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paroxetine (Paxil, Pexeva, Seroxat, Brisdelle)

Tradenames: Paxil (paroxetine hydrochloride), Paxeva (paroxetine mesylate). Indications: - treatment of depression, mania [23] - treatment of anxiety [4,12] - obsessive-compulsive disorder (OCD) - self-injurious behavior - irritable bowel syndrome (IBS) [11] - treatment of post menopausal hot flashes (Brisdelle) [27,28] - premenstrual syndrome [23] Contraindications: 1) do NOT use with 14 days of MAO inhibitor 2) < 18 years of age; risk of suicidal ideation [14] 3) no clinical efficacy in children; increased risk of serious adverse effects [16] 4) ineffective, & even harmful, for treating major depression in adolescents [25] 5) classified as pregnancy category D [30] Dosage: 1) start 10 mg PO QD 2) max 50 mg/day 3) optimal dose for major depression is 20 mg QD [26] 3) do not abruptly discontinue; taper over 2-4 weeks [6,13] Tabs: 10, 20, 30, 40 mg. Suspension: 10 mg/5 mL. Paxil CR*: enteric coated, controlled release, QD dosing Tabs: 12.5, 25, 37.5 mg (correspond to 10, 20 & 30 mg of Paxil, respectively) [9] * Paxil CR (Galaxo) NOT longer acting, but released lower in the intestine than Paxil. Allegedly reduces nausea. [15] Pharmacokinetics: 1) only 80% of Paxil CR dose absorbed 2) extensive cyt P450 metabolism by cyt P450 2D6 3) elimination 1/2life: 21 hours (7-37 hours, shortest 1/2life among SSRI) [31] 4) metabolites excreted in the urine & bile Adverse effects: 1) common (> 10%) - headache, asthenia, nausea*, dry mouth, constipation, diarrhea*, somnolence, dizziness, insomnia, sweating, sexual dysfunction, 2) less common (1-10%) - tremor, anorexia, flatulence, nervousness, anxiety, paresthesias, vomiting, decreased libido, palpitations, vasodilation, postural hypotension 3) other - SIADH & hyponatremia [10] - greater potential for anti-cholinergic effects than fluoxetine (Prozac) - may be symptoms of withdrawal including delirium after chronic use or high dose [6,21] - may increase risk of suicidal behavior in children & adolescents [13,19] - SSRI-induced neonatal withdrawal syndrome - increased risk of birth defects, but absolute risk is small [24] - ventricular septal defect [17,18] - anencephaly (risk 0.05%) [24] - atrial septal defects - right ventricular outflow tract obstruction cardiac defects - gastroschisis [24] - omphalocele [24] - exposure during the 1st trimester may increase risk for congenital malformations, particularly cardiac [18] - bruxism [21] * Paxil CR marketed to have fewer GI effects [9] Drug interactions: 1) increased effects/toxicity when used concurrently with: a) tryptophan b) alcohol c) cimetidine d) MAO inhibitors (hyperpyrexic crisis) 3) trazodone, nefazodone (serotonin syndrome) 2) increased effects/toxicity of: c) sertraline d) phenothiazines e) class 1C antiarrhythmic agents f) warfarin 3) decreased effect when used concurrently with: a) phenobarbital b) phenytoin 4) paroxetine strongly inhibits cyt P450 2D6, thus increased levels & potentiation of drugs metabolized by cyt P450 2D6 a) donepezil b) tricyclic antidepressants c) risperidone (Risperdal) [7] d) fluoxetine (Prozac) e) oxycodone [29] f) inhibits its own metabolism Laboratory: 1) specimen: plasma (EDTA) 2) methods: HPLC 3) labs with Loincs - paroxetine in specimen - paroxetine in tissue - paroxetine in body fluid - paroxetine in blood - paroxetine in gastric fluid - paroxetine in serum/plasma - paroxetine in urine Mechanism of action: 1) selective serotonin re-uptake inhibitor (SSRI) 2) less stimulating that fluoxetine (Prozac) 3) more sedating than other SSRIs 4) inhibits cyt P450 2D6 5) mild muscarinic receptor antagonism (rarely significant)

Interactions

drug interactions drug adverse effects (more general classes)

Related

cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6)

General

selective serotonin reuptake inhibitor (SSRI)

