Venlafaxine

{{Short description|SNRI antidepressant}} {{Use dmy dates|date=January 2024}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | verifiedrevid = 459442662 | image = Venlafaxine flat.svg | image_class = skin-invert-image | width = 200px | chirality = Racemic mixture | alt = | caption =

| alt2 =  | class = Serotonin–norepinephrine reuptake inhibitor | pronounce = {{IPAc-en|ˌ|v|ɛ|n|l|ə|ˈ|f|æ|k|s|iː|n}} {{respell|ven|lə|FAK|seen}} | tradename = Effexor, others<ref name=brands /> | Drugs.com = {{drugs.com|monograph|Venlafaxine_Hydrochloride}} | MedlinePlus = a694020 | DailyMedID = Venlafaxine | pregnancy_AU = B2 | pregnancy_AU_comment = <ref name=TGA /> | pregnancy_category = | routes_of_administration = Oral | ATC_prefix = N06 | ATC_suffix = AX16 | ATC_supplemental =  | legal_AU = S4 | legal_AU_comment = <ref name=TGA /> | legal_BR = C1 | legal_BR_comment = <ref>{{cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=31 March 2023 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=3 August 2023 |access-date=16 August 2023 |publisher=Diário Oficial da União |language=pt-BR |publication-date=4 April 2023}}</ref> | legal_CA = Rx-only | legal_CA_comment = | legal_DE =  | legal_DE_comment = | legal_NZ =  | legal_NZ_comment = | legal_UK = POM | legal_UK_comment = <ref>{{cite web | title=Efexor XL 75 mg hard prolonged release capsules - Summary of Product Characteristics (SmPC) | website=(emc) | date=16 March 2020 | url=https://www.medicines.org.uk/emc/product/5474/smpc | access-date=15 April 2020 | archive-date=7 October 2020 | archive-url=https://web.archive.org/web/20201007180409/https://www.medicines.org.uk/emc/product/5474/smpc | url-status=live }}</ref> | legal_US = Rx-only | legal_US_comment = <ref name="Effexor FDA label">{{cite web | title=Effexor XR- venlafaxine hydrochloride capsule, extended release | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=53c3e7ac-1852-4d70-d2b6-4fca819acf26 | access-date=11 May 2021 | archive-date=12 May 2021 | archive-url=https://web.archive.org/web/20210512072156/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=53c3e7ac-1852-4d70-d2b6-4fca819acf26 | url-status=live }}</ref><ref name="Venbysi XR FDA label">{{cite web | title=Venlafaxine tablet, extended release | website=DailyMed | date=30 June 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e81a2daf-b8b2-7c05-b532-bc775700b100 | access-date=7 January 2023}}</ref> | legal_EU = Rx-only | legal_EU_comment = <ref>{{cite web | date=12 March 2008 | title=Opinion following an Article 30 referral for Efexor and associated names International Non-Proprietary Name (INN): venlafaxine: Background information | publisher=European Medicines Agency | url=https://www.ema.europa.eu/en/documents/referral/efexor-article-30-referral-annex-i-ii-iii_en.pdf}}</ref> | legal_UN =  | legal_UN_comment = | legal_status =

| bioavailability = 42±15%<ref name=TGA/> | protein_bound = 27±2% (parent compound), 30±12% (active metabolite, desvenlafaxine)<ref name="Effexor FDA label" /> | metabolism = Extensively metabolised by the liver,<ref name=TGA/><ref name="Effexor FDA label" /> primarily via CYP2D6<ref>{{cite book | vauthors = Dean L |title=Venlafaxine Therapy and CYP2D6 Genotype |url=https://www.ncbi.nlm.nih.gov/books/NBK305561/#:~:text=Venlafaxine%20is%20metabolized%20into%20its,reduced%20or%20absent%20CYP2D6%20activity. |date=2015 |publisher=National Center for Biotechnology Information (US) | pmid=28520361 |access-date=28 December 2018 |archive-date=29 November 2017 |archive-url=https://web.archive.org/web/20171129181900/https://www.ncbi.nlm.nih.gov/books/NBK305561/#:~:text=Venlafaxine%20is%20metabolized%20into%20its,reduced%20or%20absent%20CYP2D6%20activity. |url-status=live | veditors = Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kane MS, Kattman BL, Malheiro AJ }}</ref> | metabolites = O-desmethylvenlafaxine (ODV), see desvenlafaxine | elimination_half-life = 5±2 h (parent compound for immediate release preparations), 15±6 h (parent compound for extended-release preparations), 11±2 h (active metabolite)<ref name=TGA/><ref name="Effexor FDA label" /> | excretion = Kidney (87%; 5% as unchanged drug; 29% as desvenlafaxine and 53% as other metabolites)<ref name=TGA/><ref name="Effexor FDA label" />

