Paroxetine, sold under the brand names Paxil and Seroxat among others, is an

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common Side effect, side-effects of antidepressants include Xerostomia, dry mouth, weig ...

of the

selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracellul ...

(SSRI) class. It is used to treat

major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Intro ...

, obsessive-compulsive disorder,

panic disorder Panic disorder is a mental and behavioral disorder, specifically an anxiety disorder characterized by reoccurring unexpected panic attacks. Panic attacks are sudden periods of intense fear that may include palpitations, sweating, shaking, short ...

social anxiety disorder Social anxiety disorder (SAD), also known as social phobia, is an anxiety disorder characterized by sentiments of fear and anxiety in social situations, causing considerable distress and impaired ability to function in at least some aspects o ...

posttraumatic stress disorder Post-traumatic stress disorder (PTSD) is a mental and behavioral disorder that can develop because of exposure to a traumatic event, such as sexual assault, warfare, traffic collisions, child abuse, domestic violence, or other threat ...

generalized anxiety disorder Generalized anxiety disorder (GAD) is a mental and behavioral disorder, specifically an anxiety disorder characterized by excessive, uncontrollable and often irrational worry about events or activities. Worry often interferes with daily function ...

and

premenstrual dysphoric disorder Premenstrual dysphoric disorder (PMDD) is a mood disorder characterized by emotional, cognitive, and physical symptoms that cause significant distress or impairment in menstruating women during the luteal phase of the menstrual cycle. The symptom ...

. It has also been used in the treatment of premature ejaculation and

hot flash Hot flashes (also known as hot flushes) are a form of flushing, often caused by the changing hormone levels that are characteristic of menopause. They are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, an ...

es due to

menopause Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...

. It is taken by mouth. Common side effects include drowsiness, dry mouth, loss of appetite, sweating,

trouble sleeping Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

, and

sexual dysfunction Sexual dysfunction is difficulty experienced by an individual or partners during any stage of normal sexual activity, including physical pleasure, desire, preference, arousal, or orgasm. The World Health Organization defines sexual dysfunction a ...

. Serious side effects may include suicidal thoughts in those under the age of 25,

serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain serotonergic medications or drugs. The degree of symptoms can range from mild to severe, including a potentiality of death. Symptoms in mild cases include high ...

, and

mania Mania, also known as manic syndrome, is a mental and behavioral disorder defined as a state of abnormally elevated arousal, affect, and energy level, or "a state of heightened overall activation with enhanced affective expression together wi ...

. While the rate of side effects appears similar compared to other SSRIs and SNRIs,

antidepressant discontinuation syndrome Antidepressant discontinuation syndrome, also called antidepressant withdrawal syndrome, is a condition that can occur following the interruption, reduction, or discontinuation of antidepressant medication following its continuous use of at lea ...

s may occur more often. Use in

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

is not recommended, while use during

breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that bre ...

is relatively safe. It is believed to work by blocking the re-uptake of the chemical

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and va ...

neurons A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa ...

in the brain. Paroxetine was approved for medical use in the United States in 1992 and initially sold by

GlaxoSmithKline GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the tent ...

. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ...

. In 2020, it was the 82nd most commonly prescribed medication in the United States, with more than 9million prescriptions. In 2018, it was in the top 10 of most prescribed

antidepressants Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

in the United States. In 2012, the

United States Department of Justice The United States Department of Justice (DOJ), also known as the Justice Department, is a federal executive department of the United States government tasked with the enforcement of federal law and administration of justice in the United Stat ...

fined

$3 billion for withholding data, unlawfully promoting use in those under 18, and preparing an article that misleadingly reported the effects of paroxetine in adolescents with depression following its clinical trial

study 329 Study 329 was a clinical trial which was conducted in North America from 1994 to 1998 to study the efficacy of paroxetine, an SSRI anti-depressant, in treating 12- to 18-year-olds diagnosed with major depressive disorder. Led by Martin Keller, t ...

Medical uses

Paroxetine is primarily used to treat

, obsessive-compulsive disorder,

post-traumatic stress disorder Post-traumatic stress disorder (PTSD) is a mental and behavioral disorder that can develop because of exposure to a traumatic event, such as sexual assault, warfare, traffic collisions, child abuse, domestic violence, or other threats o ...

, and

. It is also occasionally used for

agoraphobia Agoraphobia is a mental and behavioral disorder, specifically an anxiety disorder characterized by symptoms of anxiety in situations where the person perceives their environment to be unsafe with no easy way to escape. These situations can i ...

and menopausal

es.

