Misplaced Pages

Revision as of 11:26, 20 September 2015

Paroxetine

Clinical data
Trade names	Paxil, Pexeva, Seroxat, Brisdelle, Rexetin
AHFS/Drugs.com	Monograph
MedlinePlus	a698032
License data	US FDA: Paroxetine
Pregnancy category	AU: D
Routes of administration	Oral
ATC code	N06AB05 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: WARNINGRx-only In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	Extensively absorbed from the GI tract, but extensive first-pass metabolism in the liver
Protein binding	93–95%
Metabolism	Extensive, hepatic (mostly CYP2D6-mediated)
Elimination half-life	21 hours
Excretion	Renal (64%; 2% unchanged and 62% as metabolites), Faecal (36%; <1% unchanged)
Identifiers
IUPAC name (3S,4R)-3--4-(4-fluorophenyl)piperidine
CAS Number	61869-08-7
PubChem CID	43815
IUPHAR/BPS	4790
DrugBank	DB00715
ChemSpider	39888
UNII	41VRH5220H
KEGG	D02362
ChEBI	CHEBI:7936
ChEMBL	ChEMBL490
CompTox Dashboard (EPA)	DTXSID3023425
ECHA InfoCard	100.112.096
Chemical and physical data
Formula	C19H20FNO3
Molar mass	329.3 g/mol g·mol
3D model (JSmol)	Interactive image
SMILES c1cc(ccc12CCNC2COc3ccc4c(c3)OCO4)F
InChI InChI=1S/C19H20FNO3/c20-15-3-1-13(2-4-15)17-7-8-21-10-14(17)11-22-16-5-6-18-19(9-16)24-12-23-18/h1-6,9,14,17,21H,7-8,10-12H2/t14-,17-/m0/s1 Key:AHOUBRCZNHFOSL-YOEHRIQHSA-N
(what is this?)  (verify)

Paroxetine (also known by the trade name Paxil among others) is an antidepressant drug of the selective serotonin reuptake inhibitor (SSRI) type. Paroxetine is used to treat major depression, obsessive-compulsive disorder, panic disorder, social anxiety, posttraumatic stress disorder, generalized anxiety disorder and vasomotor symptoms (e.g. hot flashes and night sweats) associated with menopause in adult outpatients.

Differences between newer antidepressants are usually fairly subtle and mostly confined to side effects. It shares the common side effects and contraindications of other SSRIs, with higher rates of nausea, sleepiness, sexual side effects, and weight gain. Discontinuing paroxetine is associated with a high risk of withdrawal syndrome. Paroxetine may be associated with a slightly increased risk of birth defects.

Marketing of the drug began in 1992 by the pharmaceutical company SmithKline Beecham, now GlaxoSmithKline. Generic formulations have been available since 2003 when the patent expired.

Medical uses

Paroxetine is primarily used to treat major depression, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), panic disorder, generalized anxiety disorder (GAD), social phobia/social anxiety disorder, premenstrual dysphoric disorder (PMDD) and menopausal hot flashes.

Paroxetine was the first antidepressant formally approved in the United States for the treatment of panic attacks.

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 or inferior to other antidepressants.

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.

Adverse effects

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 diarrhoea, 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.

Suicide

Paroxetine may increase the risk of suicidal ideation and suicidal behaviour in children and adolescents. Because suicide is rare, it is difficult to test its relationship with the use of paroxetine. Some studies instead analyze suicidality, which generally refers to suicidal ideation and suicidal behaviour. 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.

Pregnancy

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.

Discontinuation syndrome

Many psychoactive medications can cause withdrawal symptoms upon discontinuation from administration. Evidence has shown that paroxetine has among the highest incidence rates and severity of withdrawal syndrome of any medication of its class. Common withdrawal symptoms for paroxetine include nausea, dizziness, lightheadedness and vertigo; insomnia, nightmares and vivid dreams; feelings of electricity in the body, as well as 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.

