Fluvoxamine: Difference between revisions

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{{Short description|SSRI antidepressant drug}}
{{distinguish|Fluoxetine}}
{{Distinguish|Fluoxetine}}
{{Drugbox| verifiedrevid = 407829219
{{Use dmy dates|date=December 2023}}
|
{{cs1 config|name-list-style=vanc|display-authors=6}}
|IUPAC_name = (''E'')-5-methoxy-1-[4-(trifluoromethyl)phenyl]pentan-1-one ''O''-2-aminoethyl oxime
{{Infobox drug
| image = Fluvoxamine structure.svg
| Verifiedfields = changed
| width = 180px
| Watchedfields = changed
| CASNo_Ref = {{cascite|correct|CAS}}
| verifiedrevid = 443824781
| image = Fluvoxamine.svg
| width =
| alt =
| caption =
| image2 = Fluvoxamine 3D 4ENH.png
| width2 =
| alt2 =

<!-- Clinical data -->
| pronounce =
| tradename = Luvox, others
| Drugs.com = {{drugs.com|monograph|fluvoxamine-maleate}}
| MedlinePlus = a695004
| DailyMedID = Fluvoxamine
| pregnancy_AU = C
| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{drugs.com|pregnancy|fluvoxamine}}</ref>
| pregnancy_category =
| routes_of_administration = [[Oral administration|By mouth]]
| class = [[Selective serotonin reuptake inhibitor]] (SSRI)
| ATC_prefix = N06
| ATC_suffix = AB08
| ATC_supplemental =

<!-- Legal status -->
| legal_AU = S4
| legal_AU_comment =
| 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 = <!--Anlage I, II, III or Unscheduled-->
| legal_DE_comment =
| legal_NZ = <!--Class A, B, C-->
| legal_NZ_comment =
| legal_UK = POM
| legal_UK_comment =
| legal_US = Rx-only
| legal_US_comment =
| legal_UN = <!--N I, II, III, IV / P I, II, III, IV-->
| legal_UN_comment =
| legal_status = <!--For countries not listed above-->

<!-- Pharmacokinetic data -->
| bioavailability = 53% (90% confidence interval: 44–62%)<ref name = LUVOX/>
| protein_bound = 77–80%<ref name = LUVOX/><ref>{{cite journal | vauthors = van Harten J | title = Clinical pharmacokinetics of selective serotonin reuptake inhibitors | journal = Clinical Pharmacokinetics | volume = 24 | issue = 3 | pages = 203–220 | date = March 1993 | pmid = 8384945 | doi = 10.2165/00003088-199324030-00003 | s2cid = 84636672 }}</ref>
| metabolism = [[Liver]] (primarily O-[[demethylation]])<br />Major: [[CYP1A2]]<br />Minor: [[CYP3A4]]<br />Minor: [[CYP2C19]]<ref name = LUVOX/>
| metabolites =
| onset =
| elimination_half-life = 12–13 hours (single dose), 22 hours (repeated dosing)<ref name = LUVOX/>
| duration_of_action =
| excretion = [[Kidney]] (98%; 94% as metabolites, 4% as unchanged drug)<ref name = LUVOX/>

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 54739-18-3
| CAS_supplemental =
| PubChem = 5324346
| IUPHAR_ligand = 7189
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB00176
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4481878
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = O4L1XPO44W
| UNII = O4L1XPO44W
| KEGG_Ref = {{keggcite|correct|kegg}}
| InChI = 1/C15H21F3N2O2/c1-21-10-3-2-4-14(20-22-11-9-19)12-5-7-13(8-6-12)15(16,17)18/h5-8H,2-4,9-11,19H2,1H3/b20-14+
| KEGG = D07984
| smiles = FC(F)(F)c1ccc(\C(=N\OCCN)CCCCOC)cc1
| ChEBI_Ref = {{ebicite|correct|EBI}}
| InChIKey = CJOFXWAVKWHTFT-XSFVSMFZBL
| ChEBI = 5138
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 814
| ChEMBL = 814
| NIAID_ChemDB =
| PDB_ligand =
| synonyms =

<!-- Chemical and physical data -->
| IUPAC_name = 2-<nowiki/>{[(''E'')-<nowiki/>{5-Methoxy-1-[4-(trifluoromethyl)phenyl] pentylidene}amino]oxy}ethanamine<ref>{{cite web|title=Luvox|work=ChemSpider|publisher=Royal Society of Chemistry|access-date=21 October 2013|url=http://www.chemspider.com/Chemical-Structure.4481878|archive-url=https://web.archive.org/web/20131115055836/http://www.chemspider.com/Chemical-Structure.4481878|archive-date=15 November 2013|url-status=dead}}</ref>
| C=15 | H=21 | F=3 | N=2 | O=2
| SMILES = FC(F)(F)c1ccc(\C(=N\OCCN)CCCCOC)cc1
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C15H21F3N2O2/c1-21-10-3-2-4-14(20-22-11-9-19)12-5-7-13(8-6-12)15(16,17)18/h5-8H,2-4,9-11,19H2,1H3/b20-14+
| StdInChI = 1S/C15H21F3N2O2/c1-21-10-3-2-4-14(20-22-11-9-19)12-5-7-13(8-6-12)15(16,17)18/h5-8H,2-4,9-11,19H2,1H3/b20-14+
| StdInChI_comment =
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = CJOFXWAVKWHTFT-XSFVSMFZSA-N
| StdInChIKey = CJOFXWAVKWHTFT-XSFVSMFZSA-N
| density =
| CAS_number=54739-18-3
| density_notes =
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| melting_point =
| ChemSpiderID = 4481878
| melting_high =
| ATC_prefix=N06
| melting_notes =
| ATC_suffix=AB08
| boiling_point =
| ATC_supplemental=
| boiling_notes =
| ChEBI = 5138
| solubility =
| PubChem=5324346
| sol_units =
| DrugBank=APRD00425
| specific_rotation =
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D07984
| C=15 | H=21 | F=3 | N=2 | O=2
| molecular_weight = 318.335
| bioavailability= 77%
| metabolism = [[Hepatic]]
| elimination_half-life= 15.6 hours
| excretion = [[Renal]]
| pregnancy_category = C
| legal_US = Rx-only
| legal_AU = S4
| routes_of_administration= Oral
}}
}}


'''Fluvoxamine''', sold under the brand name '''Luvox''' among others, is an [[antidepressant]] of the [[selective serotonin reuptake inhibitor]] (SSRI) class.<ref>{{cite web | title=Fluvoxamine Maleate Information | website=U.S. [[Food and Drug Administration]] (FDA) | date=15 July 2015 | url=https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fluvoxamine-maleate-information | archive-url=https://web.archive.org/web/20191129061058/https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fluvoxamine-maleate-information | archive-date=29 November 2019 | url-status=live | access-date=28 November 2019}}</ref> It is primarily used to treat [[major depressive disorder]] and [[obsessive–compulsive disorder]] (OCD),<ref name="pmid20140100">{{cite journal | vauthors = McCain JA | title = Antidepressants and suicide in adolescents and adults: a public health experiment with unintended consequences? | journal = P & T | volume = 34 | issue = 7 | pages = 355–378 | date = July 2009 | pmid = 20140100 | pmc = 2799109 }}</ref> but is also used to treat [[anxiety disorder]]s<ref>{{cite journal | vauthors = | title = Fluvoxamine for the treatment of anxiety disorders in children and adolescents. The Research Unit on Pediatric Psychopharmacology Anxiety Study Group | journal = The New England Journal of Medicine | volume = 344 | issue = 17 | pages = 1279–1285 | date = April 2001 | pmid = 11323729 | doi = 10.1056/NEJM200104263441703 | doi-access = free }}</ref> such as [[panic disorder]], [[social anxiety disorder]], and [[post-traumatic stress disorder]].<ref>{{cite journal | vauthors = Figgitt DP, McClellan KJ | title = Fluvoxamine. An updated review of its use in the management of adults with anxiety disorders | journal = Drugs | volume = 60 | issue = 4 | pages = 925–954 | date = October 2000 | pmid = 11085201 | doi = 10.2165/00003495-200060040-00006 | s2cid = 265712201 }}</ref><ref>{{cite journal | vauthors = Irons J | title = Fluvoxamine in the treatment of anxiety disorders | journal = Neuropsychiatric Disease and Treatment | volume = 1 | issue = 4 | pages = 289–299 | date = December 2005 | pmid = 18568110 | pmc = 2424117 }}</ref><ref>{{cite journal | vauthors = Asnis GM, Hameedi FA, Goddard AW, Potkin SG, Black D, Jameel M, Desagani K, Woods SW | title = Fluvoxamine in the treatment of panic disorder: a multi-center, double-blind, placebo-controlled study in outpatients | journal = Psychiatry Research | volume = 103 | issue = 1 | pages = 1–14 | date = August 2001 | pmid = 11472786 | doi = 10.1016/S0165-1781(01)00265-7 | s2cid = 40412606 }}</ref>
'''Fluvoxamine''' (brand name '''Luvox''') is an [[antidepressant]] which functions as a [[selective serotonin reuptake inhibitor]] (SSRI). Fluvoxamine was first approved by the [[Food and Drug Administration (United States)|U.S. Food and Drug Administration]] (FDA) in 1993 for the treatment of [[obsessive compulsive disorder]] (OCD).<ref>
[http://www.thefreelibrary.com/FDA+ADVISORY+COMMITTEE+RECOMMENDS+LUVOX+(FLUVOXAMINE)+TABLETS+FOR...-a014258615 "FDA Advisory Committee Recommends Luvox (Fluvoxamine) Tablets for Obsessive Compulsive Disorder," PRNewswire, 10/18/93]</ref> Fluvoxamine CR (controlled release) is approved to treat [[social anxiety disorder]].<ref name="Stahl, S. Stahl's Essential Psychopharmacology 2009. pp.215">Stahl, S. Stahl's Essential Psychopharmacology: The Prescriber's Guide. Cambridge University Press. New York, NY. 2009. pp.215</ref> Fluvoxamine is also prescribed to treat [[major depressive disorder]] (MDD) and [[anxiety disorders]], such as [[generalized anxiety disorder]] (GAD), [[panic disorder]], and [[post-traumatic stress disorder]] (PTSD).<ref>{{cite journal | first = David P. Figgitt | last = Karen J. McClellan | date = Drugs October 2000 | title = Fluvoxamine An Updated Review of its Use in the Management of Adults with Anxiety Disorders | journal = Adis Drug Evaluation | volume = 60 | issue = 4 | pages = 925–954}}</ref>


