In October 2004, the Food and Drug Administration (FDA) directed pharmaceutical manufacturers to add a black box warning to antidepressants describing the increased risk of suicidality in children. The FDA ruling elicited controversy reflecting the fundamental trade-offs associated with weighing risks against benefits under conditions of scientific uncertainty. Supporters argued that evidence of elevated risks of suicidality linked to use of antidepressants in youth was sufficiently serious to warrant informing providers and consumers. Critics countered that FDA actions would reduce the use of an effective treatment for depression thereby producing poorer mental health outcomes (including some upward pressure on the risk of suicide) in an under-treated population. This application examines the potential gains and unintended consequences of FDA regulatory policy. Unlike most prior work, the primary focus of this application is not whether antidepressants increase suicide risk, but rather the heightened risk of individuals being under or untreated for illnesses for which effective treatments exist.
Aim 1 assesses the impact of FDA actions on treatment choice for children and adults with major depression and anxiety diagnoses.
Aim 2 examines the impact of FDA actions on receipt of appropriate treatment for children and adults with a major depression diagnosis.
Aim 3 studies the impact of declines in antidepressant use attributable to FDA action on indicators of medically-treated suicide attempts in youth.
Aim 4 assesses whether pharmaceutical manufacturers altered promotional content and strategy in response to FDA actions. Outpatient, inpatient and pharmaceutical claims data from a large insured population will be used to conduct Aims 1-3. Individuals will be followed over time and episodes of treatment will be constructed to assess how regulation affects treatment choice and receipt of appropriate care.
In Aim 4, a mixed methods approach will be employed to develop a richer understanding of manufacturer response than might be ascertained from either quantitative or qualitative methods alone. This application is premised on the inevitability of both expected benefits and unintended consequences arising from policy decisions. The broad objective that guides the application is to promote an evidence-based approach to understanding and managing uncertainty inherent in FDA regulatory decisions. Because under-treatment of depression is a substantial public health problem in the U.S., reductions in antidepressant treatment unaccompanied by increases in alternative treatments is not a desirable policy outcome. The significance of this project lies in its potential to help clinicians and policymakers assess and manage competing risk and benefit claims. ? ? ?

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Application #
Study Section
Mental Health Services in MH Specialty Settings (SRSP)
Program Officer
Rupp, Agnes
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Yale University
Public Health & Prev Medicine
Schools of Medicine
New Haven
United States
Zip Code
Busch, Susan H; Golberstein, Ezra; Meara, Ellen (2014) The FDA And ABCs: Unintended Consequences Of Antidepressant Warnings On Human Capital. J Hum Resour 49:540-571
Le Cook, Benjamin; Barry, Colleen L; Busch, Susan H (2013) Racial/ethnic disparity trends in children's mental health care access and expenditures from 2002 to 2007. Health Serv Res 48:129-49
Barry, Colleen L; Martin, Andres; Busch, Susan H (2012) ADHD medication use following FDA risk warnings. J Ment Health Policy Econ 15:119-25
Busch, Susan H; Frank, Richard G; Martin, Andres et al. (2011) Characterizing declines in pediatric antidepressant use after new risk disclosures. Med Care Res Rev 68:96-111
Busch, Susan H; Frank, Richard G; Leslie, Douglas L et al. (2010) Antidepressants and suicide risk: how did specific information in FDA safety warnings affect treatment patterns? Psychiatr Serv 61:11-6
Barry, Colleen L; Busch, Susan H (2010) News coverage of FDA warnings on pediatric antidepressant use and suicidality. Pediatrics 125:88-95
Busch, Susan H; Barry, Colleen L (2009) Pediatric antidepressant use after the black-box warning. Health Aff (Millwood) 28:724-33
Busch, Susan H; Barry, Colleen L (2009) Does private insurance adequately protect families of children with mental health disorders? Pediatrics 124 Suppl 4:S399-406