Paroxetine ( ), sold under the brand name Paxil among others, is an antidepressant medication 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 primarily work by blo ...

(SSRI) class 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 depression (mood), low mood, low self-esteem, and anhedonia, loss of interest or pleasure in normally ...

obsessive–compulsive disorder Obsessive–compulsive disorder (OCD) is a mental disorder in which an individual has intrusive thoughts (an ''obsession'') and feels the need to perform certain routines (''Compulsive behavior, compulsions'') repeatedly to relieve the dis ...

(OCD),

panic disorder Panic disorder is a mental 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, shortness of breath ...

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 impairing ability to function in at least some asp ...

post-traumatic stress disorder Post-traumatic stress disorder (PTSD) is a mental disorder that develops from experiencing a Psychological trauma, traumatic event, such as sexual assault, domestic violence, child abuse, warfare and its associated traumas, natural disaster ...

(PTSD),

generalized anxiety disorder Generalized anxiety disorder (GAD) is an anxiety disorder characterized by excessive, uncontrollable and often irrational worry about events or activities. Worry often interferes with daily functioning. Individuals with GAD are often overly con ...

, and

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

. It has also been used in the treatment of

premature ejaculation Premature ejaculation (PE) is a male sexual dysfunction that occurs when a male Ejaculation, expels semen (and most likely experiences orgasm) soon after beginning sexual activity, and with minimal penile stimulation. It has also been called ''e ...

, and

hot flash 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 may typically last from t ...

es due to

menopause Menopause, also known as the climacteric, is the time when Menstruation, menstrual periods permanently stop, marking the end of the Human reproduction, reproductive stage for the female human. It typically occurs between the ages of 45 and 5 ...

. It is taken orally (by mouth). Common side effects include drowsiness, dry mouth, loss of appetite, sweating, trouble sleeping, 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 ...

. 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 Serotonin, serotonergic medications or Recreational drug use, drugs. The symptoms can range from mild to severe, and are potentially fatal. Symptoms in mild c ...

, and

mania Mania, also known as manic syndrome, is a Psychiatry, psychiatric Abnormality (behavior), behavioral syndrome defined as a state of Abnormality (behavior), abnormally elevated arousal, affect (psychology), affect, and energy level. During a mani ...

. 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 le ...

may occur more often. Use in

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

is not recommended, while use during

breastfeeding Breastfeeding, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...

is relatively safe. It is believed to work by blocking the reuptake of the chemical

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

neurons A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

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

GlaxoSmithKline GSK plc (an acronym from its former name GlaxoSmithKline plc) is a British Multinational corporation, multinational Pharmaceutics, pharmaceutical and biotechnology company with headquarters in London. It was established in 2000 by a Mergers an ...

. 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 ch ...

. In 2022, it was the 92nd most commonly prescribed medication in the United States, with more than 7million prescriptions. In 2018, it was in the top 10 of most prescribed

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

s in the United States.

Medical uses

Paroxetine is primarily used to treat

, and

. It is also occasionally used for

agoraphobia Agoraphobia is an anxiety disorder characterized by symptoms of anxiety in situations where the person perceives their environment to be unsafe with no way to escape. These situations can include public transit, shopping centers, crowds and q ...

, 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 panic disorder. Several studies have concluded that paroxetine is superior to placebo in the treatment of panic disorder. Paroxetine has demonstrated efficacy for the treatment of social anxiety disorder in adults and children. It is also beneficial for people with co-occurring social anxiety disorder and

alcohol use disorder Alcoholism is the continued drinking of alcohol despite it causing problems. Some definitions require evidence of dependence and withdrawal. Problematic use of alcohol has been mentioned in the earliest historical records. The World Hea ...

. 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 Clomipramine, sold under the brand name Anafranil among others, is a tricyclic antidepressant (TCA). It is used in the treatment of various conditions, most notably obsessive–compulsive disorder but also many other disorders, including hyper ...

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, pani ...

. Paroxetine is also effective for children with obsessive-compulsive disorder. Paroxetine is approved for the 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 generalized anxiety disorder.

Menopausal hot flashes

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

night sweats Night sweats or nocturnal hyperhydrosis is the repeated occurrence of excessive sweating during sleep. The person may or may not also perspire excessively while awake. One of the most common causes of night sweats in women over 40 is the horm ...

associated with menopause. 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, insomnia, and

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

, and

. While the rate of side effects appears similar compared to other SSRIs and SNRIs, antidepressant discontinuation syndromes may occur more often. Use in pregnancy is not recommended, while use during

is relatively safe. The Federal Aviation Administration (FAA), the U.S. agency responsible for regulating civil aviation, considers paroxetine to be an antidepressant medication that is ineligible for an FAA Authorization of Special Issuance (SI) or Special Consideration (SC) of a

medical certificate A medical certificate or doctor's certificate is a written statement from a physician or another medically qualified health care provider which attests to the result of a medical examination of a patient. It can serve as a sick note ( UK: fit no ...