Fluvoxamine's side-effect profile is very similar to other SSRIs: [[constipation]], [[gastrointestinal|gastrointestinal problems]], [[headache]], [[anxiety]], [[irritation]], [[Sexual dysfunction|sexual problems]], [[dry mouth]], [[sleep problems]] and a risk of [[suicide]] at the start of treatment by lifting the psychomotor inhibition, but these effects appear to be significantly weaker than with other SSRIs (except gastrointestinal side-effects).<ref>Vezmar, S. et al., « Pharmacokinetics and Efficacy of Fluvoxamine and Amitriptyline in Depression », J Pharmacol Sci, vol. 110, no 1, 2009, p. 98 – 104 (ISSN 1347-8648)</ref>
==History==
Fluvoxamine was developed by [[Solvay (company)|Solvay Pharmaceuticals]] and was the first non-[[tricyclic antidepressant|TCA]] drug approved by the U.S. Food and Drug Administration (FDA) specifically for the treatment of OCD.<ref>[http://www.brainphysics.com/medications.php Pharmalot | BrainPhysics.com| Medications for OCD].</ref> It was one of the first SSRI antidepressants to be launched (1984 in Switzerland), and following its FDA approval in 1993, it was launched in the U.S. in December 1994, Australia in February 1999 and Japan in June 1999.<ref>[http://www.solvay.com.au/default.asp?page=therapeutic+areas/neuroscience/ Solvay Pharmaceuticals Australia | Luvox].</ref> At the end of 1995, more than 10 million patients worldwide had been treated with fluvoxamine.<ref>{{cite journal | first = | last = | year = 1999 | title = | journal = Fluvoxamine Product Monograph | volume = | issue = | pages = }}</ref> Fluvoxamine was the first SSRI to be registered for the treatment of obsessive compulsive disorder in children by the FDA in 1997.<ref>{{cite journal | first = | last = | date = | title = Luvox Approved For Obsessive Compulsive Disorder in Children and Teens | journal = Http://www.pslgroup.com/dg/2261a.htm | volume = | issue = | pages = }}</ref> Fluvoxamine was the first drug approved for the treatment of social anxiety disorder in Japan in 2005.<ref>{{cite journal | first = | last = | date = | title = Solvay’s Fluvoxamine maleate is first drug approved for the treatment of social anxiety disorder in Japan | journal = Http://www.solvaypress.com/pressreleases/0,,33713-2-83,00.htm | volume = | issue = | pages = }}</ref>


Although the many drug-drug interactions of fluvoxamine can be problematic (and may temper enthusiasm for its prescribing, advocation and usage to some), its tolerance-profile itself is actually superior in some respects to other SSRIs (particularly with respect to cardiovascular complications), despite its age.<ref name = "Westenberg_2006">{{cite journal | vauthors = Westenberg HG, Sandner C | title = Tolerability and safety of fluvoxamine and other antidepressants | journal = International Journal of Clinical Practice | volume = 60 | issue = 4 | pages = 482–491 | date = April 2006 | pmid = 16620364 | pmc = 1448696 | doi = 10.1111/j.1368-5031.2006.00865.x }}</ref> Compared to [[escitalopram]] and [[sertraline]], indeed, fluvoxamine's gastrointestinal profile may be less intense,<ref name="Oliva Lippi Paci Del Fabro 2021 p. 110266">{{cite journal | vauthors = Oliva V, Lippi M, Paci R, Del Fabro L, Delvecchio G, Brambilla P, De Ronchi D, Fanelli G, Serretti A | title = Gastrointestinal side effects associated with antidepressant treatments in patients with major depressive disorder: A systematic review and meta-analysis | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 109 | pages = 110266 | date = July 2021 | pmid = 33549697 | doi = 10.1016/j.pnpbp.2021.110266 | publisher = Elsevier BV | s2cid = 231809760 }}</ref> often being limited to [[nausea]].<ref name="pmid18568110">{{cite journal | vauthors = Irons J | title = Fluvoxamine in the treatment of anxiety disorders | journal = Neuropsychiatric Disease and Treatment | volume = 1 | issue = 4 | pages = 289–299 | date = December 2005 | pmid = 18568110 | pmc = 2424117 | doi = }}</ref> [[Mosapride]] has demonstrated efficacy in treating fluvoxamine-induced nausea.<ref name="Ueda Yoshimura Shinkai Terao 2001 pp. 259–264">{{cite journal | vauthors = Ueda N, Yoshimura R, Shinkai K, Terao T, Nakamura J | title = Characteristics of fluvoxamine-induced nausea | journal = Psychiatry Research | volume = 104 | issue = 3 | pages = 259–264 | date = November 2001 | pmid = 11728615 | doi = 10.1016/s0165-1781(01)00320-1 | publisher = Elsevier BV | s2cid = 38761139 }}</ref> It is also advised practice to divide total daily doses of fluvoxamine greater than 100 milligrams, with the higher fraction being taken at bedtime (e.g., 50&nbsp;mg at the beginning of the waking day and 200&nbsp;mg at bedtime). In any case, high starting daily doses of fluvoxamine rather than the recommended gradual titration (starting at 50 milligrams and gradually titrating, up to 300 if necessary) may predispose to nauseous discomfort.<ref name="Ware 1997 pp. 15–23">{{cite journal |last=Ware |first=Michael R. |title=Fluvoxamine: A Review of the Controlled Trials in Depression |journal=The Journal of Clinical Psychiatry |publisher=Physicians Postgraduate Press, Inc. |volume=58 |issue=suppl 5 |date=1 March 1997 |issn=0160-6689 |url=https://www.psychiatrist.com/read-pdf/7342/ |access-date=1 December 2023 |pages=15–23 |pmid=9184623 |archive-date=6 December 2022 |archive-url=https://web.archive.org/web/20221206050356/https://www.psychiatrist.com/read-pdf/7342/ |url-status=live }}</ref>
In 1999, fluvoxamine came under great public scrutiny after it was discovered that [[Eric Harris and Dylan Klebold|Eric Harris]], one of the two teenage shooters involved in the [[Columbine High School massacre]], had been taking the drug. Many immediately pointed fingers at fluvoxamine and its manufacturer Solvay Pharmaceuticals.<ref name="DenverPost">{{cite news |url=http://www.denverpost.com/golf/ci_5094436 |title=Judge: Seal Columbine papers for 25 years |accessdate=2008-03-03 |date=January 26, 2007 |format= |work=The Denver Post |first=Howard |last=Pankratz}}</ref> Sales fell, and Solvay withdrew the medication from the U.S. market in 2002.<ref>{{cite journal | first = | last = | date = | title =Solvay Pharmaceuticals, Inc. Withdraws LUVOX | journal = Http://www.solvaypharmaceuticals-us.com/newsroom/pressreleases/0,,14517-2-0,00.htm | volume = | issue = | pages = }}</ref> In 2007, Solvay re-introduced Luvox to the U.S. market, which is now manufactured by Palo Alto, California-based Jazz Pharmaceuticals, Inc., with a generic version of Luvox available from [[IVAX Pharmaceuticals]], Inc. On February 28, 2008, the FDA approved a controlled-release formulation of fluvoxamine for Solvay Pharmaceuticals, to be marketed as '''Luvox CR'''.<ref>{{cite web |url=http://www.jazzpharma.com/news.php?id=59 |title=Jazz Pharmaceuticals press release, February 28, 2008 – FDA APPROVES LUVOX CR (FLUVOXAMINE MALEATE) EXTENDED-RELEASE CAPSULES FOR THE TREATMENT OF SOCIAL ANXIETY DISORDER (SAD) AND OBSESSIVE COMPULSIVE DISORDER (OCD) |accessdate=2008-03-14 |format= |work= |archiveurl = http://web.archive.org/web/20080526082602/http://www.jazzpharma.com/news.php?id=59 <!-- Bot retrieved archive --> |archivedate = 2008-05-26}}</ref><ref>{{cite web |title=Luvox CR | Prescribing Info |url=http://www.luvoxcr.com/LUVOX-CR-PI.pdf |accessdate=2008-02-21}}</ref>


It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref>
==Indications==
Fluvoxamine is widely prescribed to treat major depressive disorder (MDD), and anxiety disorders such as obsessive compulsive disorder (OCD), generalized anxiety disorder (GAD), panic disorder, social phobia, and post-traumatic stress disorder (PTSD). Fluvoxamine is indicated for children and adolescents with OCD<ref>{{cite journal | first = | last = | month = March | year = 2005 | title = US-FDA Fluvoxamine Product Insert | journal = | volume = | issue = | pages = }}</ref> and [[social anxiety disorder]].<ref name="Stahl, S. Stahl's Essential Psychopharmacology 2009. pp.215"/>


