Serotonin Reuptake Inhibitor

From Anvita Health Wiki

Contents 1 More Specific Terms 2 Pharmacology 3 Indications 4 Contraindications 5 Adverse-effects 6 Mechanism-of-action 7 Complications 8 More General Terms 9 Additional Terms 10 References

More Specific Terms

• citalopram (Celexa, nitalapram)
• fluoxetine (Prozac, Sarafem)
• fluvoxamine (Luvox)
• paroxetine (Paxil, Pexeva, Seroxat)
• sertraline (Zoloft)
• sibutramine (Meridia, Reductil)
• vilazodone (Viibryd)

Pharmacology

• results in a sudden increase in serotonin, predominantly in the somatodendritic area (not axon terminals)
• serotonin interacts with somatodendritic 5HT1A autoreceptors resulting in decreased serotonin release
• with chronic use, somatodendritic autoreceptors desensitize resulting in an increase in serotonin release from axon terminals (2 weeks)
• with increased release of serotonin & continued reuptake block, eventual desensitization of post synaptic receptors occurs

Indications

• depression*
• obsessive-compulsive disorder ( OCD)
• self-injurious behavior

• * No major differences in response among SSRIs or SSRIs & atypical antidepressants. Switching for lack of response not indicated [5,14]

Contraindications

• children, adolescents [10] (caution)
• NO benefit for coronary artery disease (non-indication) [15]

Adverse-effects

• serotonin syndrome
• GI bleeding* (< 2%)
• SIADH & hyponatremia [6]
• may inhibit growth hormone secretion & thus growth in children [7]
• in utero effects [9,12]

• lower Apgar scores at birth
• delayed fine motor development
• common, but seldom serious [12]

• may be associated with bone loss [16]
• exacerbation of parkinsonism [17]
• may trigger manic attack in bipolar affective disorder, especially when not combined with lithium carbonate
• increase in stroke risk in post- menopausal women, largely due to an increase in hemorrhagic stroke (consistent with SSRI's antiplatelet effects) ( hazzard ratio 1.45) [18]
• sexual dysfunction, orgasm disorder

• * diminished serotonin in platelets due to diminished uptake [3,4,8,13]
  

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

Mechanism-of-action

• SSRI inhibit the serotonin transporter, thus the reuptake of serotonin by serotoninergic neurons
• inhibition of serotonin uptake by platelets can impair platelet aggregation -> may decrease risk of myocardial infarction [4]

Complications

• suicide children, adolescents [10], adults [11]

More General Terms

• second generation antidepressant

Additional Terms

• Na+-dependent serotonin transporter; 5HT transporter; 5HTT; solute carrier family 6 member 4 (SLC6A4, HTT, SERT)
• serotonin & norepinephrine reuptake inhibitor (SNRI, dual-acting reuptake inhibitor)
• serotonin syndrome (serotonism)
• serotonin [5HT] receptor
• serotonin [5HT]-1A receptor; 5-hydroxytryptamine receptor 1A; 5-HT-1A; 5-HT1A; serotonin receptor 1A; G-21 (HTR1A, ADRB2RL1, ADRBRL1)
• serotonin; 5-hydroxytryptamine

