Fluvoxamine
Encyclopedia
Fluvoxamine is an antidepressant
which functions as a selective serotonin reuptake inhibitor
(SSRI). Fluvoxamine was first approved by the U.S. Food and Drug Administration (FDA) in 1993 for the treatment of obsessive compulsive disorder (OCD). Fluvoxamine CR (controlled release) is approved to treat social anxiety disorder
. Fluvoxamine is also prescribed to treat major depressive disorder (MDD) and anxiety disorders, such as panic disorder
and post-traumatic stress disorder
(PTSD).
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. Sexual side effects with fluvoxamine are less pronounced than with other SSRIs.
over the norepinephrine transporter
. It has negligible affinity for the dopamine transporter
or any other receptor
, with the sole exception of the σ1 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 σ1 receptor
agonists, such as sertraline
and escitalopram
(not verified but likely to be), display enhanced antidepressant efficacy. 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). In fact, the TCA opipramol
, a σ1 receptor agonist without effects on the serotonin, dopamine, or norepinephrine systems, has considerable antidepressant and anxiolytic
efficacy in its own right.
of fluvoxamine is 53%. The plasma protein binding is about 80%.
demethylation
(producing fluvoxamine acid and its N-acetyl
analog) and deamination
(producing fluvoxethanol). Only fluvoxamine acid has been shown to have SERT
inhibitor activity, roughly 1-2 orders of magnitude
less potent than the parent compound.
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%.
half-life
of all SSRIs, with a mean of 15.6 hours.
, 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. A recent warning has been published regarding potentially serious interaction with tizanidine
, based on CYP1A2 metabolism. The half-life of caffeine is significantly extended by the use of fluvoxamine, which can cause insomnia and irritability in coffee drinkers.
Fluvoxamine inhibits metabolism of diazepam
and phenytoin
via CYP2C19
and metabolism of aripiprazole
, chlorpromazine
, clozapine
, haloperidol
, olanzapine
, perphenazine
, risperidone
, thioridazine
and zuclopenthixol
via CYP2D6
as well as of aripiprazole
, clozapine
, haloperidol
, quetiapine
and ziprasidone
via CYP3A4
.
Fluvoxamine has low potential for the drug interaction
s which are based on inhibition of enzyme Cytochrome P450 CYP2D6
, less than most other SSRIs.
Naturally the other SSRIs which are metabolized by CYP2D6 will have more CYP2D6-based interactions with TCAs
, antiarrhythmics, B-blockers, phenytoin
, opioids and neuroleptics.
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.
Fluvoxamine also inhibits CYP2C9
.
) to have a monocyclic structure.
and was the first non-TCA
drug approved by the U.S. Food and Drug Administration (FDA) specifically for the treatment of OCD. 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. At the end of 1995, more than 10 million patients worldwide had been treated with fluvoxamine. Fluvoxamine was the first SSRI to be registered for the treatment of obsessive compulsive disorder in children by the FDA in 1997. Fluvoxamine was the first drug approved for the treatment of social anxiety disorder in Japan in 2005.
In 1999, fluvoxamine came under great public scrutiny after it was discovered that 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. Sales fell, and Solvay withdrew the medication from the U.S. market in 2002. 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.
One of two shooters at the Columbine High School massacre
, Eric Harris
, was taking Luvox. Some analysts, such as psychiatrist Peter Breggin
, have argued that this medication may have contributed to Harris's actions. Breggin claimed that side-effects of these drugs include increased aggression, loss of remorse, depersonalization, and mania.
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
which functions as a selective serotonin reuptake inhibitor
Selective serotonin reuptake inhibitor
Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed...
(SSRI). Fluvoxamine was first approved by the U.S. Food and Drug Administration (FDA) in 1993 for the treatment of obsessive compulsive disorder (OCD). Fluvoxamine CR (controlled release) is approved to treat social anxiety disorder
Social anxiety disorder
Social anxiety disorder , also known as social phobia, is an anxiety disorder characterized by intense fear in social situations causing considerable distress and impaired ability to function in at least some parts of daily life...
. Fluvoxamine is also prescribed to treat major depressive disorder (MDD) and anxiety disorders, such as panic disorder
Panic disorder
Panic disorder is an anxiety disorder characterized by recurring severe panic attacks. It may also include significant behavioral change lasting at least a month and of ongoing worry about the implications or concern about having other attacks. The latter are called anticipatory attacks...
and post-traumatic stress disorder
Post-traumatic stress disorder
Posttraumaticstress disorder is a severe anxiety disorder that can develop after exposure to any event that results in psychological trauma. This event may involve the threat of death to oneself or to someone else, or to one's own or someone else's physical, sexual, or psychological integrity,...