Overdose

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

GlaxoSmithKline cautions that drug interactions may create or increase specific risks, including Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions:

The development of a potentially life-threatening serotonin syndrome or Neuroleptic Malignant Syndrome (NMS)-like reactions have been reported with SNRIs and SSRIs alone, including treatment with PAXIL, but particularly with concomitant use of serotonergic drugs (including triptans) with drugs that impair metabolism of serotonin (including MAOIs), or with 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.

Pharmacology

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 inhibits the reuptake of norepinephrine more than the other SSRIs, just as sertraline inhibits the reuptake of dopamine more than the other SSRIs.

Its affinities are as follows:

• SERT (K_i = 0.08 nM)
• NET (K_i = 56.7 nM)
• DAT (K_i = 573.7 nM)
• The following muscarinic acetylcholine receptors (mAChRs):
  • M₁ (K_i=186 nM)
  • M₂ (K_i=340 nM)
  • M₃ (K_i=80 nM)
  • M₄ (K_i=320 nM)
  • M₅ (K_i=650 nM)
• α₁ adrenoceptor (K_i>100,000 nM)
• Histamine H₁ receptor (K_i=22,000 nM)

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 to 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.

Withdrawal symptoms

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.

Off-label marketing to children

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 had not been demonstrated, as this would undermine the profile of paroxetine".

In 2012 the U.S. Justice Department announced that GSK had agreed to plead guilty and pay a $3 billion fine, in part for promoting the use of Paxil for children.

Sales

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.

Trade names

Aropax, Brisdelle, Deroxat, Paxil, Pexeva, Paxtine, Paraxyl, Sereupin and Seroxat.

Research

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

There is also evidence that paroxetine may be effective in the treatment of compulsive gambling and hot flashes.

Benefits of paroxetine prescription for diabetic neuropathy or chronic tension headache 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.

