Paroxetine, sold under the brand name Paxil among others, is an antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class[6] used to treat major depressive disorder, obsessive–compulsive disorder (OCD), panic disorder, social anxiety disorder, post-traumatic stress disorder (PTSD), generalized anxiety disorder, and premenstrual dysphoric disorder.[6] It has also been used in the treatment of premature ejaculation, and hot flashes due to menopause.[6][7] It is taken orally (by mouth).[6]
Common side effects include drowsiness, dry mouth, loss of appetite, sweating, trouble sleeping, and sexual dysfunction.[6] In some patients, sexual dysfunction may persist even after the drug is discontinued, a condition known as post-SSRI sexual dysfunction; regulatory agencies including the European Medicines Agency and Health Canada have recommended that paroxetine's product labeling warn of this risk. Serious side effects may include suicidal thoughts in those under the age of 25, serotonin syndrome, and mania.[6]
Paroxetine was approved for medical use in the United States in 1992 and initially sold by GlaxoSmithKline.[6][8] It is on the World Health Organization's List of Essential Medicines.[9] It is available as a generic medication.[10] In 2023, it was the 72nd most commonly prescribed medication in the United States, with more than 9million prescriptions.[11][12] In 2018, it was in the top 10 of most prescribed antidepressants in the United States.[13]
Medical uses
Paroxetine is primarily used to treat major depressive disorder, obsessive–compulsive disorder, post-traumatic stress disorder, social anxiety disorder, and panic disorder. It is also occasionally used for agoraphobia, generalized anxiety disorder, premenstrual dysphoric disorder, and menopausal hot flashes.[14][15][16][17][18]
Depression
Adverse effects
Common side effects include drowsiness, dry mouth, loss of appetite, sweating, insomnia, and sexual dysfunction.[6] Serious side effects may include suicide in those under the age of 25, serotonin syndrome, and mania.[6] While the rate of side effects appears similar compared to other SSRIs and SNRIs, antidepressant discontinuation syndromes may occur more often.[41][42] Use in pregnancy is not recommended, while use during breastfeeding is relatively safe.[43]
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.[44]
Overdose
Acute overdosage is often manifested by vomiting, lethargy, ataxia, tachycardia, and seizures. 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.[84][85] Along with the other SSRIs, sertraline and fluoxetine, paroxetine is considered a low-risk drug in cases of overdose.[86]
Interactions
Interactions with other drugs acting on the serotonin system or impairing the metabolism of serotonin may increase the risk of serotonin syndrome or neuroleptic malignant syndrome (NMS)-like reaction. Such reactions have been observed with SNRIs and SSRIs alone, but particularly with concurrent use of triptans, MAO inhibitors, 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, thioridazine, tryptophan, or warfarin.[73]
Paroxetine interacts with the following cytochrome P450 enzymes:[87][88]
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 serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors (SSRIs).[90] It also binds to the allosteric site of the serotonin transporter, similarly to escitalopram, though less potently so.[91] Paroxetine also inhibits the reuptake of norepinephrine to a lesser extent (<50 nmol/L).[92] 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.[88] Paroxetine is a phenylpiperidine and might have some affinity for opioid receptors.[93]
Society and culture
Paroxetine was approved for medical use in the United States in 1992 and initially sold by GlaxoSmithKline.[6][100] It is available as a generic medication.[10] In 2022, it was the 92nd most commonly prescribed medication in the United States, with more than 7million prescriptions.[101][12] It is on the World Health Organization's List of Essential Medicines.[9]
GlaxoSmithKline has paid substantial fines, paid settlements in class-action lawsuits, and become the subject of several highly critical books about its marketing of paroxetine, in particular, the
Research
There is evidence that paroxetine may be effective in the treatment of compulsive gambling[120] and hot flashes.[121]
Benefits of paroxetine prescription for diabetic neuropathy[122] or chronic tension headache[123] are uncertain.
Although the evidence is conflicting, paroxetine may be effective for the treatment of dysthymia, a chronic disorder involving depressive symptoms for most days of the year.[124]
There is evidence to support that paroxetine selectively binds to and inhibits G protein-coupled receptor kinase 2 (GRK2) in mice with heart failure.
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.[129]
Other organisms
Paroxetine is a common finding in wastewater. It is highly toxic to the alga Pseudokirchneriella subcapitata (syn. Raphidocelis subcapitata).[130]
It also is toxic to the soil nematode Caenorhabditis elegans.[131]
Alberca et al., 2016 found that paroxetine acts as a trypanocide against T. cruzi.[132]
Alberca et al., 2016 finds a leishmanicide effect. Alberca finds that paroxetine produces cell death of the promastigotes of L. infantum. The mechanism of action remains unknown.[133]
Various types of bacteria can break down paroxetine in the environment.
External links
References
- Anvisa. RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial Diário Oficial da União, 31 March 2023, retrieved 3 August 2023^
- Sandoz Pty Ltd. Product Information Paroxetine Sandoz 20Mg Film-Coated Tablets Therapeutic Goods Administration, 18 January 2012, retrieved 22 November 2013^
- Mylan Institutional Inc. Paroxetine (paroxetine hydrochloride hemihydrate) tablet, film coated