Depression

A variety of meta analyses have been conducted to evaluate the efficacy of paroxetine in depression. They have variously concluded that paroxetine is superior or equivalent to placebo and that it is equivalent to other antidepressants. Despite this, there was no clear evidence that paroxetine was better or worse compared with other antidepressants at increasing response to treatment at any point in time.

Anxiety disorders

Paroxetine was the first antidepressant approved in the United States for the treatment of

. Several studies have concluded that paroxetine is superior to placebo in the treatment of panic disorder. Paroxetine has demonstrated efficacy for the treatment of

in adults and children. It is also beneficial for people with co-occurring social anxiety disorder and

alcohol use disorder Alcoholism is, broadly, any drinking of alcohol that results in significant mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predomin ...

. It appears to be similar to a number of other SSRIs. Paroxetine is used in the treatment of obsessive-compulsive disorder. Comparative efficacy of paroxetine is equivalent to that of clomipramine and

venlafaxine Venlafaxine, sold under the brand name Effexor among others, is an antidepressant medication of the serotonin-norepinephrine reuptake inhibitor (SNRI) class. It is used to treat major depressive disorder, generalized anxiety disorder, panic ...

. Paroxetine is also effective for children with obsessive-compulsive disorder. Paroxetine is approved for treatment of PTSD in the United States, Japan and Europe. In the United States it is approved for short-term use. Paroxetine is also FDA-approved for

Menopausal hot flashes

In 2013, low-dose paroxetine was approved in the US for the treatment of moderate-to-severe vasomotor symptoms such as

es and

night sweats Night sweats, also referred to as nocturnal hyperhidrosis (Hyperhidrosis - a medical term for excessive sweating + nocturnal - night), is the repeated occurrence of excessive sweating during sleep Sleep is a sedentary state of mind and bo ...

associated with

. At the low dose used for menopausal hot flashes, side effects are similar to placebo and dose tapering is not required for discontinuation.

Fibromyalgia

Studies have also shown paroxetine "appears to be well-tolerated and improve the overall symptomatology in patients with fibromyalgia" but is less robust in helping with the pain involved.

Adverse effects

Common side effects include drowsiness, dry mouth, loss of appetite, sweating,

, and

. Serious side effects may include

suicide Suicide is the act of intentionally causing one's own death. Mental disorders (including depression, bipolar disorder, schizophrenia, personality disorders, anxiety disorders), physical disorders (such as chronic fatigue syndrome), and ...

in those under the age of 25,

, and

. While the rate of side effects appears similar compared to other SSRIs and SNRIs,

s may occur more often. Use in

is not recommended while use during

is relatively safe. Paroxetine shares many of the common adverse effects of SSRIs, including (with the corresponding rates seen in people treated with placebo in parentheses): * nausea 26% (9%) * diarrhea 12% (8%) * constipation 14% (9%) * dry mouth 18% (12%) * somnolence 23% (9%) * insomnia 13% (6%) * headache 18% (17%) *

hypomania Hypomania (literally "under mania" or "less than mania") is a mental and behavioural disorder, characterised essentially by an apparently non-contextual elevation of mood (euphoria) that contributes to persistently disinhibited behaviour. Th ...

1% (0.3%) * blurred vision 4% (1%) * loss of appetite 6% (2%) * nervousness 5% (3%) *

paraesthesia Paresthesia is an abnormal sensation of the skin (tingling, pricking, chilling, burning, numbness) with no apparent physical cause. Paresthesia may be transient or chronic, and may have any of dozens of possible underlying causes. Paresthesias ar ...

4% (2%) * dizziness 13% (6%) * asthenia (weakness; 15% (6%)) * tremor 8% (2%) * sweating 11% (2%) * sexual dysfunction (≥10% incidence). Most of these adverse effects are transient and go away with continued treatment. Central and peripheral 5-HT₃ receptor stimulation is believed to result in the gastrointestinal effects observed with SSRI treatment. Compared to other SSRIs, it has a lower incidence of diarrhea, but a higher incidence of anticholinergic effects (e.g., dry mouth, constipation, blurred vision, etc.), sedation/somnolence/drowsiness, sexual side effects, and weight gain. Due to reports of adverse withdrawal reactions upon terminating treatment, the

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regardin ...

