|Trade names||Paxil, Pexeva, Seroxat, Brisdelle, Rexetin|
|ATC code||N06AB05 (WHO)|
|Bioavailability||Extensively absorbed from the GI tract, but extensive first-pass metabolism in the liver|
|Metabolism||Extensive, hepatic (mostly CYP2D6-mediated)|
|Biological half-life||21 hours|
|Excretion||Renal (64%; 2% unchanged and 62% as metabolites), Faecal (36%; <1% unchanged)|
|Chemical and physical data|
|Molar mass||329.3 g/mol|
|3D model (Jmol)||Interactive image|
|(what is this?)|
Paroxetine, also known by the trade names Paxil and Seroxat among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive-compulsive disorder, social anxiety disorder, panic disorder, posttraumatic stress disorder, generalized anxiety disorder and premenstrual dysphoric disorder. It has also been used in the treatment of hot flashes and night sweats associated with menopause.
It has a similar tolerability profile to other SSRIs. The common side effects include drowsiness, dry mouth, loss of appetite, sweating, trouble sleeping and delayed ejaculation. It may also be associated with a slightly increased risk of birth defects. The incidence of withdrawal symptoms is higher with paroxetine and venlafaxine. Several studies have associated paroxetine with suicidal thinking and behavior in children and adolescents.
Marketing of the drug began in 1992 by the pharmaceutical company SmithKline Beecham, known since 2000 as GlaxoSmithKline. Generic formulations have been available since 2003 when the patent expired. The United States Department of Justice fined GlaxoSmithKline $3 billion in 2012, including a sum for withholding data on paroxetine, unlawfully promoting it for under-18s and preparing an article, following one of its clinical trials, study 329, that misleadingly reported the drug was effective in treating adolescent depression.
Paroxetine is primarily used to treat major depressive disorder, obsessive-compulsive disorder, post-traumatic stress disorder, social anxiety disorder, panic disorder, generalized anxiety disorder, premenstrual dysphoric disorder and menopausal hot flashes.
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 or inferior 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 time point.
Paroxetine was the first antidepressant formally 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.
Social anxiety disorder
Paroxetine has demonstrated efficacy for the treatment of social anxiety in adults and children. There was a significant improvement in scores on the Liebowitz Social Anxiety Scale and Social Phobia Inventory compared with placebo. It is also beneficial for people with co-occurring social anxiety disorder and alcohol use disorder.
Paroxetine is used in the treatment of obsessive-compulsive disorder. Comparative efficacy of paroxetine is equivalent to that of clomipramine and venlafaxine. Paroxetine is also effective for children with obsessive-compulsive disorder.
Menopausal hot flashes
On June 28, 2013 U.S. FDA approved low dose paroxetine for the treatment of moderate-to-severe vasomotor symptoms (e.g. hot flashes and night sweats) associated with menopause. Randomized controlled trials have shown modest relief in such cases. At the low dose used for menopausal hot flashes side effects are similar to placebo and dose tapering is not required for discontinuation.
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 1% (0.3%), blurred vision 4%(1%), loss of appetite 6% (2%), nervousness 5% (3%), paraesthesia 4% (2%), dizziness 13% (6%), asthenia (weakness; 15% (6%)), tremor 8% (2%), sweating 11% (2%) and 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, 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 (CHMP) at the European Medicines Agency recommends to reduce gradually over several weeks or months if the decision to withdraw is made. See also Discontinuation syndrome (withdrawal).
Mania or hypomania may occur in 1% of patients with depression and up to 12% of patients with bipolar disorder. 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.
Like other antidepressants, paroxetine may increase the risk of suicidal thinking and behaviour in children and adolescents. The FDA conducted a statistical analysis of paroxetine clinical trials in children and adolescents in 2004, finding an increase in "suicidality" and ideation as compared to placebo; the trend for increased "suicidality" was observed in both trials for depression and for anxiety disorders. In 2015 a paper published in the BMJ that reanalysed the original case notes, argued that in Study 329, assessing paroxetine and imipramine against placebo in adolescents with depression, the incidence of suicidal behavior had been under-reported and efficacy exaggerated for paroxetine.
