Paroxetine

Effects

Overview

Paroxetine, sold under the brand name Paxil among others, is an antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class 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. It has also been used in the treatment of premature ejaculation, and hot flashes due to menopause. It is taken orally (by mouth).[1][2][3] WP

Common side effects include drowsiness, dry mouth, loss of appetite, sweating, trouble sleeping, and sexual dysfunction. 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.[1][4][5] WP

Paroxetine was approved for medical use in the United States in 1992 and initially sold by GlaxoSmithKline. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2023, it was the 72nd most commonly prescribed medication in the United States, with more than 9 million prescriptions. In 2018, it was in the top 10 of most prescribed antidepressants in the United States.[1][6–11] WP

History

Legal status

Society and culture

Paroxetine was approved for medical use in the United States in 1992 and initially sold by GlaxoSmithKline. It is available as a generic medication. In 2022, it was the 92nd most commonly prescribed medication in the United States, with more than 7 million prescriptions. It is on the World Health Organization's List of Essential Medicines.[1][6–10] WP

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 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.[19][20] WP

Marketing

In 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 [in children] had not been demonstrated, as this would undermine the profile of paroxetine".[21][22] WP

In 2012, the United States Department of Justice fined GlaxoSmithKline $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.[19][20][23] WP

In February 2016, the UK Competition and Markets Authority imposed record fines of £45 million on companies that were found to have infringed European Union and UK Competition law by entering into agreements to delay the market entry of generic versions of the drug in the UK. GlaxoSmithKline 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. GlaxoSmithKline 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 by the companies which were fined.[24–29] WP

GSK marketed paroxetine through television advertisements in the 1990s and 2000s. Commercials also aired for the CR version of the drug beginning in 2003.[30] WP

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.[31][32][33] WP

Brand names

Brand names include Aropax, Paretin, Brisdelle, Deroxat, Paxil, Pexeva, Paxtine, Paxetin, Paroxat, Paraxyl, Sereupin, Daparox and Seroxat.[34][35] WP

Pharmacology

Pharmacodynamics

Paroxetine is the most potent and one of the most specific selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors (SSRIs). It also binds to the allosteric site of the serotonin transporter, similarly to escitalopram, though less potently so. Paroxetine also inhibits the reuptake of norepinephrine 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. Paroxetine is a phenylpiperidine and might have some affinity for opioid receptors.[37][40–44] WP⚠ A table follows this text in the source and is not copied here. Open the source to see it.

Pharmacokinetics

Paroxetine is well-absorbed following oral administration. It has an absolute bioavailability of about 50%, with evidence of a saturable first pass effect. 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.[37][45] WP

Paroxetine is a mechanism-based inhibitor of CYP2D6.[46][47] WP

Receptor binding · Wikipedia

Binding profile Paroxetine

Every row cites [36–39]

Chemistry

Formula

C19H20FNO3 PC

CAS number

61869-08-7 PC

Molar mass (g/mol)

329.4 PC

IUPAC name (computed by PubChem)

(3S,4R)-3-(1,3-benzodioxol-5-yloxymethyl)-4-(4-fluorophenyl)piperidine PC

SMILES

C1CNC[C@H]([C@@H]1C2=CC=C(C=C2)F)COC3=CC4=C(C=C3)OCO4 PC

InChIKey

AHOUBRCZNHFOSL-YOEHRIQHSA-N PC

PubChem CID

43815

Pop culture

No references added yet.