(CHMP) at the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Eur ...

recommends gradually reducing over several weeks or months if the decision to withdraw is made. See also Discontinuation syndrome (withdrawal).

Mania Mania, also known as manic syndrome, is a mental and behavioral disorder defined as a state of abnormally elevated arousal, affect, and energy level, or "a state of heightened overall activation with enhanced affective expression together wi ...

may occur in 1% of patients with depression and up to 12% of patients with

bipolar disorder Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of Depression (mood), depression and periods of abnormally elevated Mood (psychology), mood that last from days to weeks each. If the elevat ...

. This side effect can occur in individuals with no history of mania but it may be more likely to occur in those with bipolar or with a family history of mania.

Suicide

Like other antidepressants, paroxetine may increase the risk of suicidal thinking and behaviour in people under the age of 25. The FDA conducted a statistical analysis of paroxetine clinical trials in children and adolescents in 2004 and found an increase in suicidality and ideation as compared to placebo, which was observed in trials for both depression and anxiety disorders. In 2015 a paper published in ''

The BMJ ''The BMJ'' is a weekly peer-reviewed medical trade journal, published by the trade union the British Medical Association (BMA). ''The BMJ'' has editorial freedom from the BMA. It is one of the world's oldest general medical journals. Origi ...

'' that reanalysed the original case notes argued that in

Study 329 Study 329 was a clinical trial which was conducted in North America from 1994 to 1998 to study the efficacy of paroxetine, an SSRI anti-depressant, in treating 12- to 18-year-olds diagnosed with major depressive disorder. Led by Martin Keller, t ...

, assessing paroxetine and imipramine against placebo in adolescents with depression, the incidence of suicidal behavior had been under-reported and the efficacy exaggerated for paroxetine.

Sexual dysfunction

Sexual dysfunction, including loss of libido,

anorgasmia Anorgasmia is a type of sexual dysfunction in which a person cannot achieve orgasm despite adequate stimulation. Anorgasmia is far more common in females (4.6 percent) than in males and is especially rare in younger men. The problem is greater in ...

, lack of vaginal lubrication, and

erectile dysfunction Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men.Cunningham GR, Rosen RC. Overview of ma ...

, is one of the most commonly encountered adverse effects of treatment with paroxetine and other SSRIs. While early clinical trials suggested a relatively low rate of sexual dysfunction, more recent studies in which the investigator actively inquires about sexual problems suggest that the incidence is higher than 70%. Symptoms of sexual dysfunction have been reported to persist after discontinuing SSRIs, although this is thought to be occasional.

Pregnancy

Antidepressant exposure (including paroxetine) is associated with shorter duration of

(by three days), increased risk of preterm delivery (by 55%), lower birth weight (by ), and lower

Apgar score The Apgar score is a quick way for doctors to evaluate the health of all newborns at 1 and 5 minutes after birth and in response to resuscitation. It was originally developed in 1952 by an anesthesiologist at Columbia University, Virginia Apgar ...

s (by <0.4 points). The

American College of Obstetricians and Gynecologists The American College of Obstetricians and Gynecologists (ACOG) is a professional association of physicians specializing in obstetrics and gynecology in the United States. Several Latin American countries are also represented within Districts of ...

recommends that for pregnant women and women planning to become pregnant, paroxetine "be avoided, if possible", as it may be associated with increased risk of

birth defects A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...

. Babies born to women who used paroxetine during the first trimester have an increased risk of cardiovascular malformations, primarily ventricular and atrial septal defects (VSDs and ASDs). Unless the benefits of paroxetine justify continuing treatment, consideration should be given to stopping or switching to another antidepressant. Paroxetine use during pregnancy is associated with about 1.5–1.7-fold increase in congenital birth defects, in particular, heart defects, cleft lip and palate, clubbed feet or any birth defects.

Discontinuation syndrome

Many psychoactive medications can cause withdrawal symptoms upon discontinuation from administration. Evidence has shown that paroxetine has among the highest incidence rates and severity of withdrawal syndrome of any medication of its class. Common withdrawal symptoms for paroxetine include nausea, dizziness, lightheadedness and vertigo; insomnia, nightmares and vivid dreams; feelings of electricity in the body, as well as rebound depression and anxiety. Liquid formulation of paroxetine is available and allows a very gradual decrease of the dose, which may prevent discontinuation syndrome. Another recommendation is to temporarily switch to

fluoxetine Fluoxetine, sold under the brand names Prozac and Sarafem, among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used for the treatment of major depressive disorder, obsessive–compulsive diso ...

