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sertraline (Zoloft)

Tradename: Zoloft. Indications: - major depression (OK for children* [10]) - well tolerated in the elderly [14] - safe for patients with cardiovascular disease [17] - seasonal affective disorder [13] - obsessive-compulsive disorder - panic attacks & anxiety disorder - premenstrual syndrome [5] - post-traumatic stress disorder - self-injurious behavior - mania [13] * may be no better than placebo, serious adverse effects more common than placebo [11] Contraindications: 1) concurrent use of MAO inhibitor -> separate by a 2 week washout 2) safe to use in patients with unstable angina or recent myocardial infarction [9] 3) ineffective in patients with moderate depression & chronic renal failure (GFR 28 mL/min/1.73 m2) [18] Dosage: 1) start 50 mg PO QHS; may be given QAM if insomnia occurs 2) dose increase weekly to a maximum of 200 mg/day 3) optimal dose for major depression is 120 mg QD 3) allow 3-6 weeks for full therapeutic effects Tabs: 50 & 100 mg. Pharmacokinetics: 1) well absorbed orally 2) when taken with food, peak levels increase by 30% 3) metabolized in liver by cyt P450 3A4 (CYP3A4) to desmethylsertraline & other metabolites 4) desmethylsertaline is 5-10 fold less potent an inhibitor of serotonin reuptake 5) elimination 1/2life is 26 hours 6) desmethylsertraline elimination 1/2life is 62-104 hours 7) excreted in the urine & feces 8) dose adjustment recommended in patients with hepatic impairment 9) cyt P450 inhibitor (CYP2D6, CYP2C9, CYP2C10, CYP2C19) at doses > 50 mg/day Adverse effects: 1) nervous system a) dizziness (13%) b) tremor (9%) c) nervousness (6%) d) serotonin syndrome [17,21] 2) gastrointestinal a) nausea (28%) b) dry mouth (15%) c) diarrhea (20%) d) constipation (7%) e) dyspepsia (8%) 3) skin a) sweating (7%) b) rash (3%) c) Stevens-Johnson syndrome, toxic epidermal necrolysis 4) blurred vision (4%) 5) other [3,4] a) sexual dysfunction, orgasm disorder, ejaculatory delay - commonly associated with decreased libido & erectile dysfunction [17] b) headache c) drowsiness d) causes less anxiety, agitation & insomnia than fluoxetine e) SIADH & hyponatremia [7,8] f) may increase risk of septal heart defects when used early in pregnancy [12]; no such association [15] - probably safest SSRI during pregnancy [15] g) moderate anticholinergic effects [19] - not a significant risk of anticholinergic toxicity [17,21] h) low risk among SSRI of QTc prolongation Incidence of SSRI withdrawal syndrome < 0.1%. Drug interactions: 1) decreased clearance of drugs metabolized by cyt P450 2D6 -> carbamazepine, diazepam (see pharmacology above) 2) sertraline decreases central hypotensive effects of clonidine 3) MAO inhibitors in combination may cause hypertension, tachycardia, seizures & death; separate by a 2 week washout 4) cisapride: sertraline decreases its metabolism; may cause prolongation of QT interval 5) selegiline: in combination increases risk of serotonin syndrome 6) any drug that inhibits cyt P450 3A4 may increase levels of sertraline 7) any drug that induces cyt P450 3A4 may diminish levels of sertraline 8) risk of serotonin syndrome increased by concurrent administration of MAO inhibitor, SNRI, tricyclic antidepressants, tramadol, meperidine, methadone, & fentanyl Laboratory: 1) specimen: a) plasma (EDTA) b) stable for 1 week at room temperature or for 7 months frozen 2) methods: HPLC, GC-MS, GC Mechanism of action: - SSRI, inhibits re-uptake of serotonin - recovery of heart rate variability (NEJM) [20] - reduction of inflammatory markers (NEJM) [20] - improvement in endothelial function (NEJM) [20] - reduction in platelet aggregation (NEJM) [20]

Interactions

drug interactions drug adverse effects (more general classes)

Related

cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6) cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4) sertraline in serum/plasma sertraline in urine

General

selective serotonin reuptake inhibitor (SSRI)

Properties

MISC-INFO: elimination route LIVER KIDNEY elimination by hemodialysis - 1/2life 25-26 HOURS pregnancy-category C 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. AHFS 96 Drug Information, GK McEnvoy et al (ed), American Society of Health-System Pharmacists, Bethesda, MD 1998
  3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  4. UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  5. Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
  6. Prescriber's Letter 9(6):35 2002
  7. Veterans Administration (VA) pharmacy, WLA 2002
  8. Prescriber's Letter 9(7):38 2002
  9. Journal Watch 22(18):144-45, 2002 Glassman AH, JAMA 288:701, 2002
  10. Prescriber's Letter 10(10):57 2003 Detail-Document#: 191003 (subscription needed) http://www.prescribersletter.com
  11. 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
  12. Pedersen LH et al Selective serotonin reuptake inhibitors in pregnancy and congenital malformations: population based cohort study BMJ 2009;339:b3569 PMID: 19776103 http://www.bmj.com/cgi/content/full/339/sep23_1/b3569 - Chambers C Selective serotonin reuptake inhibitors and congenital malformations BMJ 2009;339:b3525 PMID: 19776102 http://www.bmj.com/cgi/content/extract/339/sep23_1/b3525
  13. Deprecated Reference
  14. Schneider LS, Nelson JC, Clary CM et al An 8-week multicenter, parallel-group, double-blind, placebo- controlled study of sertraline in elderly outpatients with major depression. Am J Psychiatry. 2003 Jul;160(7):1277-85. PMID: 12832242
  15. 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
  16. 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
  17. Medical Knowledge Self Assessment Program (MKSAP) 17, 18. American College of Physicians, Philadelphia 2015, 2018 - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  18. Hedayati SS, Gregg LP, Carmody T et al. Effect of sertraline on depressive symptoms in patients with chronic kidney disease without dialysis dependence: The CAST randomized clinical trial. JAMA. 2017;318(19):1876-1890. Nov 3. https://jamanetwork.com/journals/jama/article-abstract/2661489 - Walther CP, Shah AA, Winkelmayer WC. Treating depression in patients with advanced CKD: Beyond the generalizability frontier. JAMA. 2017;318(19):1873-1874. Nov 3; PMID: 29101401 https://jamanetwork.com/journals/jama/article-abstract/2661488
  19. Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
  20. NEJM Knowledge+ Psychiatry
  21. Malcolm B, Thomas K. Serotonin toxicity of serotonergic psychedelics. Psychopharmacology (Berl). 2021. PMID: 34251464