paroxetine (Paxil, Pexeva, Seroxat, Brisdelle)
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Introduction
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
- do NOT use with 14 days of MAO inhibitor
- < 18 years of age; risk of suicidal ideation[14]
- no clinical efficacy in children; increased risk of serious adverse effects[16]
- ineffective, & even harmful, for treating major depression in adolescents[25]
- classified as pregnancy category D[30]
Dosage
- start 10 mg PO QD
- max 50 mg/day
- optimal dose for major depression is 20 mg QD[26]
- 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
- only 80% of Paxil CR dose absorbed
- extensive cyt P450 metabolism by cyt P450 2D6
- elimination 1/2life: 21 hours (7-37 hours, shortest 1/2life among SSRI)[31]
- metabolites excreted in the urine & bile
elimination via liver
elimination via kidney
1/2life = 7-37 hours
protein binding = 95 %
elimination by hemodialysis = -
Adverse effects
- common (> 10%)
- less common (1-10%)
- tremor, anorexia, flatulence, nervousness, anxiety, paresthesias, vomiting, decreased libido, palpitations, vasodilation, postural hypotension
- 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 adverse effects of SSRIs
- drug adverse effects of antidepressants
- drug adverse effects of psychotropic agents
Drug interactions
- increased effects/toxicity when used concurrently with:
- tryptophan
- alcohol
- cimetidine
- MAO inhibitors (hyperpyrexic crisis)
- trazodone, nefazodone (serotonin syndrome)
- increased effects/toxicity of:
- decreased effect when used concurrently with:
- paroxetine strongly inhibits cyt P450 2D6, thus increased levels & potentiation of drugs metabolized by cyt P450 2D6
- donepezil
- tricyclic antidepressants
- risperidone (Risperdal)[7]
- fluoxetine (Prozac)
- oxycodone[29]
- inhibits its own metabolism
- drug interaction(s) of oral anticoagulants with selective serotonin reuptake inhibitor (SSRI)
- drug interaction(s) of ondanstetron with SSRIs
- drug interaction(s) of dextromethorphan with SSRIs
- drug interaction(s) of trazodone with SSRIs
- drug interaction(s) of tramadol with SSRIs
- drug interaction(s) of triptans with SSRIs
- drug interaction(s) of anti-platelet agents with SSRIs
- drug interaction(s) of methylene blue with SSRIs
- drug interaction(s) of linezolid with SSRIs
- drug interaction(s) of statins with SSRIs
- drug interaction(s) of hypericum perforatum (Sr John's wort) with SSRI
- drug interaction(s) of tamoxifen with SSRI
- drug interaction(s) of benzodiazepines with antidepressants
- drug interaction(s) of antidepressants with benzodiazepines
- drug interaction(s) of NSAIDs with SSRIs
- drug interaction(s) of NSAIDs with antidepressants
- drug interaction(s) of tamoxifen with paroxetine
- drug interaction(s) of coxib with SSRI
Laboratory
Mechanism of action
- selective serotonin re-uptake inhibitor (SSRI)
- less stimulating that fluoxetine (Prozac)
- more sedating than other SSRIs
- inhibits cyt P450 2D6
- mild muscarinic receptor antagonism (rarely significant)
More general terms
Additional terms
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Prescriber's Letter 7(2):8, Feb. 2000
- ↑ 4.0 4.1 Prescriber's Letter 8(5):28 2001
- ↑ Department of Veterans Affairs, VA National Formulary
- ↑ 6.0 6.1 6.2 Prescriber's Letter 8(10):55-56 2001
- ↑ 7.0 7.1 Prescriber's Letter 8(12):67 2001
- ↑ Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
- ↑ 9.0 9.1 9.2 Prescriber's Letter 9(5):27 2002
- ↑ 10.0 10.1 Prescriber's Letter 9(7):38 2002
- ↑ 11.0 11.1 Prescriber's Letter 9(12):71 2002
- ↑ 12.0 12.1 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: https://www.ncbi.nlm.nih.gov/pubmed/12668365
- ↑ 13.0 13.1 13.2 Prescriber's Letter 10(7):40 2003
- ↑ 14.0 14.1 Prescriber's Letter 10(10):57 2003 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=191003&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 15.0 15.1 Prescriber's Letter 10(12):68 2003
- ↑ 16.0 16.1 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: https://www.ncbi.nlm.nih.gov/pubmed/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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/15073072 <Internet> http://bmj.bmjjournals.com/cgi/content/full/328/7444/879 - ↑ 17.0 17.1 Prescriber's Letter 12(9): 2005 Paxil (Paroxetine) and Birth Defects Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=211006&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 18.0 18.1 18.2 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
- ↑ 19.0 19.1 FDA MedWatch http://www.fda.gov/medwatch/safety/2006/safety06.htm#paxil
- ↑ Prescriber's Letter 13(1): 2006 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220103&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 21.0 21.1 21.2 Medical Knowledge Self Assessment Program (MKSAP) 16, 19. American College of Physicians, Philadelphia 2012, 2021
- ↑ 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#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=291109&pb=PRL (subscription needed) http://www.prescribersletter.com - ↑ 23.0 23.1 23.2 Deprecated Reference
- ↑ 24.0 24.1 24.2 24.3 24.4 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26156519 <Internet> http://www.bmj.com/content/351/bmj.h3190
- ↑ 25.0 25.1 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: https://www.ncbi.nlm.nih.gov/pubmed/26376805
Doshi P No correction, no retraction, no apology, no comment: paroxetine trial reanalysis raises questions about institutional responsibility. BMJ 2015;351:h4629 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26377109 <Internet> http://www.bmj.com/content/351/bmj.h4629
Henry D, Fitzpatrick T Liberating the data from clinical trials BMJ 2015;351:h4601 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26377210 <Internet> http://www.bmj.com/content/351/bmj.h4601 - ↑ 26.0 26.1 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; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26552940 <Internet> http://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2015.15030331
- ↑ 27.0 27.1 Carroll DG, Lisenby KM, Carter TL. Critical appraisal of paroxetine for the treatment of vasomotor symptoms. Int J Womens Health 2015; 7:615 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26124682 Free PMC Article
- ↑ 28.0 28.1 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: https://www.ncbi.nlm.nih.gov/pubmed/25137243 Free PMC Article
- ↑ 29.0 29.1 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: https://www.ncbi.nlm.nih.gov/pubmed/3520131 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2789401
- ↑ 30.0 30.1 Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
- ↑ 31.0 31.1 NEJM Knowledge+
Database
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=43815
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4691
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5284605
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=2065272
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=62879