, which has a longer

half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ...

and thus decreases the severity of discontinuation syndrome. In 2002, the U.S. FDA published a warning regarding "severe" discontinuation symptoms among those terminating paroxetine treatment, including paraesthesia, nightmares, and dizziness. The Agency also warned of case reports describing agitation, sweating, and nausea. In connection with a Glaxo spokesperson's statement that withdrawal reactions occur only in 0.2% of patients and are "mild and short-lived", the

International Federation of Pharmaceutical Manufacturers Associations The International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) is a trade association that represents leading innovative pharmaceutical companies at the international level and in official relations with the United Nations. I ...

said GSK had breached two of the Federation's codes of practice. Paroxetine prescribing information posted at GlaxoSmithKline has been updated related to the occurrence of a discontinuation syndrome, including serious discontinuation symptoms.

Overdose

Acute overdosage is often manifested by

emesis Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteriti ...

lethargy Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overwo ...

ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...

, and

seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with lo ...

. Plasma, serum, or blood concentrations of paroxetine may be measured to monitor therapeutic administration, confirm a diagnosis of poisoning in hospitalized patients or to aid in the medicolegal investigation of fatalities. Plasma paroxetine concentrations are generally in a range of 40–400 μg/L in persons receiving daily therapeutic doses and 200–2,000 μg/L in poisoned patients. Postmortem blood levels have ranged from 1–4 mg/L in acute lethal overdose situations. Along with the other SSRIs,

sertraline Sertraline, sold under the brand name Zoloft among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. The efficacy of sertraline for depression is similar to that of other antidepressants, and the diffe ...

and

, paroxetine is considered a low-risk drug in cases of overdose.

Interactions

Interactions with other drugs acting on the serotonin system or impairing the metabolism of serotonin may increase the risk of

neuroleptic malignant syndrome Neuroleptic malignant syndrome (NMS) is a rare but life-threatening reaction that can occur in response to neuroleptic or antipsychotic medication. Symptoms include high fever, confusion, rigid muscles, variable blood pressure, sweating, and fa ...

(NMS)-like reaction. Such reactions have been observed with SNRIs and SSRIs alone, but particularly with concurrent use of triptans,

MAO inhibitors Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, especi ...

, antipsychotics, or other dopamine antagonists. The prescribing information states that paroxetine should "not be used in combination with an MAOI (including linezolid, an antibiotic which is a reversible non-selective MAOI), or within 14 days of discontinuing treatment with an MAOI", and should not be used in combination with

pimozide Pimozide (sold under the brand name Orap) is an antipsychotic drug of the diphenylbutylpiperidine class. It was discovered at Janssen Pharmaceutica in 1963. It has a high potency compared to chlorpromazine (ratio 50-70:1). On a weight basis ...

thioridazine Thioridazine (Mellaril or Melleril) is a first generation antipsychotic drug belonging to the phenothiazine drug group and was previously widely used in the treatment of schizophrenia and psychosis. The branded product was withdrawn worldwid ...

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic ...

, or

warfarin Warfarin, sold under the brand name Coumadin among others, is a medication that is used as an anticoagulant (blood thinner). It is commonly used to prevent blood clots such as deep vein thrombosis and pulmonary embolism, and to prevent st ...

. Paroxetine interacts with the following

cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...

enzymes: *

CYP2D6 Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra. CYP2D ...

for which it is both a substrate and a potent inhibitor. *

CYP2B6 Cytochrome P450 2B6 is an enzyme that in humans is encoded by the ''CYP2B6'' gene. CYP2B6 is a member of the cytochrome P450 group of enzymes. Along with CYP2A6, it is involved with metabolizing nicotine, along with many other substances. Func ...

(''strong'') inhibitor. *

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules ( xenobiotics), such as toxins or drugs, so that they can be removed from ...

(''weak'') inhibitor. *

CYP1A2 Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the ''CYP1A2'' gene. Function ...

(''weak'') inhibitor. *

CYP2C9 Cytochrome P450 family 2 subfamily C member 9 (abbreviated CYP2C9) is an enzyme protein. The enzyme is involved in metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the pro ...

(''weak'') inhibitor. *

CYP2C19 Cytochrome P450 2C19 (abbreviated CYP2C19) is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes that catalyze metabolism of xenobiotics, including some p ...