Sexual dysfunction, including loss of libido, anorgasmia, 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 >70%. Symptoms of sexual dysfunction have been reported to persist after discontinuing SSRIs, although this is thought to be occasional.
The American College of Obstetricians and Gynecologists recommends that for pregnant women and women planning to become pregnant, "treatment with all SSRIs or selective norepinephrine reuptake inhibitors or both during pregnancy be individualized and paroxetine use among pregnant women or women planning to become pregnant be avoided, if possible." According to the prescribing information "epidemiological studies have shown that infants born to women who had first trimester paroxetine exposure had an increased risk of cardiovascular malformations, primarily ventricular and atrial septal defects (VSDs and ASDs). In general, septal defects range from those that are symptomatic and may require surgery to those that are asymptomatic and may resolve spontaneously. If a patient becomes pregnant while taking paroxetine, she should be advised of the potential harm to the fetus. Unless the benefits of paroxetine to the mother justify continuing treatment, consideration should be given to either discontinuing paroxetine therapy or switching to another antidepressant." These conclusions are supported by multiple systematic reviews and meta-analyses that found that, on average, the use of paroxetine during pregnancy is associated with about 1.5–1.7-fold increase in congenital birth defects, in particular, heart defects.
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 crying 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, which has a longer half-life and thus decreases the severity of discontinuation syndrome.
Acute overdosage is often manifested by emesis, 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 200–2000 μg/L in poisoned patients. Postmortem blood levels have ranged from 1–4 mg/L in acute lethal overdose situations. It is usually considered, along with the other SSRIs, sertraline and fluoxetine to be a low-risk drug in cases of overdose.
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.
Paroxetine interacts with the following cytochrome P450 enzymes:
- CYP2D6 for which it is both a substrate and a potent inhibitor.
- CYP2B6 (strong) inhibitor.
- CYP3A4 (weak) inhibitor.
- CYP1A2 (weak) inhibitor.
- CYP2C9 (weak) inhibitor.
- CYP2C19 (weak) inhibitor.
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, but less potently than escitalopram. This activity of the drug on brain neurons is thought to be responsible for its antidepressant effects. Paroxetine also inhibits the reuptake of norepinephrine to a lesser extent (<50 nmol/L).
Society and culture
GlaxoSmithKline has paid substantial fines, paid settlements in class action lawsuits, and become the subject of several highly critical books in relation to 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.
In 2002 the U.S. FDA published a warning regarding "severe" discontinuation symptoms among those terminating paroxetine treatment, including paraesthesia, bad dreams, 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 now acknowledges the occurrence of a discontinuation syndrome, including serious discontinuation symptoms.
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 had said, "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".
On 12 February 2016, the UK Competition and Markets Authority imposed record fines of £45,000,000 on companies which 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 United Kingdom. GlaxoSmithKline 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. GlaxoSmithKline 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 by the companies which were fined.
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 United States 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.
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 6–13-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.
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.
- United States Department of Justice, July 2012: "The United States alleges that, among other things, GSK participated in preparing, publishing and distributing a misleading medical journal article that misreported that a clinical trial of Paxil demonstrated efficacy in the treatment of depression in patients under age 18, when the study failed to demonstrate efficacy."
- "PRODUCT INFORMATION PAROXETINE SANDOZ 20mg FILM-COATED TABLETS" (PDF). TGA eBusiness Services. Sandoz Pty Ltd. 18 January 2012. Retrieved 22 November 2013.
- "PAROXETINE (paroxetine hydrochloride hemihydrate) tablet, film coated [Mylan Institutional Inc.]". DailyMed. Mylan Institutional Inc. January 2012. Retrieved 22 November 2013.
- "Paroxetine 20 mg Tablets – Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Sandoz Limited. 21 March 2013. Retrieved 22 November 2013.
- "Paxil, Paxil CR (paroxetine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 22 November 2013.
- Food and Drug Administration (June 28, 2013). "FDA NEWS RELEASE: FDA approves the first non-hormonal treatment for hot flashes associated with menopause".
