drug adverse effects of SSRIs
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Adverse effects
- serotonin syndrome
- withdrawal reactions after discontinuation[8][15][21][25]
- more common with short-acting SSRIs, especially paroxetine
- dizziness, gait instability
- electric shock sensations
- headache
- nausea[25]
- delirium[21]
- generally occur 1-3 days after discontinuation
- generally resolve within 10 days
- GI bleeding* (< 2%)
- mitigated by concurrent administration of proton pump inhibitor[19]
- SSRI do not cause inflammatory changes in the colon[25]
- SIADH & hyponatremia[4]
- may inhibit growth hormone secretion & thus growth in children[5]
- in utero effects[7][11][13]
- lower Apgar scores at birth
- delayed fine motor development
- SSRI-induced neonatal withdrawal syndrome (30%)[13][14]
- newborn pulmonary hypertension associated with SSRI use in 2nd & 2rd trimester, perhaps related to serotonin- mediated pulmonary vasoconstriction (HR=2.1)[13][14][24]
- increased, but rare congenital anomalies associated with SSRI use in 1st trimester[22]
- fetal alcohol spectrum disorders
- no substantial increase in prevalence of overall cardiac birth defects[33]
- increased risk of autism in offspring of pregnant women using SSRI[23]
- relative risk < 1.61[29]; 2.17[36]
- not associated with stillbirth or infant mortality[27]
- weight at 1 year not affected by SSRI use or depression during pregnancy[28]
- exposure to SSRI in late pregnancy (>= 20 weeks of gestation) increases risk of pulmonary hypertension in newborns (RR = 2.5)[30]
- SSRI exposure reduces risks for preterm birth & C section in mothers with psychiatric diagnoses[35]
- increased likelihood of newborn admission to the NICU[37]
- discontinuation of SSRI during pregnancy associated with depression relapse, prematurity, & postpartum depression that may negatively affect a child's development[37]
- may be associated with bone loss[16]
- may increase risk of fracture in perimenopausal women[34]
- exacerbation of parkinsonism[17]
- SSRIs worsen symptoms of restless legs syndrome[25]
- REM sleep behavioral disorder[25]
- 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)
- increased risk of intracranial hemorrhage in the general population[26] (1 additional case of hemorrhagic stroke per 10,000 patients/year)
- increased risk of mortality when SSRI initiated after stroke[32]
- sexual dysfunction, orgasm disorders[21]
- commonly associated with decreased libido & erectile dysfunction[21]
- substitute with or add bupropion[40]
- higher SSRI doses may be associated with self-harm in children & young adults[31]
- no association is adults > 60 years of age[26]
- increased risk for violence & aggressive behavior?[38]
- increased risk of falls in the elderly 36-39% in first year[39]
- QTc prolongation (see drug-induced prolongation of the QT interval)
* diminished serotonin in platelets due to diminished uptake [2][3][6][9][18]
* patients with anxiety disorder should be counseled on potential of adverse effects & when they do occur are likely to be benign & shortlived, often a manifestation of the underlying disorder[25]
Complications
More general terms
References
- ↑ UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
- ↑ 2.0 2.1 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: https://www.ncbi.nlm.nih.gov/pubmed/11566827
- ↑ 3.0 3.1 Prescriber's Letter 8(11):62 2001 Sauer WH et al Selective serotonin reuptake inhibitors and myocardial infarction. Circulation 104:1894, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11602490
- ↑ 4.0 4.1 Prescriber's Letter 9(7):38 2002
- ↑ 5.0 5.1 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: https://www.ncbi.nlm.nih.gov/pubmed/12090838
- ↑ 6.0 6.1 Prescriber's Letter 10(3):14 2003
- ↑ 7.0 7.1 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: https://www.ncbi.nlm.nih.gov/pubmed/12712058
- ↑ 8.0 8.1 Journal Watch 25(7):58, 2005 Sanz EJ, De-las-Cuevas C, Kiuru A, Bate A, Edwards R. Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis. Lancet. 2005 Feb 5;365(9458):482-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15705457
- ↑ 9.0 9.1 Prescriber's Letter 12(7): 2005 Selective Serotonin Reuptake Inhibitors (SSRIs) and Antiplatelet Activity Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=210715&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 10.0 10.1 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
