | s2cid = 28153571 }}{{cite journal | vauthors = Nakhai-Pour HR, Broy P, Bérard A | title = Use of antidepressants during pregnancy and the risk of spontaneous abortion | journal = CMAJ | volume = 182 | issue = 10 | pages = 1031–1037 | date = July 2010 | pmid = 20513781 | pmc = 2900326 | doi = 10.1503/cmaj.091208 }} Consequently, venlafaxine should only be used during pregnancy if clearly needed. A large case-control study done as part of the National Birth Defects Prevention Study and published in 2012 found a significant association between venlafaxine use during pregnancy and several birth defects including anencephaly, cleft palate, septal heart defects and coarctation of the aorta.{{cite journal | vauthors = Polen KN, Rasmussen SA, Riehle-Colarusso T, Reefhuis J | title = Association between reported venlafaxine use in early pregnancy and birth defects, national birth defects prevention study, 1997-2007 | journal = Birth Defects Research. Part A, Clinical and Molecular Teratology | volume = 97 | issue = 1 | pages = 28–35 | date = January 2013 | pmid = 23281074 | pmc = 4484721 | doi = 10.1002/bdra.23096 }} Prospective studies have not shown any statistically significant congenital malformations.{{cite journal | vauthors = Gentile S | title = The safety of newer antidepressants in pregnancy and breastfeeding | journal = Drug Safety | volume = 28 | issue = 2 | pages = 137–152 | year = 2005 | pmid = 15691224 | doi = 10.2165/00002018-200528020-00005 | s2cid = 24798891 }} There have, however, been some reports of self-limiting effects on newborn infants.{{cite journal | vauthors = de Moor RA, Mourad L, ter Haar J, Egberts AC | title = [Withdrawal symptoms in a neonate following exposure to venlafaxine during pregnancy] | journal = Nederlands Tijdschrift voor Geneeskunde | volume = 147 | issue = 28 | pages = 1370–1372 | date = July 2003 | pmid = 12892015 }} As with other serotonin reuptake inhibitors (SRIs), these effects are generally short-lived, lasting only 3 to 5 days,{{cite journal | vauthors = 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 = 52–59 | date = January 2007 | pmid = 17200271 | doi = 10.1542/peds.2006-2133 | s2cid = 27443298 }} and rarely resulting in severe complications.{{cite journal | vauthors = 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 = 2372–2383 | date = May 2005 | pmid = 15900008 | doi = 10.1001/jama.293.19.2372 | s2cid = 30284439 }}

According to the ISBD Task Force report on antidepressant use in bipolar disorder,{{cite journal | vauthors = Pacchiarotti I, Bond DJ, Baldessarini RJ, Nolen WA, Grunze H, Licht RW, Post RM, Berk M, Goodwin GM, Sachs GS, Tondo L, Findling RL, Youngstrom EA, Tohen M, Undurraga J, González-Pinto A, Goldberg JF, Yildiz A, Altshuler LL, Calabrese JR, Mitchell PB, Thase ME, Koukopoulos A, Colom F, Frye MA, Malhi GS, Fountoulakis KN, Vázquez G, Perlis RH, Ketter TA, Cassidy F, Akiskal H, Azorin JM, Valentí M, Mazzei DH, Lafer B, Kato T, Mazzarini L, Martínez-Aran A, Parker G, Souery D, Ozerdem A, McElroy SL, Girardi P, Bauer M, Yatham LN, Zarate CA, Nierenberg AA, Birmaher B, Kanba S, El-Mallakh RS, Serretti A, Rihmer Z, Young AH, Kotzalidis GD, MacQueen GM, Bowden CL, Ghaemi SN, Lopez-Jaramillo C, Rybakowski J, Ha K, Perugi G, Kasper S, Amsterdam JD, Hirschfeld RM, Kapczinski F, Vieta E | title = The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders | journal = The American Journal of Psychiatry | volume = 170 | issue = 11 | pages = 1249–1262 | date = November 2013 | pmid = 24030475 | pmc = 4091043 | doi = 10.1176/appi.ajp.2013.13020185 | doi-access = free }} during the course of treatment for depression with those suffering from bipolar I and II, venlafaxine "appears to carry a particularly high risk of inducing pathologically elevated states of mood and behavior." Because venlafaxine appears to be more likely than SSRIs and bupropion to induce mania and mixed episodes in these patients, provider discretion is advised through "carefully evaluating individual clinical cases and circumstances."