(PTSD).
Medical uses
Fluvoxamine's primary use is the treatment of obsessive compulsive disorder (OCD). Fluvoxamine has been found to be useful in the treatment of major depressive disorder (MDD), and anxiety disorders such as panic disorder, social anxiety disorder, post-traumatic stress disorder (PTSD), and obsessive-compulsive spectrum disorders. Fluvoxamine is indicated for children and adolescents with OCD.Adverse effects
Side effectsAdverse effect (medicine)
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
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. Sexual side effects with fluvoxamine are less pronounced than with other SSRIs.
Pharmacology
Fluvoxamine is a potent and selective serotonin reuptake inhibitor with approximately 100-fold affinity for the serotonin transporterSerotonin transporter
The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...
over the norepinephrine transporter
Norepinephrine transporter
The norepinephrine transporter , also known as solute carrier family 6 member 2 , is a protein that in humans is encoded by the SLC6A2 gene....
. It has negligible affinity for the dopamine transporter
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...
or any other receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
, with the sole exception of the σ1 receptor
Sigma-1 receptor
The sigma-1 receptor is a chaperone protein at the endoplasmatic reticulum that modulates calcium signaling through the IP3 receptor. In humans, the sigma-1 receptor is encoded by the SIGMAR1 gene....
. It behaves as a potent agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
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 σ1 receptor
Sigma-1 receptor
The sigma-1 receptor is a chaperone protein at the endoplasmatic reticulum that modulates calcium signaling through the IP3 receptor. In humans, the sigma-1 receptor is encoded by the SIGMAR1 gene....
agonists, such as sertraline
Sertraline
Sertraline hydrochloride is an antidepressant of the selective serotonin reuptake inhibitor class. It was introduced to the market by Pfizer in 1991. Sertraline is primarily used to treat major depression in adult outpatients as well as obsessive–compulsive, panic, and social anxiety disorders in...
and escitalopram
Escitalopram
Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor class. It is approved by the U.S...
(not verified but likely to be), display enhanced antidepressant efficacy. 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). In fact, the TCA opipramol
Opipramol
Opipramol is an antidepressant and anxiolytic used in Germany and other European countries. Although it is a member of the tricyclic antidepressants, opipramol's primary mechanism of action is much different in comparison...
, a σ1 receptor agonist without effects on the serotonin, dopamine, or norepinephrine systems, has considerable antidepressant and anxiolytic
Anxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
efficacy in its own right.
Pharmacokinetics
The oral bioavailabilityBioavailability
In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
of fluvoxamine is 53%. The plasma protein binding is about 80%.
Metabolism
Fluvoxamine is strongly metabolized in the liver, mostly by the processes of oxidativeRedox
Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....
demethylation
Demethylation
Demethylation is the chemical process resulting in the removal a of methyl group from a molecule.A common way of demethylation is the replacement of a methyl group by a hydrogen atom, resulting in a net loss of one carbon and two hydrogen atoms....
(producing fluvoxamine acid and its N-acetyl
Acetyl
In organic chemistry, acetyl is a functional group, the acyl with chemical formula COCH3. It is sometimes represented by the symbol Ac . The acetyl group contains a methyl group single-bonded to a carbonyl...
analog) and deamination
Deamination
Deamination is the removal of an amine group from a molecule. Enzymes which catalyse this reaction are called deaminases.In the human body, deamination takes place primarily in the liver, however glutamate is also deaminated in the kidneys. Deamination is the process by which amino acids are...
(producing fluvoxethanol). Only fluvoxamine acid has been shown to have SERT
Serotonin transporter
The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...
inhibitor activity, roughly 1-2 orders of magnitude
Order of magnitude
An order of magnitude is the class of scale or magnitude of any amount, where each class contains values of a fixed ratio to the class preceding it. In its most common usage, the amount being scaled is 10 and the scale is the exponent being applied to this amount...
less potent than the parent compound.
Radio-labeled
Isotopic labeling
Isotopic labeling is a technique for tracking the passage of a sample of substance through a system. The substance is 'labeled' by including unusual isotopes in its chemical composition...
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
Empirical
The word empirical denotes information gained by means of observation or experimentation. Empirical data are data produced by an experiment or observation....
ly proven to contain 60% fluvoxamine acid and its N-acetyl analog, and 10% fluvoxethanol, with the other six metabolites making up 30%.
Elimination
Fluvoxamine has the shortest serumBlood serum
In blood, the serum is the component that is neither a blood cell nor a clotting factor; it is the blood plasma with the fibrinogens removed...
half-life
Half-life
Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...
of all SSRIs, with a mean of 15.6 hours.