==Side effects==
==Medical uses==
In many countries (e.g., Australia,<ref name = AMH/><ref>{{cite web|url=https://www.nps.org.au/medical-info/medicine-finder/luvox-tablets|title=Luvox Tablets|website=NPS MedicineWise|access-date=22 October 2018|archive-date=22 October 2018|archive-url=https://web.archive.org/web/20181022153450/https://www.nps.org.au/medical-info/medicine-finder/luvox-tablets|url-status=live}}</ref> the United Kingdom,<ref name = BNF/> and Russia<ref>{{cite web|title=Summary of Full Prescribing Information: Fluvoxamine|url=http://www.rlsnet.ru/mnn_index_id_307.htm|website=Drug Registry of Russia (RLS) Drug Compendium|access-date=21 March 2015|language=ru|archive-date=2 April 2015|archive-url=https://web.archive.org/web/20150402162017/http://www.rlsnet.ru/mnn_index_id_307.htm|url-status=live}}</ref>) it is commonly used for [[major depressive disorder]]. Fluvoxamine is also approved in the United States for [[obsessive–compulsive disorder]] (OCD),<ref name = DailyMed/><ref name="pmid20140100" /> and [[social anxiety disorder]].<ref name="Luvox CR approved for OCD and SAD">{{cite web|url=https://www.empr.com/home/news/luvox-cr-approved-for-ocd-and-sad/|title=Luvox CR approved for OCD and SAD|date=29 February 2008|website=MPR|access-date=2 March 2019|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828090440/https://www.empr.com/home/news/luvox-cr-approved-for-ocd-and-sad/|url-status=live}}</ref> In Japan, it is also approved to treat [[Obsessive–compulsive disorder|OCD]], [[social anxiety disorder]] and major depressive disorder.<ref>{{cite web|url=https://www.astellas.com/en/corporate/news/detail/luvox-receives-approval-for-so.html|title=2005 News Releases|website=Astellas Pharma|access-date=16 September 2018|archive-date=16 September 2018|archive-url=https://web.archive.org/web/20180916235231/https://www.astellas.com/en/corporate/news/detail/luvox-receives-approval-for-so.html|url-status=dead}}</ref><ref>{{cite web|url=https://www.medscape.com/viewarticle/514804|title=International Approvals: Ebixa, Depromel/Luvox, M-Vax|website=www.medscape.com|access-date=16 September 2018|archive-date=29 October 2020|archive-url=https://web.archive.org/web/20201029173810/https://www.medscape.com/viewarticle/514804|url-status=live}}</ref> Fluvoxamine is indicated for children and adolescents with OCD.<ref>{{cite web | date = March 2005 | title = Fluvoxamine Product Insert | url = https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022235lbl.pdf | work = Jazz Pharmaceuticals, Inc. | publisher = U.S. Food and Drug Administration | access-date = 4 November 2022 | archive-date = 4 November 2022 | archive-url = https://web.archive.org/web/20221104055928/https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022235lbl.pdf | url-status = live }}</ref> The [[National Institute for Health and Care Excellence|NICE]] guidelines in the United Kingdom have, as of 2005, authorized its use for [[obsessive-compulsive disorder]] in adults and adolescents of any age and children over the age of 7.{{medcn|date=April 2024}}
[[Adverse effect (medicine)|Side effects]] most commonly observed with fluvoxamine include nausea, vomiting, drowsiness, insomnia, dizziness, nervousness, feeling anxious, dry mouth, abdominal pain, constipation, diarrhea, heart burn, loss of appetite, muscle weakness, pins and needles, abnormal taste, headache, faster heart beat, sweating, weight gain, weight loss or unusual bruising. Other side effects which are observed more frequently in children include abnormal thoughts or behaviour, cough, increased period pain, nose bleeds, increased restlessness, infection and sinusitis.<ref>[http://www.betterhealth.vic.gov.au/BHCV2/bhcmed.nsf/pages/smcluvox/$File/smcluvox.pdf LUVOX® Consumer Medicine Information | Better Health Channel]</ref> Sexual side effects with fluvoxamine are less pronounced than with other SSRIs.<ref>{{cite journal | first = Waldinger MD | last = Hengeveld VW et al. | last2 = Hengeveld | year = 1998 | first2 = MW | last3 = Zwinderman | first3 = AH | last4 = Olivier | first4 = B | title = Effect of SSRI antidepressants on ***: a double blind, randomised, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine and sertraline | journal = Journal of Clinical Psychopharmacology | volume = 18 | pmid = 9690692 | issue = 4| pages = 274–281 | doi = 10.1097/00004714-199808000-00004}}</ref>


There is evidence that fluvoxamine is effective for [[Social anxiety disorder|generalised social anxiety]] in adults, although, as with other [[SSRI]]s, some of the results may be compromised by having been funded by pharmaceutical companies.<ref>{{cite journal | vauthors = Williams T, Hattingh CJ, Kariuki CM, Tromp SA, van Balkom AJ, Ipser JC, Stein DJ | title = Pharmacotherapy for social anxiety disorder (SAnD) | journal = The Cochrane Database of Systematic Reviews | volume = 10 | issue = 10 | pages = CD001206 | date = October 2017 | pmid = 29048739 | pmc = 6360927 | doi = 10.1002/14651858.CD001206.pub3 }}</ref><ref>{{cite journal |vauthors=Liu X, Li X, Zhang C, Sun M, Sun Z, Xu Y, Tian X |title=Efficacy and tolerability of fluvoxamine in adults with social anxiety disorder: A meta-analysis |journal=Medicine (Baltimore) |volume=97 |issue=28 |pages=e11547 |date=July 2018 |pmid=29995828 |pmc=6076099 |doi=10.1097/MD.0000000000011547 |url=}}</ref> Of the [[SSRI]]s, however, fluvoxamine, [[paroxetine]] and [[sertraline]] do appear consistent as viable treatments for generalised social anxiety.<ref> Williams, T., McCaul, M., Schwarzer, G., Cipriani, A., Stein, D. J., & Ipser, J. (2020). Pharmacological treatments for social anxiety disorder in adults: a systematic review and network meta-analysis. Acta neuropsychiatrica, 32(4), 169–176. https://doi.org/10.1017/neu.2020.6</ref><ref> Davidson J. R. (2003). Pharmacotherapy of social phobia. Acta psychiatrica Scandinavica. Supplementum, (417), 65–71. https://doi.org/10.1034/j.1600-0447.108.s417.7.x</ref> [[Phenelzine]],<ref>Tancer, M. E., & Uhde, T. W. (1997). Role of serotonin drugs in the treatment of social phobia. The Journal of clinical psychiatry, 58 Suppl 5, 50–54.</ref><ref> Aarre T. F. (2003). Phenelzine efficacy in refractory social anxiety disorder: a case series. Nordic journal of psychiatry, 57(4), 313–315. https://doi.org/10.1080/08039480310002110</ref> [[brofaromine]], [[venlafaxine]], [[gabapentin]], [[pregabalin]] and [[clonazepam]] represent other viable options for the pharmacological treatment of generalised social anxiety.{{medcn|date=April 2024}}
==Pharmacology==
Fluvoxamine is a potent and selective [[serotonin reuptake inhibitor]] with approximately 100-fold affinity for the [[serotonin transporter]] over the [[norepinephrine transporter]]. It has negligible affinity for the [[dopamine transporter]] or any other [[receptor (biochemistry)|receptor]], with the sole exception of the [[sigma-1 receptor|σ<sub>1</sub> receptor]]. It behaves as a potent [[agonist]] at this receptor and has the highest affinity of any SSRI for doing so. This may contribute to its antidepressant and anxiolytic effects inside the brain. Indeed, other SSRIs which also act as [[sigma-1 receptor|σ<sub>1</sub> receptor]] agonists, such as [[sertraline]] and [[escitalopram]] (not verified but likely to be), display enhanced antidepressant efficacy.<ref>{{cite journal | first = Narita N | last = Hashimoto K et al. | year = 1996 | title = Interactions of selective reuptake inhibitors with subtypes of sigma receptor in rat brain | journal = Eur J Pharmacol| volume = 307 | issue = 1| pages = 117–9 | doi = 10.1016/0014-2999(96)00254-3 | pmid = 8831113 | last2 = Hashimoto | first2 = K | last3 = Tomitaka | first3 = S | last4 = Minabe | first4 = Y}}</ref> suggesting that it may have particular benefits in the treatment of depressed patients who show features of anxiety/stress and for whom memory impairment is particularly undesirable (such as in depressed elderly patients, and also in treating psychotic depression).<ref>{{cite journal | first = Carrasco JL | last = C.Sandner | month = December | year = 2005 | title = Clinical effects of pharmacological variations in selective serotonin reuptake inhibitors: an overview | journal = International Journal of Clinical Practice | volume = 59 | issue = 12 | pages = 1428–1434 | doi = 10.1111/j.1368-5031.2005.00681.x | pmid = 16351675 | last2 = Sandner | first2 = C}}</ref> In fact, the TCA [[opipramol]], a σ<sub>1</sub> receptor agonist without effects on the serotonin, dopamine, or norepinephrine systems, has considerable antidepressant and [[anxiolytic]] efficacy in its own right.


Fluvoxamine is also effective for treating a range of [[anxiety disorder]]s in children and adolescents, including [[generalized anxiety disorder]], social anxiety disorder, panic disorder and [[separation anxiety disorder]].<ref name=":02">{{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 |publisher=National Institute for Health and Care Research |doi=10.3310/nihrevidence_53342 |s2cid=253347210 |url-access=subscription |access-date=7 November 2022 |archive-date=5 November 2022 |archive-url=https://web.archive.org/web/20221105153958/https://evidence.nihr.ac.uk/collection/antidepressants-for-children-and-teenagers-what-works-anxiety-depression/ |url-status=live }}</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 | pages = 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>
==Pharmacokinetics==
The oral [[bioavailability]] of fluvoxamine is 53%. The plasma protein binding is about 80%.<ref name="drugs.com PI">{{cite web |url=http://www.drugs.com/pro/fluvoxamine.html |title=Fluvoxamine Official FDA information, side effects and uses |author=Barr Laboratories Inc |year=2010 |month=October |at=Subsection: Fluvoxamine - Clinical Pharmacology -> Pharmacokinetics |accessdate=2011-02-15}}</ref>


The drug works long-term, and retains its therapeutic efficacy for at least one year.<ref name="pmid7507038">{{cite journal | vauthors = Wilde MI, Plosker GL, Benfield P | title = Fluvoxamine. An updated review of its pharmacology, and therapeutic use in depressive illness | journal = Drugs | volume = 46 | issue = 5 | pages = 895–924 | date = November 1993 | pmid = 7507038 | doi = 10.2165/00003495-199346050-00008 | s2cid = 195691900 }}</ref> It has also been found to possess some analgesic properties in line with other SSRIs and [[tricyclic antidepressant]]s.<ref>{{cite journal | vauthors = Kwasucki J, Stepień A, Maksymiuk G, Olbrych-Karpińska B | title = [Evaluation of analgesic action of fluvoxamine compared with efficacy of imipramine and tramadol for treatment of sciatica--open trial] | journal = Wiadomosci Lekarskie | volume = 55 | issue = 1–2 | pages = 42–50 | year = 2002 | pmid = 12043315 }}</ref><ref>{{cite journal | vauthors = Schreiber S, Pick CG | title = From selective to highly selective SSRIs: a comparison of the antinociceptive properties of fluoxetine, fluvoxamine, citalopram and escitalopram | journal = European Neuropsychopharmacology | volume = 16 | issue = 6 | pages = 464–468 | date = August 2006 | pmid = 16413173 | doi = 10.1016/j.euroneuro.2005.11.013 | s2cid = 39278756 }}</ref><ref>{{cite journal | vauthors = Coquoz D, Porchet HC, Dayer P | title = Central analgesic effects of desipramine, fluvoxamine, and moclobemide after single oral dosing: a study in healthy volunteers | journal = Clinical Pharmacology and Therapeutics | volume = 54 | issue = 3 | pages = 339–344 | date = September 1993 | pmid = 8375130 | doi = 10.1038/clpt.1993.156 | s2cid = 8229797 }}</ref>
===Metabolism===
Fluvoxamine is strongly metabolized in the liver, mostly by the processes of [[redox|oxidative]] [[demethylation]] (producing fluvoxamine acid and its N-[[acetyl]] [[structural analog|analog]]) and [[deamination]] (producing fluvoxethanol). Only fluvoxamine acid has been shown to have [[serotonin transporter|SERT]] inhibitor activity, roughly 1-2 [[order of magnitude|orders of magnitude]] less potent than the parent compound.<ref name="Rxlist Data">{{cite web |title=Luvox Tablets (Fluvoxamine Maleate) Drug Information: Uses, Side Effects, Drug Interactions and Warnings at RxList |url=http://www.rxlist.com/luvox-drug.htm |accessdate=2009-02-17 }}</ref>