- Papakostas GI (2008). "Tolerability of modern antidepressants". J Clin Psychiatry. 69 (Suppl E1): 8–13. PMID 18494538.
- "ACOG Committee Opinion No. 354: Treatment with selective serotonin reuptake inhibitors during pregnancy". Obstet Gynecol. 108 (6): 1601–3. 2006. doi:10.1097/00006250-200612000-00058. PMID 17138801.
- Yonkers, KA; Blackwell, KA; Glover, J; Forray, A (2014). "Antidepressant use in pregnant and postpartum women.". Annual Review of Clinical Psychology. 10: 369–92. doi:10.1146/annurev-clinpsy-032813-153626. PMC 4138492. PMID 24313569.
- Hosenbocus, Sheik; Chahal, Raj (2011-02-01). "SSRIs and SNRIs: A review of the Discontinuation Syndrome in Children and Adolescents". Journal of the Canadian Academy of Child and Adolescent Psychiatry. 20 (1): 60–67. ISSN 1719-8429. PMC 3024727. PMID 21286371.
- Apter, Alan; Lipschitz, Alan; Fong, Regan; Carpenter, David J.; Krulewicz, Stan; Davies, John T.; Wilkinson, Christel; Perera, Philip; Metz, Alan (2006-03-01). "Evaluation of Suicidal Thoughts and Behaviors in Children and Adolescents Taking Paroxetine". Journal of Child and Adolescent Psychopharmacology. 16 (1-2): 77–90. doi:10.1089/cap.2006.16.77. ISSN 1044-5463.
- Smith, Aaron (May 11, 2005). "New profit twist for drugmakers". CNN Money.
- "GlaxoSmithKline to Plead Guilty and Pay $3 Billion to Resolve Fraud Allegations and Failure to Report Safety Data", United States Department of Justice, 2 July 2012.
- United States v. GlaxoSmithKline, United States District Court for the District of Massachusetts, 26 October 2011 (for paroxetine, pp. 3–19).
- Thomas, Katie; Schmidt, Michael S. "Glaxo Agrees to Pay $3 Billion in Fraud Settlement", The New York Times, 2 July 2012.
- Wagstaff, Antona J.; Cheer, Susan M.; Matheson, Anna J.; Ormrod, Douglas; Goa, Karen L. (2002-01-01). "Paroxetine: an update of its use in psychiatric disorders in adults". Drugs. 62 (4): 655–703. doi:10.2165/00003495-200262040-00010. ISSN 0012-6667. PMID 11893234.
- Lotke, Pamela; Garcia, Francisco (2004-01-01). "Paroxetine controlled release was effective and tolerable for treating menopausal hot flash symptoms in women". Evidence Based Medicine. 9 (1): 23–23. doi:10.1136/ebm.9.1.23. ISSN 1473-6810.
- Cipriani A, Furukawa TA, Salanti G, et al. (February 2009). "Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis". Lancet. 373 (9665): 746–58. doi:10.1016/S0140-6736(09)60046-5. PMID 19185342.
- Fava, Maurizio; Amsterdam, Jay; Deltito, Joseph; Salzman, Carl; Schwaller, Michael; Dunner, David. "A Double-Blind Study of Paroxetine, Fluoxetine, and Placebo in Outpatients with Major Depression". Annals of Clinical Psychiatry. 10 (4): 145–150. doi:10.3109/10401239809147030.
- Sugarman, Michael A.; Loree, Amy M.; Baltes, Boris B.; Grekin, Emily R.; Kirsch, Irving (2014-08-27). "The Efficacy of Paroxetine and Placebo in Treating Anxiety and Depression: A Meta-Analysis of Change on the Hamilton Rating Scales". PLoS ONE. 9 (8): e106337. doi:10.1371/journal.pone.0106337. PMC 4146610. PMID 25162656.
- Purgato, Marianna; Papola, Davide; Gastaldon, Chiara; Trespidi, Carlotta; Magni, Laura R; Rizzo, Carla; Furukawa, Toshi A; Watanabe, Norio; Cipriani, Andrea (2014-04-03). Paroxetine versus other anti-depressive agents for depression. John Wiley & Sons. doi:10.1002/14651858.cd006531.pub2. ISSN 1465-1858.