References

1. "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
2. ^ "PRODUCT INFORMATION PAROXETINE SANDOZ 20mg FILM-COATED TABLETS" (PDF). TGA eBusiness Services. Sandoz Pty Ltd. 18 January 2012. Retrieved 22 November 2013.
3. ^ "PAROXETINE (paroxetine hydrochloride hemihydrate) tablet, film coated [Mylan Institutional Inc.]". DailyMed. Mylan Institutional Inc. January 2012. Retrieved 22 November 2013.
4. ^ "Paroxetine 20 mg Tablets – Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Sandoz Limited. 21 March 2013. Retrieved 22 November 2013.
5. ^ "Paxil, Paxil CR (paroxetine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 22 November 2013.
6. Katzman MA (2009). "Current considerations in the treatment of generalized anxiety disorder". CNS Drugs. 23 (2): 103–20. doi:10.2165/00023210-200923020-00002. PMID 19173371.
7. Food and Drug Administration (June 28, 2013). "FDA NEWS RELEASE: FDA approves the first non-hormonal treatment for hot flashes associated with menopause".
8. Papakostas GI (2008). "Tolerability of modern antidepressants". J Clin Psychiatry. 69 (Suppl E1): 8–13. PMID 18494538.
9. ^ Haddad PM (2001). "Antidepressant discontinuation syndromes". Drug Saf. 24 (3): 183–97. doi:10.2165/00002018-200124030-00003. PMID 11347722.
10. ^ 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.
11. ^ "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.
12. 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. PMID 24313569. {{cite journal}}: |access-date= requires |url= (help)
13. Grigoriadis, S; VonderPorten, EH; Mamisashvili, L; Roerecke, M; Rehm, J; Dennis, CL; Koren, G; Steiner, M; Mousmanis, P; Cheung, A; Ross, LE (April 2013). "Antidepressant exposure during pregnancy and congenital malformations: is there an association? A systematic review and meta-analysis of the best evidence". The Journal of clinical psychiatry. 74 (4): e293-308. doi:10.4088/JCP.12r07966. PMID 23656855.
14. Smith, Aaron (May 11, 2005). "New profit twist for drugmakers". CNN Money.
15. Baldwin DS, Anderson IM, Nutt DJ, Bandelow B, Bond A, Davidson JR, den Boer JA, Fineberg NA, Knapp M, Scott J, Wittchen HU (2005). "Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology". Journal of Psychopharmacology. 19 (6): 567–596. doi:10.1177/0269881105059253. PMID 16272179.{{cite journal}}: CS1 maint: multiple names: authors list (link)
16. Baldwin D, Bobes J, Stein DJ, Scharwächter I, Faure M (1999). "Paroxetine in social phobia/social anxiety disorder. Randomised, double-blind, placebo-controlled study. Paroxetine Study Group". The British Journal of Psychiatry. 175 (2): 120–6. doi:10.1192/bjp.175.2.120. PMID 10627793.{{cite journal}}: CS1 maint: multiple names: authors list (link)
17. Yonkers KA, Gullion C, Williams A, Novak K, Rush AJ (1996). "Paroxetine as a treatment for premenstrual dysphoric disorder". Journal of Clinical Psychopharmacology. 16 (1): 3–8. doi:10.1097/00004714-199602000-00002. PMID 8834412.{{cite journal}}: CS1 maint: multiple names: authors list (link)
18. Turner, Francis Joseph (2005). Social Work Diagnosis in Contemporary Practice. Oxford University Press US. ISBN 0-19-516878-X.
19. Hansen R, Gaynes B, Thieda P, et al. (October 2008). "Meta-analysis of major depressive disorder relapse and recurrence with second-generation antidepressants". Psychiatr Serv. 59 (10): 1121–30. doi:10.1176/appi.ps.59.10.1121. PMC 2840386. PMID 18832497.
20. Dunner DL, Lipschitz A, Pitts CD, Davies JT (December 2005). "Efficacy and tolerability of controlled-release paroxetine in the treatment of severe depression: post hoc analysis of pooled data from a subset of subjects in four double-blind clinical trials". Clin Ther. 27 (12): 1901–11. doi:10.1016/j.clinthera.2005.12.013. PMID 16507376.{{cite journal}}: CS1 maint: multiple names: authors list (link)
21. Carpenter DJ, Fong R, Kraus JE, Davies JT, Moore C, Thase ME (November 2011). "Meta-analysis of efficacy and treatment-emergent suicidality in adults by psychiatric indication and age subgroup following initiation of paroxetine therapy: a complete set of randomized placebo-controlled trials". J Clin Psychiatry. 72 (11): 1503–14. doi:10.4088/JCP.08m04927blu. PMID 21367354.{{cite journal}}: CS1 maint: multiple names: authors list (link)
22. Barbui C, Furukawa TA, Cipriani A (Jan 29, 2008). "Effectiveness of paroxetine in the treatment of acute major depression in adults: a systematic re-examination of published and unpublished data from randomized trials". CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 178 (3): 296–305. doi:10.1503/cmaj.070693. PMC 2211353. PMID 18227449. {{cite journal}}: Missing pipe in: |journal= (help)CS1 maint: multiple names: authors list (link)
23. Tignol J, Stoker MJ, Dunbar GC (November 1992). "Paroxetine in the treatment of melancholia and severe depression". Int Clin Psychopharmacol. 7 (2): 91–4. doi:10.1097/00004850-199207020-00005. PMID 1487627.{{cite journal}}: CS1 maint: multiple names: authors list (link)