Drug interactions
Fluvoxamine inhibits cytochrome P450 enzyme CYP1A2CYP1A2
Cytochrome P450 1A2 , a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body...
, which metabolises agomelatine, caffeine
Caffeine
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
, clozapine
Clozapine
Clozapine is an antipsychotic medication used in the treatment of schizophrenia, and is also used off-label in the treatment of bipolar disorder. Wyatt. R and Chew...
, haloperidol
Haloperidol
Haloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....
, phenacetin
Phenacetin
Phenacetin is an analgesic, once widely used; its use has declined because of its adverse effects.-History:Phenacetin was introduced in 1887, and was used principally as an analgesic, and was one of the first synthetic fever reducers to go on the market...
, tacrine
Tacrine
Tacrine is a centrally acting anticholinesterase and indirect cholinergic agonist . It was the first centrally-acting cholinesterase inhibitor approved for the treatment of Alzheimer's disease, and was marketed under the trade name Cognex. Tacrine was first synthesised by Adrien Albert at the...
, theophylline
Theophylline
Theophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD and asthma under a variety of brand names. Because of its numerous side-effects, the drug is now rarely administered for clinical use. As a member of the xanthine family, it...
, and olanzapine
Olanzapine
Olanzapine is an atypical antipsychotic, approved by the FDA for the treatment of schizophrenia and bipolar disorder...
. 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. A recent warning has been published regarding potentially serious interaction with tizanidine
Tizanidine
Tizanidine is a drug that is used as a muscle relaxant. It is a centrally acting α2 adrenergic agonist. It is used to treat the spasms, cramping, and tightness of muscles caused by medical problems such as multiple sclerosis, spastic diplegia, back pain, or certain other injuries to the spine or...
, based on CYP1A2 metabolism. The half-life of caffeine is significantly extended by the use of fluvoxamine, which can cause insomnia and irritability in coffee drinkers.
Fluvoxamine inhibits metabolism of diazepam
Diazepam
Diazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...
and phenytoin
Phenytoin
Phenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...
via CYP2C19
CYP2C19
Cytochrome P450 2C19 , a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. It is involved in the metabolism of several...
and metabolism of aripiprazole
Aripiprazole
Aripiprazole is an atypical antipsychotic and antidepressant used in the treatment of schizophrenia, bipolar disorder, and clinical depression...
, chlorpromazine
Chlorpromazine
Chlorpromazine is a typical antipsychotic...
, clozapine
Clozapine
Clozapine is an antipsychotic medication used in the treatment of schizophrenia, and is also used off-label in the treatment of bipolar disorder. Wyatt. R and Chew...
, haloperidol
Haloperidol
Haloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....
, olanzapine
Olanzapine
Olanzapine is an atypical antipsychotic, approved by the FDA for the treatment of schizophrenia and bipolar disorder...
, perphenazine
Perphenazine
Perphenazine is a typical antipsychotic drug. Chemically, it is classified as a piperazinyl phenothiazine. It has been in clinical use for decades....
, risperidone
Risperidone
Risperidone is a second generation or atypical antipsychotic, sold under the trade name . It is used to treat schizophrenia , schizoaffective disorder, the mixed and manic states associated with bipolar disorder, and irritability in people with autism...
, thioridazine
Thioridazine
Thioridazine is a piperidine typical antipsychotic drug belonging to the phenothiazine drug group and was previously widely used in the treatment of schizophrenia and psychosis...
and zuclopenthixol
Zuclopenthixol
Zuclopenthixol , also known as zuclopentixol, is a typical antipsychotic drug of the thioxanthene class...
via CYP2D6
CYP2D6
Cytochrome P450 2D6 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. Also, many substances are bioactivated by CYP2D6 to form their active compounds...
as well as of aripiprazole
Aripiprazole
Aripiprazole is an atypical antipsychotic and antidepressant used in the treatment of schizophrenia, bipolar disorder, and clinical depression...
, clozapine
Clozapine
Clozapine is an antipsychotic medication used in the treatment of schizophrenia, and is also used off-label in the treatment of bipolar disorder. Wyatt. R and Chew...
, haloperidol
Haloperidol
Haloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....
, quetiapine
Quetiapine
Quetiapine , is an atypical antipsychotic approved for the treatment of schizophrenia, and bipolar disorder....
and ziprasidone
Ziprasidone
Ziprasidone was the fifth atypical antipsychotic to gain FDA approval . In the United States, Ziprasidone is Food and Drug Administration approved for the treatment of schizophrenia, and the intramuscular injection form of ziprasidone is approved for acute agitation in schizophrenic patients...
via CYP3A4
CYP3A4
Cytochrome P450 3A4 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. CYP3A4 is involved in the oxidation of the largest range of substrates of all the CYPs. As a result, CYP3A4 is present in...