- Turner, Francis Joseph (2005). Social Work Diagnosis in Contemporary Practice. Oxford University Press US. ISBN 0-19-516878-X.
- Ballenger, J. C.; Wheadon, D. E.; Steiner, M.; Bushnell, W.; Gergel, I. P. (1998-01-01). "Double-blind, fixed-dose, placebo-controlled study of paroxetine in the treatment of panic disorder". The American Journal of Psychiatry. 155 (1): 36–42. doi:10.1176/ajp.155.1.36. ISSN 0002-953X. PMID 9433336.
- Sugarman, Michael A.; Loree, Amy M.; Baltes, Boris B.; Grekin, Emily R.; Kirsch, Irving (2014-08-27). "The Efficacy of Paroxetine and Placebo in Treating Anxiety and Depression: A Meta-Analysis of Change on the Hamilton Rating Scales". PLoS ONE. 9 (8): e106337. doi:10.1371/journal.pone.0106337. PMC 4146610. PMID 25162656.
- Stein MB; Liebowitz MR; Lydiard R; Pitts CD; Bushnell W; Gergel I (1998-08-26). "Paroxetine treatment of generalized social phobia (social anxiety disorder): A randomized controlled trial". JAMA. 280 (8): 708–713. doi:10.1001/jama.280.8.708. ISSN 0098-7484. PMID 9728642.
- Manassis, Katharina (2005-05-01). "Paroxetine improves social anxiety disorder in children and adolescents". Evidence Based Mental Health. 8 (2): 43–43. doi:10.1136/ebmh.8.2.43. ISSN 1468-960X. PMID 15851806.
- Stein DJ; Versiani M; Hair T; Kumar R (2002-12-01). "Efficacy of paroxetine for relapse prevention in social anxiety disorder: A 24-week study". Archives of General Psychiatry. 59 (12): 1111–1118. doi:10.1001/archpsyc.59.12.1111. ISSN 0003-990X.
- Randall, Carrie L.; Johnson, Michael R.; Thevos, Angelica K.; Sonne, Susan C.; Thomas, Suzanne E.; Willard, Shauna L.; Brady, Kathleen T.; M.d., Jonathan R. Davidson, (2001-01-01). "Paroxetine for social anxiety and alcohol use in dual-diagnosed patients". Depression and Anxiety. 14 (4): 255–262. doi:10.1002/da.1077. ISSN 1520-6394.
- Germann, D; Ma, G; Han, F; Tikhomirova, A (2013). "Paroxetine hydrochloride.". Profiles of drug substances, excipients, and related methodology. 38: 367–406. doi:10.1016/B978-0-12-407691-4.00008-3. PMID 23668408.
- Zohar, J.; Judge, R. (1996-10-01). "Paroxetine versus clomipramine in the treatment of obsessive-compulsive disorder. OCD Paroxetine Study Investigators.". The British Journal of Psychiatry. 169 (4): 468–474. doi:10.1192/bjp.169.4.468. ISSN 0007-1250. PMID 8894198.
- Denys, Damiaan; van der Wee, Nic; van Megen, Harold J. G. M.; Westenberg, Herman G. M. (2003-12-01). "A double blind comparison of venlafaxine and paroxetine in obsessive-compulsive disorder". Journal of Clinical Psychopharmacology. 23 (6): 568–575. doi:10.1097/01.jcp.0000095342.32154.54. ISSN 0271-0749. PMID 14624187.
- Ipser, JC; Stein, DJ; Hawkridge, S; Hoppe, L (8 July 2009). "Pharmacotherapy for anxiety disorders in children and adolescents.". The Cochrane database of systematic reviews (3): CD005170. doi:10.1002/14651858.CD005170.pub2. PMID 19588367.
