sertraline (Zoloft)
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Introduction
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
- concurrent use of MAO inhibitor
- separate by a 2 week washout
- safe to use in patients with unstable angina or recent myocardial infarction[9]
- ineffective in patients with moderate depression & chronic renal failure (GFR 28 mL/min/1.73 m2)[18]
Dosage
- start 50 mg PO QHS; may be given QAM if insomnia occurs
- dose increase weekly to a maximum of 200 mg/day
- optimal dose for major depression is 120 mg QD
- allow 3-6 weeks for full therapeutic effects
Tabs: 50 & 100 mg.
Pharmacokinetics
- well absorbed orally
- when taken with food, peak levels increase by 30%
- metabolized in liver by cyt P450 3A4 (CYP3A4) to desmethylsertraline & other metabolites
- desmethylsertaline is 5-10 fold less potent an inhibitor of serotonin reuptake
- elimination 1/2life is 26 hours
- desmethylsertraline elimination 1/2life is 62-104 hours
- excreted in the urine & feces
- dose adjustment recommended in patients with hepatic impairment
- cyt P450 inhibitor (CYP2D6, CYP2C9, CYP2C10, CYP2C19) at doses > 50 mg/day
elimination via liver
elimination via kidney
elimination by hemodialysis = -
1/2life = 25-26 hours
Adverse effects
- nervous system
- dizziness (13%)
- tremor (9%)
- nervousness (6%)
- serotonin syndrome[17][21]
- gastrointestinal
- nausea (28%)
- dry mouth (15%)
- diarrhea (20%)
- constipation (7%)
- dyspepsia (8%)
- skin
- blurred vision (4%)
- other[3][4]
- sexual dysfunction, orgasm disorder, ejaculatory delay
- commonly associated with decreased libido & erectile dysfunction[17]
- headache
- drowsiness
- causes less anxiety, agitation & insomnia than fluoxetine
- SIADH & hyponatremia[7][8]
- may increase risk of septal heart defects when used early in pregnancy[12]; no such association[15]
- moderate anticholinergic effects[19]
- not a significant risk of anticholinergic toxicity[17][21]
- low risk among SSRI of QTc prolongation
- sexual dysfunction, orgasm disorder, ejaculatory delay
Incidence of SSRI withdrawal syndrome < 0.1%.
- drug adverse effects of SSRIs
- drug adverse effects of antidepressants
- drug adverse effects of psychotropic agents
Drug interactions
- decreased clearance of drugs metabolized by cyt P450 2D6
- carbamazepine, diazepam (see pharmacology above)
- sertraline decreases central hypotensive effects of clonidine
- MAO inhibitors in combination may cause hypertension, tachycardia, seizures & death; separate by a 2 week washout
- cisapride: sertraline decreases its metabolism; may cause prolongation of QT interval
- selegiline: in combination increases risk of serotonin syndrome
- any drug that inhibits cyt P450 3A4 may increase levels of sertraline
- any drug that induces cyt P450 3A4 may diminish levels of sertraline
- risk of serotonin syndrome increased by concurrent administration of MAO inhibitor, SNRI, tricyclic antidepressants, tramadol, meperidine, methadone, & fentanyl
- 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 coxib with SSRI
Laboratory
- specimen:
- plasma (EDTA)
- stable for 1 week at room temperature or for 7 months frozen
- 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]
More general terms
Additional terms
- 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)
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ AHFS 96 Drug Information, GK McEnvoy et al (ed), American Society of Health-System Pharmacists, Bethesda, MD 1998
- ↑ 3.0 3.1 Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ 4.0 4.1 UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
- ↑ 5.0 5.1 Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
- ↑ Prescriber's Letter 9(6):35 2002
- ↑ 7.0 7.1 Veterans Administration (VA) pharmacy, WLA 2002
- ↑ 8.0 8.1 Prescriber's Letter 9(7):38 2002
- ↑ 9.0 9.1 Journal Watch 22(18):144-45, 2002 Glassman AH, JAMA 288:701, 2002
- ↑ 10.0 10.1 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
- ↑ 11.0 11.1 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 - ↑ 12.0 12.1 Pedersen LH et al Selective serotonin reuptake inhibitors in pregnancy and congenital malformations: population based cohort study BMJ 2009;339:b3569 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19776103 <Internet> http://www.bmj.com/cgi/content/full/339/sep23_1/b3569
Chambers C Selective serotonin reuptake inhibitors and congenital malformations BMJ 2009;339:b3525 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19776102 <Internet> http://www.bmj.com/cgi/content/extract/339/sep23_1/b3525 - ↑ 13.0 13.1 13.2 Deprecated Reference
- ↑ 14.0 14.1 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: https://www.ncbi.nlm.nih.gov/pubmed/12832242
- ↑ 15.0 15.1 15.2 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
- ↑ 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
- ↑ 17.0 17.1 17.2 17.3 17.4 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 - ↑ 18.0 18.1 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: https://www.ncbi.nlm.nih.gov/pubmed/29101401 https://jamanetwork.com/journals/jama/article-abstract/2661488 - ↑ 19.0 19.1 Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022
- ↑ 20.0 20.1 20.2 20.3 20.4 NEJM Knowledge+ Psychiatry
- ↑ 21.0 21.1 21.2 Malcolm B, Thomas K. Serotonin toxicity of serotonergic psychedelics. Psychopharmacology (Berl). 2021. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34251464