A rare but serious side effect of venlafaxine is liver injury. It appears to affect both male and female patients with a median age of 44. Cessation of venlafaxine is one of the appropriate measures of management. While the mechanism of venlafaxine-related liver injury remains unclear, findings suggest that it may be related to a CYP2D6 polymorphism.{{cite journal | vauthors = Stadlmann S, Portmann S, Tschopp S, Terracciano LM | title = Venlafaxine-induced cholestatic hepatitis: case report and review of literature | journal = The American Journal of Surgical Pathology | volume = 36 | issue = 11 | pages = 1724–1728 | date = November 2012 | pmid = 23073329 | doi = 10.1097/pas.0b013e31826af296 | publisher = Ovid Technologies (Wolters Kluwer Health) }}

Most patients overdosing with venlafaxine develop only mild symptoms. Plasma venlafaxine concentrations in overdose survivors have ranged from 6 to 24 mg/L, while postmortem blood levels in fatalities are often in the 10–90 mg/L range.{{cite book| vauthors = Baselt R |title=Disposition of Toxic Drugs and Chemicals in Man |edition=8th |publisher=Biomedical Publications |location=Foster City, CA |year=2008 |pages=1634–1637 |isbn=978-0-9626523-7-0}} 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.{{cite web |year=2006 |title=Wyeth Letter to Health Care Providers |publisher=Wyeth Pharmaceuticals Inc |url=https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm150546.htm |access-date=6 August 2009 |archive-date=27 August 2009 |archive-url=https://web.archive.org/web/20090827092615/http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm150546.htm |url-status=dead }} It is usually reserved as a second-line treatment for depression due to a combination of its superior efficacy to the first-line treatments like fluoxetine, paroxetine and citalopram and greater frequency of side effects like nausea, headache, insomnia, drowsiness, dry mouth, constipation, sexual dysfunction, sweating and nervousness.{{cite journal | vauthors = Taylor D, Lenox-Smith A, Bradley A | title = A review of the suitability of duloxetine and venlafaxine for use in patients with depression in primary care with a focus on cardiovascular safety, suicide and mortality due to antidepressant overdose | journal = Therapeutic Advances in Psychopharmacology | volume = 3 | issue = 3 | pages = 151–161 | date = June 2013 | pmid = 24167687 | pmc = 3805457 | doi = 10.1177/2045125312472890 }}

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 benzodiazepines 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.{{cite journal | vauthors = Hanekamp BB, Zijlstra JG, Tulleken JE, Ligtenberg JJ, van der Werf TS, Hofstra LS | title = Serotonin syndrome and rhabdomyolysis in venlafaxine poisoning: a case report | journal = The Netherlands Journal of Medicine | volume = 63 | issue = 8 | pages = 316–318 | date = September 2005 | pmid = 16186642 | url = http://www.njmonline.nl/getpdf.php?id=432 | access-date = 6 November 2013 | url-status = live | format = PDF | archive-url = https://web.archive.org/web/20160304231924/http://www.njmonline.nl/getpdf.php?id=432 | archive-date = 4 March 2016 }}