(''weak'') inhibitor. Paroxetine has been shown to be an inhibitor of

G protein-coupled receptor kinase 2 G-protein-coupled receptor kinase 2 (GRK2) is an enzyme that in humans is encoded by the ''ADRBK1'' gene. GRK2 was initially called Beta-adrenergic receptor kinase (βARK or βARK1), and is a member of the G protein-coupled receptor kinase subfam ...

(GRK2).

Pharmacology

Pharmacodynamics

Paroxetine is the most potent and one of the most specific selective

(5-hydroxytryptamine, 5-HT) reuptake inhibitors (SSRIs). It also binds to the

allosteric In biochemistry, allosteric regulation (or allosteric control) is the regulation of an enzyme by binding an effector molecule at a site other than the enzyme's active site. The site to which the effector binds is termed the ''allosteric sit ...

site of the serotonin transporter, similarly, but less potently, than

escitalopram Escitalopram, sold under the brand names Lexapro and Cipralex, among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. Escitalopram is mainly used to treat major depressive disorder and generalized anxiet ...

. Paroxetine also inhibits the reuptake of

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad ...

to a lesser extent (<50 nmol/L). Based on evidence from four weeks of administration in rats, the equivalent of 20 mg paroxetine taken once daily occupies approximately 88% of serotonin transporters in the

prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA ...

Pharmacokinetics

Paroxetine is well-absorbed following oral administration. It has an absolute bioavailability of about 50%, with evidence of a saturable

first pass effect The first pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism whereby the concentration of a drug, specifically when administered orally, is greatly reduced before it reaches the system ...

. When taken orally, it achieves maximum concentration in about 6–10 hours and reaches steady-state in 7–14 days. Paroxetine exhibits significant interindividual variations in volume of distribution and clearance. Less than 2% of an oral dose is excreted in urine unchanged. Paroxetine is a mechanism-based inhibitor of

Society and culture

has paid substantial fines, paid settlements in

class-action A class action, also known as a class-action lawsuit, class suit, or representative action, is a type of lawsuit where one of the parties is a group of people who are represented collectively by a member or members of that group. The class action ...

lawsuits, and become the subject of several highly critical books about its marketing of paroxetine, in particular the off-label marketing of paroxetine for children, the suppression of negative research results relating to its use in children, and allegations that it failed to warn consumers of substantial withdrawal effects associated with use of the drug. Paroxetine was approved for medical use in the United States in 1992 and initially sold by

. It is currently available as a

. In 2017, it was the 68th most commonly prescribed medication in the United States, with more than eleven million prescriptions. The

fined GlaxoSmithKline $3 billion in 2012, for withholding data, unlawfully promoting use in those under 18, and preparing an article that misleadingly reported the effects of paroxetine in adolescents with depression following its clinical trial

Marketing

In early 2004, GSK agreed to settle charges of consumer fraud for $2.5 million. The legal discovery process also uncovered evidence of deliberate, systematic suppression of unfavorable Paxil research results. One of GSK's internal documents read, "It would be commercially unacceptable to include a statement that efficacy n childrenhad not been demonstrated, as this would undermine the profile of paroxetine". In 2012 the

U.S. Justice Department The United States Department of Justice (DOJ), also known as the Justice Department, is a federal executive department of the United States government tasked with the enforcement of federal law and administration of justice in the United States ...

announced that GSK agreed to plead guilty and pay a $3 billion fine, in part for promoting the use of Paxil for children. On 12 February 2016, the UK

Competition and Markets Authority The Competition and Markets Authority (CMA) is the competition regulator in United Kingdom. It is a non-ministerial government department in the United Kingdom, responsible for strengthening business competition and preventing and reducing anti-com ...

imposed record fines of £45 million on companies which were found to have infringed

European Union The European Union (EU) is a supranational union, supranational political union, political and economic union of Member state of the European Union, member states that are located primarily in Europe, Europe. The union has a total area of ...

and UK Competition law by entering into agreements to delay the market entry of

generic Generic or generics may refer to: In business * Generic term, a common name used for a range or class of similar things not protected by trademark * Generic brand, a brand for a product that does not have an associated brand or trademark, other ...

versions of the drug in the UK.

received the bulk of the fines, being fined £37,600,757. Other companies, which produce generics, were issued fines which collectively total £7,384,146. UK public health services are likely to claim damages for being overcharged in the period where the generic versions of the drug were illegally blocked from the market, as the generics are over 70% less expensive.

may also face actions from other generics manufacturers who incurred loss as a result of the anticompetitive conduct. On 18 April 2016, appeals were lodged with the

Competition Appeal Tribunal The Competition Appeal Tribunal (CAT) of the United Kingdom was created by Section 12 and Schedule 2 to the Enterprise Act 2002 which came into force on 1 April 2003. The Competition Service is an executive non-departmental public body which ...

by the companies which were fined. GSK marketed paroxetine through television advertisements throughout the late 1990s and early 2000s. Commercials also aired for the CR version of the drug beginning in 2003.