| index2_label = as HCl | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 93413-69-5 | CAS_number2 = 99300-78-4 | CAS_supplemental = | PubChem = 5656 | PubChem2 = 62923 | IUPHAR_ligand = | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00285 | DrugBank2 = DBSALT000186 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 5454 | ChemSpiderID2 = 56641 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = GRZ5RCB1QG | UNII2 = 7D7RX5A8MO | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D08670 | KEGG2 = D00821 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 9943 | ChEBI2 = 9944 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 637 | ChEMBL2 = 1201066 | NIAID_ChemDB = | PDB_ligand = | synonyms =  | IUPAC_name = (''RS'')-1-[2-dimethylamino-1-(4-methoxyphenyl)-ethyl]cyclohexanol | C = 17 | H = 27 | N = 1 | O = 2 | SMILES = OC2(C(c1ccc(OC)cc1)CN(C)C)CCCCC2 | 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 }}

'''Venlafaxine''', sold under the brand name '''Effexor''' among others, is an antidepressant medication of the serotonin–norepinephrine reuptake inhibitor (SNRI) class.<ref name="Effexor FDA label" /><ref name=AHFS2018/> It is used to treat major depressive disorder, generalized anxiety disorder, panic disorder, and social anxiety disorder.<ref name=AHFS2018/> Studies have shown that venlafaxine improves post-traumatic stress disorder (PTSD) as a recommended first-line treatment.<ref>{{cite report |url=https://effectivehealthcare.ahrq.gov/topics/ptsd-adult-treatment-update/research-2018 |title=Psychological and Pharmacological Treatments for Adults With Posttraumatic Stress Disorder: A Systematic Review Update |vauthors=Forman-Hoffman V, Middleton JC, Feltner C, Gaynes BN, Weber RP, Bann C, Viswanathan M, Lohr KN, Baker C, Green J |date=17 May 2018 |publisher=Agency for Healthcare Research and Quality (AHRQ) |doi=10.23970/ahrqepccer207 |pmid=30204376 |doi-access=free |access-date=29 July 2023 |archive-date=10 July 2018 |archive-url=https://web.archive.org/web/20180710011511/https://effectivehealthcare.ahrq.gov/topics/ptsd-adult-treatment-update/research-2018 }}</ref> It may also be used for chronic neuropathic pain.<ref>{{cite web |title=Antidepressants: Another weapon against chronic pain |url=https://www.mayoclinic.org/pain-medications/art-20045647 |website=Mayo Clinic |access-date=25 January 2020 |archive-date=26 October 2021 |archive-url=https://web.archive.org/web/20211026225927/https://www.mayoclinic.org/pain-medications/art-20045647 |url-status=live }}</ref> It is taken orally (swallowed by mouth).<ref name=AHFS2018/> It is also available as the salt venlafaxine besylate (venlafaxine benzenesulfonate monohydrate) in an extended-release formulation (Venbysi XR).<ref name="Venbysi XR FDA label" />

