Antidepressants and suicide risk

The relationship between antidepressant use and suicide risk is a subject of medical research and has faced varying levels of debate. This problem was thought to be serious enough to warrant intervention by the U.S. Food and Drug Administration to label greater likelihood of suicide as a risk of using antidepressants.^[1] Some studies have shown that the use of certain antidepressants correlate with an increased risk of suicide in some patients relative to other antidepressants.^[2] However, these conclusions have faced considerable scrutiny and disagreement: A multinational European study indicated that antidepressants decrease risk of suicide at the population level,^[3] and other reviews of antidepressant use claim that there is not enough data to indicate antidepressant use increases risk of suicide.^[4][5][6]

Youth

Antidepressants could increase the risk of suicidal thoughts and behavior in people with depression under the age of 25. In 2004, the U.S. Food and Drug Administration along with the Neuro-Psychopharmacologic Advisory Committee and the Anti-Infective Drugs Advisory Committee, concluded that there was a causal link between newer antidepressants and pediatric suicidality.^[7] Federal health officials unveiled proposed changes to the labels on antidepressant drugs in December 2006 to warn people of this danger.^{[citation needed]}

A 2016 review of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) which looked at four outcomes—death, suicidality, aggressive behaviour, and agitation—found that while the data was insufficient to draw strong conclusions, adults taking these drugs did not appear to be at increased risk for any of the four outcomes, but that for people under the age of 18, the risks of suicidality and for aggression doubled. The authors expressed frustration with incomplete reporting and lack of access to data, and with some aspects of the clinical trial designs, which may have resulted in significant under-reporting of harms.^[8]

Boxed warning for desvenlafaxine, an SNRI

Warnings

The Food and Drug Administration (FDA) requires "black box warnings" on all SSRIs, which state that they double suicidal ideation rates (from 2 in 1,000 to 4 in 1,000) in children and adolescents.^[9] It remains controversial whether increased risk of suicide is due to the medication (a paradoxical effect) or part of the depression itself (i.e. the antidepressant enables those who are severely depressed—who ordinarily would be paralyzed by their depression—to become more alert and act out suicidal urges before being fully recovered from their depressive episode).^[10] The increased risk for suicidality and suicidal behaviour among adults under 25 approaches that seen in children and adolescents.^[11] Young patients should be closely monitored for signs of suicidal ideation or behaviors, especially in the first eight weeks of therapy. Sertraline, tricyclic agents and venlafaxine were found to increase the risk of attempted suicide in severely depressed adolescents on Medicaid.^[12]

Increased risk for quitting medication

A 2009 study showed increased risk of suicide after initiation, titration, and discontinuation of medication.^[13] A study of 159,810 users of either amitriptyline, fluoxetine, paroxetine or dothiepin found that the risk of suicidal behavior is increased in the first month after starting antidepressants, especially during the first 1 to 9 days.^[14]

Prevalence

On September 6, 2007, the Centers for Disease Control and Prevention reported that the suicide rate in American adolescents, (especially girls, 10 to 24 years old), increased 8% (2003 to 2004), the largest jump in 15 years,^[15] to 4,599 suicides in Americans ages 10 to 24 in 2004, from 4,232 in 2003, giving a suicide rate of 7.32 per 100,000 people that age. The rate previously dropped to 6.78 per 100,000 in 2003 from 9.48 per 100,000 in 1990. Jon Jureidini, a critic of this study, says that the US "2004 suicide figures were compared simplistically with the previous year, rather than examining the change in trends over several years".^[16] It has been noted that the pitfalls of such attempts to infer a trend using just two data points (years 2003 and 2004) are further demonstrated by the fact that, according to the new epidemiological data, the suicide rate in 2005 in children and adolescents actually declined despite the continuing decrease of SSRI prescriptions. "It is risky to draw conclusions from limited ecologic analyses of isolated year-to-year fluctuations in antidepressant prescriptions and suicides.^[17]

One promising epidemiological approach involves examining the associations between trends in psychotropic medication use and suicide over time across a large number of small geographic regions. Until the results of more detailed analyses are known, prudence dictates deferring judgment concerning the public health effects of the FDA warnings."^[18][19] Subsequent follow-up studies have supported the hypothesis that antidepressant drugs reduce suicide risk.^[20][21]

Suicide risk

In those under the age of 25 antidepressants appear to increase the risk of suicidal thoughts and behaviors.^[22][23] In the United States they contain a black box warning regarding this concern.^[22]