References

1. Taylor MJ, Freemantle N, Geddes JR, Bhagwagar Z. Early onset of selective serotonin reuptake inhibitor antidepressant action: systematic review and meta-analysis. Arch Gen Psychiatry. 2006 Nov;63(11):1217-23. Review. PMID: &dopt=Abstract
2. UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
3. Journal Watch 21(22):179, 2001 van Walraven C et al Inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding in elderly patients: retrospective cohort study. BMJ 323:655, 2001 PMID: [1]
4. Prescriber's Letter 8(11):62 2001 Sauer WH et al Selective serotonin reuptake inhibitors and myocardial infarction. Circulation 104:1894, 2001 PMID: [2]
5. Journal Watch 22(3):20, 2002 Kroenke et al, Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: a randomized trial. JAMA 286:2947, 2001 PMID: [3] Stimon G. Choosing a first-line antidepressant: equal on average does not mean equal for everyone. JAMA 286:3003, 2001 PMID: [4]
6. Prescriber's Letter 9(7):38 2002
7. Journal Watch 22(16):127, 2002 Weintrob N et al Decreased growth during therapy with selective serotonin reuptake inhibitors. Arch Pediatr Adolesc Med 156:696, 2002 PMID: [5]
8. Prescriber's Letter 10(3):14 2003
9. Journal Watch 23(13):106, 2003 Casper RC et al, Follow-up of children of depressed mothers exposed or not exposed to antidepressant drugs during pregnancy. J Pediatr 142:402, 2003 PMID: [6]
10. 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: [7] 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: [8] <Internet> [9]
11. Journal Watch 25(8):65, 2005 Martinez C, Rietbrock S, Wise L, Ashby D, Chick J, Moseley J, Evans S, Gunnell D. Antidepressant treatment and the risk of fatal and non-fatal self harm in first episode depression: nested case-control study. BMJ. 2005 Feb 19;330(7488):389. <PubMed> PMID: &dopt=Abstract <Internet> [10]
    - Gunnell D, Saperia J, Ashby D. Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomised controlled trials submitted to the MHRA's safety review. BMJ. 2005 Feb 19;330(7488):385. <PubMed> PMID: [11] <Internet> [12]
    - Fergusson D, Doucette S, Glass KC, Shapiro S, Healy D, Hebert P, Hutton B. Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials. BMJ. 2005 Feb 19;330(7488):396. Review. Erratum in: BMJ. 2005 Mar 19;330(7492):653. <PubMed> PMID: [13] <Internet> [14]
    - Cipriani A, Barbui C, Geddes JR. Suicide, depression, and antidepressants. BMJ. 2005 Feb 19;330(7488):373-4. No abstract available. PMID: [15]
12. Journal Watch 25(12):97, 2005 Moses-Kolko EL, Bogen D, Perel J, Bregar A, Uhl K, Levin B, Wisner KL. Neonatal signs after late in utero exposure to serotonin reuptake inhibitors: literature review and implications for clinical applications. JAMA. 2005 May 18;293(19):2372-83. Review. PMID: [16]
13. Prescriber's Letter 12(7): 2005 Selective Serotonin Reuptake Inhibitors (SSRIs) and Antiplatelet Activity Detail-Document#: [17] (subscription needed) [18]
14. Hansen RA, Gartlehner G, Lohr KN, Gaynes BN, Carey TS. Efficacy and safety of second-generation antidepressants in the treatment of major depressive disorder. Ann Intern Med. 2005 Sep 20;143(6):415-26. Review. PMID: [19]
15. Lespoerance F et al, Effects of citalopram and interpersonal psychotherapy on depression in patients with coronary artery disease: The Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial. JAMA 2007, 297:367 PMID: [20]
    - Glassman AH and Bigger JT Antidepressants in coronary artery disease: SSRI reduce depression, but do they save lives? JAMA 2007, 297:411 PMID: [21]
16. Diem SJ et al, Use of Antidepressants and Rates of Hip Bone Loss in Older Women - The Study of Osteoporotic Fractures Arch Intern Med. 2007;167:1240-1245.
    - Haney EM et al, Association of Low Bone Mineral Density With Selective Serotonin Reuptake Inhibitor Use by Older Men Arch Intern Med. 2007;167:1246-1251
17. Gonul AS and Aksu M SSRI-induced parkinsonism may be an early sign of future Parkinson's disease. J Clin Psychiatry 1999, 60:410 PMID: [22]
    - Anonymous Extrpyramidal effects of SSRI antidepressants Prescrire 2001, 10:118 PMID: [23]
    - Vajda FJ and Solinas C Current approaches to management of depression in Parkinson's disease. J Clin Neurosci 2005, 12:739 PMID: [24]
18. Smoller JW et al Antidepressant Use and Risk of Incident Cardiovascular Morbidity and Mortality Among Postmenopausal Women in the Women's Health Initiative Study Arch Intern Med. 2009;169(22):2128-2139. <PubMed> PMID: [25] <Internet> [26]
19. Medical Knowledge Self Assessment Program (MKSAP) 15, American College of Physicians, Philadelphia 2009
20. National Guideline Clearinghouse
    - Recommendations from the EGAPP working group: testing for cytochrome P450 polymorphisms in adults with nonpsychotic depression treated with selective serotonin reuptake inhibitors. Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. ngc-guideline: [27]

selective serotonin reuptake inhibitor (SSRI)