Sertraline

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Contents 1 Introduction 2 Indications 3 Contraindications 4 Dosage 5 Pharmacokinetics 6 Adverse-effects 7 Drug-interactions 8 Laboratory 9 Mechanism-of-action 10 More General Terms 11 Additional Terms 12 Internet Database 13 References

Introduction

• Tradename: Zoloft.

Indications

• major depression (OK for children* [10])
• obsessive-compulsive disorder
• panic attacks & anxiety disorder
• premenstrual syndrome [5]
• post-traumatic stress disorder
• self-injurious behavior

• * 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]
  

• pregnancy category = c
• safety in lactation = ?

Dosage

• start 50 mg PO QHS; may be given QAM if insomnia occurs
• dose increase weekly to a maximum of 200 mg/day
• 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%)

• gastrointestinal

• nausea (28%)
• dry mouth (15%)
• diarrhea (20%)
• constipation (7%)
• dyspepsia (8%)

• skin

• sweating (7%)
• rash (3%)
• Stevens-Johnson syndrome, toxic epidermal necrolysis

• blurred vision (4%)
• other [3,4]

• ejaculatory delay
• 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]

• Incidence of SSRI withdrawal syndrome < 0.1%.
  

• drug adverse effects of SSRIs
• drug adverse effects of antidepressants

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
  
• 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 hypericum perforatum (Sr John's wort) with SSRI
• drug interaction(s) of tamoxifen with SSRI
• drug interaction(s) of antidepressants with benzodiazepines
• drug interaction(s) of NSAIDs with SSRIs

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

More General Terms

• selective serotonin reuptake inhibitor (SSRI)

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)

Internet Database

PubChem: 68617
PubChem: 5203
PubChem: 54375
PubChem: 63009

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#: [1] (subscription needed) [2]
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: [3]
    - 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: [4] <Internet> [5]
12. Pedersen LH et al Selective serotonin reuptake inhibitors in pregnancy and congenital malformations: population based cohort study BMJ 2009;339:b3569 <PubMed> PMID: [6] <Internet> [7]
    - Chambers C Selective serotonin reuptake inhibitors and congenital malformations BMJ 2009;339:b3525 <PubMed> PMID: [8] <Internet> [9]

sertraline (Zoloft)