{{Main|Antidepressant withdrawal syndrome}}

People stopping venlafaxine commonly experience SSRI withdrawal symptoms such as dysphoria, headaches, nausea, irritability, emotional lability, sensation of electric shocks (commonly called "brain zaps"{{cite journal | vauthors = Papp A, Onton JA | title = Brain Zaps: An Underappreciated Symptom of Antidepressant Discontinuation | journal = The Primary Care Companion for CNS Disorders | volume = 20 | issue = 6 | pages = 18m02311 | date = December 2018 | pmid = 30605268 | doi = 10.4088/PCC.18m02311 | s2cid = 58577252 }}{{cite journal | vauthors = Rizkalla M, Kowalkowski B, Prozialeck WC | title = Antidepressant Discontinuation Syndrome: A Common but Underappreciated Clinical Problem | journal = The Journal of the American Osteopathic Association | volume = 120 | issue = 3 | pages = 174–178 | date = February 2020 | pmid = 32077900 | doi = 10.7556/jaoa.2020.030 }}), and sleep disturbance.{{cite journal | vauthors = Petit J, Sansone RA | title = A case of interdose discontinuation symptoms with venlafaxine extended release | journal = The Primary Care Companion for CNS Disorders | volume = 13 | issue = 5 | date = 2011 | pmid = 22295261 | pmc = 3267502 | doi = 10.4088/PCC.11l01140 }} Venlafaxine has a higher rate of moderate to severe withdrawal symptoms relative to other antidepressants (similar to the SSRI paroxetine).{{cite journal | vauthors = Hosenbocus S, Chahal R | title = SSRIs and SNRIs: A review of the Discontinuation Syndrome in Children and Adolescents | journal = Journal of the Canadian Academy of Child and Adolescent Psychiatry | volume = 20 | issue = 1 | pages = 60–67 | date = February 2011 | pmid = 21286371 | pmc = 3024727 }}

The higher risk and increased severity of withdrawal symptoms relative to other antidepressants may be related to the short half-life of venlafaxine and its active metabolite.{{cite journal | vauthors = Haddad PM | title = Antidepressant discontinuation syndromes | journal = Drug Safety | volume = 24 | issue = 3 | pages = 183–197 | date = March 2001 | pmid = 11347722 | doi = 10.2165/00002018-200124030-00003 | s2cid = 26897797 }} After stopping venlafaxine, the levels of both serotonin and norepinephrine decrease, leading to the hypothesis that the withdrawal symptoms could result from an overly rapid reduction of neurotransmitter levels.{{cite journal | vauthors = Campagne DM | title = Venlafaxine and serious withdrawal symptoms: warning to drivers | journal = MedGenMed | volume = 7 | issue = 3 | pages = 22 | date = July 2005 | pmid = 16369248 | pmc = 1681629 }}

In rare cases, drug-induced akathisia can occur after use in some people.{{cite web | title = Venlafaxine Side Effects in Detail | url = https://www.drugs.com/sfx/venlafaxine-side-effects.html | access-date = 3 January 2018 | archive-date = 3 October 2020 | archive-url = https://web.archive.org/web/20201003115943/https://www.drugs.com/sfx/venlafaxine-side-effects.html | url-status = live }}

Venlafaxine should be used with caution in hypertensive patients. Venlafaxine must be discontinued if significant hypertension persists.{{cite journal | vauthors = Khurana RN, Baudendistel TE | title = Hypertensive crisis associated with venlafaxine | journal = The American Journal of Medicine | volume = 115 | issue = 8 | pages = 676–677 | date = December 2003 | pmid = 14656626 | doi = 10.1016/S0002-9343(03)00472-8 }}{{cite journal | vauthors = Thase ME | title = Effects of venlafaxine on blood pressure: a meta-analysis of original data from 3744 depressed patients | journal = The Journal of Clinical Psychiatry | volume = 59 | issue = 10 | pages = 502–508 | date = October 1998 | pmid = 9818630 | doi = 10.4088/JCP.v59n1002 }}{{cite journal | vauthors = Edvardsson B | title = Venlafaxine as single therapy associated with hypertensive encephalopathy | journal = SpringerPlus | volume = 4 | issue = 1 | pages = 97 | date = 26 February 2015 | pmid = 25763307 | pmc = 4348355 | doi = 10.1186/s40064-015-0883-0 | doi-access = free }} It can also have undesirable cardiovascular effects.{{cite journal | vauthors = Johnson EM, Whyte E, Mulsant BH, Pollock BG, Weber E, Begley AE, Reynolds CF | title = Cardiovascular changes associated with venlafaxine in the treatment of late-life depression | journal = The American Journal of Geriatric Psychiatry | volume = 14 | issue = 9 | pages = 796–802 | date = September 2006 | pmid = 16943176 | doi = 10.1097/01.JGP.0000204328.50105.b3 }}