In 2019 Hengartner and Plöderl published the research, which was based on the integrated safety summaries provided by the FDA for all phase II and III trials conducted by the pharmaceutical industry for adults with major depression, treated with sertraline, paroxetine, venlafaxine, nefazodone, mirtazapine, venlafaxine ER, citalopram, escitalopram, duloxetine, desvenlafaxine, trazodone ER, vilazodone, levomilnacipram, and vortioxetine versus placebo. They found 37 deaths by suicide in the antidepressant group (31.781 patients), and only 4 deaths by suicide in the placebo group (10.080 patients). Apart from this the rates of suicide attempts were 250 % higher in the people taking antidepressants than in those who were given the placebo: 206 suicide attempts in people taking antidepressants, versus 28 suicide attempts in people taking placebo.^[24]

See also

• Citalopram
• Paradoxical effect
• Substance-induced psychosis

References

1. Research, Center for Drug Evaluation and (2018-11-03). "Suicidality in Children and Adolescents Being Treated With Antidepressant Medications". FDA.
2. C, Coupland; T, Hill; R, Morriss; A, Arthur; M, Moore; J, Hippisley-Cox (2015-02-18). "Antidepressant Use and Risk of Suicide and Attempted Suicide or Self Harm in People Aged 20 to 64: Cohort Study Using a Primary Care Database". BMJ (Clinical Research Ed.). 350: h517. doi:10.1136/bmj.h517. PMC 4353276. PMID 25693810.
3. Gusmão, Ricardo; Quintão, Sónia; McDaid, David; Arensman, Ella; Van Audenhove, Chantal; Coffey, Claire; Värnik, Airi; Värnik, Peeter; Coyne, James; Hegerl, Ulrich (2013-06-19). "Antidepressant Utilization and Suicide in Europe: An Ecological Multi-National Study". PLOS ONE. 8 (6): e66455. Bibcode:2013PLoSO...866455G. doi:10.1371/journal.pone.0066455. ISSN 1932-6203. PMC 3686718. PMID 23840475.
4. G, Isacsson; Cl, Rich (April 2014). "Antidepressant Drugs and the Risk of Suicide in Children and Adolescents". Paediatric Drugs. 16 (2): 115–22. doi:10.1007/s40272-013-0061-1. PMID 24452997. S2CID 904085.
5. Shain, Benjamin; Adolescence, Committee On (2016-07-01). "Suicide and Suicide Attempts in Adolescents". Pediatrics. 138 (1): e20161420. doi:10.1542/peds.2016-1420. ISSN 0031-4005. PMID 27354459.
6. C, Adegbite-Adeniyi; B, Gron; Bm, Rowles; Ca, Demeter; Rl, Findling (October 2012). "An Update on Antidepressant Use and Suicidality in Pediatric Depression". Expert Opinion on Pharmacotherapy. 13 (15): 2119–30. doi:10.1517/14656566.2012.726613. PMID 22984934. S2CID 23771296.
7. Leslie, Laurel K.; Newman, Thomas B.; Chesney, P. Joan; Perrin, James M. (2005). "The Food and Drug Administration's Deliberations on Antidepressant Use in Pediatric Patients". Pediatrics. 116 (1): 195–204. doi:10.1542/peds.2005-0074. PMC 1550709. PMID 15995053.
8. Sharma, Tarang; Guski, Louise Schow; Freund, Nanna; Gøtzsche, Peter C. (2016-01-27). "Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports". BMJ. 352: i65. doi:10.1136/bmj.i65. ISSN 1756-1833. PMC 4729837. PMID 26819231.
9. Lenzer, J. (2006). "Antidepressants double suicidality in children, says FDA". BMJ. 332 (7542): 626. doi:10.1136/bmj.332.7542.626-c. PMC 1403224. PMID 16543316.
10. "SSRI Antidepressants". Patient.info. 2010-10-27. Retrieved 2012-11-30.
11. Stone, M.; Laughren, T.; Jones, M L.; Levenson, M.; Holland, P C.; Hughes, A.; Hammad, T. A; Temple, R.; Rochester, G. (2009). "Risk of suicidality in clinical trials of antidepressants in adults: Analysis of proprietary data submitted to US Food and Drug Administration". BMJ. 339: b2880. doi:10.1136/bmj.b2880. PMC 2725270. PMID 19671933.
12. Olfson, Mark; Marcus, Steven; Shaffer, David (Aug 2006). "Antidepressant Drug Therapy and Suicide in Severely Depressed Children and Adults". Arch Gen Psychiatry. 63 (8): 865–72. doi:10.1001/archpsyc.63.8.865. PMID 16894062.
13. Valuck, Robert J.; Orton, Heather D.; Libby, Anne M. (2009). "Antidepressant Discontinuation and Risk of Suicide Attempt". The Journal of Clinical Psychiatry. 70 (8): 1069–77. doi:10.4088/JCP.08m04943. PMID 19758520. S2CID 24870988.
14. Jick, H.; Kaye, JA; Jick, SS (2004). "Antidepressants and the Risk of Suicidal Behaviors". JAMA. 292 (3): 338–43. doi:10.1001/jama.292.3.338. PMID 15265848.
15. Carey, Benedict (September 7, 2007). "Suicide Rises in Youth; Antidepressant Debate Looms". New York Times.
16. Jureidini, J. (2007). "The Black Box Warning: Decreased Prescriptions and Increased Youth Suicide?". American Journal of Psychiatry. 164 (12): 1907, author reply 1908–10. doi:10.1176/appi.ajp.2007.07091463. PMID 18056248. S2CID 27774152.
17. "Adverse Effects of Anti-depressants". Archived from the original on 2 April 2015. Retrieved 23 March 2015.
18. Olfson, M.; Shaffer, D. (2007). "SSRI Prescriptions and the Rate of Suicide". American Journal of Psychiatry. 164 (12): 1907–1908. doi:10.1176/appi.ajp.2007.07091467. PMID 18056247.
19. Kung HC, Hoyert DL, Xu J, Murphy SL. "N C H S - Health E Stats - Deaths: Preliminary Data for 2005". National Center for Health Statistics. Archived from the original on 12 December 2007. Retrieved 2007-12-12.
20. Bridge, Jeffrey A.; Iyengar, S; Salary, CB; Barbe, RP; Birmaher, B; Pincus, HA; Ren, L; Brent, DA (2007). "Clinical Response and Risk for Reported Suicidal Ideation and Suicide Attempts in Pediatric Antidepressant Treatment: A Meta-analysis of Randomized Controlled Trials". JAMA. 297 (15): 1683–96. doi:10.1001/jama.297.15.1683. PMID 17440145.
21. Beasley, Charles M.; Ball, Susan G.; Nilsson, Mary E.; Polzer, John; Tauscher-Wisniewski, Sitra; Plewes, John; Acharya, Nayan (2007). "Fluoxetine and Adult Suicidality Revisited". Journal of Clinical Psychopharmacology. 27 (6): 682–6. doi:10.1097/jcp.0b013e31815abf21. PMID 18004137. S2CID 32153323.
22. "Fluoxetine Hydrochloride Monograph for Professionals". Drugs.com. Retrieved 15 October 2019.
23. Brent, DA (September 2016). "Antidepressants and Suicidality". The Psychiatric Clinics of North America. 39 (3): 503–12. doi:10.1016/j.psc.2016.04.002. PMID 27514302.
24. Hengartner, Michael; Plöderl, Martin (2019). "Newer-Generation Antidepressants and Suicide Risk in Randomized Controlled Trials: A Re-Analysis of the FDA Database". Psychother Psychosom. 88 (4): 247–248. doi:10.1159/000501215. PMID 31234169.

