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antidepressant

Indications: - depression - depressive psychosis* - seasonal affective disorder - bipolar disorder, mania - obsessive-compulsive disorder: only venlafaxine effective* [21] - attention-deficit hyperactivity disorder [13] - may mitigate effects of prenatal maternal anxiety on auditory sensory gating, a measure of attentional function [11] - anorexia nervosa, bulimia nervosa obesity [13] - post-traumatic stress disorder - urticaria, pruritus, atopic dermatitis, lichen simplex chronicus - neuralgia, diabetic neuropathy, chronic musculoskeletal pain, muscle spasm, neuropathic pain: only amitryptyline effective* [21] - migraine prophylaxis, cluster headache - cataplexy, narcolepsy, parkinsonism - premenstrual syndrome, menopause, hot flash - insomnia - enuresis - smoking cessation - attention-deficit hyperhyperactivity disorder - fibromyalgia - panic disorder [13]: only escitalopram effective* [21] - generalized anxiety disorder, social phobia [13] * 25% of antidepressant prescriptions in Canada for off-label use 2006-2015 [20] * of the off-label uses, only 3 with strong evidence supporting use [21] Contraindications: - treatment of back pain or knee osteoarthritis [28] Epidemiology: - 1 in 7 reproductive age women on antidepressants Adverse effects: 1) anxiety, agitation & restlessness with initiation of therapy 2) suicide in adolescents ? (FDA warning) [3] adults? [5] - antidpressant use down among young people & suicide attempts up after FDA warning [15] - doubling of risk for suicidality & aggression in children & adolescents using antidepressants [17] 3) adverse effects of specific agents (not all inclusive) a) venlafaxine: nausea & vomiting b) sertraline: diarrhea c) mirtazapine: weight gain d) trazodone: somnolence e) paroxetine & venlafaxine: withdrawal f) paroxetine: sexual dysfunction; bupropion (less sexual dysfunction) g) SSRIs: suicide attempts 4) increased risk of autism with maternal use during pregnancy [11] 5) no association with osteoporosis or osteopenia [12] - association with hip fracture questioned [27] 6) cardiovascular risk low, but variable [19] 7) associated with risk of dementia & Alzheimer's disease (RR=3.7 for SSRI, RR= 4.7 for SNRI, RR=3.3 for TCA, RR=4.9 for MAO inhibitor) [22] 8) increased risk of psychiatric disorders in offspring [23] - 8% if mom did not use antidepressant - 12% if mom used antidepressant before but not during pregnancy - 14% if mom used antidepressant both before & during pregnancy - 15% if mom started antidepressant during pregnancy 9) increased risk for type 2 diabetes in young people (RR=1.9) [24] 10) withdrawal symptoms of dizziness & insomnia [25,31] 11) weight gain [26] 12) antidepressants may facilitate antibiotic resistance [30] Management: 1) efficacy a) response rate for all antidepressants is 60-70%, with placebo response rate of ~ 30% b) benefits of antidepressants fall below accepted criteria for clinical significance [7] 2) selection of antidepressant: a) no major differences in response among SSRIs or SSRIs & atypical antidepressants* [4,9] b) major difference in antidepressants is adverse effects* [4,9] c) select agent based on adverse-effect profiles, cost, & patient preferences [9] d) regular assessment for response & adverse effects, starting 1 to 2 weeks after initiating therapy e) modification of treatment if response is inadequate at 6 to 8 weeks f) continuation of treatment for 4-9 months after a satisfactory response (longer for patients with prior episode of major depression) [9] 3) deprescribing - cognitive-behavioral therapy during antidepressant taper is as effective as continuing antidepressant [29] * escitalopram, mirtazapine, sertraline, & venlafaxine are the most efficacious [10] * escitalopram & sertraline have the 'best possible balance between efficacy & acceptability' [10] * sertraline is less expensive [10]

Interactions

drug interactions drug adverse effects (more general classes)

Specific

agomelatine (Valdoxan, Melitor, Thymanax) antidepressant combination esketamine (Spravato) gepirone (Exxua) monoamine oxidase [MAO] inhibitor second generation antidepressant tricyclic antidepressant (TCA) vortioxetine (Trintellix) zuranolone (Zurzuvae)

