Skip to main content
SpringerLink
Log in

Antidepressant Regulatory Warnings, Prescription Patterns, Suicidality and Other Aggressive Behaviors in Major Depressive Disorder and Anxiety Disorders

  • Original Paper
  • Published:
Psychiatric Quarterly Aims and scope Submit manuscript

Abstract

In 2004 the Food and Drug Administration issued a warning on the risk of suicidality in children and adolescents receiving antidepressants. This was followed by reports of changes in antidepressant prescription patterns, suicidality and other aggressive behaviors, but debate is continuing regarding the nature and magnitude of these changes. We examined a large physician database for impact of the warning on antidepressant prescriptions, suicidality and other aggressive behaviors in major depressive disorder (MDD) and anxiety disorders in adult and pediatric patients. We analyzed electronic database covering over 100,000 patients, treated in Pre- (before 2003) and Post- (after 2004) warning periods. We compared strength of the association between the measures and the time period with two tests. Multivariate logistic regression analyses were performed to ascertain the unique effect of each parameter. Of 10,089 MDD (61.0 %) and anxiety disorders (39.0 %) patients, 65.2 % received antidepressant prescription and 16.1 % were pediatric patients. In post-warning period, there was a greater reduction in adult versus pediatric antidepressant prescription rates. Logistic modeling showed greater likelihood of antidepressant prescription in MDD as compared with anxiety disorders in post-warning period. Pediatric patients were more likely than adults to receive fluoxetine during the post-warning period. There was an overall reduction in suicidality and other aggressive behaviors in the post-warning period. Regulatory warnings may have had an impact on antidepressant benefit/risk assessment and consequent utilization, therapeutic effects, and adverse events. Our observations suggest that psychiatrists may heed regulatory warnings, but may also exert professional independence and discrimination in their application.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Simon RI.: Suicide Risk: Assessing the Unpredictable, 1st edn., Arlington, American Psychiatric Publishing Inc., 2006.

    Google Scholar 

  2. Kessler RC, G Borges, EE Walters.: Prevalence of and risk factors for lifetime suicide attempts in the National Comorbidity Survey. Archives of General Psychiatry 56:617–626, 1999.

  3. Sareen J, et al.: Anxiety disorders and risk for suicidal ideation and suicide attempts: a population-based longitudinal study of adults. Archives of General Psychiatry 62:1249–1257, 2005.

    Article  PubMed  Google Scholar 

  4. APA.: Practice Guideline for the Treatment of Patients with Major Depressive Disorder, 2010.

  5. Canton J, Scott KM, Glue P.: Optimal treatment of social phobia: Systematic review and meta-analysis. Neuropsychiatric Disease and Treatment, 8:203–215, 2012.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Goldblatt MJ, Schatzberg, AF: Does treatment with antidepressant medication increase suicidal behavior? International Clinical Psychopharmacology 6:219–226, 1991.

  7. Montgomery SA, Pinder RM: Do some antidepressants promote suicide? Psychopharmacology (Berl) 92:265–266, 1987.

    Article  CAS  Google Scholar 

  8. Teicher MH, Glod C, Cole JO: Emergence of intense suicidal preoccupation during fluoxetine treatment. American Journal of Psychiatry 147:207–210, 1990.

    Article  CAS  PubMed  Google Scholar 

  9. Donovan S, et al.: Deliberate self-harm and antidepressant drugs. Investigation of a possible link. British Journal of Psychiatry 177:551–556, 2000.

    Article  CAS  PubMed  Google Scholar 

  10. Healy D, Whitaker C: Antidepressants and suicide: Risk-benefit conundrums. Journal of Psychiatry and Neuroscience 28:331–337, 2003.

    PubMed  PubMed Central  Google Scholar 

  11. Jick H, Kaye JA, Jick SS: Antidepressants and the risk of suicidal behaviors. JAMA 292:338–343, 2004.

    Article  CAS  PubMed  Google Scholar 

  12. Moore TJ, Glenmullen J, Furberg CD: Prescription drugs associated with reports of violence towards others. PLoS One 5:e15337, 2010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Miller M, et al.: Antidepressant dose, age, and the risk of deliberate self-harm. JAMA Internal Medicine 174:899–909, 2014.

  14. Bouvy PF, Liem M: Antidepressants and lethal violence in the Netherlands 1994–2008. Psychopharmacology (Berl) 222:499–506, 2012.

    Article  CAS  Google Scholar 

  15. MHRA: Selective serotonin reuptake inhibitors (SSRIs): Overview of regulatory status and CSM advice relating to major depressive disorder (MDD) in children and adolescents including a summary of available safety and efficacy data, 2003. http://www.mhra.gov.uk/Safetyinformation/Safetywarningsalertsandrecalls/Safetywarningsandmessagesformedicines/CON019494?useSecondary=&showpage=3.

  16. FDA: Historical information on antidepressant use in children, adolescents, and adults, 2014. http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm096293.htm.

  17. FDA: FDA proposes new warnings about suicidal thinking, behavior in young adults who take antidepressant medications, 2007 http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm108905.htm.

