View source for Fluvoxamine

{{Drugbox|
|IUPAC_name = ''2-[(5-methoxy-1- [4-(trifluoromethyl) phenyl]pentylidene) amino]oxyethanamine''
| image=Fluvoxamine structure.svg
| width=140
| CAS_number=54739-18-3
| ATC_prefix=N06
| ATC_suffix=AB08
| ATC_supplemental=
| PubChem=5324346
| DrugBank=APRD00425
| 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_status = Schedule VI <small>[[US]]</small>
| routes_of_administration= Oral
}}
'''Fluvoxamine''' (brand name as '''Luvox'''®, '''Faverin'''®, '''Fevarin'''® and '''Dumyrox'''®) is an antidepressant which functions pharmacologically as a [[selective serotonin reuptake inhibitor]]. Though it is in the same class as other SSRI drugs, it is most often used to treat [[obsessive-compulsive disorder]].

==History==
Fluvoxamine was one of the first of the SSRI antidepressants to be launched (1984 - Switzerland) and was developed by [[Solvay (company)|Solvay Pharmaceuticals]]. It has been in use in clinical practice since 1983 and has a clinical trial database comprised of approximately 35,000 patients. It was launched in the US in December 1994 and in Japan in June 1999. As of the end of 1995, more than 10 million patients worldwide have been treated with fluvoxamine.<ref>{{cite journal | first = | last =  | date = 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 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>

==Indication==
===Approved===
Fluvoxamine is widely prescribed to treat [[Clinical depression|depression]], and [[anxiety disorder]]s such as [[Obsessive-Compulsive Disorder]], [[Obsessive-Compulsive Spectrum Disorder]], [[Panic Disorder]], [[Social Phobia]], and [[Post-Traumatic Stress Disorder]].<ref>{{cite journal | first = David P. Figgit | last = Karen J. McClellan | date = Drugs Oct 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 is indicated for children and adolescents with OCD.<ref>{{cite journal | first = | last = | date = March 2005 | title = US-FDA Fluvoxamine Product Insert | journal = | volume = | issue = | pages = }}</ref>

===Unapproved/Off-label/Investigational===
Fluvoxamine is also used for the treatment of children and adolescents with social phobia, [[separation anxiety disorder]], or [[generalized anxiety disorder]].<ref>{{cite journal | first = Michael J. Labelarte MD et.al. | last = John T Walker MD | date = April 26, 2001 | title = Fluvoxamine for the treatment of anxiety disorders in children and adolescents | journal = The New England Journal of Medicine | volume = 344 | issue = | pages = 1279-1285}}</ref>

Fluvoxamine may help in the treatment of [[Irritable Bowel Syndrome]].<ref>{{cite journal | first = et al. | last = Emmanuel | date = 1997 | title = Treatment of Irritable Bowel Syndrome with Fluvoxamine | journal = Am J Psychiatry | volume = 154 | issue = | pages = 711-712}}</ref>

==Mode of Action==
Fluvoxamine is one of the few SSRI class of drugs to have a monocyclic structure.

Although all SSRIs inhibit the reuptake of serotonin, fluvoxamine has different pharmacological and side effects profiles from other drugs in its class. Fluvoxamine has been shown to be selective for serotonin reuptake, and has little effect on dopamine and noradrenaline uptake systems compared to other SSRI. For this reason, fluvoxamine can be of benefit to patients who experience unusual or limiting [[Adverse drug reaction|side-effects]] from other antidepressants. It appears to cause fewer side effects than other SSRIs. In addition, these differences also are a result of the lack of direct effects at other [[neurotransmitter receptor]]s compared to other SSRIs. Affinity for these receptors, for example [[cholinergic]] [[muscarinic]] (dry mouth, constipation) sites, [[histaminergic]] (sedation) sites, [[alpha]] (postural hypertension) sites and [[dopamine]] ([[extrapyramidal]])sites, leads to many side effects. Compared to other SSRIs, fluvoxamine has a very low affinity to all of these sites.<ref>{{cite journal | first = Hyttel | last = J. | date = 1993 | title = Comparative pharmacology of selective serotonin reuptake inhibitors (SSRIs) | journal = Nordisk Journal of Psychiatric | volume = 47 | issue = Suppl 30 | pages = 5-12 }}</ref>