Venlafaxine is usually categorized as a serotonin-norepinephrine reuptake inhibitor (SNRI), but it has also been referred to as a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI).{{ClinicalTrialsGov|NCT00001483|Acute Effectiveness of Additional Drugs to the Standard Treatment of Depression}}{{cite journal | vauthors = Goeringer KE, McIntyre IM, Drummer OH | title = Postmortem tissue concentrations of venlafaxine | journal = Forensic Science International | volume = 121 | issue = 1–2 | pages = 70–75 | date = September 2001 | pmid = 11516890 | doi = 10.1016/S0379-0738(01)00455-8 }} It is described as 'synthetic phenethylamine bicyclic derivative with antidepressant activity'.{{cite web |url=https://www.cancer.gov/publications/dictionaries/cancer-drug/def/venlafaxine |title=venlafaxine |publisher=National Cancer Institute |archive-url=https://web.archive.org/web/20220124090908/https://www.cancer.gov/publications/dictionaries/cancer-drug/def/venlafaxine |archive-date=24 January 2022 }}{{cite book|chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK535363/|title=StatPearls|chapter=Venlafaxine|year=2022|publisher=StatPearls|pmid=30570984 |access-date=24 January 2022|archive-date=30 June 2022|archive-url=https://web.archive.org/web/20220630225510/https://www.ncbi.nlm.nih.gov/books/NBK535363/|url-status=live| vauthors = Singh D, Saadabadi A }} It works by blocking the transporter "reuptake" proteins for key neurotransmitters 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.{{cite journal | vauthors = Wellington K, Perry CM | title = Venlafaxine extended-release: a review of its use in the management of major depression | journal = CNS Drugs | volume = 15 | issue = 8 | pages = 643–669 | year = 2001 | pmid = 11524036 | doi = 10.2165/00023210-200115080-00007 | s2cid = 26795121 }} The frontal cortex largely lacks dopamine transporters; therefore venlafaxine can increase dopamine neurotransmission in this part of the brain.{{cite web |url=http://stahlonline.cambridge.org/prescribers_drug.jsf?page=0521683505c95_p539-544.html.therapeutics&name=Venlafaxine&title=Therapeutics |title=Stahl's Essential Psychopharmacology – Cambridge University Press |publisher=Stahlonline.cambridge.org |access-date=21 November 2013 |archive-date=27 February 2012 |archive-url=https://web.archive.org/web/20120227144244/http://stahlonline.cambridge.org/prescribers_drug.jsf?page=0521683505c95_p539-544.html.therapeutics&name=Venlafaxine&title=Therapeutics |url-status=live }}{{cite journal | vauthors = Delgado PL, Moreno FA | title = Role of norepinephrine in depression | journal = The Journal of Clinical Psychiatry | volume = 61 | issue = Suppl 1 | pages = 5–12 | year = 2000 | pmid = 10703757 }}{{full citation needed|date=November 2013}}

Venlafaxine selectively inhibits the serotonin transporter at lower doses, but at a dose of 225 mg per day it additionally blocks the norepinephrine transporter (NET), as measured by the intravenous tyramine pressor test.{{cite journal | vauthors = Aldosary F, Norris S, Tremblay P, James JS, Ritchie JC, Blier P | title = Differential Potency of Venlafaxine, Paroxetine, and Atomoxetine to Inhibit Serotonin and Norepinephrine Reuptake in Patients With Major Depressive Disorder | journal = The International Journal of Neuropsychopharmacology | volume = 25 | issue = 4 | pages = 283–292 | date = April 2022 | pmid = 34958348 | pmc = 9017767 | doi = 10.1093/ijnp/pyab086 }}