References

1. Other Paroxetine Hydrochloride Monograph for Professionals
2. Journal / agency Raisi F, Soleimani R, Ahmadzadeh A, Sadati SN, Fakhrian A, Jalali MM. Efficacy and safety of pharmacological treatments in patients with premature ejaculation: an umbrella review of meta-analyses of randomized controlled trials. The Journal of Sexual Medicine. June 2025. doi:10.1093/jsxmed/qdaf094 · PMID 40326158
3. Journal / agency Fischer A. FDA approves the first non-hormonal treatment for hot flashes associated with menopause. 28 June 2013
4. Journal / agency Healy D, Bahrick A, Bak M, Barbato A, Calabro RS, Chubak BM. Diagnostic criteria for enduring sexual dysfunction after treatment with antidepressants, finasteride and isotretinoin. International Journal of Risk & Safety in Medicine. 2022. doi:10.3233/JRS-210023 · PMID 34719438 · PMC8925105
5. Journal / agency PRAC recommendations on signals adopted at the 13-16 May 2019 PRAC meeting. 11 June 2019
6. Other Food and Drug Administration. Approved Drug Products with Therapeutic Equivalence Evaluations – FDA Orange Book 31st Edition (2011): FDA Orange Book 31st Edition (2011). 2011
7. Other World Health Organization. The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). 2023
8. Other British national formulary: BNF 76. 2018
9. Other Top 300 of 2023
10. Other Paroxetine Drug Usage Statistics, United States, 2014 - 2023
11. Other Grohol JM. Top 25 Psychiatric Medications for 2018. 15 December 2019
12. Journal / agency Finley, P. R. Drug Interactions with Lithium: An Update. (2016)
13. Journal / agency Hawley CJ, Loughlin PJ, Quick SJ, Gale TM, Sivakumaran T, Hayes J, McPhee S. Efficacy, safety and tolerability of combined administration of lithium and selective serotonin reuptake inhibitors: a review of the current evidence. (2000)
14. Journal / agency Müller-Oerlinghausen, B. Drug Interactions with Lithium. (1999)
15. Journal / agency Bauer, Michael PhD, MD; Linden, Michael MD; Schaaf, Berthold; Weber, Hans J. MD. Adverse Events and Tolerability of the Combination of Fluoxetine/Lithium Compared With Fluoxetine. (1996)
16. Journal / agency Feduccia, A. A., Jerome, L., Mithoefer, M. C., & Holland, J. Discontinuation of medications classified as reuptake inhibitors affects treatment response of MDMA-assisted psychotherapy
17. Journal / agency Sarparast, A., Thomas, K., Malcolm, B., & Stauffer, C. S. Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review
18. Journal / agency Malcolm, B., & Thomas, K. Serotonin toxicity of serotonergic psychedelics
19. Other GlaxoSmithKline to Plead Guilty and Pay $3 Billion to Resolve Fraud Allegations and Failure to Report Safety Data. 2 July 2012
20. Other https://www.justice.gov/sites/default/files/opa/legacy/2012/07/02/us-complaint.pdf. 26 October 2011
21. Other Angell M. Drug Companies & Doctors: A Story of Corruption. 15 January 2009
22. Journal / agency Kondro W, Sibbald B. Drug company experts advised staff to withhold data about SSRI use in children. CMAJ. March 2004. doi:10.1503/cmaj.1040213 · PMID 14993169 · PMC343848
23. Other Thomas K, Schmidt MS. Glaxo Agrees to Pay $3 Billion in Fraud Settlement. 2 July 2012
24. Other CMA fines pharma companies £45 million
25. Other GlaxoSmithKline Summary
26. Other Generics Summary
27. Other Xellia Summary
28. Other Merck Summary
29. Other Actavis Summary
30. Other Paxil CR -- Nametag -- (2003):30 (USA) | Adland. 3 April 2004
31. Other Top 200 generic drugs by units in 2006. Top 200 brand-name drugs by units
32. Other Top 200 generic drugs by units in 2007. 18 February 2008
33. Other Top 200 brand drugs by units in 2007
34. Journal / agency Nevels RM, Gontkovsky ST, Williams BE. Paroxetine-The Antidepressant from Hell? Probably Not, But Caution Required. Psychopharmacology Bulletin. March 2016. PMID 27738376 · PMC5044489
35. Other Coleman A. Dictionary of Psychology. 2006
36. Other Brunton L, Chabner B, Knollman B. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 2010
37. Journal / agency Sanchez C, Reines EH, Montgomery SA. A comparative review of escitalopram, paroxetine, and sertraline: Are they all alike?. International Clinical Psychopharmacology. July 2014. doi:10.1097/YIC.0000000000000023 · PMID 24424469 · PMC4047306
38. Journal / agency Owens MJ, Knight DL, Nemeroff CB. Second-generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine. Biological Psychiatry. September 2001. doi:10.1016/s0006-3223(01)01145-3 · PMID 11543737
39. Other Roth BL, Driscol J. PDSP Kᵢ Database. 12 January 2011
40. Journal / agency Mellerup ET, Plenge P. High affinity binding of 3H-paroxetine and 3H-imipramine to rat neuronal membranes. Psychopharmacology. July 1986. doi:10.1007/BF02412117 · PMID 2944152
41. Journal / agency Mansari ME, Wiborg O, Mnie-Filali O, Benturquia N, Sánchez C, Haddjeri N. Allosteric modulation of the effect of escitalopram, paroxetine and fluoxetine: in-vitro and in-vivo studies. The International Journal of Neuropsychopharmacology. February 2007. doi:10.1017/S1461145705006462 · PMID 16448580
42. Journal / agency Owens JM, Knight DL, Nemeroff CB. Second generation SSRIS: human monoamine transporter binding profile of escitalopram and R-fluoxetine. L'Encephale. 1 August 2002. PMID 12232544
43. Journal / agency Brackley AD, Jeske NA. Paroxetine Increases δ Opioid Responsiveness in Sensory Neurons. eNeuro. 2022. doi:10.1523/ENEURO.0063-22.2022 · PMID 35882549 · PMC9347309
44. Journal / agency Duman EN, Kesim M, Kadioglu M, Yaris E, Kalyoncu NI, Erciyes N. Possible Involvement of Opioidergic and Serotonergic Mechanisms in Antinociceptive Effect of Paroxetine in Acute Pain. Journal of Pharmacological Sciences. 2004. doi:10.1254/jphs.94.161 · PMID 14978354
45. Journal / agency Kaye CM, Haddock RE, Langley PF, Mellows G, Tasker TC, Zussman BD, Greb WH. A review of the metabolism and pharmacokinetics of paroxetine in man. Acta Psychiatrica Scandinavica. Supplementum. 1989. doi:10.1111/j.1600-0447.1989.tb07176.x · PMID 2530793
46. Journal / agency Stepan AF, Mascitti V, Beaumont K, Kalgutkar AS. Metabolism-guided drug design. MedChemComm. 2013. doi:10.1039/C2MD20317K
47. Journal / agency Jornil J, Jensen KG, Larsen F, Linnet K. Identification of cytochrome P450 isoforms involved in the metabolism of paroxetine and estimation of their importance for human paroxetine metabolism using a population-based simulator. Drug Metabolism and Disposition. March 2010. doi:10.1124/dmd.109.030551 · PMID 20007670

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), TripSit factsheets, PubChem (public domain). Each value links to the exact revision it came from.