Fluvoxamine
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| Image:Fluvoxamine.png | |
| Fluvoxamine
| |
| Systematic (IUPAC) name | |
| 2-[(5-methoxy-1- [4-(trifluoromethyl) phenyl]pentylidene) amino]oxyethanamine | |
| Identifiers | |
| CAS number | 54739-18-3 |
| ATC code | N06AB08 |
| PubChem | 5324346 |
| DrugBank | APRD00425 |
| Chemical data | |
| Formula | C15H21F3N2O2 |
| Mol. weight | 318.335 |
| Pharmacokinetic data | |
| Bioavailability | 77% |
| Metabolism | Hepatic |
| Half life | 15.6 hours |
| Excretion | Renal |
| Therapeutic considerations | |
| Pregnancy cat. |
C |
| Legal status |
Schedule VI US |
| Routes | Oral |
Fluvoxamine (brand name as Luvox®, Faverin®, Fevarin® and Dumyrox®) is an antidepressant which functions pharmacologically as a selective serotonin reuptake inhibitor. Fluvoxamine is widely prescribed to treat depression, and anxiety disorder such as Obsessive-Compulsive Disorder, Obsessive-Compulsive Spectrum Disorder, Panic Disorder, Social Phobia and Post-Traumatic Stress Disorder.
Although all SSRIs inhibit the reuptake of serotonin, Fluvoxamine has different pharmacological and side effects profiles from other drugs in its class. For this reason, Fluvoxamine can be of benefit to patients who experience unusual or limiting side-effects from other antidepressants. It appears to cause fewer side effects than other SSRIs. These differences are a result of the lack of direct effects at other neurotransmitter receptors 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 for all these sites.
Fluvoxamine has the least incidence of side effects on sexual dysfunctions, or loss of sex drive of all the SSRIs.
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.
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[edit] History
Fluvoxamine was the first of the SSRI antidepressants to be launched (1984 - Switzerland) and was developed by Solvay Pharmaceuticals. In the US, it was launched in 1994 and the first SSRI in Japan in 1999.
[edit] Dosage & Administration
The normal dosage for depression and anxiety is to 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.
[edit] Drug Interactions
Fluvoxamine has a low potential for drug interactions. However, it does inhibit Cytochrome P450 enzyme CYP1A2, which metabolises theophylline, caffeine, phenacetin, tacrine, clozapine, olanzapine, and tricyclic antidepressants. This substances can cause increase serum levels when administered together with fluvoxamine. Therefore, it is untrue if fluxoxamine will lead to more drug interactions. Its all depend on the type of inhibition of P450 enzyme. For example, CYP2D6 will have more interactions with TCAs, antiarrythmics, B-blockers, phenytoin, opiates and neuroleptics. Among all the the SSRI, Fluvoxamine does not inhibit of CYP2D6. It has only modest effects on CYP2C and CYP3A3/4.
In addition, Fluvoxamine has relatively short plasma half life ~15 hours, and has no active metabolites. With this properties, Fluvoxamine has less chances 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.
[edit] Side effects
Side effects of fluvoxamine can include: anorexia, constipation, dry mouth, headache, nausea, nervousness, skin rash, sleep problems, somnolence, liver toxicity, mania, increased urination, seizures, increased sweating, tremors, or Tourette's syndrome.
[edit] Historical relevance
In 1999, fluvoxamine came under great public scrutiny after it was discovered that 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. 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.[1] The UK and Health Canada have taken similar actions.
[edit] 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.
[edit] External links
