Antidepressants and suicide risk

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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]

Contents

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 Warning on desvenlafaxine.jpg
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

Related Research Articles

<span class="mw-page-title-main">Antidepressant</span> Class of medication used to treat depression and other conditions

Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction.

<span class="mw-page-title-main">Paroxetine</span> SSRI antidepressant medication

Paroxetine, sold under the brand name Paxil among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive–compulsive disorder (OCD), panic disorder, social anxiety disorder, post-traumatic stress disorder (PTSD), generalized anxiety disorder, and premenstrual dysphoric disorder. It has also been used in the treatment of premature ejaculation and hot flashes due to menopause. It is taken orally.

<span class="mw-page-title-main">Sertraline</span> Antidepressant (SSRI class) medication

Sertraline, sold under the brand name Zoloft among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. The effectiveness of sertraline for depression is similar to that of other antidepressants such as Fluoxetine or Paroxetine. Sertraline is better tolerated than the older tricyclic antidepressants. Sertraline is effective for panic disorder, social anxiety disorder, generalized anxiety disorder, and obsessive–compulsive disorder (OCD). Although approved for post-traumatic stress disorder (PTSD), findings have shown sertraline leads to only modest improvements in symptoms. Sertraline also alleviates the symptoms of premenstrual dysphoric disorder and can be used in sub-therapeutic doses or intermittently for its treatment.

<span class="mw-page-title-main">Escitalopram</span> SSRI antidepressant

Escitalopram, sold under the brand names Lexapro and Cipralex, among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. Escitalopram is mainly used to treat major depressive disorder and generalized anxiety disorder. It is taken by mouth, available commercially as an oxalate salt exclusively.

<span class="mw-page-title-main">Citalopram</span> SSRI antidepressant

Citalopram, sold under the brand name Celexa among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive compulsive disorder, panic disorder, and social phobia. The antidepressant effects may take one to four weeks to occur. It is typically taken orally. In some European countries, it is sometimes given intravenously to initiate treatment, before switching to the oral route of administration for continuation of treatment. It has also been used intravenously in other parts of the world in some other circumstances.

<span class="mw-page-title-main">Bupropion</span> Medication mainly used for depression and smoking cessation

Bupropion, formerly called amfebutamone, and sold under the brand name Wellbutrin among others, is an atypical antidepressant that is US FDA-approved to treat major depressive disorder, seasonal affective disorder and to support smoking cessation. It is also popular as an add-on medication in the cases of "incomplete response" to the first-line selective serotonin reuptake inhibitor (SSRI) antidepressant. Bupropion has several features that distinguish it from other antidepressants: it does not usually cause sexual dysfunction, it is not associated with weight gain and sleepiness, and it is more effective than SSRIs at improving symptoms of hypersomnia and fatigue. Bupropion, particularly the immediate-release formulation, carries a higher risk of seizure than many other antidepressants, hence caution is recommended in patients with a history of seizure disorder. The medication is taken by mouth.

<span class="mw-page-title-main">Venlafaxine</span> Antidepressant medication

Venlafaxine, sold under the brand name Effexor among others, is an antidepressant medication of the serotonin–norepinephrine reuptake inhibitor (SNRI) class. It is used to treat major depressive disorder, generalized anxiety disorder, panic disorder, and social anxiety disorder. Studies have shown that venlafaxine improves post-traumatic stress disorder (PTSD). It may also be used for chronic neuropathic pain. It is taken orally. It is also available as the salt venlafaxine besylate in an extended-release formulation.

<span class="mw-page-title-main">Duloxetine</span> Antidepressant medication used also for the treatment of anxiety and chronic pain


Duloxetine, sold under the brand name Cymbalta among others, is a medication used to treat major depressive disorder, generalized anxiety disorder, obsessive-compulsive disorder, fibromyalgia, neuropathic pain and central sensitization. It is taken by mouth.

<span class="mw-page-title-main">David Healy (psychiatrist)</span> Irish-born pharmacologist

David HealyFRCPsych, a professor of psychiatry at Bangor University in the United Kingdom, is a psychiatrist, psychopharmacologist, scientist and author. His main areas of research are the contribution of antidepressants to suicide, conflict of interest between pharmaceutical companies and academic medicine, and the history of pharmacology. Healy has written more than 150 peer-reviewed articles, 200 other articles, and 20 books, including The Antidepressant Era, The Creation of Psychopharmacology, The Psychopharmacologists Volumes 1–3, Let Them Eat Prozac and Mania: A Short History of Bipolar Disorder.

