Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental study

Objective To investigate if the widely publicized warnings in 2003 from the US Food and Drug Administration about a possible increased risk of suicidality with antidepressant use in young people were associated with changes in antidepressant use, suicide attempts, and completed suicides among young people. Design Quasi-experimental study assessing changes in outcomes after the warnings, controlling for pre-existing trends. Setting Automated healthcare claims data (2000-10) derived from the virtual data warehouse of 11 health plans in the US Mental Health Research Network. Participants Study cohorts included adolescents (around 1.1 million), young adults (around 1.4 million), and adults (around 5 million). Main outcome measures Rates of antidepressant dispensings, psychotropic drug poisonings (a validated proxy for suicide attempts), and completed suicides. Results Trends in antidepressant use and poisonings changed abruptly after the warnings. In the second year after the warnings, relative changes in antidepressant use were −31.0% (95% confidence interval −33.0% to −29.0%) among adolescents, −24.3% (−25.4% to −23.2%) among young adults, and −14.5% (−16.0% to −12.9%) among adults. These reflected absolute reductions of 696, 1216, and 1621 dispensings per 100 000 people among adolescents, young adults, and adults, respectively. Simultaneously, there were significant, relative increases in psychotropic drug poisonings in adolescents (21.7%, 95% confidence interval 4.9% to 38.5%) and young adults (33.7%, 26.9% to 40.4%) but not among adults (5.2%, −6.5% to 16.9%). These reflected absolute increases of 2 and 4 poisonings per 100 000 people among adolescents and young adults, respectively (approximately 77 additional poisonings in our cohort of 2.5 million young people). Completed suicides did not change for any age group. Conclusions Safety warnings about antidepressants and widespread media coverage decreased antidepressant use, and there were simultaneous increases in suicide attempts among young people. It is essential to monitor and reduce possible unintended consequences of FDA warnings and media reporting.

[1]  Fang Zhang,et al.  Methods for estimating confidence intervals in interrupted time series analyses of health interventions. , 2009, Journal of clinical epidemiology.

[2]  Robert D Gibbons,et al.  Strategies for Quantifying the Relationship between Medications and Suicidal Behaviour What Has Been Learned? Population-based Changes in Suicide Rates May Quantifying the Relationship between Medications and Suicidal Behaviour 377 , 2022 .

[3]  J. Racoosin,et al.  Suicidality in pediatric patients treated with antidepressant drugs. , 2006, Archives of general psychiatry.

[4]  H. Jick,et al.  Antidepressants and the risk of suicidal behaviors. , 2004, JAMA.

[5]  C. Pamer,et al.  Changes in US antidepressant and antipsychotic prescription patterns during a period of FDA actions , 2010, Pharmacoepidemiology and drug safety.

[6]  Sarah M. Greene,et al.  Building a research consortium of large health systems: the Cancer Research Network. , 2005, Journal of the National Cancer Institute. Monographs.

[7]  Elaine H Morrato,et al.  Spillover effects on treatment of adult depression in primary care after FDA advisory on risk of pediatric suicidality with SSRIs. , 2007, The American journal of psychiatry.

[8]  J. Fairbank,et al.  The Treatment for Adolescents With Depression Study (TADS): long-term effectiveness and safety outcomes. , 2007, Archives of general psychiatry.

[9]  C. Barbui.  Antidepressants and the risk of suicidal behaviors. , 2004, JAMA.

[10]  R. Baldessarini,et al.  Suicidal risk in antidepressant drug trials. , 2006, Archives of general psychiatry.

[11]  W. Shadish,et al.  Experimental and Quasi-Experimental Designs for Generalized Causal Inference , 2001 .

[12]  R. Rosenheck,et al.  Antidepressants and suicide risk: how did specific information in FDA safety warnings affect treatment patterns? , 2010, Psychiatric services.

[13]  A K Wagner,et al.  Segmented regression analysis of interrupted time series studies in medication use research , 2002, Journal of clinical pharmacy and therapeutics.

[14]  S. Schneeweiss,et al.  Variation in the risk of suicide attempts and completed suicides by antidepressant agent in adults: a propensity score-adjusted analysis of 9 years' data. , 2010, Archives of general psychiatry.

