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]
- 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 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 - ↑ 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+