Among the SSRIs, fluvoxamine has the highest affinity for [[sigma receptor]] subtype 1 (σ<sub>1</sub>receptors)<ref>{{cite journal | first = Narita N | last = Hashimoto K et al. | date = 1996 | title = Interactions of selective reuptake inhibitors with subtypes of sigma receptor in rat brain | journal = Eur J Pharmacol| volume = 307 | issue = | pages = 117-9}}</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 | date = December 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}}</ref>

==Pharmacokinetics==
===Absorption===
The oral absorption of fluvoxamine is equal to or more than 94%.

===Distribution===
The plasma protein binding is only about 77%.

===Metabolism===
Fluvoxamine is extensively metabolised in the liver. It has no active metabolites.

===Elimination===
Fluvoxamine has the shortest [[half-life]] of all the SSRIs.  Its mean [[serum]] half-life is 15 hours after a single dose, and 17 to 22 hours after repeated doses.

==Dosage & Administration==
The normal dosage for depression and anxiety starts at 50mg per day, rising to 100mg after a few days.  It may be raised after evaluation of the effects by a doctor.

Fluvoxamine has shown generally effective for OCD at 150mg and above, and dosages can reach 300mg or more for some patients.

==Drug Interactions==
Fluvoxamine has a low potential for [[drug interaction]]s. In terms of inhibition of enzyme [[Cytochrome P450]] [[CYP2D6]], fluvoxamine is the cleanest among all the SSRI because importantly it does not inhibit CYP2D6.<ref>{{cite journal | first = Baumann | last = P. | date = 1996 | title = Pharmacokinetic-pharmacodynamic relationship of the Selective serotonin reuptake inhibitors | journal = Clinical Pharmacokinetics | volume = 31 | issue = | pages = 444-469}}</ref><ref>{{cite journal | first = DeVane CL | last = Gill HS | date = 1997 | title = Clinical Pharmacokinetics of Fluvoxamine: applications to dosage regime design | journal = Journal of Clinical Psychiatric | volume = 58 | issue = Suppl 5 | pages = 7-14}}</ref><ref>{{cite journal | first =  CL | last = DeVane| date = 1998 | title = Translational pharmacokinetics: current issues with newer antidepressants | journal = Depression and Anxiety | volume = 8 | issue = Suppl 1 | pages = 64-70}}</ref>
Drugs that interacts with CYP2D6 will have more interactions with TCAs, antiarrythmics, B-blockers, phenytoin, opiates (eg. codeine, dextromethophon, morphine, tramadol) and neuroleptics (eg. haloperidol, risperidon). It does, however, inhibit Cytochrome P450 enzyme [[CYP1A2]], which metabolises [[theophylline]], [[caffeine]], [[phenacetin]], [[tacrine]], [[clozapine]], and [[olanzapine]],  . These substances can cause increased serum levels when administered together with fluvoxamine. It has only modest effects on [[CYP2C]] and [[CYP3A3/4]]. Therefore, different SSRI have different level of drug interactions depending on the inhibition of Cytochrome P450 enzymez. 

In addition, fluvoxamine has relatively short plasma half life, roughly 15 hours, and has no active metabolites. With these properties, fluvoxamine has less of a chance of drug accumulations and interactions.

The plasma protein binding of fluvoxamine is only about 77%. Drugs with low protein binding are less likely to displace other protein bound drugs, and therefore have a lower potential to cause drug interactions.