The average therapeutic dose for fluvoxamine is 100 to 300&nbsp;mg/day, with 300&nbsp;mg being the upper daily limit normally recommended. [[Obsessive-compulsive disorder]], however, often requires higher doses; doses of up to 450&nbsp;mg/day may be prescribed in this case.<ref>Seibell PJ, Hamblin RJ, Hollander E. Obsessive-compulsive disorder: Overview and standard treatment strategies. Psychiatric Annals. 2015 Jun 1;45(6):297-302.</ref><ref>Rivas-Vazquez, R.A. and Blais, M.A., 1997. Selective serotonin reuptake inhibitors and atypical antidepressants: A review and update for psychologists. Professional Psychology: Research and Practice, 28(6), p.526.</ref><ref>Middleton, R., Wheaton, M.G., Kayser, R. and Simpson, H.B., 2019. Treatment resistance in obsessive-compulsive disorder. Treatment resistance in psychiatry: risk factors, biology, and management, pp.165-177.</ref> In any case with fluvoxamine, treatment is generally begun at 50 mg and increased in 50 mg increments every 4 to 7 days until a therapeutic optimum is reached.<ref>Figgitt, D.P. and McClellan, K.J., 2000. Fluvoxamine: an updated review of its use in the management of adults with anxiety disorders. Drugs, 60, pp.925-954.</ref>
[[isotopic labeling|Radio-labeled]] administration of a dose of fluvoxamine produced nine identifiable metabolites, constituting 85% of the absorbed dosage (thus 15% of the fluvoxamine remained unchanged). This isolate of metabolites was [[empirical]]ly proven to contain 60% fluvoxamine acid and its N-acetyl analog, and 10% fluvoxethanol, with the other six metabolites making up 30%.<ref name="Rxlist Data" />


===Elimination===
==Adverse effects==
Fluvoxamine's side-effect profile is very similar to other SSRIs, with [[gastrointestinal]] side effects more characteristic of those receiving treatment with fluvoxamine.<ref name=LUVOX>{{cite web |title=Product Information Luvox |work=TGA eBusiness Services |publisher=Abbott Australasia Pty Ltd |date=15 January 2013 |access-date=21 October 2013 |url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-07140-3 |archive-date=9 October 2017|archive-url=https://web.archive.org/web/20171009014348/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-07140-3 |url-status=live}}</ref><ref name=DailyMed>{{cite web |title=Fluvoxamine Maleate tablet, coated prescribing information |work=[[DailyMed]] |publisher=U.S. National Library of Medicine |date=14 December 2018 |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7ecd83ec-88f5-4f85-9cc2-9068375d8820 |access-date=28 November 2019 |archive-date=19 October 2020 |archive-url=https://web.archive.org/web/20201019235438/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7ecd83ec-88f5-4f85-9cc2-9068375d8820 |url-status=live}}</ref><ref name="AMH">{{cite book |veditors=Rossi S |isbn=978-0-9805790-9-3 |title=Australian Medicines Handbook |place=Adelaide |publisher=The Australian Medicines Handbook Unit Trust |year=2013 |edition=2013}}</ref><ref name="BNF">{{cite book |isbn=978-0-85711-084-8 |title=British National Formulary (BNF) |last1=Joint Formulary Committee |year=2013 |publisher=Pharmaceutical Press |location=London, UK |edition=65th |url-access=registration |url=https://archive.org/details/bnf65britishnati0000unse}}</ref><ref name="Maudsley">{{cite book |isbn=978-0-470-97948-8 |title=The Maudsley prescribing guidelines in psychiatry |vauthors=Taylor D, Paton C, Shitij K |year=2012 |publisher=Wiley-Blackwell |location=West Sussex}}</ref><ref>{{cite web |title=Faverin 100 mg film-coated tablets – Summary of Product Characteristics (SPC) |work=electronic Medicines Compendium |publisher=Abbott Healthcare Products Limited |date=14 May 2013 |access-date=21 October 2013 |url-status=live |url=http://www.medicines.org.uk/emc/medicine/22124/SPC/Faverin+100+mg+film-coated+tablets/ |archive-date=21 October 2013 |archive-url=https://web.archive.org/web/20131021042737/http://www.medicines.org.uk/emc/medicine/22124/SPC/Faverin+100+mg+film-coated+tablets/}}</ref>
Fluvoxamine has the shortest [[Blood serum|serum]] [[half-life]] of all SSRIs, with a mean of 15.6 hours.<ref>Center for Drug Evaluation and Research, (2000). Fluvoxamine Maleate Tablets. Application Number: 75901, Retrieved July 28, 2008, from http://www.fda.gov/cder/foi/anda/2000/75901_Fluvoxamine%20Maleate_Prntlbl.pdf</ref>


===Common===
==Drug interactions==
Common side effects occurring with 1–10% incidence:
Fluvoxamine has a low potential for the [[drug interaction]]s which are based on inhibition of enzyme [[Cytochrome P450]] [[CYP2D6]]. Fluvoxamine shows the least interaction of the SSRIs, in regard to this specific enzyme.<ref>{{cite journal | first = Baumann | last = P. | year = 1996 | title = Pharmacokinetic-pharmacodynamic relationship of the Selective serotonin reuptake inhibitors | journal = Clinical Pharmacokinetics | volume = 31 | issue = 6| pages = 444–469 | doi = 10.2165/00003088-199631060-00004 | pmid = 8968657}}</ref><ref>{{cite journal | first = DeVane CL | last = Gill HS | year = 1997 | title = Clinical Pharmacokinetics of Fluvoxamine: applications to dosage regime design | journal = Journal of Clinical Psychiatry | volume = 58 | issue = Suppl 5 | pages = 7–14}}</ref><ref>{{cite journal | first = CL | last = DeVane| year = 1998 | title = Translational pharmacokinetics: current issues with newer antidepressants | journal = Depression and Anxiety | volume = 8 | issue = Suppl 1 | pages = 64–70 | doi = 10.1002/(SICI)1520-6394(1998)8:1+<64::AID-DA10>3.0.CO;2-S | pmid = 9809216}}</ref>
{{div col |colwidth=20em}}
Naturally the other SSRIs which are metabolized by CYP2D6 will have more CYP2D6-based interactions with [[tricyclic antidepressant|TCAs]], [[antiarrhythmics]], [[B-blockers]], [[phenytoin]], [[opioids]] and [[neuroleptics]].
* Abdominal pain
* Agitation
* Anxiety
* [[Asthenia]] (weakness)
* [[Constipation]]
* [[Diarrhea]]
* Dizziness
* [[Dyspepsia]] (indigestion)
* Headache
* [[Hyperhidrosis]] (excess sweating)
* Insomnia
* Loss of appetite
* [[Malaise]]
* Nausea
* Nervousness
* [[Palpitations]]
* Restlessness
* [[Sexual dysfunction]] (including delayed ejaculation, erectile dysfunction, decreased libido, etc.)
* [[Somnolence]] (drowsiness)
* [[Tachycardia]] (high heart rate)
* [[Tremor]]
* Vomiting
* Weight loss
* [[Xerostomia]] (dry mouth)
* Yawning
{{div col end}}


===Uncommon===
Fluvoxamine does, however, inhibit cytochrome P450 enzyme [[CYP1A2]], which metabolises [[agomelatine]], [[caffeine]], [[clozapine]], [[haloperidol]], [[phenacetin]], [[tacrine]], [[theophylline]], and [[olanzapine]]. These substances can cause increased serum levels when administered together with fluvoxamine. Of major concern is the fact that the [[polycyclic aromatic hydrocarbons]] found in [[tobacco smoke]] are potent inducers of CYP1A2 so that smokers may require significant modification of medication dosage.<ref>{{cite journal| last = Kroom| first = Lisa A.| authorlink = | coauthors = | title = Drug Interactions With Smoking| journal = Am J Health-Syst Pharm.| volume = 64| issue = 18| pages = 1917–1921| publisher = American Society of Health-System Pharmacists| location = Medscape| date = 10-01-2007| url = http://www.medscape.com/viewarticle/562754_print| doi = 10.2146/ajhp060414| id = | accessdate = 2008-01-31| pmid = 17823102}}</ref> A recent warning has been published regarding potentially serious interaction with [[tizanidine]], based on CYP1A2 metabolism.<ref>{{cite web| last = Waknine| first = Yael| authorlink = | coauthors = | title = Prescribers Warned of Tizanidine Drug Interactions| work = Medscape News| publisher = Medscape| date = April 13, 2007| url = http://www.medscape.com/viewarticle/555194_print| format = | doi = | accessdate = 2008-02-01}}</ref>
Uncommon side effects occurring with 0.1–1% incidence:
{{div col |colwidth=30em}}
* [[Arthralgia]]
* Confusional state
* Cutaneous hypersensitivity reactions (e.g. oedema [buildup of fluid in the tissues], rash, pruritus)
* Extrapyramidal side effects (e.g. dystonia, parkinsonism, tremor, etc.)
* Hallucination
* [[Orthostatic hypotension]]
{{div col end}}


===Rare===
Fluvoxamine inhibits metabolism of [[diazepam]] and [[phenytoin]] via [[CYP2C19]] and metabolism of [[aripiprazole]], [[chlorpromazine]], [[clozapine]], [[haloperidol]], [[olanzapine]], [[perphenazine]], [[risperidone]], [[thioridazine]] and [[zuclopenthixol]] via [[Cytochrome P450|CYP2D6]] as well as of [[aripiprazole]], [[clozapine]], [[haloperidol]], [[quetiapine]] and [[ziprasidone]] via [[Cytochrome P450|CYP3A4]].<ref>{{cite journal| last = Bondy| first = Brigitta| authorlink =
Rare side effecs occurring with 0.01–0.1% incidence:
| coauthors = Illja Spellmann| title = Pharmacogenetics of Antipsychotics: Useful For the Clinician?
{{div col |colwidth=32em}}
| journal = Curr Opin Psychiatry| volume = 20| issue = 1| pages = 126–130| publisher = Lippincott Williams & Wilkins| location = Medscape| year = 2007| url = http://www.medscape.com/viewarticle/552100_print| doi = 10.1097/YCO.0b013e328017f69f
* Abnormal hepatic (liver) function
| id = | accessdate = 2008-02-01| pmid = 17278909 }}</ref>
* Galactorrhoea (expulsion of breast milk unrelated to pregnancy or breastfeeding)
* [[Mania]]
* Photosensitivity (being abnormally sensitive to light)
* Seizures
{{div col end}}