- FDA NEWS RELEASE: FDA approves the first non-hormonal treatment for hot flashes associated with menopause, Jun. 28, 2013http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm359030.htm
- Orleans, Ronald J.; Li, Li; Kim, Myong-Jin; Guo, Jia; Sobhan, Mahboob; Soule, Lisa; Joffe, Hylton V. (2014). "FDA Approval of Paroxetine for Menopausal Hot Flushes". New England Journal of Medicine. 370 (19): 1777–1779. doi:10.1056/NEJMp1402080. ISSN 0028-4793. PMID 24806158.
- Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (12th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-162442-8.
- Ciraulo, DA; Shader, RI, eds. (2011). Pharmacotherapy of Depression. SpringerLink (2nd ed.). New York, NY: Humana Press. doi:10.1007/978-1-60327-435-7. ISBN 978-1-60327-434-0.
- "Press release, CHMP meeting on Paroxetine and other SSRIs" (PDF). European Medicines Agency. 2004-12-09. Retrieved 2007-08-24.
- "www.accessdata.fda.gov" (PDF).
- Morishita S, Arita S (October 2003). "Induction of mania in depression by paroxetine". Hum Psychopharmacol. 18 (7): 565–8. doi:10.1002/hup.531. PMID 14533140.
- "www.fda.gov" (PDF).
- "FDA Launches a Multi-Pronged Strategy to Strengthen Safeguards for Children Treated With Antidepressant Medications".
- Hammad TA (2004-08-16). "Review and evaluation of clinical data: relationship between psychotropic drugs and pediatric suicidality" (PDF). Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and Pediatric Advisory Committee. September 13–14, 2004. Briefing Information. FDA. p. 30. Retrieved 2009-01-27.
- Keller MB; et al. (2001). "Efficacy of Paroxetine in the Treatment of Adolescent Major Depression: A Randomized, Controlled Trial". J Am Acad Child Adolesc Psychiatry. 40 (7): 762–772. doi:10.1097/00004583-200107000-00010. PMID 11437014.
- Le Noury, Joanna, et al. "Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence", BMJ, 351, 16 September 2015. doi:10.1136/bmj.h4320 PMID 26376805 Godlee, Fiona. "Study 329", BMJ, 351, 17 September 2015. doi:10.1136/bmj.h4973 Doshi, Peter. "No correction, no retraction, no apology, no comment: paroxetine trial reanalysis raises questions about institutional responsibility", BMJ, 351, 16 September 2015. doi:10.1136/bmj.h4629 PMID 26377109 Henry, David; Fitzpatrick, Tiffany. "Liberating the data from clinical trials", BMJ, 351, 16 September 2015. doi:10.1136/bmj.h4601 PMID 26377210 Boseley, Sarah. "Seroxat study under-reported harmful effects on young people, say scientists", The Guardian, 16 September 2015.
- Clark MS, Jansen K, Bresnahan M (November 2013). "Clinical inquiry: How do antidepressants affect sexual function?". J Fam Pract. 62 (11): 660–1. PMID 24288712.
- Csoka AB, Csoka A, Bahrick A, Mehtonen OP (2008). "Persistent sexual dysfunction after discontinuation of selective serotonin reuptake inhibitors". The Journal of Sexual Medicine. 5 (1): 227–33. doi:10.1111/j.1743-6109.2007.00630.x. PMID 18173768.
- Csoka AB, Shipko S (2006). "Persistent sexual side effects after SSRI discontinuation" (PDF). Psychotherapy and Psychosomatics. 75 (3): 187–8. doi:10.1159/000091777. PMID 16636635. Retrieved 30 January 2014.
- http://pi.lilly.com/us/prozac.pdf Page 14.
- "PAXIL (paroxetine hydrochloride) Tablets and Oral Suspension: PRESCRIBING INFORMATION" (PDF). Research Triangle Park, NC: GlaxoSmithKline. August 2007. Archived (PDF) from the original on 2011-08-25. Retrieved 2007-08-14.
- Thormahlen GM (October 2006). "Paroxetine use during pregnancy: is it safe?". Ann Pharmacother. 40 (10): 1834–7. doi:10.1345/aph.1H116. PMID 16926304.
- Way CM (2007). "Safety of newer antidepressants in pregnancy". Pharmacotherapy. 27 (4): 546–52. doi:10.1592/phco.27.4.546. PMID 17381382.