==Side effects==
Fluvoxamine has the least incidence of side effects on sexual dysfunctions, or loss of sex drive of all the SSRIs.<ref>{{cite journal | first = Waldinger MD | last = Hengeveld VW et al. | date = 1998 | title = Effect of SSRI antidepressants on ejaculation: a double blind, randomised, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine and sertraline | journal = Journal of Clinical Psychopharmacology | volume = 18 | issue = | pages = 274-281}}</ref>

Side effects of fluvoxamine can include: 
common
decreased sex drive or ability, drowsiness, tiredness, diarrhea, dizziness or light-headedness, [[constipation]],  [[headache]], [[nausea]], [[nervousness]], [[sleep]] problems, increased [[sweating]], [[tremors]], serious [[skin rash]] and other allergic problems such as difficulty breathing, fever, confusion, severe weakness,  intense agitation or anxiety, restlessness, [[hypomania]], [[mania]],  [[seizures]].

==Historical relevance==
In [[1999]], fluvoxamine came under great public scrutiny after it was discovered that [[Eric Harris and Dylan Klebold|Eric Harris]], one of the two teenaged shooters involved in the [[Columbine High School massacre]], had been taking the drug as treatment for depression.  Many immediately pointed fingers at fluvoxamine and its manufacturer Solvay Pharmaceuticals (which sells fluvoxamine under the widely known brandname Luvox), since Solvay's own clinical trials indicated the drug had the propensity to induce mania in 4% of the youth who took it. What was not made public however was that Solvay concealed from the public the fact that a homicide occurred during the clinical trials involving adults.  Solvay, while acknowledging the risks inherent in taking an SSRI medication like fluvoxamine, downplayed any role the drug may have had in the killings.  The [[American Psychiatric Association]] (A.P.A.) took a similar stance; Rodrigo Munoz, M.D., President of the A.P.A., said: "Despite a decade of research, there is little valid evidence to prove a causal relationship between the use of anti-depressant medications and destructive behavior. On the other hand, there is ample evidence that undiagnosed and untreated mental illness exacts a heavy toll on those who suffer from these disorders as well as those around them."  It was also pointed out by many that Luvox was often safer than the other SSRI medications available--for example, fluoxetine (Prozac) caused mania in 6% of youth tested on the drug (versus fluvoxamine's 4%).  Nonetheless, the reputation of Luvox was irreparably damaged.  Sales fell, and Solvay withdrew the medication from the U.S. market in 2002; the company maintains, however, that this move had nothing to do with the safety profile of fluvoxamine, which they still sell in many countries around the world.  In the United States, fluvoxamine can only be purchased generically.

The FDA currently issues the following warning with Luvox:
Taking antidepressants may increase suicidal thoughts and actions in about 1 out of 50 people 18 years or younger.[http://www.fda.gov/cder/drug/infopage/fluvoxamine/default.htm]
The UK and Health Canada have taken similar actions.

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==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.

The Columbine killer [[Eric Harris]] had taken Luvox, which reports claimed may have been the cause for his shooting rampage, along with [[Dylan Klebold]].

"Stuttering" John Melendez, formerly of The Howard Stern Show, had taken Luvox for a period of time before his departure from the show.
-->

==References==
<div class="references-small">{{reflist|2}}</div>

==External links==
* [http://www.rxlist.com/cgi/generic/fluvox.htm RxList.com - Fluvoxamine]
* [http://www.drugs.com/cons/Fluvoxamine.html Drugs.com - Fluvoxamine]
* [http://www.solvay.com/solvayproducts/pharmaceuticals/psychiatry/0,,1532-2-0,00.htm Solvay S.A. Mental Health Pharmaceuticals - Luvox®]

{{Antidepressants}}
[[Category:Selective serotonin reuptake inhibitors]]

[[fr:Fluvoxamine]]
[[it:Fluvoxamina]]
[[ja:フルボキサミン]]
[[no:Fluvoksamin]]
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[[ru:Флувоксамин]]