. 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%) *

somnolence Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling aslee ...

23% (9%) * dry mouth 18% (12%) * headache 18% (17%) * asthenia (weakness) 15% (6%) * constipation 14% (9%) * dizziness 13% (6%) * insomnia 13% (6%) * diarrhea 12% (8%) * sweating 11% (2%) * tremor 8% (2%) * loss of appetite 6% (2%) * nervousness 5% (3%) * blurred vision 4% (1%) *

paraesthesia Paresthesia is a sensation of the skin that may feel like numbness (''hypoesthesia''), tingling, pricking, chilling, or burning. It can be temporary or chronic and has many possible underlying causes. Paresthesia is usually painless and can oc ...

4% (2%) *

hypomania Hypomania (literally "under mania" or "less than mania") is a Psychiatry, psychiatric Abnormality (behavior), behavioral syndrome characterized essentially by an apparently non-contextual elevation of Mood (psychology), mood (i.e., euphoria) th ...

1% (0.3%) * 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 the Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regar ...

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 pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

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

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

bipolar disorder Bipolar disorder (BD), 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 each last from days to weeks, and in ...

. This side effect can occur in individuals with no history of mania, but it may be more likely to occur in those with bipolar disorder or with a family history of mania. Paroxetine is described as a 'hepatoxic agent' and has been associated with hepatoxicity and jaundice.

Suicide

Like other antidepressants, paroxetine may increase the risk of suicidal thinking and behaviour in people under the age of 25. The

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

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 fortnightly peer-reviewed medical journal, published by BMJ Publishing Group Ltd, which in turn is wholly-owned by the British Medical Association (BMA). ''The BMJ'' has editorial freedom from the BMA. It is one of the world ...

'' that reanalysed the original case notes argued that in Study 329, assessing paroxetine and

imipramine Imipramine, sold under the brand name Tofranil, among others, is a tricyclic antidepressant (TCA) mainly used in the treatment of depression. It is also effective in treating anxiety and panic disorder. Imipramine is taken by mouth. Common s ...

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 In psychology, libido (; ) is psychic drive or energy, usually conceived of as sexual in nature, but sometimes conceived of as including other forms of desire. The term ''libido'' was originally developed by Sigmund Freud, the pioneering origin ...

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

, lack of vaginal lubrication, and erectile dysfunction, 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 pregnancy (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 health professionals 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, ...

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 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 range from mild to severe. Birth de ...

. Babies born to women who used paroxetine during the first trimester have an increased risk of cardiovascular malformations, primarily ventricular and atrial septal defects. 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– to 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. 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. A 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 name Prozac, among others, is an Antidepressant, antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class used for the treatment of major depressive disorder, Anxiety disorder, anx ...

, which has a longer

half-life Half-life is a mathematical and scientific description of exponential or gradual decay. Half-life, half life or halflife may also refer to: Film * Half-Life (film), ''Half-Life'' (film), a 2008 independent film by Jennifer Phang * ''Half Life: ...

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 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

vomiting Vomiting (also known as emesis, puking and throwing up) is the 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, gastroenteritis, pre ...

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, overw ...

ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...

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 A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

. 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, antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class used to treat major depressive disorder, generalized anxiety disorder, socia ...

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 antipsychotics (neuroleptic) or other drugs that block the effects of dopamine. Symptoms include high fever, confusion, rigid muscles, va ...

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

triptan Triptans are a family of tryptamine-based medication, drugs used as abortive medication in the treatment of migraines and cluster headaches. This drug class was first commercially introduced in the 1990s. While effective at treating individual h ...

s, MAO inhibitors, antipsychotics, or other dopamine antagonists. The prescribing information states that paroxetine should "not be used in combination with an

MAOI Monoamine oxidase inhibitors (MAOIs) are a drug class, 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 antidepressa ...

(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 a neuroleptic medication, 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 weigh ...

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 aromat ...

, or

warfarin Warfarin, sold under the brand name Coumadin among others. It is used as an anticoagulant, anticoagulant medication. It is commonly used to prevent deep vein thrombosis and pulmonary embolism, and to protect against stroke in people who ha ...

. Paroxetine interacts with the following

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

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. CYP2 ...

for which it is both a

substrate Substrate may refer to: Physical layers *Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached ** Substrate (aquatic environment), the earthy material that exi ...

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, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

(''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 the metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, t ...

(''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 ...

(''weak'') inhibitor. Paroxetine has been shown to be an inhibitor of G protein-coupled receptor kinase 2 (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 the fields of biochemistry and pharmacology an allosteric regulator (or allosteric modulator) is a substance that binds to a site on an enzyme or receptor distinct from the active site, resulting in a conformational change that alters the p ...

site of the serotonin transporter, similarly to

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

, though less potently so. Paroxetine also inhibits the reuptake of

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

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. It is the association cortex in the frontal lobe. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, ...