- Bellantuono C, Migliarese G, Gentile S (2007). "Serotonin reuptake inhibitors in pregnancy and the risk of major malformations: a systematic review". Hum Psychopharmacol. 22 (3): 121–8. doi:10.1002/hup.836. PMID 17397101.
- Källén B (July 2007). "The safety of antidepressant drugs during pregnancy". Expert Opin Drug Saf. 6 (4): 357–70. doi:10.1517/147403220.127.116.117. PMID 17688379.
- Bar-Oz B, Einarson T, Einarson A, Boskovic R, O'Brien L, Malm H, Bérard A, Koren G (May 2007). "Paroxetine and congenital malformations: meta-Analysis and consideration of potential confounding factors". Clin Ther. 29 (5): 918–26. doi:10.1016/j.clinthera.2007.05.003. PMID 17697910.
- "Anti-depressant addiction warning". BBC News. 2001-06-11. Retrieved 2010-05-21.
- Haddad PM (2001). "Antidepressant discontinuation syndromes". Drug Saf. 24 (3): 183–97. doi:10.2165/00002018-200124030-00003. PMID 11347722.
- Haddad PM, Anderson IM (November 2007). "Recognising and managing antidepressant discontinuation symptoms". Advances in Psychiatric Treatment. 13 (6): 447–457. doi:10.1192/apt.bp.105.001966.
- on Antidepressants & Halting SSRIs by Dr David Healy MD, FRCPsych. benzo.org.uk. Retrieved on 2013-04-23.
- Goeringer KE, Raymon L, Christian GD, Logan BK (May 2000). "Postmortem forensic toxicology of selective serotonin reuptake inhibitors: a review of pharmacology and report of 168 cases". J. Forensic Sci. 45 (3): 633–48. PMID 10855970.
- R. Baselt,Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1190–1193.
- White N, Litovitz T, Clancy C (December 2008). "Suicidal antidepressant overdoses: a comparative analysis by antidepressant type". Journal of Medical Toxicology. 4 (4): 238–250. doi:10.1007/BF03161207. PMC 3550116. PMID 19031375.
- Mellerup ET, Plenge P (July 1986). "High affinity binding of 3H-paroxetine and 3H-imipramine to rat neuronal membranes". Psychopharmacology. 89 (4): 436–9. doi:10.1007/BF02412117. PMID 2944152.
- Mansari ME, Wiborg O, Mnie-Filali O, Benturquia N, Sánchez C, Haddjeri N (February 2007). "Allosteric modulation of the effect of escitalopram, paroxetine and fluoxetine: in-vitro and in-vivo studies". The International Journal of Neuropsychopharmacology. 10 (1): 31–40. doi:10.1017/S1461145705006462. PMID 16448580.
- Owens, J. M.; Knight, D. L.; Nemeroff, C. B. (2002-08-01). "[Second generation SSRIS: human monoamine transporter binding profile of escitalopram and R-fluoxetine]". L'Encéphale. 28 (4): 350–355. ISSN 0013-7006. PMID 12232544.
- Owens, MJ; Knight, DL; Nemeroff, CB (1 September 2001). "Second-generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine.". Biological Psychiatry. 50 (5): 345–50. doi:10.1016/s0006-3223(01)01145-3. PMID 11543737.
- Roth, BL; Driscol, J (12 January 2011). "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Archived from the original on November 8, 2013. Retrieved 22 November 2013.
- Tonks A (February 2002). "Withdrawal from paroxetine can be severe, warns FDA". BMJ. 324 (7332): 260. doi:10.1136/bmj.324.7332.260. PMC 1122195. PMID 11823353.
- Angell M (15 January 2009). "Drug Companies & Doctors: A Story of Corruption". New York Review of Books. 56 (1).
- Kondro W, Sibbald B (March 2004). "Drug company experts advised staff to withhold data about SSRI use in children". CMAJ. 170 (5): 783. doi:10.1503/cmaj.1040213. PMC 343848. PMID 14993169.