===Unknown frequency===
The plasma protein binding of fluvoxamine is about 77%. Drugs with low protein binding are less likely to displace other protein bound drugs, and therefore have a lower potential to cause protein binding-related drug interactions.
{{div col |colwidth=30em}}
* [[Akathisia]]{{snd}} a sense of inner restlessness that presents itself with the inability to stay still
* Bed-wetting
* [[Bone fracture]]s
* [[Dysgeusia]]
* [[Ecchymosis|Ecchymoses]]
* [[Glaucoma]]
* [[Haemorrhage]]
* [[Hyperprolactinaemia]] (elevated plasma prolactin levels leading to galactorrhoea, amenorrhoea [cessation of menstrual cycles], etc.)
* [[Hyponatraemia]]
* [[Mydriasis]]
* [[Neuroleptic malignant syndrome]] – practically identical presentation to serotonin syndrome except with a more prolonged onset
* [[Paraesthesia]]
* [[Serotonin syndrome]] – a potentially fatal condition characterised by abrupt onset muscle rigidity, hyperthermia (elevated body temperature), [[rhabdomyolysis]], mental status changes (e.g. coma, hallucinations, agitation), etc.
* Suicidal ideation and behaviour
* [[Syndrome of inappropriate antidiuretic hormone secretion]]
* Urinary incontinence
* Urinary retention
* Violence towards others<ref name = LUVOXTIME>{{cite magazine |title=Top Ten Legal Drugs Linked to Violence |magazine=Time |date=7 January 2011 |access-date=10 September 2014 |url=http://healthland.time.com/2011/01/07/top-ten-legal-drugs-linked-to-violence/ |vauthors=Szalavitz M |archive-date=21 September 2014 |archive-url=https://web.archive.org/web/20140921052039/http://healthland.time.com/2011/01/07/top-ten-legal-drugs-linked-to-violence/ |url-status=live }}</ref>
* Weight changes
* Withdrawal symptoms
{{div col end}}


== Interactions ==
Fluvoxamine also inhibits [[CYP2C9]].<ref name="Rxlist Data" /><ref name="half-life">{{cite web |title=Brain Elimination Half-Life of Fluvoxamine |url=http://ajp.psychiatryonline.org/cgi/content/full/155/3/380 }}</ref>


[[File:Luvox.jpg|thumb|Luvox (fluvoxamine) 100&nbsp;mg film-coated scored tablets]]
==Appearance in popular culture==
The drug was given visibility in the American television series [[The Sopranos]] produced by [[HBO]], in the second season, episode 10. Dr. [[Jennifer Melfi]], the psychiatrist treating the character named [[Tony Soprano]], is prescribed Luvox by her own psychiatrist, to treat a strong inclination toward alcohol.


Fluvoxamine inhibits the following [[cytochrome P450]] enzymes:<ref name=Pharm>{{cite book| vauthors = Ciraulo DA, Shader RI | veditors = Ciraulo DA, Shader RI | title=Pharmacotherapy of Depression|year=2011|publisher=Springer|isbn=978-1-60327-435-7|page=49 |edition= 2nd |doi=10.1007/978-1-60327-435-7}}</ref><ref name="GG">{{cite book | isbn = 978-0-07-162442-8 | title = Goodman and Gilman's The Pharmacological Basis of Therapeutics | edition = 12th | vauthors = Brunton L, Chabner B, Knollman B | year = 2010 | publisher = McGraw-Hill Professional | location = New York | title-link = Goodman and Gilman's The Pharmacological Basis of Therapeutics }}</ref><ref>{{cite journal | vauthors = Baumann P | title = Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors | journal = Clinical Pharmacokinetics | volume = 31 | issue = 6 | pages = 444–469 | date = December 1996 | pmid = 8968657 | doi = 10.2165/00003088-199631060-00004 | s2cid = 31923953 }}</ref><ref>{{cite journal | vauthors = DeVane CL, Gill HS | title = Clinical pharmacokinetics of fluvoxamine: applications to dosage regimen design | journal = The Journal of Clinical Psychiatry | volume = 58 | issue = Suppl 5 | pages = 7–14 | year = 1997 | pmid = 9184622 }}</ref><ref>{{cite journal | vauthors = DeVane CL | title = Translational pharmacokinetics: current issues with newer antidepressants | journal = Depression and Anxiety | volume = 8 | issue = Suppl 1 | pages = 64–70 | year = 1998 | pmid = 9809216 | doi = 10.1002/(SICI)1520-6394(1998)8:1+<64::AID-DA10>3.0.CO;2-S | s2cid = 22297498 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Bondy B, Spellmann I | title = Pharmacogenetics of antipsychotics: useful for the clinician? | journal = Current Opinion in Psychiatry | volume = 20 | issue = 2 | pages = 126–130 | date = March 2007 | pmid = 17278909 | doi = 10.1097/YCO.0b013e328017f69f | s2cid = 23859992 }}</ref><ref>{{cite journal | vauthors = Kroon LA | title = Drug interactions with smoking | journal = American Journal of Health-System Pharmacy | volume = 64 | issue = 18 | pages = 1917–1921 | date = September 2007 | pmid = 17823102 | doi = 10.2146/ajhp060414 }}</ref><ref>{{cite web| vauthors = Waknine Y| title = Prescribers Warned of Tizanidine Drug Interactions| work = Medscape News| publisher = Medscape| date = 13 April 2007| url = http://www.medscape.com/viewarticle/555194_print| access-date = 1 February 2008| archive-date = 21 February 2013| archive-url = https://web.archive.org/web/20130221020721/http://www.medscape.com/viewarticle/555194_print| url-status = live}}</ref><ref>{{cite web|url=https://www.mayoclinic.org/drugs-supplements/fluvoxamine-oral-route/precautions/drg-20066874?p=1|title=Fluvoxamine (Oral Route) Precautions|website=Mayo Clinic|access-date=2 November 2018|archive-date=6 March 2019|archive-url=https://web.archive.org/web/20190306043631/https://www.mayoclinic.org/drugs-supplements/fluvoxamine-oral-route/precautions/drg-20066874?p=1|url-status=live}}</ref>{{Excessive citations inline|date=April 2024}}<!--there should be citations near the relevant enzymes/substances rather than the whole list of citations with unknown relevance-->
"Stuttering" John Melendez, formerly of The Howard Stern Show, had taken Luvox for a period of time before his departure from the show.
* [[CYP1A2]] (strongly) which metabolizes [[agomelatine]], [[amitriptyline]], [[caffeine]], [[clomipramine]], [[clozapine]], [[duloxetine]], [[haloperidol]], [[imipramine]], [[phenacetin]], [[tacrine]], [[tamoxifen]], [[theophylline]], [[olanzapine]], etc.
* [[CYP3A4]] (moderately) which metabolizes [[alprazolam]], [[aripiprazole]], [[clozapine]], [[haloperidol]], [[quetiapine]], [[pimozide]], [[ziprasidone]], etc.<ref name=":0">{{cite journal | vauthors = Hemeryck A, Belpaire FM | title = Selective serotonin reuptake inhibitors and cytochrome P-450 mediated drug-drug interactions: an update | journal = Current Drug Metabolism | volume = 3 | issue = 1 | pages = 13–37 | date = February 2002 | pmid = 11876575 | doi = 10.2174/1389200023338017 }}</ref>
* [[CYP2D6]] (weakly) which metabolizes [[aripiprazole]], [[chlorpromazine]], [[clozapine]], [[codeine]], [[fluoxetine]], [[haloperidol]], [[olanzapine]], [[oxycodone]], [[paroxetine]], [[perphenazine]], [[pethidine]], [[risperidone]], [[sertraline]], [[thioridazine]], [[zuclopenthixol]], etc.<ref name="FDA_drug_development">{{cite journal|title=Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers|journal=FDA|date=26 May 2021|url=https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers|access-date=25 December 2020|archive-date=4 November 2020|archive-url=https://web.archive.org/web/20201104173036/https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers|url-status=live}}</ref>
* [[CYP2C9]] (moderately) which metabolizes [[nonsteroidal anti-inflammatory drugs]], [[phenytoin]], [[sulfonylureas]], etc.
* [[CYP2C19]] (strongly) which metabolizes [[clonazepam]], [[diazepam]], [[phenytoin]], etc.
* [[CYP2B6]] (weakly) which metabolizes [[bupropion]], [[cyclophosphamide]], [[sertraline]], [[tamoxifen]], [[valproate]], etc.


By so doing, fluvoxamine can increase serum concentration of the substrates of these enzymes.<ref name = Pharm/>
==Synthesis==
[[File:Luvox.jpg|thumb|350px|Luvox (fluvoxamine) 100 mg tablets ([[Australia|AU]])]]
[[File:Fluvoxamine rxn.png|600px]]


Fluvoxamine may also elevate plasma levels of olanzapine by approximately two times.<ref>{{cite journal | vauthors = Spina E, de Leon J | title = Metabolic drug interactions with newer antipsychotics: a comparative review | journal = Basic & Clinical Pharmacology & Toxicology | volume = 100 | issue = 1 | pages = 4–22 | date = January 2007 | pmid = 17214606 | doi = 10.1111/j.1742-7843.2007.00017.x | doi-access = free }}</ref> Combined olanzapine and fluvoxamine, which may cause increased sedation,<ref name="pmid11063782">{{cite journal | vauthors = Bogetto F, Bellino S, Vaschetto P, Ziero S | title = Olanzapine augmentation of fluvoxamine-refractory obsessive-compulsive disorder (OCD): a 12-week open trial | journal = Psychiatry Research | volume = 96 | issue = 2 | pages = 91–98 | date = October 2000 | pmid = 11063782 | doi = 10.1016/s0165-1781(00)00203-1 | s2cid = 43395897 }}</ref> should be used cautiously and controlled clinically and by therapeutic drug monitoring to avoid olanzapine induced adverse effects and/or intoxication.<ref>{{cite journal | vauthors = Hiemke C, Peled A, Jabarin M, Hadjez J, Weigmann H, Härtter S, Modai I, Ritsner M, Silver H | title = Fluvoxamine augmentation of olanzapine in chronic schizophrenia: pharmacokinetic interactions and clinical effects | journal = Journal of Clinical Psychopharmacology | volume = 22 | issue = 5 | pages = 502–506 | date = October 2002 | pmid = 12352274 | doi = 10.1097/00004714-200210000-00010 | s2cid = 38073367 }}</ref><ref>{{cite web |date=23 November 2020 |title=Movox |url=https://www.nps.org.au/medicine-finder/movox-tablets |access-date=4 November 2022 |website=NPS MedicineWise |archive-date=4 November 2022 |archive-url=https://web.archive.org/web/20221104034758/https://www.nps.org.au/medicine-finder/movox-tablets |url-status=live }}</ref>
Fluvoxamine is one of only two SSRIs (along with [[alaproclate]]<ref>{{cite journal |title=Alaproclate acts as a potent, reversible and noncompetitive antagonist of the NMDA receptor coupled ion flow |author=A Wilkinson, M Courtney, A Westlind-Danielsson, G Hallnemo and K E Akerman |journal=JPET |date=December |year=1994 |volume=271 |issue=3 |pages=1314–1319}}</ref><ref>{{cite journal |title=Evaluation of the phencyclidine-like discriminative stimulus effects of novel NMDA channel blockers in rats |author=K L Nicholson and R L Balster |journal=Psychopharmacology |date= 23 April |year=2003}}</ref>) to have a monocyclic structure.