Further reading

• Fergusson D, Doucette S, Cranley-Glass K (2005). "The association between suicide attempts and SSRIs: A systematic review of 677 randomised controlled trials representing 85,470 participants". British Medical Journal. 330 (7488): 396–399. doi:10.1136/bmj.330.7488.396. PMC 549110. PMID 15718539.
• Healy D, Herxheimer A, Menkes D (2006). Antidepressants and violence: Problems at the interface of medicine and law. PLoS Medicine 3, September
• Healy D, Harris M, Tranter R, Gutting P, Austin R, Jones-Edwards G, Roberts AP (2006). Lifetime suicide rates in treated schizophrenia: 1875–1924 and 1994–1998 cohorts compared. British Journal of Psychiatry 188, 223–228. With Commentary by T Turner, 229–230.
• Reseland S, Le Noury J, Aldred G (2008). "National suicide rates 1961–2003: further analysis of Nordic data for suicide, autopsies and ill-defined death rates". Psychotherapy and Psychosomatics. 77 (2): 78–82. doi:10.1159/000112884. PMID 18230940. S2CID 23306023.
• Healy D, Brent D (2009). "Are Selective Serotonin Reuptake Inhibitors a risk factor for adolescent suicides?". Canadian Journal of Psychiatry. 54 (2): 69–71. doi:10.1177/070674370905400201. PMID 19254434.
• Healy D (2011). "Science, rhetoric and the causality of adverse events". International Journal of Risk & Safety in Medicine. 23 (3): 149–162. doi:10.3233/JRS-2011-0534. PMID 22020395. S2CID 41674770.

External links

• message about antidepressants and suicide in youth from the National Institutes of Health