General

psychotropic agent

References

  1. Prescriber's Letter 11(5):26 2004 Detail-Document#: 200503 (subscription needed) http://www.prescribersletter.com
  2. Prescriber's Letter: Comparison of Commonly Used Antidepressants Detail-Document#: 200606 (subscription needed) http://www.prescribersletter.com
  3. Prescriber's Letter 11(12): 2004 Suicidality in Children and Adolescents Being Treated With Antidepressant Medications Detail-Document#: 201212 (subscription needed) http://www.prescribersletter.com http://www.fda.gov/cder/drug/antidepres sants/SSRIPHA200410.htm http://www.psych.org/news_room/press_releases/04-55apaonfdablackboxwarning.pdf http://www.aacap.org/Announcements/antidepressants.htm
  4. 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: 16172440
  5. FDA Medwatch Public Health Advisory: Suicidality in Adults Being Treated with Antidepressant Medications http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm#antidepressant
  6. Prescriber's Letter 15(4): 2008 Antidepressant Efficacy Detail-Document#: 240409 (subscription needed) http://www.prescribersletter.com
  7. Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med. 2008 Feb;5(2):e45. PMID: 18303940
  8. Prescriber's Letter 15(5): 2008 Comparison of Commonly Used Antidepressants Detail-Document#: 240509 (subscription needed) http://www.prescribersletter.com
  9. Qaseem A et al. Using second-generation antidepressants to treat depressive disorders: A clinical practice guideline from the American College of Physicians. Ann Intern Med 2008 Nov 18; 149:725. PMID: 19017591 (Correponding NGC guideline withdrawn Jan 2014) - Gartlehner G et al. Comparative benefits and harms of second-generation antidepressants: Background paper for the American College of Physicians. Ann Intern Med 2008 Nov 18; 149:734. PMID: 19017592
  10. Cipriani A et al, Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis Lancet 29 January 2009 doi:10.1016/S0140-6736(09)60046-5 PMID: 19185342
  11. Hunter SK et al. Antidepressants may mitigate the effects of prenatal maternal anxiety on infant auditory sensory gating. Am J Psychiatry 2012 Jun 1; 169:616 PMID: 22581104 http://psychiatryonline.org/article.aspx?articleid=1148701&journalid=13
  12. Diem SJ et al. Rates of bone loss among women initiating antidepressant medication use in midlife. J Clin Endocrinol Metab 2013 Sep 3 PMID: 24001746
  13. Deprecated Reference
  14. Prescriber's Letter 20(12): 2013 Detail-Document#: 291206 Comparison of Antidepressants (subscription needed) http://www.prescribersletter.com
  15. Lu CY et al Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi- experimental study. BMJ 2014;348:g3596 PMID: 24942789 http://www.bmj.com/content/348/bmj.g3596
  16. Prescriber's Letter 21(7): 2014 Choosing and Switching Antidepressants. Detail-Document#: 300721 (subscription needed) http://www.prescribersletter.com
  17. Sharma T et al Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports. BMJ 2016;352:i65 PMID: 26819231 http://www.bmj.com/content/352/bmj.i65 - Moncrieff J Misrepresenting harms in antidepressant trials. BMJ 2016;352:i217 PMID: 26819231 http://www.bmj.com/content/352/bmj.i217
  18. Dawson AL et al Antidepressant Prescription Claims Among Reproductive-Aged Women With Private Employer-Sponsored Insurance - United States 2008-2013 http://www.cdc.gov/mmwr/volumes/65/wr/mm6503a1.htm
  19. Coupland C, Hill T, Morriss R et al Antidepressant use and risk of cardiovascular outcomes in people aged 20 to 64: cohort study using primary care database. BMJ 2016;352:i1350 PMID: 27005565 Free full text http://www.bmj.com/content/352/bmj.i1350
  20. Wong J et al Treatment Indications for Antidepressants Prescribed in Primary Care in Quebec, Canada, 2006-2015. JAMA. 2016;315(20):2230-2232 PMID: 27218634 http://jama.jamanetwork.com/article.aspx?articleid=2524175