The plasma levels of oxidatively metabolized [[benzodiazepine]]s (e.g., [[triazolam]], [[midazolam]], [[alprazolam]] and [[diazepam]]) are likely to be increased when co-administered with fluvoxamine. However, the clearance of [[benzodiazepine]]s metabolized by [[glucuronidation]] (e.g., [[lorazepam]]; [[oxazepam]], which is coincidentally a metabolite of diazepam;<ref name="pmid28903606">{{cite journal | vauthors = Dinis-Oliveira RJ | title = Metabolic profile of oxazepam and related benzodiazepines: clinical and forensic aspects | journal = Drug Metabolism Reviews | volume = 49 | issue = 4 | pages = 451–463 | date = November 2017 | pmid = 28903606 | doi = 10.1080/03602532.2017.1377223 | s2cid = 4528255 }}</ref> [[temazepam]])<ref>{{cite web|url=http://paindr.com/wp-content/uploads/2015/10/Revised-BZD_-9-30.pdf|title=Benzodiazepine Metabolism and Pharmacokinetics|vauthors=Raouf M|date=2016|veditors=Fudin J|access-date=16 September 2018|archive-date=12 July 2018|archive-url=https://web.archive.org/web/20180712232038/http://paindr.com/wp-content/uploads/2015/10/Revised-BZD_-9-30.pdf|url-status=live}}</ref><ref>{{cite journal | vauthors = Peppers MP | title = Benzodiazepines for alcohol withdrawal in the elderly and in patients with liver disease | journal = Pharmacotherapy | volume = 16 | issue = 1 | pages = 49–57 | date = 1996 | pmid = 8700792 | doi = 10.1002/j.1875-9114.1996.tb02915.x | s2cid = 1389910 }}</ref> are not affected by fluvoxamine and may be safely taken alongside fluvoxamine should concurrent treatment with a benzodiazepine be necessary.<ref>{{cite web|url=http://www.mylan.ca/-/media/mylanca/documents/english/product%20pdf/pdfs%20dec%202015/luvox-pm-2016.01.08.pdf|title=fluvoxamine maleate: PRODUCT MONOGRAPH|date=2016|access-date=16 September 2018|archive-date=16 September 2018|archive-url=https://web.archive.org/web/20180916130322/http://www.mylan.ca/-/media/mylanca/documents/english/product%20pdf/pdfs%20dec%202015/luvox-pm-2016.01.08.pdf|url-status=live}}</ref> Additionally, it appears that benzodiazepines metabolized by nitro-reduction ([[clonazepam]], [[nitrazepam]]) may also, in a somewhat similar vein, be unlikely to be affected by fluvoxamine.<ref>{{cite web|url=http://www.medsafe.govt.nz/profs/datasheet/l/luvoxtab.pdf|title=Luvox Data Sheet|date=2017|publisher=Medsafe, New Zealand|access-date=16 September 2018|archive-date=29 March 2018|archive-url=https://web.archive.org/web/20180329045516/http://www.medsafe.govt.nz/profs/datasheet/l/luvoxtab.pdf|url-status=dead}}</ref><ref>{{cite web |title=Faverin Tablets |url=https://www.nps.org.au/medicine-finder/faverin-tablets |access-date=4 November 2022 |website=NPS MedicineWise |date=July 2022 |archive-date=4 November 2022 |archive-url=https://web.archive.org/web/20221104201934/https://www.nps.org.au/medicine-finder/faverin-tablets |url-status=live }}</ref>
==See also==
*[[SSRI discontinuation syndrome]]
*[[Selective serotonin reuptake inhibitor]]


Using fluvoxamine and [[alprazolam]] together can increase [[alprazolam]] plasma concentrations.<ref>{{cite journal | vauthors = Suzuki Y, Shioiri T, Muratake T, Kawashima Y, Sato S, Hagiwara M, Inoue Y, Shimoda K, Someya T | title = Effects of concomitant fluvoxamine on the metabolism of alprazolam in Japanese psychiatric patients: interaction with CYP2C19 mutated alleles | journal = European Journal of Clinical Pharmacology | volume = 58 | issue = 12 | pages = 829–833 | date = April 2003 | pmid = 12698310 | doi = 10.1007/s00228-003-0563-9 | s2cid = 32559753 }}</ref> If [[alprazolam]] is coadministered with fluvoxamine, the initial [[alprazolam]] dose should be reduced to the lowest effective dose.<ref>{{cite book|url=https://books.google.com/books?id=AmQlBAAAQBAJ&pg=PA131|title=Psychiatric Drugs in Children and Adolescents: Basic Pharmacology and Practical Applications|vauthors=Gerlach M, Warnke A, Greenhill L|publisher=Springer-Verlag Wien|year=2014|isbn=978-3-7091-1500-8|pages=131|access-date=21 May 2020|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110041817/https://books.google.com/books?id=AmQlBAAAQBAJ&pg=PA131|url-status=live}}</ref><ref>{{cite journal | vauthors = Fleishaker JC, Hulst LK | title = A pharmacokinetic and pharmacodynamic evaluation of the combined administration of alprazolam and fluvoxamine | journal = European Journal of Clinical Pharmacology | volume = 46 | issue = 1 | pages = 35–39 | date = 1994 | pmid = 8005185 | doi = 10.1007/bf00195913 | s2cid = 2161450 }}</ref>
==References==

{{reflist|1}}
Fluvoxamine and [[ramelteon]] coadministration is not indicated.<ref>{{cite journal | vauthors = Obach RS, Ryder TF | title = Metabolism of ramelteon in human liver microsomes and correlation with the effect of fluvoxamine on ramelteon pharmacokinetics | journal = Drug Metabolism and Disposition | volume = 38 | issue = 8 | pages = 1381–1391 | date = August 2010 | pmid = 20478852 | doi = 10.1124/dmd.110.034009 | s2cid = 8421997 }}</ref><ref>{{cite journal | vauthors = Pandi-Perumal SR, Spence DW, Verster JC, Srinivasan V, Brown GM, Cardinali DP, Hardeland R | title = Pharmacotherapy of insomnia with ramelteon: safety, efficacy and clinical applications | journal = Journal of Central Nervous System Disease | volume = 3 | pages = 51–65 | date = 12 April 2011 | pmid = 23861638 | pmc = 3663615 | doi = 10.4137/JCNSD.S1611 }}</ref>

Fluvoxamine has been observed to increase serum concentrations of [[mirtazapine]], which is mainly metabolized by CYP1A2, CYP2D6, and CYP3A4, by three- to four-fold in humans.<ref name="AnttilaRasanen2001">{{cite journal | vauthors = Anttila AK, Rasanen L, Leinonen EV | title = Fluvoxamine augmentation increases serum mirtazapine concentrations three- to fourfold | journal = The Annals of Pharmacotherapy | volume = 35 | issue = 10 | pages = 1221–1223 | date = October 2001 | pmid = 11675851 | doi = 10.1345/aph.1A014 | s2cid = 44807359 }}</ref> Caution and adjustment of dosage as necessary are warranted when combining fluvoxamine and [[mirtazapine]].<ref name="AnttilaRasanen2001" />

Fluvoxamine seriously affects the [[pharmacokinetics]] of [[tizanidine]] and increases the intensity and duration of its effects. Because of the potentially hazardous consequences, the concomitant use of [[tizanidine]] with fluvoxamine, or other potent inhibitors of [[CYP1A2]], should be avoided.<ref>{{cite journal | vauthors = Granfors MT, Backman JT, Neuvonen M, Ahonen J, Neuvonen PJ | title = Fluvoxamine drastically increases concentrations and effects of tizanidine: a potentially hazardous interaction | journal = Clinical Pharmacology and Therapeutics | volume = 75 | issue = 4 | pages = 331–341 | date = April 2004 | pmid = 15060511 | doi = 10.1016/j.clpt.2003.12.005 | s2cid = 25781307 }}</ref>