- ↑ 11.0 11.1 11.2 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: https://www.ncbi.nlm.nih.gov/pubmed/15718538 <Internet> http://bmj.bmjjournals.com/cgi/content/full/330/7488/389
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: https://www.ncbi.nlm.nih.gov/pubmed/15718537 <Internet> http://bmj.bmjjournals.com/cgi/content/full/330/7488/385
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: https://www.ncbi.nlm.nih.gov/pubmed/15718539 <Internet> http://bmj.bmjjournals.com/cgi/content/full/330/7488/396
Cipriani A, Barbui C, Geddes JR. Suicide, depression, and antidepressants. BMJ. 2005 Feb 19;330(7488):373-4. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15718515 - ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/15900008
- ↑ 13.0 13.1 13.2 13.3 Levinson-Castiel R et al, Neonatal abstinence syndrome after in utero exposure to selective serotonin reuptake inhibitors in term infants. Arch Pediatr Adolisc Med 2006; 160:173 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16461873
Chambers CD et al, Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. N Engl J Med 2006; 354:579 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16461545 - ↑ 14.0 14.1 14.2 Prescriber's Letter 13(4): 2006 Use of Selective Serotonin Reuptake Inhibitor Medications During Pregnancy Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220408&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 15.0 15.1 Prescriber's Letter 13(5): 2006 How to Switch antidepressants Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220605&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 16.0 16.1 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 - ↑ 17.0 17.1 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: https://www.ncbi.nlm.nih.gov/pubmed/10401924
Anonymous Extrpyramidal effects of SSRI antidepressants Prescrire 2001, 10:118 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11718183
Vajda FJ and Solinas C Current approaches to management of depression in Parkinson's disease. J Clin Neurosci 2005, 12:739 PMID: https://www.ncbi.nlm.nih.gov/pubmed/15911816 - ↑ 18.0 18.1 de Abajo FJ, Garcia-Rodriguez LA. Risk of upper gastrointestinal tract bleeding associated with selective serotonin reuptake inhibitors and venlafaxine therapy: interaction with nonsteroidal anti-inflammatory drugs and effect of acid-suppressing agents. Arch Gen Psychiatry. 2008 Jul;65(7):795-803. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18606952
- ↑ 19.0 19.1 Targownik LE et al Selective serotonin reuptake inhibitors are associated with a modest increase in the risk of upper gastrointestinal bleeding. Am J Gastroenterol 2009 Jun; 104:1475. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19491861
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/20008698 <Internet> http://archinte.ama-assn.org/cgi/content/short/169/22/2128
- ↑ 21.0 21.1 21.2 21.3 21.4 Medical Knowledge Self Assessment Program (MKSAP) 15, 19 American College of Physicians, Philadelphia 2009, 2021
- ↑ 22.0 22.1 Malm H et al. Selective serotonin reuptake inhibitors and risk for major congenital anomalies. Obstet Gynecol 2011 Jul; 118:111. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21646927
- ↑ 23.0 23.1 Croen LA et al. Antidepressant use during pregnancy and childhood autism spectrum disorders. Arch Gen Psychiatry 2011 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21874331
- ↑ 24.0 24.1 Kieler H et al. Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: Population based cohort study from the five Nordic countries. BMJ 2012 Jan 12; 344:d8012. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22240235 <Internet> http://dx.doi.org/10.1136/bmj.d8012
Koren G and Nordeng H. SSRIs and persistent pulmonary hypertension of the newborn. BMJ 2012 Jan 12; 344:d7642 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22240234 <Internet> http://dx.doi.org/10.1136/bmj.d7642 - ↑ 25.0 25.1 25.2 25.3 25.4 25.5 25.6 Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010
Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022 - ↑ 26.0 26.1 26.2 26.3 Hackam DG et al Selective serotonin reuptake inhibitors and brain hemorrhage A meta-analysis Neurology. October 17, 2012 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23077009 <Internet> http://www.neurology.org/content/early/2012/10/17/WNL.0b013e318271f848.abstract