Venlafaxine indirectly affects opioid receptors as well as the α₂-adrenergic receptor, and was shown to increase pain threshold in mice. These benefits with respect to pain were reversed with naloxone, an opioid antagonist, thus supporting an opioid mechanism.{{cite book | vauthors = Stern TA, Fava M, Wilens TE, Rosenbaum JF |title=Massachusetts General Hospital Comprehensive Clinical Psychiatry |date=2015 |publisher=Elsevier Health Sciences |isbn=978-0-323-29507-9 |page=860 |url=https://books.google.com/books?id=deR1BwAAQBAJ&pg=PA860 |access-date=9 May 2020 |archive-date=27 August 2021 |archive-url=https://web.archive.org/web/20210827181241/https://books.google.com/books?id=deR1BwAAQBAJ&pg=PA860 |url-status=live }}

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, now marketed as a separate medication named Pristiq{{cite journal | vauthors = Pae CU | title = Desvenlafaxine in the treatment of major depressive disorder | journal = Expert Opinion on Pharmacotherapy | volume = 12 | issue = 18 | pages = 2923–2928 | date = December 2011 | pmid = 22098230 | doi = 10.1517/14656566.2011.636033 | s2cid = 33558428 }}), which is just as potent an SNRI as the parent compound, meaning that the differences in metabolism between extensive and poor metabolisers are not clinically important in terms of efficacy. Side effects, however, are reported to be more severe in CYP2D6 poor metabolisers.{{cite journal | vauthors = Shams ME, Arneth B, Hiemke C, Dragicevic A, Müller MJ, Kaiser R, Lackner K, Härtter S | title = CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine | journal = Journal of Clinical Pharmacy and Therapeutics | volume = 31 | issue = 5 | pages = 493–502 | date = October 2006 | pmid = 16958828 | doi = 10.1111/j.1365-2710.2006.00763.x | s2cid = 22236102 | doi-access = free }}{{cite book | title=Medical Genetics Summaries | chapter=Venlafaxine Therapy and CYP2D6 Genotype | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK305561/ | veditors=Pratt VM, McLeod HL, Rubinstein WS, Scott SA, Dean LC, Kattman BL, Malheiro AJ | display-editors=3 | publisher=National Center for Biotechnology Information (NCBI) | year=2015 | pmid=28520361 | id=Bookshelf ID: NBK305561 | vauthors=Dean L | url=https://www.ncbi.nlm.nih.gov/books/NBK61999/ | access-date=7 February 2020 | archive-date=26 October 2020 | archive-url=https://web.archive.org/web/20201026145821/https://www.ncbi.nlm.nih.gov/books/NBK61999/ | url-status=live }} 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. The half-life of venlafaxine is relatively short, so patients are directed to adhere to a strict medication routine, avoiding missing a dose. Even a single missed dose can result in withdrawal symptoms.{{cite journal | vauthors = Parker G, Blennerhassett J | title = Withdrawal reactions associated with venlafaxine | journal = The Australian and New Zealand Journal of Psychiatry | volume = 32 | issue = 2 | pages = 291–294 | date = April 1998 | pmid = 9588310 | doi = 10.3109/00048679809062742 | s2cid = 34824025 }}