When a beta-blocker is required, [[atenolol]],<ref name="pmid7988100">{{cite journal | vauthors = Perucca E, Gatti G, Spina E | title = Clinical pharmacokinetics of fluvoxamine | journal = Clinical Pharmacokinetics | volume = 27 | issue = 3 | pages = 175–190 | date = September 1994 | pmid = 7988100 | doi = 10.2165/00003088-199427030-00002 | s2cid = 22472247 }}</ref> [[pindolol]]<ref name="pmid11543734">{{cite journal | vauthors = Zanardi R, Serretti A, Rossini D, Franchini L, Cusin C, Lattuada E, Dotoli D, Smeraldi E | title = Factors affecting fluvoxamine antidepressant activity: influence of pindolol and 5-HTTLPR in delusional and nondelusional depression | journal = Biological Psychiatry | volume = 50 | issue = 5 | pages = 323–330 | date = September 2001 | pmid = 11543734 | doi = 10.1016/s0006-3223(01)01118-0 | s2cid = 22692759 }}</ref><ref>{{cite journal | vauthors = Sluzewska A, Szczawinska K | title = The effects of pindolol addition to fluvoxamine and buspirone in chronic mild stress model of depression. | journal = Behavioural Pharmacology | date = May 1996 | volume = 7 | pages = 105 }}</ref><ref name="pmid9817627">{{cite journal | vauthors = Mundo E, Guglielmo E, Bellodi L | title = Effect of adjuvant pindolol on the antiobsessional response to fluvoxamine: a double-blind, placebo-controlled study | journal = International Clinical Psychopharmacology | volume = 13 | issue = 5 | pages = 219–224 | date = September 1998 | pmid = 9817627 | doi = 10.1097/00004850-199809000-00005 | s2cid = 23946424 }}</ref> and, possibly, [[metoprolol]]<ref name="pmid9681670">{{cite journal | vauthors = Belpaire FM, Wijnant P, Temmerman A, Rasmussen BB, Brøsen K | title = The oxidative metabolism of metoprolol in human liver microsomes: inhibition by the selective serotonin reuptake inhibitors | journal = European Journal of Clinical Pharmacology | volume = 54 | issue = 3 | pages = 261–264 | date = May 1998 | pmid = 9681670 | doi = 10.1007/s002280050456 | s2cid = 28105445 }}</ref><ref name="pmid8904628">{{cite journal | vauthors = Xu ZH, Xie HG, Zhou HH | title = In vivo inhibition of CYP2C19 but not CYP2D6 by fluvoxamine | journal = British Journal of Clinical Pharmacology | volume = 42 | issue = 4 | pages = 518–521 | date = October 1996 | pmid = 8904628 | pmc = 2042705 | doi = 10.1046/j.1365-2125.1996.45319.x | doi-broken-date = 22 April 2024 }}</ref><ref name=":0"/><ref>{{cite journal | vauthors = Belpaire FM, Wijnant P, Tammerman A, Bogaert M, Rasmussen B, Brosen K | title = Inhibition of the oxidative metabolism of metoprolol by selective serotonin reuptake inhibitors in human liver microsomes. | journal = Fundamental and Clinical Pharmacology | date = 1997 | volume = 2 | issue = 11 | pages = 147 }}</ref> may be safer choices than [[propranolol]], as the latter's metabolism is seriously, potentially dangerously, inhibited by fluvoxamine.<ref name="pmid8846617">{{cite journal | vauthors = van Harten J | title = Overview of the pharmacokinetics of fluvoxamine | journal = Clinical Pharmacokinetics | volume = 29 | issue = Suppl 1| pages = 1–9 | date = 1995 | pmid = 8846617 | doi = 10.2165/00003088-199500291-00003 | s2cid = 71812133 }}</ref> Indeed, fluvoxamine may increase propranolol blood-levels by five-fold.<ref name="pmid22311403">{{cite journal | vauthors = Muscatello MR, Spina E, Bandelow B, Baldwin DS | title = Clinically relevant drug interactions in anxiety disorders | journal = Human Psychopharmacology | volume = 27 | issue = 3 | pages = 239–253 | date = May 2012 | pmid = 22311403 | doi = 10.1002/hup.2217 | s2cid = 11592004 }}</ref>

[[Clomipramine]] increases fluvoxamine levels and, conversely-likewise, fluvoxamine increases [[clomipramine]] levels (thereby its serotoninergic potential) and inhibits its metabolism to its strongly-noradrenergic metabolite, [[norclomipramine]].<ref name="pmid8666564">{{cite journal | vauthors = Szegedi A, Wetzel H, Leal M, Härtter S, Hiemke C | title = Combination treatment with clomipramine and fluvoxamine: drug monitoring, safety, and tolerability data | journal = The Journal of Clinical Psychiatry | volume = 57 | issue = 6 | pages = 257–264 | date = June 1996 | pmid = 8666564 | doi = }}</ref><ref name="pmid34777510">{{cite journal | vauthors = Hardy NE, Walkup JT | title = Clomipramine in Combination with Fluvoxamine: A Potent Medication Combination for Severe or Refractory Pediatric OCD | journal = Journal of the Canadian Academy of Child and Adolescent Psychiatry | volume = 30 | issue = 4 | pages = 273–277 | date = November 2021 | pmid = 34777510 | pmc = 8561855 | doi = }}</ref>

==Pharmacology==
{| class="wikitable floatright"
|+Receptor affinity profile<ref>{{cite journal | vauthors = Ishikawa M, Ishiwata K, Ishii K, Kimura Y, Sakata M, Naganawa M, Oda K, Miyatake R, Fujisaki M, Shimizu E, Shirayama Y, Iyo M, Hashimoto K | title = High occupancy of sigma-1 receptors in the human brain after single oral administration of fluvoxamine: a positron emission tomography study using [11C]SA4503 | journal = Biological Psychiatry | volume = 62 | issue = 8 | pages = 878–883 | date = October 2007 | pmid = 17662961 | doi = 10.1016/j.biopsych.2007.04.001 | s2cid = 728565 }}</ref><ref>{{cite book |title=The American Psychiatric Publishing textbook of psychopharmacology | vauthors = Schatzberg AF, Nemeroff CB |publisher= American Psychiatric Pub. |year=2009 |isbn=978-1-585-62386-0 |edition=4th |location=Arlington, VA |pages=354 |oclc=320111564}}</ref><ref>{{cite journal | vauthors = Yahata M, Chiba K, Watanabe T, Sugiyama Y | title = Possibility of Predicting Serotonin Transporter Occupancy From the In Vitro Inhibition Constant for Serotonin Transporter, the Clinically Relevant Plasma Concentration of Unbound Drugs, and Their Profiles for Substrates of Transporters | journal = Journal of Pharmaceutical Sciences | volume = 106 | issue = 9 | pages = 2345–2356 | date = September 2017 | pmid = 28501470 | doi = 10.1016/j.xphs.2017.05.007 | doi-access = free }}</ref>
|-
! Site !! K<sub>i</sub> (nM)
|-
| {{abbrlink|SERT|Serotonin transporter}} || 2.5
|-
| {{abbrlink|NET|Norepinephrine transporter}} || 1,427
|-
| [[5-HT2C receptor|5-HT<sub>2C</sub>]] || 5,786
|-
| [[Alpha-1 adrenergic receptor|α<sub>1</sub>-adrenergic]] || 1,288
|-
| [[Sigma-1 receptor|σ<sub>1</sub>]] || 36
|}

Fluvoxamine is a potent [[selective serotonin reuptake inhibitor]] with around 100-fold affinity for the [[serotonin transporter]] over the [[norepinephrine transporter]].<ref name = GG/> It has negligible affinity for the [[dopamine transporter]] or any other site, with the sole exception of the [[sigma-1 receptor|σ<sub>1</sub> receptor]].<ref name = sig>{{cite journal | vauthors = Hashimoto K | title = Sigma-1 receptors and selective serotonin reuptake inhibitors: clinical implications of their relationship | journal = Central Nervous System Agents in Medicinal Chemistry | volume = 9 | issue = 3 | pages = 197–204 | date = September 2009 | pmid = 20021354 | doi = 10.2174/1871524910909030197 }}</ref><ref name = "Westenberg_2006" /> It behaves as a potent [[agonist]] at this receptor and has the highest affinity (36&nbsp;nM) of any SSRI for doing so.<ref name = sig/> This may contribute to its antidepressant and [[anxiolytic]] effects and may also afford it some efficacy in treating the cognitive symptoms of depression.<ref name = cog>{{cite journal | vauthors = Hindmarch I, Hashimoto K | title = Cognition and depression: the effects of fluvoxamine, a sigma-1 receptor agonist, reconsidered | journal = Human Psychopharmacology | volume = 25 | issue = 3 | pages = 193–200 | date = April 2010 | pmid = 20373470 | doi = 10.1002/hup.1106 | s2cid = 26491662 }}</ref> Unlike some other SSRIs, fluvoxamine's metabolites are pharmacologically neutral.<ref name="pmid1931931">{{cite journal | vauthors = Hrdina PD | title = Pharmacology of serotonin uptake inhibitors: focus on fluvoxamine | journal = Journal of Psychiatry & Neuroscience | volume = 16 | issue = 2 Suppl 1 | pages = 10–18 | date = July 1991 | pmid = 1931931 | pmc = 1188307 }}</ref>