Sales

In 2007, paroxetine was ranked 94th on the

list of bestselling drugs Best selling pharmaceuticals of U.S. Market The top 5 best selling pharmaceuticals 2015-2019. Sales in billion USD. Best selling pharmaceuticals of 2017/18 The top 16 best selling pharmaceuticals of 2017/18. Largest selling pharmaceutic ...

, with over $1 billion in sales. In 2006, paroxetine was the fifth-most prescribed antidepressant in the U.S. retail market, with more than 19.7 million prescriptions. In 2007, sales had dropped slightly to 18.1 million but paroxetine remained the fifth-most prescribed antidepressant in the U.S.

Trade names

Trade names include Aropax, Paretin, Brisdelle, Deroxat, Paxil, Pexeva, Paxtine, Paxetin, Paroxat, Paraxyl, Sereupin, Daparox and Seroxat.

Research

Several studies have suggested that paroxetine can be used in the treatment of premature ejaculation. In particular, intravaginal ejaculation latency time (IELT) was found to increase with 6- to 13-fold, which was somewhat longer than the delay achieved by the treatment with other SSRIs (fluvoxamine, fluoxetine, sertraline, and citalopram). However, paroxetine taken acutely ("on demand") 3–10 hours before coitus resulted only in a "clinically irrelevant and sexually unsatisfactory" 1.5-fold delay of ejaculation and was inferior to clomipramine, which induced a fourfold delay. There is also evidence that paroxetine may be effective in the treatment of

compulsive gambling Problem gambling or ludomania is repetitive gambling behavior despite harm and negative consequences. Problem gambling may be diagnosed as a mental disorder according to ''DSM-5'' if certain diagnostic criteria are met. Pathological gambling is ...

and

hot flashes Hot flashes (also known as hot flushes) are a form of flushing, often caused by the changing hormone levels that are characteristic of menopause. They are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and ...

. Benefits of paroxetine prescription for

diabetic neuropathy Diabetic neuropathy is various types of nerve damage associated with diabetes mellitus. Symptoms depend on the site of nerve damage and can include motor changes such as weakness; sensory symptoms such as numbness, tingling, or pain; or autonomic c ...

or chronic

tension headache Tension headache, also known as stress headache, or tension-type headache (TTH), is the most common type of primary headache. The pain can radiate from the lower back of the head, the neck, eyes or other muscle groups in the body typically affect ...

are uncertain. Although the evidence is conflicting, paroxetine may be effective for the treatment of

dysthymia Dysthymia ( ), also known as persistent depressive disorder (PDD), is a mental and behavioral disorder, specifically a disorder primarily of mood, consisting of similar cognitive and physical problems as major depressive disorder, but with l ...

, a chronic disorder involving depressive symptoms for most days of the year. There is evidence to support that paroxetine selectively binds to and inhibits

(GRK2) in mice with heart failure. Since GRK2 regulates the activity of the beta

adrenergic receptor The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like bet ...

, which becomes desensitized in cases of

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, ...

, paroxetine (or a paroxetine derivative) could be used as a heart failure treatment in the future. Paroxetine has been identified as a potential disease-modifying osteoarthritis drug.

Other organisms

Paroxetine is a common finding in waste water. It is highly toxic to the alga ''Pseudokirchneriella subcapitata'' (syn. '' Raphidocelis subcapitata''). It also is toxic to the soil nematode ''

Caenorhabditis elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (r ...

''. Alberca ''et al.'', 2016 finds paroxetine acts as a

trypanocide A trypanocidal agent is an antiprotozoal agent that acts upon trypanosome parasites. Examples include: * Aminoquinuride * benzonidazole * blasticidin S * DAPI * diminazene * diminazene aceturate * eflornithine * ethidium * isometamidium chl ...

against '' T. cruzi''.

References

External links

*
Detailed Paroxetine Consumer Information: Uses, Precautions, Side Effects
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