  21. Wong J, Motulsky A, Abrahamowicz M et al. Off-label indications for antidepressants in primary care: Descriptive study of prescriptions from an indication based electronic prescribing system. BMJ 2017;356:j603 PMID: 28228380 Free PMC Article http://www.bmj.com/content/356/bmj.j603
  22. Then CK et al. Risk analysis of use of different classes of antidepressants on subsequent dementia: A nationwide cohort study in Taiwan. PLoS One 2017 Apr 6; 12:e0175187 PMID: 28384235 Free Article
  23. Liu X, Agerbo E, Ingstrup KG et al Antidepressant use during pregnancy and psychiatric disorders in offspring: Danish nationwide register based cohort study. BMJ 2017;358:j3668 PMID: 28877907 http://www.bmj.com/content/358/bmj.j3668 - Nordeng H, Lupattelli A, Wood M. Prenatal exposure to antidepressants and increased risk of psychiatric disorders. BMJ 2017;358:j3950 PMID: 28877910 http://www.bmj.com/content/358/bmj.j3950
  24. Burcu M, Zito JM, Safer DJ et al Association of Antidepressant Medications With Incident Type 2 Diabetes Among Medicaid-Insured Youths. JAMA Pediatr. Published online October 16, 2017 PMID: 29049533 https://jamanetwork.com/journals/jamapediatrics/article-abstract/2656620
  25. Orciari Herman A, Sadoughi S, Sofair A Millions of Americans Keep Taking Antidepressants for Years, Often Because of Severe Withdrawal Symptoms. David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org - Carey B, Gebeloff R. Many People Taking Antidepressants Discover They Cannot Quit. New York Times. April 7, 2018 https://www.nytimes.com/2018/04/07/health/antidepressants-withdrawal-prozac-cymbalta.html
  26. Gafoor R, Booth HP, Gulliford MC. Antidepressant utilisation and incidence of weight gain during 10 years' follow-up: population based cohort study. BMJ 2018;361:k1951 PMID: 29793997 Free PMC Article https://www.bmj.com/content/361/bmj.K1951 - Serretti A, Porcelli S. Antidepressant induced weight gain. BMJ 2018 May 23; 361:k2151 PMID: 29792297 https://www.bmj.com/content/361/bmj.k2151
  27. Brannstrom J, Lovheim H, Gustafson Y et al Association Between Antidepressant Drug Use and Hip Fracture in Older People Before and After Treatment Initiation. JAMA Psychiatry. Published online January 2, 2019 PMID: 30601883 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2719274 - Iaboni A, Maust DT A Status Update on the Association Between Antidepressants and Fractures Breaking Up? JAMA Psychiatry. Published online January 2, 2019 PMID: 30601880 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2719272
  28. Ferreira GE, McLachlan AJ, Lin CWC et al Efficacy and safety of antidepressants for the treatment of back pain and osteoarthritis: systematic review and meta-analysis. BMJ 2021;372:m4825 PMID: 33472813 Free article https://www.bmj.com/content/372/bmj.m4825 - Underwood M, Tysall C. Antidepressants for musculoskeletal pain. BMJ 2021;372:n80 PMID: 33472842 https://www.bmj.com/content/372/bmj.n80
  29. Breedvelt JJF et al. Continuation of antidepressants vs sequential psychological interventions to prevent relapse in depression. JAMA Psychiatry 2021 May 19; [e-pub]. PMID: 34009273 PMCID: PMC8135055 (available on 2022-05-19) https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2780290
  30. Drew L How antidepressants help bacteria resist antibiotics. A laboratory study unravels ways non-antibiotic drugs can contribute to drug resistance. Nature News. Jan 24, 2023 https://www.nature.com/articles/d41586-023-00186-y
  31. Iacobucci G. Stopping antidepressants causes symptoms in one in six people, study estimates. BMJ. 2024 Jun 6;385:q1246. PMID: 38843886 No abstract available.