Common side effects include loss of appetite, constipation, dry mouth, dizziness, sweating, insomnia, drowsiness and sexual problems.<ref name="AHFS2018" /> In some patients, sexual dysfunction may persist even after the drug is discontinued, a condition known as post-SSRI sexual dysfunction.<ref name="Healy2022" /> Severe side effects include an increased risk of suicide, mania, and serotonin syndrome.<ref name=AHFS2018/> Antidepressant withdrawal syndrome may occur if stopped.<ref name=AHFS2018/> A meta-analysis of randomized trials in depression found an increased rate of serious adverse events, particularly sexual dysfunction and anorexia, and several non-serious adverse effects, including nervousness, asthenia, and tremor.<ref>{{cite journal | vauthors = Kamp CB, Petersen JJ, Faltermeier P, Juul S, Siddiqui F, Moncrieff J, Horowitz MA, Hengartner MP, Kirsch I, Gluud C, Jakobsen JC | title = The risks of adverse events with venlafaxine for adults with major depressive disorder: a systematic review of randomised clinical trials with meta-analysis and Trial Sequential Analysis | journal = Epidemiology and Psychiatric Sciences | volume = 33 | article-number = e51 | date = October 2024 | pmid = 39440379 | pmc = 11561525 | doi = 10.1017/S2045796024000520 | doi-access = free }}</ref> There are concerns that use during the later part of pregnancy can harm the baby.<ref name=AHFS2018/> Venlafaxine's mechanism of action is not entirely clear, but it seems to be related to the potentiation of the activity of some neurotransmitters in the brain.<ref name=AHFS2018/>

Venlafaxine was approved for medical use in the United States in 1993.<ref name=AHFS2018>{{cite web |title=Venlafaxine Hydrochloride Monograph for Professionals |url=https://www.drugs.com/monograph/venlafaxine-hydrochloride.html |website=Drugs.com |publisher=AHFS |access-date=24 December 2018 |archive-date=27 November 2020 |archive-url=https://web.archive.org/web/20201127001402/https://www.drugs.com/monograph/venlafaxine-hydrochloride.html |url-status=live }}</ref> It is available as a generic medication.<ref name=AHFS2018/> In 2023, it was the 51st most commonly prescribed medication in the United States, with more than 13 million prescriptions.<ref name="Top300Drugs">{{cite web | title=Top 300 of 2023 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=12 August 2025 | archive-date=12 August 2025 | archive-url=https://web.archive.org/web/20250812130026/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Venlafaxine Drug Usage Statistics, United States, 2014 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Venlafaxine | access-date = 18 August 2025 }}</ref>

== Medical uses == Venlafaxine is used primarily for the treatment of depression, general anxiety disorder, social phobia, panic disorder, and vasomotor symptoms.<ref name=AHFS>{{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 }}</ref>

Concerns that noradrenergic reuptake might precipitate anxiety have not been borne out in randomized trials: a 2016 systematic review of 52 double-blind, placebo-controlled studies (mostly with venlafaxine or duloxetine) found clinically significant improvements in anxiety symptoms and no signal for treatment-emergent anxiety attributable to SNRIs.<ref>{{cite journal | vauthors = Montoya A, Bruins R, Katzman MA, Blier P | title = The noradrenergic paradox: implications in the management of depression and anxiety | journal = Neuropsychiatric Disease and Treatment | volume = 12 | pages = 541–557 | date = 2016 | pmid = 27042068 | pmc = 4780187 | doi = 10.2147/NDT.S91311 | doi-access = free }}</ref>

Venlafaxine has been used off label for the treatment of diabetic neuropathy<ref>{{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 }}</ref> and migraine prevention.<ref>{{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 }}</ref> It may work on pain via effects on the opioid receptor.<ref name="Academic Press">{{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 }}</ref> 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.<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 |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 }}</ref><ref>{{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 }}</ref>

Due to its action on both the serotonergic 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 |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 }}</ref> Some open-label and three double-blind studies have suggested the efficacy of venlafaxine in the treatment of attention deficit-hyperactivity disorder (ADHD).<ref>{{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 | url = https://figshare.com/articles/journal_contribution/20969569 }}</ref> Clinical trials have found possible efficacy in those with post-traumatic stress disorder (PTSD).<ref>{{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 }}</ref> Case reports, open trials and blinded comparisons with established medications have suggested the efficacy of venlafaxine in the treatment of obsessive–compulsive disorder.<ref>{{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 }}</ref>

=== Depression === 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.<ref name=pmid19185342>{{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 }}</ref><ref>{{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 }}</ref>