  18. Busch SH, Barry CL: Pediatric antidepressant use after the black-box warning. Health Affairs (Millwood) 28:724–733, 2009.

    Article  Google Scholar 

  19. Busch, SH, et al.: Antidepressants and suicide risk: How did specific information in FDA safety warnings affect treatment patterns? Psychiatric Services 61:11–16, 2010.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Gibbons RD, et al.: Early evidence on the effects of regulators’ suicidality warnings on SSRI prescriptions and suicide in children and adolescents. American Journal of Psychiatry 164:1356–1363, 2007.

    Article  PubMed  Google Scholar 

  21. Hassanin H, et al.: Changes in antidepressant medications prescribing trends in children and adolescents in Hawai’i following the FDA black box warning. Hawaii Medical Journal 69:17–19, 2010.

    PubMed  PubMed Central  Google Scholar 

  22. Katz LY, et al.: Effect of regulatory warnings on antidepressant prescription rates, use of health services and outcomes among children, adolescents and young adults. CMAJ 178:1005–1111, 2008.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Libby AM, Orton HD, Valuck RJ. Persisting decline in depression treatment after FDA warnings. Archives of General Psychiatry 66:633–639, 2009.

    Article  PubMed  Google Scholar 

  24. Valuck RJ, et al.: Spillover effects on treatment of adult depression in primary care after FDA advisory on risk of pediatric suicidality with SSRIs. American Journal of Psychiatry 164:1198–1205, 2007.

    Article  PubMed  Google Scholar 

  25. Lu, CY, et al.: Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: Quasi-experimental study. BMJ 348:3596, 2014.

    Article  Google Scholar 

  26. Chen SY, Toh S.: National trends in prescribing antidepressants before and after an FDA advisory on suicidality risk in youths. Psychiatric Services 62:727–733, 2011.

    Article  PubMed  Google Scholar 

  27. Gibbons RD, et al.: Suicidal thoughts and behavior with antidepressant treatment: Reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine. Archives of General Psychiatry 69:580–587, 2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Valluri S, et al.: Impact of the 2004 Food and Drug Administration pediatric suicidality warning on antidepressant and psychotherapy treatment for new-onset depression. Medical Care 48:947–954, 2010.

    Article  PubMed  Google Scholar 

  29. Hammad TA, Mosholder AD: Suicide and antidepressants. Beware extrapolation from ecological data. BMJ 341:6844, 2010.

    Google Scholar 

  30. Zito JM, et al.: Prevalence variations in psychotropic treatment of children. Journal of Child Adolescent Psychopharmacology 8:99–105, 1998.

    Article  CAS  PubMed  Google Scholar 

  31. Barron TI, Bennett K, Feely J: A competing risks prescription refill model of compliance and persistence. Value in Health 13:796–804, 2010.

    Article  PubMed  Google Scholar 

  32. Fiske CT, et al.: Accuracy of pharmacy and coded-diagnosis information in identifying tuberculosis in patients with rheumatoid arthritis. Pharmacoepidemiology and Drug Safety 21:666–669, 2012.

    Article  PubMed  PubMed Central  Google Scholar 

  33. SAS, SAS 9.3, 2011, SAS Institute Inc: Cary, NC.

  34. Anghelescu IG, et al.: Therapeutic effects of venlafaxine extended release for patients with depressive and anxiety disorders in the German outpatient setting—results of 2 observational studies including 8500 patients. Fortschritte der Neurologie-Psychiatrie 77:646–654, 2009.

    Article  PubMed  Google Scholar 

  35. Wijlaars LP, Nazareth I, Petersen I: Trends in depression and antidepressant prescribing in children and adolescents: A cohort study in The Health Improvement Network (THIN). PLoS One 7:e33181, 2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Mann JJ, Kapur S: The emergence of suicidal ideation and behavior during antidepressant pharmacotherapy. Archives of General Psychiatry 48:1027–1033, 1991.

    Article  CAS  PubMed  Google Scholar 

  37. Culpepper L, et al.: Suicidality as a possible side effect of antidepressant treatment. Journal of Clinical Psychiatry 65:742–749, 2004.

    Article  PubMed  Google Scholar 

  38. Barry CL, Busch SH: News coverage of FDA warnings on pediatric antidepressant use and suicidality. Pediatrics 125:88–95, 2010.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA

    Saurabh Gupta

  2. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA

    Kenneth Ronald Gersing

  3. Department of Biostatistics & Bioinformatics, Duke University, Durham, NC, USA

    Alaattin Erkanli

  4. Duke Clinical Research Institute, Duke University, Durham, NC, USA

    Tal Burt

Authors
  1. Saurabh Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kenneth Ronald Gersing
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alaattin Erkanli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tal Burt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Saurabh Gupta.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gupta, S., Gersing, K.R., Erkanli, A. et al. Antidepressant Regulatory Warnings, Prescription Patterns, Suicidality and Other Aggressive Behaviors in Major Depressive Disorder and Anxiety Disorders. Psychiatr Q 87, 329–342 (2016). https://doi.org/10.1007/s11126-015-9389-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11126-015-9389-8

Keywords

Search

Navigation