. Paroxetine is a phenylpiperidine and might have some affinity for opioid receptors.

Pharmacokinetics

Paroxetine is well-absorbed following oral administration. It has an absolute

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

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 at a specific location in the body which leads to a reduction in the concentration of the active drug before it reaches the ...

. 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

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

. It is available as a

. In 2022, it was the 92nd most commonly prescribed medication in the United States, with more than 7million prescriptions. It is on the

. GlaxoSmithKline has paid substantial fines, paid settlements in

class-action A class action A class action is a form of lawsuit. Class Action may also refer to: * ''Class Action'' (film), 1991, starring Gene Hackman and Mary Elizabeth Mastrantonio * Class Action (band), a garage house band * "Class Action" (''Teenage R ...

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 the use of the drug.

Marketing

In 2004, GSK agreed to settle charges of consumer fraud for $2.5 million. The

legal discovery Discovery, in the law of common law jurisdictions, is a phase of pretrial procedure in a lawsuit in which each party, through the law of civil procedure, can obtain Evidence (law), evidence from other parties. This is by means of methods of dis ...

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

United States Department of Justice The United States Department of Justice (DOJ), also known as the Justice Department, is a United States federal executive departments, federal executive department of the U.S. government that oversees the domestic enforcement of Law of the Unite ...

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. In February 2016, the UK

Competition and Markets Authority The Competition and Markets Authority (CMA) is the principal competition regulator in the United Kingdom. It is a non-ministerial government department in the United Kingdom, responsible for promoting competitive markets and tackling unfair beh ...

imposed record fines of £45 million on companies that 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 Geography of the European Union, located primarily in Europe. The u ...

and UK Competition law by entering into agreements to delay the market entry of generic versions of the drug in the UK.

received the bulk of the fines, being fined £37,600,757. Other companies that 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 generic manufacturers who incurred losses as a result of the anticompetitive conduct. In 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, Enterprise Act 2002 which came into force on 1 April 2003. The Competition Service is an executive non-department ...

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

Economics

In 2007, paroxetine was ranked 94th on the list of bestselling drugs, 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.

Brand names

Brand 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

. In particular, intravaginal ejaculation latency time (IELT) was found to increase 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

, which induced a fourfold delay. There is also evidence that paroxetine may be effective in the treatment of compulsive gambling and hot flashes. Benefits of paroxetine prescription for

diabetic neuropathy Diabetic neuropathy includes various types of nerve damage associated with diabetes mellitus. The most common form, diabetic peripheral neuropathy, affects 30% of all diabetic patients. Studies suggests that cutaneous nerve branches, such as the s ...

or chronic

tension headache Tension headache, stress headache, or tension-type headache (TTH), is the most common type of primary headache. The pain usually radiates from the lower back of the head, the neck, the eyes, or other muscle groups in the body typically affecting b ...

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

dysthymia Dysthymia ( ), known as persistent depressive disorder (PDD) in the DSM-5-TR and dysthymic disorder in ICD-11, is a psychiatric condition marked by symptoms that are similar to those of major depressive disorder, but which persist for at leas ...

, a chronic disorder involving depressive symptoms for most days of the year. There is evidence to support that paroxetine selectively binds to and inhibits G protein-coupled receptor kinase 2 (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 b ...

, which becomes desensitized in cases of

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...

, 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 A disease-modifying osteoarthritis drug (DMOAD) is a disease-modifying drug that would inhibit or even reverse the progression of osteoarthritis. Since the main hallmark of osteoarthritis is cartilage loss, a typical DMOAD would prevent the loss o ...

Veterinary use

Paroxetine may be useful in the treatment of canine or feline behavioral diagnoses and is effective in the treatment of social anxiety, depression, and agitation associated with depression.

Other organisms

Paroxetine is a common finding in wastewater. 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 Hybrid word, blend of the Greek ''caeno-'' (recent), ''r ...

''. Alberca ''et al.'', 2016 found that paroxetine acts as a trypanocide against '' T. cruzi''. This review cites this study. Alberca ''et al.'', 2016 finds a leishmanicide effect. Alberca finds that paroxetine produces

cell death Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, as in programmed cell death, or may result from factors such as di ...

of the promastigotes of '' L. infantum''. The

mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical Drug interaction, interaction through which a Medication, drug substance produces its pharmacological effect. A mechanism of action usually includes mention o ...

remains unknown. This review cites this research. Various types of bacteria can break down paroxetine in the environment. These include, for example '' Pseudomonas sp.'', '' Bosea sp.'', '' Shewanella sp., Species of Chitinophagaceae and '' Acinetobacter sp.

References

External links

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