[15]  H. Spiller,et al.  Epidemiological trends of suicide and attempted suicide by poisoning in the US: 2000-2008. , 2010, Legal medicine.

[16]  Richard W. Kobylinski,et al.  Identifying physician-recognized depression from administrative data: consequences for quality measurement. , 2003, Health services research.

[17]  Edwin D Boudreaux,et al.  Trends in US emergency department visits for attempted suicide and self-inflicted injury, 1993-2008. , 2012, General hospital psychiatry.

[18]  R. Davis,et al.  Health Maintenance Organizations/Health Plans , 2012 .

[19]  A. Creanga,et al.  Abortion surveillance--United States, 2009. , 2012, Morbidity and mortality weekly report. Surveillance summaries.

[20]  D. Klein,et al.  The Flawed Basis for FDA Post-Marketing Safety Decisions: The Example of Anti-Depressants and Children , 2006, Neuropsychopharmacology.

[21]  J. Gfroerer,et al.  Suicidal thoughts and behaviors among adults aged ≥18 years--United States, 2008-2009. , 2011, Morbidity and mortality weekly report. Surveillance summaries.

[22]  D. Brent,et al.  Decline in treatment of pediatric depression after FDA advisory on risk of suicidality with SSRIs. , 2007, The American journal of psychiatry.

[23]  R. Valuck,et al.  Persisting decline in depression treatment after FDA warnings. , 2009, Archives of general psychiatry.

[24]  Fang Zhang,et al.  How complete are E‐codes in commercial plan claims databases? , 2014, Pharmacoepidemiology and drug safety.

[25]  M. Olfson,et al.  A case-control study of antidepressants and attempted suicide during early phase treatment of major depressive episodes. , 2008, The Journal of clinical psychiatry.

[26]  Joseph L. Annest,et al.  Suicide Among Adults Aged 35–64 Years — United States, 1999–2010 , 2013, MMWR. Morbidity and mortality weekly report.

[27]  G. Simon.  The antidepressant quandary--considering suicide risk when treating adolescent depression. , 2006, The New England journal of medicine.

[28]  F. Degruy,et al.  Frequency of provider contact after FDA advisory on risk of pediatric suicidality with SSRIs. , 2008, The American journal of psychiatry.

[29]  S. Busch,et al.  News Coverage of FDA Warnings on Pediatric Antidepressant Use and Suicidality , 2010, Pediatrics.

[30]  Richard M Glass,et al.  Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents with Depression Study (TADS) randomized controlled trial. , 2005, The Journal of pediatrics.

[31]  Sebastian Schneeweiss,et al.  Identification of hospitalizations for intentional self‐harm when E‐codes are incompletely recorded , 2010, Pharmacoepidemiology and drug safety.

[32]  Connie Lim,et al.  Youth risk behavior surveillance - United States, 2011. , 2012, Morbidity and mortality weekly report. Surveillance summaries.

[33]  J. Savarino,et al.  Suicide risk during antidepressant treatment. , 2006, The American journal of psychiatry.

[34]  J. Leckman,et al.  A developmental perspective on the controversy surrounding the use of SSRIs to treat pediatric depression. , 2007, The American journal of psychiatry.

[35]  S. Soumerai,et al.  Effects of professional and media warnings about the association between aspirin use in children and Reye's syndrome. , 1992, The Milbank quarterly.

[36]  J L Collins,et al.  Youth Risk Behavior Surveillance--United States, 1997. State and Local YRBSS Coordinators. , 1998, The Journal of school health.

[37]  J. Mann,et al.  Suicidal thoughts and behavior with antidepressant treatment: reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine. , 2012, Archives of general psychiatry.

[38]  Sarah M. Greene,et al.  Building a virtual cancer research organization. , 2005, Journal of the National Cancer Institute. Monographs.

[39]  Mark Olfson,et al.  A systematic review of validated methods for identifying depression using administrative data , 2012, Pharmacoepidemiology and drug safety.

[40]  Joel B Greenhouse,et al.  Do antidepressants cause suicidality in children? A Bayesian meta-analysis , 2006, Clinical trials.