- ↑ 27.0 27.1 Stephansson O et al Selective serotonin reuptake inhibitors during pregnancy and risk of stillbirth and infant mortality. JAMA. 2013 Jan 2;309(1):48-54 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23280224
- ↑ 28.0 28.1 Wisner KL et al. Does fetal exposure to SSRIs or maternal depression impact infant growth? Am J Psychiatry 2013 Mar 20 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23511234 <Internet> http://ajp.psychiatryonline.org/article.aspx?articleID=1669748
- ↑ 29.0 29.1 Hviid A et al. Use of selective serotonin reuptake inhibitors during pregnancy and risk of autism. N Engl J Med 2013 Dec 19; 369:2406 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24350950 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1301449
- ↑ 30.0 30.1 Grigoriadis S et al Prenatal exposure to antidepressants and persistent pulmonary hypertension of the newborn: systematic review and meta-analysis. BMJ 2014;348:f6932 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24429387 <Internet> http://www.bmj.com/content/348/bmj.f6932
- ↑ 31.0 31.1 Roy-Byrne P Higher SSRI Doses Linked to Greater Risk for Self-Harm in Youth. NEJM Journal Watch. May 5, 2014 Massachusetts Medical Society (subscription needed) http://www.jwatch.org
Miller M et al. Antidepressant dose, age, and the risk of deliberate self-harm. JAMA Intern Med 2014 Apr 28 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24782035 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=1863925
Brent DA and Gibbons R. Initial dose of antidepressant and suicidal behavior in youth: Start low, go slow. JAMA Intern Med 2014 Apr 28 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24781493 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=1863917 - ↑ 32.0 32.1 Ayerbe L et al. Explanatory factors for the increased mortality of stroke patients with depression. Neurology 2014 Nov 25; 83:2007. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25355829 <Internet> http://www.neurology.org/content/83/22/2007
Bartoli F and Paolucci S. Association of depression and SSRIs with mortality after stroke. Neurology 2014 Nov 25; 83:1998. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25355834 <Internet> http://www.neurology.org/content/83/22/1998 - ↑ 33.0 33.1 33.2 Furu K et al. Selective serotonin reuptake inhibitors and venlafaxine in early pregnancy and risk of birth defects: Population based cohort study and sibling design. BMJ 2015 Apr 17; 350:h1798 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25888213
- ↑ 34.0 34.1 Sheu YH et al. SSRI use and risk of fractures among perimenopausal women without mental disorders. Inj Prev 2015 Jun 25 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26113668
- ↑ 35.0 35.1 Malm H et al. Pregnancy complications following prenatal exposure to SSRIs or maternal psychiatric disorders: Results from population- based national register data. Am J Psychiatry 2015 Aug 4 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26238606 <Internet> http://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2015.14121575
- ↑ 36.0 36.1 Boukhris T et al Antidepressant Use During Pregnancy and the Risk of Autism Spectrum Disorder in Children. JAMA Pediatr. Published online December 14, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26660917 <Internet> http://archpedi.jamanetwork.com/article.aspx?articleid=2476187
King BH Assessing Risk of Autism Spectrum Disorder in Children After Antidepressant Use During Pregnancy. JAMA Pediatr. Published online December 14, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26660503 <Internet> http://archpedi.jamanetwork.com/article.aspx?articleid=2476185 - ↑ 37.0 37.1 37.2 Norby U, Forsberg L, Wide K et al. Neonatal morbidity after maternal use of antidepressant drugs during pregnancy. Pediatrics 2016 Oct 25; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27940758 <Internet> http://pediatrics.aappublications.org/content/early/2016/10/21/peds.2016-0181
- ↑ 38.0 38.1 Knoll JL, Pies RW. The SSRI-Violence Link: Myth or Menace? Medscape - Aug 20, 2020. https://www.medscape.com/viewarticle/935846
- ↑ 39.0 39.1 Haddad YK, Kakara R, Marcum ZA. A comparative analysis of selective serotonin reuptake inhibitors and fall risk in older adults. J Am Geriatr Soc. February 8, 2022. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35132611
- ↑ 40.0 40.1 NEJM Knowledge+