<span class="mw-page-title-main">Serotonin–norepinephrine reuptake inhibitor</span> Class of antidepressant medication

Serotonin–norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant medications used to treat major depressive disorder (MDD), anxiety disorders, social phobia, chronic neuropathic pain, fibromyalgia syndrome (FMS), and menopausal symptoms. Off-label uses include treatments for attention-deficit hyperactivity disorder (ADHD), and obsessive–compulsive disorder (OCD). SNRIs are monoamine reuptake inhibitors; specifically, they inhibit the reuptake of serotonin and norepinephrine. These neurotransmitters are thought to play an important role in mood regulation. SNRIs can be contrasted with the selective serotonin reuptake inhibitors (SSRIs) and norepinephrine reuptake inhibitors (NRIs), which act upon single neurotransmitters.

Antidepressant discontinuation syndrome, also called antidepressant withdrawal syndrome, is a condition that can occur following the interruption, reduction, or discontinuation of antidepressant medication following its continuous use of at least a month. The symptoms may include flu-like symptoms, trouble sleeping, nausea, poor balance, sensory changes, akathisia, intrusive thoughts, depersonalization and derealization, mania, anxiety, and depression. The problem usually begins within three days and may last for several weeks or months. Psychosis may rarely occur.

<span class="mw-page-title-main">Suicidal ideation</span> Thoughts, ideas, or ruminations about the possibility of ending ones life

Suicidal ideation, or suicidal thoughts, is the thought process of having ideas, or ruminations about the possibility of completing suicide. It is not a diagnosis but is a symptom of some mental disorders, use of certain psychoactive drugs, and can also occur in response to adverse life circumstances without the presence of a mental disorder.

<span class="mw-page-title-main">Olanzapine/fluoxetine</span> Antidepressant medication

Olanzapine/fluoxetine is a fixed-dose combination medication containing olanzapine (Zyprexa), an atypical antipsychotic, and fluoxetine (Prozac), a selective serotonin reuptake inhibitor (SSRI). Olanzapine/fluoxetine is primarily used to treat the depressive episodes of bipolar I disorder as well as treatment-resistant depression.

<span class="mw-page-title-main">Fluoxetine</span> SSRI antidepressant

Fluoxetine, sold under the brand name Prozac, among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used for the treatment of major depressive disorder, obsessive–compulsive disorder (OCD), anxiety, bulimia nervosa, panic disorder, and premenstrual dysphoric disorder. It is also approved for treatment of major depressive disorder in adolescents and children 8 years of age and over. It has also been used to treat premature ejaculation. Fluoxetine is taken by mouth.

Challenge–dechallenge–rechallenge (CDR) is a medical testing protocol in which a medicine or drug is administered, withdrawn, then re-administered, while being monitored for adverse effects at each stage. The protocol is used when statistical testing is inappropriate due to an idiosyncratic reaction by a specific individual, or a lack of sufficient test subjects and unit of analysis is the individual. During the dechallenge (withdrawal) phase, the medication is allowed to wash out of the system in order to determine what effect the medication is having on an individual.

<span class="mw-page-title-main">Vilazodone</span> Antidepressant medication

Vilazodone, sold under the brand name Viibryd among others, is a medication used to treat major depressive disorder. It is classified as a serotonin modulator and is taken by mouth.

Management of depression is the treatment of depression that may involve a number of different therapies: medications, behavior therapy, psychotherapy, and medical devices.

<span class="mw-page-title-main">Depression in childhood and adolescence</span> Pediatric depressive disorders

Major depressive disorder, often simply referred to as depression, is a mental disorder characterized by prolonged unhappiness or irritability. It is accompanied by a constellation of somatic and cognitive signs and symptoms such as fatigue, apathy, sleep problems, loss of appetite, loss of engagement, low self-regard/worthlessness, difficulty concentrating or indecisiveness, or recurrent thoughts of death or suicide.

<span class="mw-page-title-main">Selective serotonin reuptake inhibitor</span> Class of antidepressant medication

Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions.

<span class="mw-page-title-main">Study 329</span> Scientific article

Study 329 was a clinical trial which was conducted in North America from 1994 to 1998 to study the efficacy of paroxetine, an SSRI anti-depressant, in treating 12- to 18-year-olds diagnosed with major depressive disorder. Led by Martin Keller, then professor of psychiatry at Brown University, and funded by the British pharmaceutical company SmithKline Beecham—known since 2000 as GlaxoSmithKline (GSK)—the study compared paroxetine with imipramine, a tricyclic antidepressant, and placebo. SmithKline Beecham had released paroxetine in 1991, marketing it as Paxil in North America and Seroxat in the UK. The drug attracted sales of $11.7 billion in the United States alone from 1997 to 2006, including $2.12 billion in 2002, the year before it lost its patent.

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. 1 2 "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.

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