Open-label evidence also suggests potential benefit in treatment-resistant cases: in a multicenter Canadian study of adults with inadequate response to prior antidepressants (''n''=159), 58% achieved response and 28% remission after 8 weeks of venlafaxine (mean 260 mg/day); tolerability was generally acceptable.<ref>{{cite journal | vauthors = de Montigny C, Silverstone PH, Debonnel G, Blier P, Bakish D | title = Venlafaxine in treatment-resistant major depression: a Canadian multicenter, open-label trial | journal = Journal of Clinical Psychopharmacology | volume = 19 | issue = 5 | pages = 401–406 | date = 1999 | pmid = 10505581 | doi = 10.1097/00004714-199910000-00003 }}</ref>

Venlafaxine was similar in efficacy to the atypical antidepressant bupropion; however, the remission rate was lower for venlafaxine.<ref name="pmid16974189">{{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 }}</ref> 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.<ref name="pmid18408525">{{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 }}</ref>

Studies have not established its efficacy for use in pediatric populations.<ref>{{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 }}</ref> In children and adolescents with depression, venlafaxine increases the risk of suicidal thoughts or attempts.<ref name=":0">{{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 }}</ref><ref name=":1">{{cite journal |author6-link=John R. Weisz | 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 }}</ref><ref name=":2">{{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 | article-number = CD013674 | date = May 2021 | pmid = 34029378 | pmc = 8143444 | doi = 10.1002/14651858.CD013674.pub2 | collaboration = Cochrane Common Mental Disorders Group }}</ref><ref name=":3">{{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 }}</ref><ref name=":4">{{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 | article-number = 717 | date = 2 September 2020 | pmid = 32982805 | pmc = 7493620 | doi = 10.3389/fpsyt.2020.00717 | doi-access = free }}</ref><ref name=":5">{{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 }}</ref>

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.<ref name="Rudolph1998">{{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 }}</ref>

Studies have shown that the extended-release is superior to the immediate-release form of venlafaxine.<ref name="Thase Asami Wajsbrot Dorries 2017 pp. 317–326"/>

A 2017 meta-analysis has shown that the efficacy of venlafaxine is not correlated with baseline severity of depression.<ref name="Thase Asami Wajsbrot Dorries 2017 pp. 317–326"/> 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.

== Contraindications == 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.<ref name=TGA>{{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 }}</ref><ref name="Effexor FDA label" /><ref name=Maudsley>{{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}}</ref> Venlafaxine might interact with tramadol or other opioids, as well as trazodone and buspirone, so caution is needed while mixing multiple serotonergic agents together.<ref>{{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 }}</ref>

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

Venlafaxine can increase eye pressure, so those with glaucoma may require more frequent eye checks.<ref name="Effexor FDA label" />

A 2017 meta-analysis estimated venlafaxine discontinuation rate due to adverse effects to be 9.4%.<ref name="Thase Asami Wajsbrot Dorries 2017 pp. 317–326">{{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 }}</ref>

=== Suicide === {{cs1 config|name-list-style=vanc|display-authors=6}} 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.<ref>{{cite journal | vauthors = Spielmans GI, Spence-Sing T, Parry P | date = 2020 | title = Duty to Warn: Antidepressant Black Box Suicidality Warning Is Empirically Justified | journal = Frontiers in Psychiatry | volume = 11 | article-number = 18 | doi = 10.3389/fpsyt.2020.00018 | pmc = 7031767 | pmid = 32116839 | doi-access = free }}</ref>

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.<ref>{{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 }}</ref>

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.<ref name="pmid17146010">{{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 }}</ref>

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.<ref name="pmid17164297">{{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 | page = 242 | date = February 2007 | pmid = 17164297 | pmc = 1790752 | doi = 10.1136/bmj.39041.445104.BE }}</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=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 }}</ref>

Venlafaxine is contraindicated in children, adolescents, and young adults. In children and adolescents with depression, venlafaxine increases the risk of suicidal thoughts or attempts.<ref name=":0" /><ref name=":1" /><ref name=":2" /><ref name=":3" /><ref name=":4" /><ref name=":5" />

=== Serotonin syndrome === The development of a potentially life-threatening serotonin syndrome (also classified as "serotonin toxicity")<ref name="Dunkley">{{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 }}</ref> 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.<ref name="Kolecki">{{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 }}</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 mg per day).<ref>{{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 }}</ref> A case of a patient with serotonin syndrome induced by low-dose venlafaxine (37.5 mg per day) has also been reported.<ref name="pmid12549949">{{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 }}</ref>