Venlafaxine is a substrate of P-glycoprotein (P-gp), which pumps it out of the brain. The gene encoding P-gp, ABCB1, has the SNP rs2032583, with alleles C and T. The majority of people (about 70% of Europeans and 90% of East Asians) have the TT variant.{{cite web |url=http://www.snpedia.com/index.php/Rs2032583 |title=Rs2032583 -SNPedia |publisher=Snpedia.com |access-date=21 November 2013 |archive-date=11 December 2013 |archive-url=https://web.archive.org/web/20131211083916/http://www.snpedia.com/index.php/Rs2032583 |url-status=live }}{{unreliable source?|date=December 2013}} A 2007 study{{cite journal | vauthors = Uhr M, Tontsch A, Namendorf C, Ripke S, Lucae S, Ising M, Dose T, Ebinger M, Rosenhagen M, Kohli M, Kloiber S, Salyakina D, Bettecken T, Specht M, Pütz B, Binder EB, Müller-Myhsok B, Holsboer F | title = Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression | journal = Neuron | volume = 57 | issue = 2 | pages = 203–209 | date = January 2008 | pmid = 18215618 | doi = 10.1016/j.neuron.2007.11.017 | s2cid = 6772775 | doi-access = free }} found that carriers of at least one C allele (variant CC or CT) are 7.72 times more likely than non-carriers to achieve remission after 4 weeks of treatment with amitriptyline, citalopram, paroxetine or venlafaxine (all P-gp substrates). The study included patients with mood disorders other than major depression, such as 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.{{citation needed|date=March 2017}}

The IUPAC name of venlafaxine is 1-[2-(dimethylamino)-1-(4 methoxyphenyl)ethyl]cyclohexanol, though it is sometimes referred to as (±)-1-[a-[a-(dimethylamino)methyl]-p-methoxybenzyl]cyclohexanol. It consists of two enantiomers present in equal quantities (termed a racemic mixture), both of which have the empirical formula of C₁₇H₂₇NO₂. It is usually sold as a mixture of the respective hydrochloride salts, (R/S)-1-[2-(dimethylamino)-1-(4 methoxyphenyl)ethyl]cyclohexanol hydrochloride, C₁₇H₂₈ClNO₂, which is a white to off-white crystalline solid. Venlafaxine is structurally and pharmacologically related to the atypical opioid analgesic tramadol, and more distantly to the newly released opioid tapentadol, but not to any of the conventional antidepressant drugs, including tricyclic antidepressants, SSRIs, MAOIs, or RIMAs.{{cite journal | vauthors = Whyte IM, Dawson AH, Buckley NA | title = Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants | journal = QJM | volume = 96 | issue = 5 | pages = 369–374 | date = May 2003 | pmid = 12702786 | doi = 10.1093/qjmed/hcg062 | doi-access = free }}

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 nausea as a side effect, resulting in better compliance.{{cite journal | vauthors = DeVane CL | title = Immediate-release versus controlled-release formulations: pharmacokinetics of newer antidepressants in relation to nausea | journal = The Journal of Clinical Psychiatry | volume = 64 | issue = Suppl 18 | pages = 14–19 | year = 2003 | pmid = 14700450 }}

Venlafaxine should be taken with caution when using St John's wort.{{cite book |title=2006 Lippincott's Nursing Drug Guide |url=https://archive.org/details/2006lippincottsn0000karc |url-access=registration | vauthors = Karch A |year=2006 |publisher=Lippincott Williams & Wilkins |location=Philadelphia, Baltimore, New York, London, Buenos Aires, Hong Kong, Sydney, Tokyo |isbn=978-1-58255-436-5}} 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.{{cite journal | vauthors = Thundiyil JG, Kearney TE, Olson KR | title = Evolving epidemiology of drug-induced seizures reported to a Poison Control Center System | journal = Journal of Medical Toxicology | volume = 3 | issue = 1 | pages = 15–19 | date = March 2007 | pmid = 18072153 | pmc = 3550124 | doi = 10.1007/BF03161033 }}

Venlafaxine can be abused as a recreational drug, with damages that can manifest within a month.{{cite journal | vauthors = Iliou T, Casta P, Lequeux J, Pochard L, Frauger E, Spadari M, Micallef J | title = Venlafaxine Abuse in a Patient With a History of Methylphenidate Abuse: A Case Report | journal = Journal of Clinical Psychopharmacology | volume = 39 | issue = 2 | pages = 172–174 | date = 2019 | pmid = 30811375 | doi = 10.1097/JCP.0000000000001011 | s2cid = 73496502 }}