==History==
Fluvoxamine was developed by Kali-Duphar,<ref name="Sittig"/> part of [[Solvay (company)|Solvay Pharmaceuticals]], Belgium, now [[Abbott Laboratories]], and introduced as Floxyfral in Switzerland in 1983.<ref name=Sittig>{{cite book|title=Sittig's Pharmaceutical Manufacturing Encyclopedia|year=2008|publisher=William Andrew|isbn=978-0-8155-1526-5|page=1699|url=http://www.armchairpatriot.com/Encyclopedias/Encyclopedia-Pharmaceutical%20Manufacturing%20%283rd%20edition%29/15265_v02_04.pdf|edition=3rd|access-date=17 October 2013|archive-date=14 October 2013|archive-url=https://web.archive.org/web/20131014042521/http://www.armchairpatriot.com/Encyclopedias/Encyclopedia-Pharmaceutical%20Manufacturing%20%283rd%20edition%29/15265_v02_04.pdf|url-status=dead}}</ref> It was approved by the U.S. [[Food and Drug Administration]] (FDA) in 1994, and introduced as Luvox in the US.<ref>{{cite journal | vauthors = Leslie LK, Newman TB, Chesney PJ, Perrin JM | title = The Food and Drug Administration's deliberations on antidepressant use in pediatric patients | journal = Pediatrics | volume = 116 | issue = 1 | pages = 195–204 | date = July 2005 | pmid = 15995053 | pmc = 1550709 | doi = 10.1542/peds.2005-0074 }}</ref> In India, it is available, among several other brands, as Uvox by Abbott.<ref name=India>{{cite web|title=Brand Index―Fluvoxamine India |url=http://www.drugsupdate.com/brand/showavailablebrands/184 |access-date=18 October 2013 |archive-url=https://web.archive.org/web/20131019151123/http://www.drugsupdate.com/brand/showavailablebrands/184 |archive-date=19 October 2013 |url-status=dead }}</ref> It was one of the first SSRI antidepressants to be launched, and is prescribed in many countries to patients with major depression.<ref name="Cochrane 2010/2013">{{cite journal | vauthors = Omori IM, Watanabe N, Nakagawa A, Cipriani A, Barbui C, McGuire H, Churchill R, Furukawa TA | title = Fluvoxamine versus other anti-depressive agents for depression | journal = The Cochrane Database of Systematic Reviews | issue = 3 | pages = CD006114 | date = March 2010 | pmid = 20238342 | pmc = 4171125 | doi = 10.1002/14651858.CD006114.pub2 }}</ref> It was the first SSRI, a non-[[tricyclic antidepressant|TCA]] drug, approved by the U.S. FDA specifically for the treatment of OCD.<ref name="OCD Medication">{{cite web|title=OCD Medication |url=http://www.brainphysics.com/medications.php |access-date=17 October 2013 |archive-url=https://web.archive.org/web/20131014072454/http://www.brainphysics.com/medications.php |archive-date=14 October 2013 |url-status=dead }}</ref> At the end of 1995, more than ten million patients worldwide had been treated with fluvoxamine.<ref>{{cite web | year = 1999 | title = Fluvoxamine Product Monograph | url = https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021519s003lbl.pdf | access-date = 15 September 2018 | archive-date = 27 October 2020 | archive-url = https://web.archive.org/web/20201027214646/https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021519s003lbl.pdf | url-status = live }}</ref>{{failed verification|reason=no discussion of ten million patients|date=November 2019}} Fluvoxamine was the first SSRI to be registered for the treatment of obsessive compulsive disorder in children by the FDA in 1997.<ref>{{cite web | title = Luvox Approved For Obsessive Compulsive Disorder in Children and Teens | url = http://www.pslgroup.com/dg/2261a.htm | access-date = 8 February 2014 | archive-url = https://web.archive.org/web/20090116004424/http://www.pslgroup.com/dg/2261a.htm | archive-date = 16 January 2009 | url-status = dead }}</ref> In Japan, fluvoxamine was the first SSRI to be approved for the treatment of depression in 1999<ref>{{cite journal | vauthors = Higuchi T, Briley M | title = Japanese experience with milnacipran, the first serotonin and norepinephrine reuptake inhibitor in Japan | journal = Neuropsychiatric Disease and Treatment | volume = 3 | issue = 1 | pages = 41–58 | date = February 2007 | pmid = 19300537 | pmc = 2654524 | doi = 10.2147/nedt.2007.3.1.41 | doi-access = free }}</ref><ref>{{cite HMDB|author1-link=David S. Wishart|url=http://www.hmdb.ca/metabolites/HMDB0014322|title=Showing metabocard for Fluvoxamine (HMDB0014322)}}</ref> and was later in 2005 the first drug to be approved for the treatment of social anxiety disorder.<ref>{{cite web | title = Solvay's Fluvoxamine maleate is first drug approved for the treatment of social anxiety disorder in Japan | url = https://www.fdanews.com/articles/81585-solvay-s-fluvoxamine-maleate-is-first-drug-approved-for-treatment-of-social-anxiety-disorder-in-japan | access-date = 15 September 2018 | archive-date = 15 September 2018 | archive-url = https://web.archive.org/web/20180915122310/https://www.fdanews.com/articles/81585-solvay-s-fluvoxamine-maleate-is-first-drug-approved-for-treatment-of-social-anxiety-disorder-in-japan | url-status = live }}</ref> Fluvoxamine was the first SSRI approved for clinical use in the United Kingdom.<ref>{{cite book | isbn = 978-0-7020-4293-5 | title = Clinical Pharmacy and Therapeutics | year = 2007 | orig-year = 1994 | publisher = Churchill Livingstone Elsevier | location = Edinburgh | edition = 4th | veditors = Walker R, Whittlesea C }}</ref> Manufacturers include BayPharma, [[Synthon (company)|Synthon]], and [[Teva Pharmaceuticals|Teva]], among others.<ref>{{cite web |title=Fluvoxamine |url=https://www.drugbank.ca/drugs/DB00176 |website=www.drugbank.ca |access-date=22 October 2019 |archive-date=4 November 2019 |archive-url=https://web.archive.org/web/20191104161742/https://www.drugbank.ca/drugs/DB00176 |url-status=live }}</ref>

== Research directions ==

While early studies have suggested potential benefits for fluvoxamine as an anti-inflammatory agent and a possible impact on reducing cytokine storms, further studies did not confirm this expected benefit on COVID-19 patients.<ref name="pmid35383578">{{cite journal | vauthors = Bhuta S, Khokher W, Kesireddy N, Iftikhar S, Beran A, Mhanna M, Patel NJ, Patel M, Burmeister C, Assaly R | title = Fluvoxamine in Nonhospitalized Patients With Acute COVID-19 Infection and the Lack of Efficacy in Reducing Rates of Hospitalization, Mechanical Ventilation, and Mortality in Placebo-Controlled Trials: A Systematic Review and Meta-Analysis | journal = American Journal of Therapeutics | volume = 29 | issue = 3 | pages = e298–e304 | date = 2022 | pmid = 35383578 | doi = 10.1097/MJT.0000000000001496 | s2cid = 247978477 | doi-access = free }}</ref><ref name="pmid36532776">{{cite journal | vauthors = Asadi Anar M, Foroughi E, Sohrabi E, Peiravi S, Tavakoli Y, Kameli Khouzani M, Behshood P, Shamshiri M, Faridzadeh A, Keylani K, Langari SF, Ansari A, Khalaji A, Garousi S, Mottahedi M, Honari S, Deravi N | title = Selective serotonin reuptake inhibitors: New hope in the fight against COVID-19 | journal = Frontiers in Pharmacology | volume = 13 | issue = | pages = 1036093 | date = 2022 | pmid = 36532776 | pmc = 9748354 | doi = 10.3389/fphar.2022.1036093 | doi-access = free }}</ref> A cytokine storm refers to an excessive immune response characterized by a release of large amounts of pro-inflammatory cytokines.<ref name="pmid32592501">{{cite journal | vauthors = Hu B, Huang S, Yin L | title = The cytokine storm and COVID-19 | journal = Journal of Medical Virology | volume = 93 | issue = 1 | pages = 250–256 | date = January 2021 | pmid = 32592501 | pmc = 7361342 | doi = 10.1002/jmv.26232 }}</ref>

In May 2022, based on a review of available scientific evidence, the U.S. [[Food and Drug Administration]] (FDA) chose not to issue an [[emergency use authorization]] covering the use of fluvoxamine to treat COVID-19, saying that, at the time, the data was not sufficient to conclude that fluvoxamine may be effective in treating non-hospitalized people with COVID-19 to prevent serious illness or hospitalization. The agency stated that study results suggest that further clinical trials may be warranted.<ref>{{cite news |title=FDA declines to authorize common antidepressant as COVID treatment |url=https://www.reuters.com/business/healthcare-pharmaceuticals/fda-declines-authorize-common-antidepressant-covid-treatment-2022-05-16/ |access-date=18 May 2022 |work=Reuters |date=16 May 2022 |archive-date=17 May 2022 |archive-url=https://web.archive.org/web/20220517202625/https://www.reuters.com/business/healthcare-pharmaceuticals/fda-declines-authorize-common-antidepressant-covid-treatment-2022-05-16/ |url-status=live }}</ref><ref>{{cite tech report |type=Memorandum |title=Memorandum Explaining Basis for Declining Request for Emergency Use Authorization of Fluvoxamine Maleate |id=4975580 |institution=Food and Drug Administration |date=16 May 2022 |url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/EUA%20110%20Fluvoxamine%20Decisional%20Memo_Redacted.pdf |archive-url=https://web.archive.org/web/20220517001646/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/EUA%20110%20Fluvoxamine%20Decisional%20Memo_Redacted.pdf |archive-date=17 May 2022 |url-status=live}} {{PD-notice}}</ref>

A large double-blind randomized controlled trial called ACTIV-6, published in 2023 in ''[[JAMA]]'', revealed that taking 200&nbsp;mg of fluvoxamine every day for about two weeks was not significantly better than placebo at shortening the duration of mild or moderate COVID-19 symptoms.<ref>{{cite web |last=Ingram |first=Ian |date=17 November 2023 |title=Higher-Dose Fluvoxamine Fails for COVID Outpatients |website=[[MedPage Today]] |url=https://www.medpagetoday.com/infectiousdisease/covid19/107439 |access-date=4 December 2023 |url-status=live |archive-url=https://web.archive.org/web/20231117222854/https://www.medpagetoday.com/infectiousdisease/covid19/107439 |archive-date=17 November 2023}}</ref>{{med cn|date=December 2023}}

There is tentative evidence that fluvoxamine may reduce the overall morbidity of [[COVID-19]] and complications thereof.<ref>{{cite journal |vauthors=Nyirenda JL, Sofroniou M, Toews I, Mikolajewska A, Lehane C, Monsef I, Abu-Taha A, Maun A, Stegemann M, Schmucker C |title=Fluvoxamine for the treatment of COVID-19 |journal=The Cochrane Database of Systematic Reviews |volume=2022 |issue=9 |pages=CD015391 |date=September 2022 |pmid=36103313 |pmc=9473347 |doi=10.1002/14651858.CD015391 |type=Systematic review}}</ref><ref>{{cite journal |vauthors=Wannigama DL, Hurst C, Phattharapornjaroen P, Hongsing P, Sirichumroonwit N, Chanpiwat K, ((Rad S. M. AH)), Storer RJ, Ounjai P, Kanthawee P, Ngamwongsatit N, Kupwiwat R, Kupwiwat C, Brimson JM, Devanga Ragupathi NK, Charuluxananan S, Leelahavanichkul A, Kanjanabuch T, Higgins PG, Badavath VN, Amarasiri M, Verhasselt V, Kicic A, Chatsuwan T, Pirzada K, Jalali F, Reiersen AM, Abe S, Ishikawa H |title=Early treatment with fluvoxamine, bromhexine, cyproheptadine, and niclosamide to prevent clinical deterioration in patients with symptomatic COVID-19: a randomized clinical trial |journal=eClinicalMedicine |volume=70 |issue= |pages=102517 |date=April 2024 |pmid=38516100 |pmc=10955208 |doi=10.1016/j.eclinm.2024.102517}}</ref>

==Environment==
Fluvoxamine is a common finding in waters near human settlement.<ref name="Runoff" /> Christensen ''et al.'' 2007 finds it is "very toxic to aquatic organisms" by [[European Union]] standards.<ref name="Runoff">
{{Unbulleted list citebundle
|{{*}} {{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 }}
|{{*}} {{cite journal | vauthors = Christensen AM, Faaborg-Andersen S, Ingerslev F, Baun A | title = Mixture and single-substance toxicity of selective serotonin reuptake inhibitors toward algae and crustaceans | journal = Environmental Toxicology and Chemistry | volume = 26 | issue = 1 | pages = 85–91 | date = January 2007 | pmid = 17269464 | doi = 10.1897/06-219R.1 | publisher = [[John Wiley & Sons, Inc.]] ([[Society of Environmental Toxicology and Chemistry]] (SETAC)) | s2cid = 6562531 | doi-access = free }}
}}
</ref>

== References ==
{{Reflist}}


{{Antidepressants}}
{{Antidepressants}}
{{Anxiolytics}}
{{Anxiolytics}}
{{OCD pharmacotherapies}}
{{Serotonergics}}
{{Monoamine reuptake inhibitors}}

{{Sigma receptor modulators}}
==External links==
{{Portal bar | Medicine}}
* [http://www.drugs.com/cons/Fluvoxamine.html Fluvoxamine consumer information from Drugs.com]


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