- Thomas, Katie; Schmidt, Michael S. (July 2, 2012). "Glaxo Agrees to Pay $3 Billion in Fraud Settlement". The New York Times.
- The paroxetine prescriptions were calculated as a total of prescriptions for Paxil CR and generic paroxetine using data from the charts for generic and brand-name drugs."Top 200 generic drugs by units in 2006. Top 200 brand-name drugs by units". Drug Topics, Mar 5, 2007. Retrieved 2007-04-08.
- The paroxetine prescriptions were calculated as a total of prescriptions for Paxil CR and generic paroxetine using data from the charts for generic and brand-name drugs."Top 200 generic drugs by units in 2007". Drug Topics. February 18, 2008. Archived from the original on 2009-07-18. Retrieved 2008-10-23.
- "Top 200 brand drugs by units in 2007". Drug Topics, Feb 18, 2008. Archived from the original on 2009-06-29. Retrieved 2008-10-23.
- Coleman, Andrew (2006). Dictionary of Psychology (Second Edition). Oxford University Press. p. 552.
- Coleman, Andrew (2006). Dictionary of Psychology (Second Edition). Oxford University Press. p. 161.
- Waldinger MD, Hengeveld MW, Zwinderman AH, Olivier B (August 1998). "Effect of SSRI antidepressants on ejaculation: a double-blind, randomized, placebo-controlled study with fluoxetine, fluvoxamine, paroxetine, and sertraline". Journal of Clinical Psychopharmacology. 18 (4): 274–81. doi:10.1097/00004714-199808000-00004. PMID 9690692.
- Waldinger MD, Zwinderman AH, Olivier B (2001). "SSRIs and ejaculation: a double-blind, randomized, fixed-dose study with paroxetine and citalopram". Journal of Clinical Psychopharmacology. 21 (6): 556–60. doi:10.1097/00004714-200112000-00003. PMID 11763001.
- Waldinger MD, Zwinderman AH, Olivier B (2004). "On-demand treatment of premature ejaculation with clomipramine and paroxetine: a randomized, double-blind fixed-dose study with stopwatch assessment". Eur. Urol. 46 (4): 510–5; discussion 516. doi:10.1016/j.eururo.2004.05.005. PMID 15363569.
- Kim SW, Grant JE, Adson DE, Shin YC, Zaninelli R (2002). "A double-blind placebo-controlled study of the efficacy and safety of paroxetine in the treatment of pathological gambling". Journal of Clinical Psychiatry. 63 (6): 501–7. doi:10.4088/JCP.v63n0606. PMID 12088161.
- Weitzner MA, Moncello J, Jacobsen PB, Minton S (2002). "A pilot trial of paroxetine for the treatment of hot flashes and associated symptoms in women with breast cancer". Journal of Pain and Symptom Management. 23 (4): 337–345. doi:10.1016/S0885-3924(02)00379-2. PMID 11997203.
- Sindrup SH, Gram LF, Brøsen K, Eshøj O, Mogensen EF (1999). "The selective serotonin reuptake inhibitor paroxetine is effective in the treatment of diabetic neuropathy symptoms". Pain. 42 (2): 135–144. doi:10.1016/0304-3959(90)91157-E. PMID 2147235.
- Langemark M, Olesen J (1994). "Sulpiride and paroxetine in the treatment of chronic tension-type headache. An explanatory double-blind trial". Headache. 34 (1): 20–4. doi:10.1111/j.1526-4610.1994.hed3401020.x. PMID 8132436.
- Gartlehner G, Gaynes BN, Hansen RA, Thieda P, DeVeaugh-Geiss A, Krebs EE, Moore CG, Morgan L, Lohr KN (November 2008). "Comparative benefits and harms of second-generation antidepressants: background paper for the American College of Physicians". Ann. Intern. Med. 149 (10): 734–50. doi:10.7326/0003-4819-149-10-200811180-00008. PMID 19017592.
|Wikimedia Commons has media related to Paroxetine.|
- List of international brand names for paroxetine
- Detailed Paroxetine Consumer Information: Uses, Precautions, Side Effects from medlibrary.org