=== Miscarriage === 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 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 }}</ref><ref>{{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 }}</ref> 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.<ref name="pmid23281074">{{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 }}</ref> Prospective studies have not shown any statistically significant congenital malformations.<ref>{{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 }}</ref> There have, however, been some reports of self-limiting effects on newborn infants.<ref>{{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 }}</ref> As with other serotonin reuptake inhibitors (SRIs), these effects are generally short-lived, lasting only 3 to 5 days,<ref>{{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 }}</ref> and rarely resulting in severe complications.<ref name="pmid15900008">{{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 }}</ref> According to the NHS, there is "no good evidence that taking venlafaxine in early pregnancy will affect your baby’s development", while also stating that a rare side effect is increased bleeding during childbirth.<ref>{{cite web|title=Pregnancy, breastfeeding and fertility while taking venlafaxine|website=NHS|url=https://www.nhs.uk/medicines/venlafaxine/pregnancy-breastfeeding-and-fertility-while-taking-venlafaxine|access-date=February 1, 2026}}</ref>

=== Bipolar disorder === {{Main|Selective serotonin reuptake inhibitor#Bipolar switch}}

According to the ISBD Task Force report on antidepressant use in bipolar disorder,<ref>{{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 }}</ref> 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."

=== Liver injury === 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.<ref name="Stadlmann Portmann Tschopp Terracciano 2012 pp. 1724–1728">{{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) }}</ref>

=== Overdose === 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.<ref>{{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}}</ref> 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=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 }}</ref> 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.<ref name=pmid19185342 /><ref>{{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 }}</ref>

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.<ref>{{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 }}</ref>

=== Withdrawal syndrome === {{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"<ref>{{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 | article-number = 18m02311 | date = December 2018 | pmid = 30605268 | doi = 10.4088/PCC.18m02311 | s2cid = 58577252 }}</ref><ref>{{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 }}</ref>), and sleep disturbance.<ref name="pmid22295261">{{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 }}</ref> Venlafaxine has a higher rate of moderate to severe withdrawal symptoms relative to other antidepressants (similar to the SSRI paroxetine).<ref name="pmid21286371">{{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 }}</ref>

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.<ref name="pmid11347722">{{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 }}</ref> 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.<ref name="PMC1681629">{{cite journal | vauthors = Campagne DM | title = Venlafaxine and serious withdrawal symptoms: warning to drivers | journal = MedGenMed | volume = 7 | issue = 3 | page = 22 | date = July 2005 | pmid = 16369248 | pmc = 1681629 }}</ref>