Image:EffexorXR 75and150mg.png

Image:Venlafaxin Krka.jpg

Venlafaxine was originally marketed as Effexor in most of the world; generic venlafaxine has been available since around 2008 and extended-release venlafaxine has been available since around 2010.{{cite news| vauthors = Staton T |title=Drugstores accuse Pfizer, Teva of blocking Effexor generics|url=http://www.fiercepharma.com/sales-and-marketing/drugstores-accuse-pfizer-teva-of-blocking-effexor-generics|work=FiercePharma|date=13 June 2012|access-date=22 June 2017|archive-date=26 November 2020|archive-url=https://web.archive.org/web/20201126124935/https://www.fiercepharma.com/sales-and-marketing/drugstores-accuse-pfizer-teva-of-blocking-effexor-generics|url-status=live}}

Venlafaxine is sold under many brand names worldwide.{{cite web|url=https://www.drugs.com/international/venlafaxine.html|title=Venlafaxine (International)|date=January 2020|website=Drugs.com|access-date=24 January 2020|archive-date=6 September 2020|archive-url=https://web.archive.org/web/20200906074924/https://www.drugs.com/international/venlafaxine.html|url-status=live}} In some countries, Effexor is marketed by Viatris after Upjohn was spun off from Pfizer.{{cite press release | title=Pfizer Completes Transaction to Combine Its Upjohn Business with Mylan | publisher=Pfizer | via=Business Wire | date=16 November 2020 | url=https://www.businesswire.com/news/home/20201116005378/en/ | access-date=17 June 2024}}{{cite web | title=Brands | website=Viatris | date=16 November 2020 | url=https://www.viatris.com/en/products/brands | access-date=17 June 2024}}

Veterinary overdose in dogs is very well treated by Cyproheptadine HCl.{{cite book | edition=2 | year=2012 | publisher=Academic Press | publication-place=Amsterdam Boston | veditors = Gupta RC | title=Veterinary Toxicology : Basic and Clinical Principles | isbn=978-0-12-385926-6 | oclc=794491298 | pages=xii+1438}}{{rp|page=1371}}

Venlafaxine is highly toxic to Bacillariophyta and Chlorophyta phytoplankton.{{cite journal | vauthors = Chia MA, Lorenzi AS, Ameh I, Dauda S, Cordeiro-Araújo MK, Agee JT, Okpanachi IY, Adesalu AT | title = Susceptibility of phytoplankton to the increasing presence of active pharmaceutical ingredients (APIs) in the aquatic environment: A review | journal = Aquatic Toxicology | volume = 234 | pages = 105809 | date = May 2021 | pmid = 33780670 | doi = 10.1016/j.aquatox.2021.105809 | publisher = Elsevier | bibcode = 2021AqTox.23405809C | s2cid = 232419482 }} Cats are drawn to the smell of venlafaxine and tend to ingest the pills, which is highly toxic to them.{{cite web |title=The Top 5 Cat Toxins |url=https://www.pethealthnetwork.com/cat-health/cat-toxins-poisons/top-5-cat-toxins |access-date=3 May 2023 |website=Pet Health Network |language=en}}

{{Reflist}}

{{refbegin}}

• {{cite book | title=Medical Genetics Summaries | chapter=Venlafaxine Therapy and CYP2D6 Genotype | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK305561/ | veditors=Pratt VM, McLeod HL, Rubinstein WS, Scott SA, Dean LC, Kattman BL, Malheiro AJ | display-editors=3 | publisher=National Center for Biotechnology Information (NCBI) | date=July 2015 | pmid=28520361 | vauthors=Dean L | url=https://www.ncbi.nlm.nih.gov/books/NBK61999/ }}

{{refend}}

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