.
Fluvoxamine has low potential for the drug interaction
Drug interaction
A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own. Typically, interaction between drugs come to mind...
s which are based on inhibition of enzyme Cytochrome P450 CYP2D6
CYP2D6
Cytochrome P450 2D6 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. Also, many substances are bioactivated by CYP2D6 to form their active compounds...
, less than most other SSRIs.
Naturally the other SSRIs which are metabolized by CYP2D6 will have more CYP2D6-based interactions with TCAs
Tricyclic antidepressant
Tricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...
, antiarrhythmics, B-blockers, phenytoin
Phenytoin
Phenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...
, opioids and neuroleptics.
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.
Fluvoxamine also inhibits CYP2C9
CYP2C9
Cytochrome P450 2C9 is a protein that in humans is encoded by the CYP2C9 gene.- Function :CYP2C9 is an important cytochrome P450 enzyme with a major role in the oxidation of both xenobiotic and endogenous compounds. CYP2C9 makes up about 18% of the cytochrome P450 protein in liver microsomes...
.
Synthesis
Fluvoxamine is one of only two SSRIs (along with alaproclateAlaproclate
Alaproclate is a psychoactive drug and research chemical that was being developed as an antidepressant by the Swedish pharmaceutical company Astra AB in the 1970s. It acts as a selective serotonin reuptake inhibitor , and along with zimelidine and indalpine, was one of the first of its kind...
) to have a monocyclic structure.
History
Fluvoxamine was developed by Solvay PharmaceuticalsSolvay (company)
Solvay S.A. is a Belgian chemical company with its head office in Ixelles, Brussels, Belgium. It was founded in 1863 by Ernest Solvay to produce sodium carbonate by the solvay process. Since then the company has diversified to two major sectors of activity: chemicals and plastics...
and was the first non-TCA
Tricyclic antidepressant
Tricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...
drug approved by the U.S. Food and Drug Administration (FDA) specifically for the treatment of OCD. 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. At the end of 1995, more than 10 million patients worldwide had been treated with fluvoxamine. Fluvoxamine was the first SSRI to be registered for the treatment of obsessive compulsive disorder in children by the FDA in 1997. Fluvoxamine was the first drug approved for the treatment of social anxiety disorder in Japan in 2005.
In 1999, fluvoxamine came under great public scrutiny after it was discovered that Eric Harris
Eric Harris and Dylan Klebold
Eric David Harris and Dylan Bennet Klebold were American high school seniors who committed the Columbine High School massacre. They killed 13 people—including teacher Dave Sanders—and injured 24 others, three of whom were injured as they escaped the attack...
, one of the two teenage shooters involved in the Columbine High School massacre
Columbine High School massacre
The Columbine High School massacre occurred on Tuesday, April 20, 1999, at Columbine High School in Columbine, an unincorporated area of Jefferson County, Colorado, United States, near Denver and Littleton. Two senior students, Eric Harris and Dylan Klebold, embarked on a massacre, killing 12...
, had been taking the drug. Many immediately pointed fingers at fluvoxamine and its manufacturer Solvay Pharmaceuticals. Sales fell, and Solvay withdrew the medication from the U.S. market in 2002. 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.
Society and culture
"Stuttering" John Melendez, formerly of The Howard Stern Show, had taken Luvox for a period of time prior to his departure from the show.One of two shooters at the Columbine High School massacre
Columbine High School massacre
The Columbine High School massacre occurred on Tuesday, April 20, 1999, at Columbine High School in Columbine, an unincorporated area of Jefferson County, Colorado, United States, near Denver and Littleton. Two senior students, Eric Harris and Dylan Klebold, embarked on a massacre, killing 12...
, Eric Harris
Eric Harris
Eric Harris may refer to:* Eric Harris , former NFL player* Eric W. Harris , businessman and Louisiana state Jaycees founder* Eric Harris , American drummer...
, was taking Luvox. Some analysts, such as psychiatrist Peter Breggin
Peter Breggin
Peter Roger Breggin is an American psychiatrist and critic of biological psychiatry and psychiatric medication. In his books, he advocates replacing psychiatry's use of drugs and electroconvulsive therapy with humanistic approaches, such as psychotherapy, education, and broader human...
, have argued that this medication may have contributed to Harris's actions. Breggin claimed that side-effects of these drugs include increased aggression, loss of remorse, depersonalization, and mania.