24. Gartlehner G, Gaynes BN, Hansen RA, et al. (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.
25. 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.
26. 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
27. 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.
28. ^ 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.{{cite book}}: CS1 maint: multiple names: authors list (link)
29. ^ Ciraulo, DA; Shader, RI, ed. (2011). Pharmacotherapy of Depression (2nd ed.). New York, NY: Humana Press. doi:10.1007/978-1-60327-435-7. ISBN 978-1-60327-434-0. {{cite book}}: |work= ignored (help)CS1 maint: multiple names: editors list (link)
30. "Press release, CHMP meeting on Paroxetine and other SSRIs" (PDF). European Medicines Agency. 2004-12-09. Retrieved 2007-08-24.
31. "www.accessdata.fda.gov" (PDF).
32. 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.
33. 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.
34. Doshi P (2015). "No correction, no retraction, no apology, no comment: paroxetine trial reanalysis raises questions about institutional responsibility". BMJ. 351: h4629. doi:10.1136/bmj.h4629. PMID 26377109.
35. 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. {{cite journal}}: Explicit use of et al. in: |author= (help)
36. ^ "PAXIL (paroxetine hydrochloride) Tablets and Oral Suspension: PRESCRIBING INFORMATION". Research Triangle Park, NC: GlaxoSmithKline. August 2007. Archived from the original (PDF) on 2011-08-25. Retrieved 2007-08-14.
37. Thormahlen GM (October 2006). "Paroxetine use during pregnancy: is it safe?". Ann Pharmacother. 40 (10): 1834–7. doi:10.1345/aph.1H116. PMID 16926304.
38. Way CM (2007). "Safety of newer antidepressants in pregnancy". Pharmacotherapy. 27 (4): 546–52. doi:10.1592/phco.27.4.546. PMID 17381382.
39. 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
40. Källén B (July 2007). "The safety of antidepressant drugs during pregnancy". Expert Opin Drug Saf. 6 (4): 357–70. doi:10.1517/14740338.6.4.357. PMID 17688379.
41. 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
42. "Anti-depressant addiction warning". BBC News. 2001-06-11. Retrieved 2010-05-21.
43. Skaehill, Penny A.; Welch, E.B. (October 1997). "Clinical Reviews: SSRI Withdrawal Syndrome". American Society of Consultant Pharmacists. Archived from the original on 2006-05-03. Retrieved 2007-08-15.
44. Bhanji NH, Chouinard G, Kolivakis T, Margolese HC (2006). "Persistent tardive rebound panic disorder, rebound anxiety and insomnia following paroxetine withdrawal: a review of rebound-withdrawal phenomena" (PDF). Can J Clin Pharmacol. 13 (1): e69–74. PMID 16456219.{{cite journal}}: CS1 maint: multiple names: authors list (link)
45. 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.
46. on Antidepressants & Halting SSRIs by Dr David Healy MD, FRCPsych. benzo.org.uk. Retrieved on 2013-04-23.
47. 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
48. R. Baselt,Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1190–1193.
49. 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
50. Mellerup ET, Plenge P (July 1986). "High affinity binding of3H-paroxetine and3H-imipramine to rat neuronal membranes". Psychopharmacology. 89 (4): 436–9. doi:10.1007/BF02412117. PMID 2944152.
51. 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
52. Roth, BL; Driscol, J (12 January 2011). "PDSP K_i Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 22 November 2013.{{cite web}}: CS1 maint: multiple names: authors list (link)
53. Angell M (15 January 2009). "Drug Companies & Doctors: A Story of Corruption". New York Review of Books. Vol. 56, no. 1.
54. 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.
55. Thomas, Katie; Schmidt, Michael S. (July 2, 2012). "Glaxo Agrees to Pay $3 Billion in Fraud Settlement". The New York Times.
56. 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.
57. 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.
58. "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.
59. Coleman, Andrew (2006). Dictionary of Psychology (Second Edition). Oxford University Press. p. 552.
60. Coleman, Andrew (2006). Dictionary of Psychology (Second Edition). Oxford University Press. p. 161.
61. 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
62. 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
63. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
64. 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
65. 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
66. 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
67. 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.
68. 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)

External links

• List of international brand names for paroxetine
• Detailed Paroxetine Consumer Information: Uses, Precautions, Side Effects from medlibrary.org

• Selective serotonin reuptake inhibitors
• Benzodioxoles
• Piperidines
• Organofluorides
• Phenol ethers