Properties

MISC-INFO: elimination route LIVER KIDNEY 1/2life 7-37 HOURS protein-binding 95% elimination by hemodialysis - pregnancy-category D safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  3. Prescriber's Letter 7(2):8, Feb. 2000
  4. Prescriber's Letter 8(5):28 2001
  5. Department of Veterans Affairs, VA National Formulary
  6. Prescriber's Letter 8(10):55-56 2001
  7. Prescriber's Letter 8(12):67 2001
  8. Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
  9. Prescriber's Letter 9(5):27 2002
  10. Prescriber's Letter 9(7):38 2002
  11. Prescriber's Letter 9(12):71 2002
  12. Journal Watch 23(10):80-81, 2003 Rickels K et al, Paroxetine treatment of generalized anxiety disorder: a double-blind, placebo-controlled study. J. Psychiatry 160(Apr):749-56, 2003 PMID: 12668365
  13. Prescriber's Letter 10(7):40 2003
  14. Prescriber's Letter 10(10):57 2003 Detail-Document#: 191003 (subscription needed) http://www.prescribersletter.com
  15. Prescriber's Letter 10(12):68 2003
  16. Journal Watch 24(11):85, 2004 Whittington CJ, Kendall T, Fonagy P, Cottrell D, Cotgrove A, Boddington E. Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data. Lancet. 2004 Apr 24;363(9418):1341-5. Review. PMID: 15110490 - Jureidini JN, Doecke CJ, Mansfield PR, Haby MM, Menkes DB, Tonkin AL. Efficacy and safety of antidepressants for children and adolescents. BMJ. 2004 Apr 10;328(7444):879-83. Review. No abstract available. Erratum in: BMJ. 2004 May 15;328(7449):1170. PMID: 15073072 http://bmj.bmjjournals.com/cgi/content/full/328/7444/879
  17. Prescriber's Letter 12(9): 2005 Paxil (Paroxetine) and Birth Defects Detail-Document#: 211006 (subscription needed) http://www.prescribersletter.com
  18. FDA MedWatch http://www.fda.gov/medwatch/safety/2005/safety05.htm#Paxil2 http://www.fda.gov/medwatch/safety/2005/safety05.htm#Paxil3 http://www.fda.gov/medwatch/safety/2006/safety06.htm#paxil
  19. FDA MedWatch http://www.fda.gov/medwatch/safety/2006/safety06.htm#paxil
  20. Prescriber's Letter 13(1): 2006 Detail-Document#: 220103 (subscription needed) http://www.prescribersletter.com
  21. Medical Knowledge Self Assessment Program (MKSAP) 16, 19. American College of Physicians, Philadelphia 2012, 2021
  22. FDA News Release: June 28, 2013 FDA approves the first non-hormonal treatment for hot flashes associated with menopause. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm359030.htm - Prescriber's Letter 20(11): 2013 Nonhormonal Therapy for Hot Flashes Detail-Document#: 291109 (subscription needed) http://www.prescribersletter.com
  23. Deprecated Reference
  24. Reefhuis J et al Specific SSRIs and birth defects: bayesian analysis to interpret new data in the context of previous reports. BMJ 2015;351:h3190 PMID: 26156519 http://www.bmj.com/content/351/bmj.h3190
  25. Le Noury J et al Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence. BMJ 2015;351:h4320 PMID: 26376805 - Doshi P No correction, no retraction, no apology, no comment: paroxetine trial reanalysis raises questions about institutional responsibility. BMJ 2015;351:h4629 PMID: 26377109 http://www.bmj.com/content/351/bmj.h4629 - Henry D, Fitzpatrick T Liberating the data from clinical trials BMJ 2015;351:h4601 PMID: 26377210 http://www.bmj.com/content/351/bmj.h4601
  26. Jakubovski E et al. Systematic review and meta-analysis: Dose-response relationship of selective serotonin reuptake inhibitors in major depressive disorder. Am J Psychiatry 2015 Nov 10; PMID: 26552940 http://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2015.15030331
  27. Carroll DG, Lisenby KM, Carter TL. Critical appraisal of paroxetine for the treatment of vasomotor symptoms. Int J Womens Health 2015; 7:615 PMID: 26124682 Free PMC Article
  28. Pinkerton JV, Joffe H, Kazempour K, Mekonnen H, Bhaskar S, Lippman J. Low-dose paroxetine (7. 5 mg) improves sleep in women with vasomotor symptoms associated with menopause. Menopause 2015 Jan; 22:50. PMID: 25137243 Free PMC Article
  29. Yunusa I, Gagne JJ, Yoshida K et al Risk of Opioid Overdose Associated With Concomitant Use of Oxycodone and Selective Serotonin Reuptake Inhibitors. JAMA Netw Open. 2022;5(2):e220194 PMID: 3520131 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2789401
  30. Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  31. NEJM Knowledge+