Hostname: page-component-8448b6f56d-dnltx Total loading time: 0 Render date: 2024-04-25T03:01:38.758Z Has data issue: false hasContentIssue false
  • English
  • Français

Evaluating suicide-related adverse events in clinical trials of fluoxetine treatment in adults for indications other than major depressive disorder

Published online by Cambridge University Press:  20 July 2007

SITRA TAUSCHER-WISNIEWSKI ,
DAMON DISCH ,
JOHN PLEWES ,
SUSAN BALL  and
CHARLES M. BEASLEY Jr
SITRA TAUSCHER-WISNIEWSKI*
Affiliation:
Eli Lilly and Company, Indianapolis, Indiana, USA Medical University of Vienna, Vienna, Austria
DAMON DISCH
Affiliation:
Eli Lilly and Company, Indianapolis, Indiana, USA
JOHN PLEWES
Affiliation:
Eli Lilly and Company, Indianapolis, Indiana, USA
SUSAN BALL
Affiliation:
Eli Lilly and Company, Indianapolis, Indiana, USA
CHARLES M. BEASLEY Jr
Affiliation:
Eli Lilly and Company, Indianapolis, Indiana, USA
*
*Address for correspondence: Sitra Tauscher-Wisniewski, M.D., Eli Lilly and Company, Drop Code 1730, Indianapolis, IN46285, USA.  (Email: sitratauscher@lilly.com)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

The association between treatment-emergent suicidality as an adverse event and fluoxetine treatment was examined using a fluoxetine double-blind placebo-controlled database of clinical trials for indications other than major depressive disorder.

Method

The database consisted of 53 trials for 16 different indications (14 psychiatric, two non-psychiatric). Within each study, patient adverse event reports and narratives were searched extensively for treatment-emergent thoughts and behaviors associated with suicide. The incidence of adverse events was classified using Food and Drug Administration (FDA) codes for completed suicide, preparatory acts, suicidal ideation and the summary category of ‘all suicidality.’ The risk difference and risk ratios between fluoxetine and placebo treatment arms were compared using Mantel–Haenszel methods.

Results

Within this large database, patients were randomly assigned to receive treatment with either fluoxetine (n=7066) or placebo (n=4382). Treatment groups did not differ in their risk for the emergence of suicidality for any FDA code; the risk ratio for ‘all suicidality’ was 0·82 (p=0·406), and there were no completed suicides in either group. Analyses based on treatment indication (bulimia, obsessive-compulsive disorder, other psychiatric and non-psychiatric illness) also showed no significant difference in risk between treatment groups. When examined by age categories (18–24, 25–30, 31–65, and ⩾65 years), fluoxetine and placebo treatments did not result in significant risk difference for the emergence of suicidality.

Conclusions

The risk of treatment-emergent suicidality does not appear to be associated with fluoxetine treatment for adults with various non-MDD conditions.

Type
Original Article
Information
Psychological Medicine , Volume 37 , Issue 11 , November 2007 , pp. 1585 - 1593
Copyright
Copyright © Cambridge University Press 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Agresti, A. (1984). Analysis of Ordinal Categorical Data. Wiley: New York.Google Scholar
APA (1994). Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSM-IV). American Psychiatric Association: Washington, DC.Google Scholar
Barak, Y. & Aizenberg, D. (2006). Association between antidepressant prescribing and suicide in Israel. Journal of Affective Diseases 21, 281–284.Google ScholarPubMed
Beasley, C. M. Jr., Dornseif, B. E., Bosomworth, J. C., Sayler, M. E., Rampey, A. H. Jr., Heiligenstein, J. H., Thompson, V. L., Murphy, D. J. & Massica, D. N. (1991). Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression. British Medical Journal 303, 685–692.CrossRefGoogle ScholarPubMed
Beasley, C. M. Jr., Potvin, J. H., Masica, D. N., Wheadon, D. E., Dornseif, B. E. & Genduso, L. A. (1992). Fluoxetine: no association with suicidality in obsessive-compulsive disorder. Journal of Affective Disorders 24, 1–10.CrossRefGoogle ScholarPubMed
DerSimonian, R. & Laird, N. (1986). Meta-analysis in clinical trials. Controlled Clinical Trials 7, 177–188.CrossRefGoogle ScholarPubMed
Didham, R. C., McConnell, D. W., Blair, H. J. & Reith, D. M. (2005). Suicide and self-harm following prescription of SSRIs and other antidepressants: confounding by indication. British Journal of Clinical Pharmacology 60, 519–525.CrossRefGoogle ScholarPubMed
Fergusson, D., Doucette, S., Glass, K. C., Shapiro, S., Healy, D., Hebert, P. & Hutton, B. (2005). Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomized controlled trials. British Medical Journal 330, 396–399. Erratum in: British Medical Journal 330, 653.CrossRefGoogle Scholar
Gibbons, R. D., Hur, K., Bhaumik, D. K. & Mann, J. J. (2005). The relationship between antidepressant medication use and rate of suicide. Archives of General Psychiatry 62, 165–172.CrossRefGoogle Scholar
Greenland, S. & Robins, J. M. (1985). Estimation of a common effect parameter from sparse follow-up data. Biometrics 41, 55–68.CrossRefGoogle ScholarPubMed
Gunnell, D., Saperia, J. & Ashby, D. (2005). Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomized controlled trials submitted to the MHRA's safety review. British Medical Journal 330, 385–388. [Erratum in: British Medical Journal (2006) 333, 30.]CrossRefGoogle Scholar
Hammad, T. A., Laughren, T. & Racoosin, J. (2006). Suicidality in pediatric patients treated with antidepressant drugs. Archives of General Psychiatry 63, 332–339.CrossRefGoogle ScholarPubMed
Isaacson, G. (2000). Suicide prevention – a medical breakthrough? Acta Psychiatrica Scandinavica 102, 113–117.CrossRefGoogle Scholar
Laughren, T. P. (2006). Briefing document for 13 December meeting of Psychopharmacologic Drugs Advisory Committee (http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4272b1-index.htm).Google Scholar
Sato, T. (1989). On the variance estimator for the Mantel-Haenszel risk difference. Biometrics 45, 1323–1324.Google Scholar
Simon, G. E. (2006). How can we know whether antidepressants increase suicide risk? American Journal of Psychiatry 163, 1861–1862.CrossRefGoogle ScholarPubMed
US Food and Drug Administration (2004). FDA Statement on Recommendations of the Psychopharmacologic Drugs and Pediatric Advisory Committees (http://www.fda.gov/bbs/topics/news2004/NEW0116.html).Google Scholar
Wheadon, D. E., Rampey, A. H. Jr., Thompson, V. L., Potvin, J. H., Masica, D. N. & Beasley, C. M. Jr. (1992). Lack of association between fluoxetine and suicidality in bulimia nervosa. Journal of Clinical Psychiatry 53, 235–241.Google ScholarPubMed