=== Post-SSRI sexual dysfunction === {{Main|Post-SSRI sexual dysfunction}}

Post-SSRI sexual dysfunction (PSSD) is an iatrogenic condition in which sexual side effects persist after discontinuation of serotonin reuptake inhibiting antidepressants, including venlafaxine.<ref name="Bala2018">{{cite journal | vauthors = Bala A, Tue Nguyen HM, Hellstrom WJ | title = Post-SSRI Sexual Dysfunction: A Literature Review | journal = Sexual Medicine Reviews | volume = 6 | issue = 1 | pages = 29–34 | date = January 2018 | pmid = 28778697 | doi = 10.1016/j.sxmr.2017.07.002 }}</ref><ref name="Healy2022">{{cite journal | vauthors = Healy D, Bahrick A, Bak M, Barbato A, Calabro RS, Chubak BM, Cosci F, Csoka AB, D'Avanzo B, Diviccaro S, Giatti S, Goldstein I, Graf H, Hellstrom WJ, Irwig MS, Jannini EA, Janssen PK, Khera M, Kumar MT, Le Noury J, Lew-Starowicz M, Linden DE, Lüning C, Mangin D, Melcangi RC, Muquebil Ali Al Shaban Rodríguez OW, Panicker JN, Patacchini A, Pearlman AM, Pukall CF, Raj S, Reisman Y, Rubin RS, Schreiber R, Shipko S, Vašečková B, Waraich A | title = Diagnostic criteria for enduring sexual dysfunction after treatment with antidepressants, finasteride and isotretinoin | journal = International Journal of Risk & Safety in Medicine | volume = 33 | issue = 1 | pages = 65–76 | date = 2022 | pmid = 34719438 | pmc = 8925105 | doi = 10.3233/JRS-210023 }}</ref> Characteristic symptoms include genital numbness, pleasureless or weak orgasm, loss of libido, and erectile dysfunction; non-sexual symptoms such as emotional blunting and cognitive impairment may also occur.<ref name="Healy2022" /> The condition can arise after even brief exposure to a serotonin reuptake inhibitor and may persist indefinitely; there is currently no established treatment.<ref name="Healy2018">{{cite journal | vauthors = Healy D, Le Noury J, Mangin D | title = Enduring sexual dysfunction after treatment with antidepressants, 5α-reductase inhibitors and isotretinoin: 300 cases | journal = International Journal of Risk & Safety in Medicine | volume = 29 | issue = 3–4 | pages = 125–134 | date = 2018 | pmid = 29733030 | doi = 10.3233/JRS-180744 | pmc = 6004900 }}</ref> A case study published in 2023 specifically documented PSSD symptoms—including low libido, delayed ejaculation, and erectile dysfunction—developing after discontinuation of venlafaxine, with 5-HT1A receptor downregulation proposed as a possible mechanism.<ref name="Klaas2023">{{cite journal | vauthors = Klaas SJ, Pouwels S, Hajji N | title = The pathophysiology of Post SSRI Sexual Dysfunction – Lessons from a case study | journal = Biomedicine & Pharmacotherapy | volume = 158 | article-number = 114165 | date = February 2023 | pmid = 36898260 | doi = 10.1016/j.biopha.2022.114165 }}</ref>

A 2023 retrospective cohort study of over 12,000 males estimated the risk of irreversible sexual dysfunction (as measured by persistent need for phosphodiesterase inhibitors after antidepressant cessation) at approximately 0.46% of patients treated with serotonergic antidepressants, including SNRIs.<ref name="BenSheetrit2023">{{cite journal | vauthors = Ben-Sheetrit J, Aizenberg D, Csoka AB, Weizman A, Hermesh H | title = Estimating the risk of irreversible post-SSRI sexual dysfunction (PSSD) due to serotonergic antidepressants | journal = Annals of General Psychiatry | volume = 22 | issue = 1 | article-number = 15 | date = April 2023 | pmid = 37076856 | pmc = 10122283 | doi = 10.1186/s12991-023-00447-0 | doi-access = free }}</ref> The DSM-5 noted in 2013 that serotonin reuptake inhibitor–induced sexual dysfunction may persist after the agent is discontinued.<ref name="Healy2024barriers">{{cite journal | vauthors = Healy D, Mangin D | title = Post-SSRI sexual dysfunction: barriers to quantifying incidence and prevalence | journal = Epidemiology and Psychiatric Sciences | volume = 33 | article-number = e52 | date = 2024 | issue = 5 | pmid = 39363727 | pmc = 11450419 | doi = 10.1017/S2045796024000532 | doi-access = free }}</ref>

In 2019, the European Medicines Agency's Pharmacovigilance Risk Assessment Committee recommended that product labels for all SSRIs and SNRIs, including venlafaxine, be updated to warn that sexual dysfunction may be long-lasting after treatment is stopped.<ref name="PRAC2019">{{cite web | title = PRAC recommendations on signals adopted at the 13–16 May 2019 PRAC meeting | publisher = European Medicines Agency | date = 11 June 2019 | url = https://www.ema.europa.eu/en/documents/prac-recommendation/prac-recommendations-signals-adopted-13-16-may-2019-prac-meeting_en.pdf | access-date = 8 April 2026 }}</ref> Health Canada followed with similar label updates in 2021, and Australia's Therapeutic Goods Administration aligned all SSRI and SNRI product information in 2024, noting that venlafaxine already carried a warning about persistent sexual dysfunction.<ref name="TGA2024">{{cite web | title = Updated warnings about persistent sexual dysfunction for antidepressants | publisher = Therapeutic Goods Administration | date = 23 May 2024 | url = https://www.tga.gov.au/news/safety-updates/updated-warnings-about-persistent-sexual-dysfunction-antidepressants | access-date = 8 April 2026 }}</ref>

=== Other === In rare cases, drug-induced akathisia can occur after use in some people.<ref>{{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 }}</ref>

Venlafaxine should be used with caution in hypertensive patients. Venlafaxine must be discontinued if significant hypertension persists.<ref>{{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 }}</ref><ref>{{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 }}</ref><ref>{{cite journal | vauthors = Edvardsson B | title = Venlafaxine as single therapy associated with hypertensive encephalopathy | journal = SpringerPlus | volume = 4 | issue = 1 | article-number = 97 | date = 26 February 2015 | pmid = 25763307 | pmc = 4348355 | doi = 10.1186/s40064-015-0883-0 | doi-access = free }}</ref> It can also have undesirable cardiovascular effects.<ref>{{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 }}</ref>

== Pharmacology == {| class="wikitable" style = "float: right; margin-left:15px; text-align:center" !Transporter !''K''i [nM]<ref name="Bymaster">{{cite journal | vauthors = Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, Shaw JL, Thompson L, Nelson DL, Hemrick-Luecke SK, Wong DT | 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 = 871–880 | date = December 2001 | pmid = 11750180 | doi = 10.1016/S0893-133X(01)00298-6 | doi-access = free }}</ref><ref name="KiDB">{{cite web |date= |title=Ki Database > Search > Venlafaxine |url=https://pdsp.unc.edu/kidb2/kidb/web/kis-results/index?KisResultsSearch%5Binput_receptors%5D=&KisResultsSearch%5Binput_sources%5D=&KisResultsSearch%5Binput_species%5D=&KisResultsSearch%5Binput_hot_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D%5B%5D=12948&KisResultsSearch%5Binput_citations%5D=&KisResultsSearch%5BsearchType%5D=&KisResultsSearch%5Bki_val_from%5D=&KisResultsSearch%5Bki_val_to%5D=&KisResultsSearch%5Bcustom_ki_val%5D=&KisResultsSearch%5Binput_receptors%5D=&KisResultsSearch%5Binput_sources%5D=&KisResultsSearch%5Binput_species%5D=&KisResultsSearch%5Binput_hot_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D%5B%5D=14677&KisResultsSearch%5Binput_citations%5D=&KisResultsSearch%5BsearchType%5D=&KisResultsSearch%5Bki_val_from%5D=&KisResultsSearch%5Bki_val_to%5D=&KisResultsSearch%5Bcustom_ki_val%5D=&KisResultsSearch%5Binput_receptors%5D=&KisResultsSearch%5Binput_sources%5D=&KisResultsSearch%5Binput_species%5D=&KisResultsSearch%5Binput_hot_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D%5B%5D=14696&KisResultsSearch%5Binput_test_ligands%5D%5B%5D=14678&KisResultsSearch%5Binput_test_ligands%5D%5B%5D=15573&KisResultsSearch%5Binput_citations%5D=&KisResultsSearch%5BsearchType%5D=&KisResultsSearch%5Bki_val_from%5D=&KisResultsSearch%5Bki_val_to%5D=&KisResultsSearch%5Bcustom_ki_val%5D=&KisResultsSearch%5Binput_receptors%5D=&KisResultsSearch%5Binput_sources%5D=&KisResultsSearch%5Binput_species%5D=&KisResultsSearch%5Binput_hot_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D%5B%5D=1947&KisResultsSearch%5Binput_citations%5D=&KisResultsSearch%5BsearchType%5D=&KisResultsSearch%5Bki_val_from%5D=&KisResultsSearch%5Bki_val_to%5D=&KisResultsSearch%5Bcustom_ki_val%5D= |website= |location= |publisher= |access-date=2025-08-13}}</ref> !IC50 [nM]<ref>{{cite journal | vauthors = Sabatucci JP, Mahaney PE, Leiter J, Johnston G, Burroughs K, Cosmi S, Zhang Y, Ho D, Deecher DC, Trybulski E | title = Heterocyclic cycloalkanol ethylamines as norepinephrine reuptake inhibitors | journal = Bioorganic & Medicinal Chemistry Letters | volume = 20 | issue = 9 | pages = 2809–2812 | date = May 2010 | pmid = 20378347 | doi = 10.1016/j.bmcl.2010.03.059 }}</ref> |- |SERT |82 |27 |- |NET |2480 |535 |- |DAT |7647 |{{abbr|ND|No data}} |} {| class="wikitable" style = "float: right; margin-left:15px; text-align:center" |- ! Receptor !! ''K''i [nM]<ref name="Bymaster"/><ref>{{cite journal | vauthors = Roth BL, Kroeze WK | title = Screening the receptorome yields validated molecular targets for drug discovery | journal = Current Pharmaceutical Design | volume = 12 | issue = 14 | pages = 1785–1795 | date = 2006 | pmid = 16712488 | doi = 10.2174/138161206776873680 | author1-link = Bryan Roth }}</ref><ref name="KiDB" /> ! Species |- | 5-HT2A || 2230 || Human |- | 5-HT2C || 2004 || Human |- | 5-HT6 || 2792 || Human |- | α1A || >1000 || Human |}

=== Pharmacodynamics === 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).<ref>{{ClinicalTrialsGov|NCT00001483|Acute Effectiveness of Additional Drugs to the Standard Treatment of Depression}}</ref><ref>{{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 }}</ref> It is described as 'synthetic phenethylamine bicyclic derivative with antidepressant activity'.<ref>{{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 }}</ref><ref>{{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 }}</ref> 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.<ref name="CNSDrugs2001-Wellington">{{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 }}</ref> The frontal cortex largely lacks dopamine transporters and instead relies on norepinephrine transporters for dopamine reuptake; therefore venlafaxine can increase dopamine neurotransmission in this part of the brain.<ref>{{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 }}</ref><ref>{{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}}</ref>

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.<ref name="Aldosary2022">{{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 }}</ref>

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.<ref>{{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 }}</ref><ref name="Academic Press"/>

===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, now marketed as a separate medication named Pristiq<ref>{{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 }}</ref>), 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.<ref name="JCPT JClinPharmTher2006-shams">{{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 }}</ref><ref>{{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 }}</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="Effexor FDA label" /> 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.<ref name="ANZ JPsych1998-parker">{{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 }}</ref>

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.<ref name="snpedia '583">{{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 }}</ref>{{unreliable source?|date=December 2013}} A 2007 study<ref name="Neuron: ABCB1">{{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 }}</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 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}}

==Chemistry== 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.<ref name="QJM2003-Whyte">{{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 }}</ref>

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.<ref>{{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 }}</ref>

=== Interactions === Venlafaxine should be taken with caution when using St John's wort.<ref>{{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}}</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 | 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 }}</ref>

==Society and culture== === Recreational use === Venlafaxine can be abused as a recreational drug, with damages that can manifest within a month.<ref name="pmid30811375">{{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 }}</ref>{{Better source needed|reason=This is a case report of a single patient. A secondary source is needed per WP:MEDRS.|date=February 2026}}

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.<ref>{{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}}</ref>

Venlafaxine is sold under many brand names worldwide.<ref name="brands">{{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}}</ref> In some countries, Effexor is marketed by Viatris after Upjohn was spun off from Pfizer.<ref>{{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}}</ref><ref>{{cite web | title=Brands | website=Viatris | date=16 November 2020 | url=https://www.viatris.com/en/products/brands | access-date=17 June 2024}}</ref>{{Primary source inline|date=February 2026}}

== Veterinary uses == Veterinary overdose in dogs is very well treated by cyproheptadine HCl.<ref name="Gupta-2012">{{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}}</ref>{{rp|page=1371}}

Venlafaxine is highly toxic to Bacillariophyta and Chlorophyta phytoplankton.<ref name="Runoff">{{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 | article-number = 105809 | date = May 2021 | pmid = 33780670 | doi = 10.1016/j.aquatox.2021.105809 | publisher = Elsevier | bibcode = 2021AqTox.23405809C | s2cid = 232419482 }}</ref> Cats are drawn to the smell of venlafaxine and tend to ingest the pills, which are highly toxic to them.<ref>{{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}}</ref>

== References == {{Reflist}}

== Further reading == {{Commons}} {{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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