Journal Mobile Options
Table of Contents
Vol. 76, No. 1, 2007
Issue release date: December 2006
Psychother Psychosom 2007;76:40–46
(DOI:10.1159/000096363)

Treatment-Associated Suicidal Ideation and Adverse Effects in an Open, Multicenter Trial of Fluoxetine for Major Depressive Episodes

Perlis R.H. · Beasley Jr. C.M. · Wines Jr. J.D. · Tamura R.N. · Cusin C. · Shear D. · Amsterdam J. · Quitkin F. · Strong R.E. · Rosenbaum J.F. · Fava M.
aDepression Clinical and Research Program, Massachusetts General Hospital and Harvard Medical School, Boston, Mass., bLilly Research Laboratories, Eli Lilly & Co., Indianapolis, Ind., cMcLean Hospital and Harvard Medical School, Belmont, Mass., dDepression Research Unit, University of Pennsylvania Medical Center, Philadelphia, Pa., eNew York State Psychiatric Institute, New York, N.Y., and fUniversity of Utah, Salt Lake City, Utah, USA

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Abstract

Background: Some reports suggest that a subset of depressed patients may experience suicidality – that is increase or emergence of suicidal ideation (SI) or behavior – after initiation of an antidepressant. The time course and clinical correlates of this phenomenon have not been characterized in detail. Method: We conducted a secondary analysis of a multicenter, prospective, open, 12-week trial of fluoxetine 20 mg in outpatients with nonpsychotic major depressive episodes. Adverse effects and other clinical features associated with the emergence of suicidality, defined using item 3 of the Hamilton Depression Rating Scale, were examined using Cox regression models. Results: Among 414 subjects without SI at baseline, 59 (14.3%) reported SI on at least 1 postbaseline visit. In a Cox regression, emergence of activation and worsening of depression severity were independently associated with emergence of SI, along with female gender, younger age and having thoughts that life was not worth living prior to treatment. Treatment response and remission were significantly less likely among subjects who developed SI. Conclusions: New SI was relatively common in this trial of fluoxetine and associated with the emergence of activation and overall symptomatic worsening. Whether prophylaxis against or aggressive treatment of adverse events can decrease emergence of SI merits further study.



Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Damluji NF, Ferguson JM: Paradoxical worsening of depressive symptomatology caused by antidepressants. J Clin Psychopharmacol 1988;8:347–349.
  2. Teicher MH, Glod C, Cole JO: Emergence of intense suicidal preoccupation during fluoxetine treatment. Am J Psychiatry 1990;147:207–210.
  3. King RA, Riddle MA, Chappell PB, Hardin MT, Anderson GM, Lombroso P, Scahill L: Emergence of self-destructive phenomena in children and adolescents during fluoxetine treatment. J Am Acad Child Adolesc Psychiatry 1991;30:179–186.
  4. Masand P, Gupta S, Dewan M: Suicidal ideation related to fluoxetine treatment. N Engl J Med 1991;324:420.
  5. Rothschild AJ, Locke CA: Reexposure to fluoxetine after serious suicide attempts by three patients: the role of akathisia. J Clin Psychiatry 1991;52:491–493.
  6. Wirshing WC, Van Putten T, Rosenberg J, Marder S, Ames D, Hicks-Gray T: Fluoxetine, akathisia and suicidality: is there a causal connection? Arch Gen Psychiatry 1992;49:580–581.
  7. US Food and Drug Administration: Psychopharmacological Drugs Advisory Committee Meeting No. 34. Rockville, 1991.
  8. Pompili M, Tondo L, Baldessarini RJ: Suicidal risk emerging during antidepressant treatment: recognition and intervention. Clin Neuropsychiatry 2005;2:66–72.
  9. Lane RM: SSRI-induced extrapyramidal side-effects and akathisia: implications for treatment. J Psychopharmacol 1998;12:192–214.
  10. Schweizer E, Dever A, Clary C: Suicide upon recovery from depression. A clinical note. J Nerv Ment Dis 1988;176:633–636.
  11. Hirschfeld RM: Suicide and antidepressant treatment. Arch Gen Psychiatry 2000;57:325–326.
  12. Benazzi F: Suicidal ideation and depressive mixed states. Psychother Psychosom 2005;74:61–62.
  13. Healy D: Lines of evidence on the risks of suicide with selective serotonin reuptake inhibitors. Psychother Psychosom 2003;72:71–79.
  14. Rihmer Z: Do SSRIs increase the risk of suicide among depressives even if they are taking only placebo? Psychother Psychosom 2003;72:357–358, author reply 359–360.
  15. Benazzi F: Do SSRIs cause suicide? Psychother Psychosom 2003;72:358–359, author reply 359–360.
  16. Balon R: Selective serotonin reuptake inhibitors and suicide: is the evidence, as with beauty, in the eye of the beholder? Psychother Psychosom 2003;72:293–299.
  17. Baldessarini RJ, Pompili M, Tondo L, Tsapakis E, Soldani F, Faedda GL: Antidepressants and suicidal behavior: are we hurting or helping? Clin Neuropsychiatry 2005;2:73–75.
  18. FDA Launches a Multi-Pronged Strategy to Strengthen Safeguards for Children Treated with Antidepressant Medications, 2004.
  19. Beasley CM Jr, Dornseif BE, Bosomworth JC, Sayler ME, Rampey AH Jr, Heiligenstein JH, Thompson VL, Murphy DJ, Masica DN: Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression. BMJ 1991;303:685–692.
  20. Khan A, Khan S, Kolts R, Brown WA: Suicide rates in clinical trials of SSRIs, other antidepressants and placebo: analysis of FDA reports. Am J Psychiatry 2003;160:790–792.
  21. Storosum JG, van Zwieten BJ, van den Brink W, Gersons BP, Broekmans AW: Suicide risk in placebo-controlled studies of major depression. Am J Psychiatry 2001;158:1271–1275.
  22. Goldstein DJ, Lu Y, Detke MJ, Wiltse C, Mallinckrodt C, Demitrack MA: Duloxetine in the treatment of depression: a double-blind placebo-controlled comparison with paroxetine. J Clin Psychopharmacol 2004;24:389–399.
  23. Simon GE, Savarino J, Operskalski B, Wang PS: Suicide risk during antidepressant treatment. Am J Psychiatry 2006;163:41–47.
  24. Horwitz RI, Singer BH, Makuch RW, Viscoli CM: Can treatment that is helpful on average be harmful to some patients? A study of the conflicting information needs of clinical inquiry and drug regulation. J Clin Epidemiol 1996;49:395–400.
  25. Fava GA: Can long-term treatment with antidepressant drugs worsen the course of depression? J Clin Psychiatry 2003;64:123–133.
  26. Teicher MH, Glod CA, Cole JO: Antidepressant drugs and the emergence of suicidal tendencies. Drug Saf 1993;8:186–212.
  27. Culpepper L, Davidson JR, Dietrich AJ, Goodman WK, Kroenke K, Schwenk TL: Suicidality as a possible side effect of antidepressant treatment. J Clin Psychiatry 2004;65:742–749.
  28. Tollefson GD, Rampey AH Jr, Beasley CM Jr, Enas GG, Potvin JH: Absence of a relationship between adverse events and suicidality during pharmacotherapy for depression. J Clin Psychopharmacol 1994;14:163–169.
  29. Jick H, Kaye JA, Jick SS: Antidepressants and the risk of suicidal behaviors. JAMA 2004;292:338–343.
  30. Stewart JW, Quitkin FM, McGrath PJ, Amsterdam J, Fava M, Fawcett J, Reimherr F, Rosenbaum J, Beasley C, Roback P: Use of pattern analysis to predict differential relapse of remitted patients with major depression during 1 year of treatment with fluoxetine or placebo. Arch Gen Psychiatry 1998;55:334–343.
  31. McGrath PJ, Stewart JW, Petkova E, Quitkin FM, Amsterdam JD, Fawcett J, Reimherr FW, Rosenbaum JF, Beasley CM Jr: Predictors of relapse during fluoxetine continuation or maintenance treatment of major depression. J Clin Psychiatry 2000;61:518–524.
  32. Quitkin FM, Petkova E, McGrath PJ, Taylor B, Beasley C, Stewart J, Amsterdam J, Fava M, Rosenbaum J, Reimherr F, Fawcett J, Chen Y, Klein D: When should a trial of fluoxetine for major depression be declared failed? Am J Psychiatry 2003;160:734–740.
  33. Spitzer RL, Williams JB, Gibbon M, First MB: Structured Clinical Interview for DSM-III-R Patient Edition (SCID-P, 9/1/89 version). New York, Biometrics Research Department, New York State Psychiatric Institute, 1989.
  34. McGlashan T: The Documentation of Clinical Psychotropic Drug Trials. Rockville, MD, USA, National Institute of Mental Health, 1973.
  35. Bech P: The Bech-Rafaelsen Melancholia Scale (MES) in clinical trials of therapies in depressive disorders: a 20-year review of its use as outcome measure. Acta Psychiatr Scand 2002;1064:252–264.

    External Resources

  36. SAS Institute Inc: SAS Version 8. Cary, SAS Institute Inc, 1999.
  37. Preda A, MacLean RW, Mazure CM, Bowers MB Jr: Antidepressant-associated mania and psychosis resulting in psychiatric admissions. J Clin Psychiatry 2001;621:30–33.

    External Resources

  38. Ghaemi SN, Hsu DJ, Soldani F, Goodwin FK: Antidepressants in bipolar disorder: the case for caution. Bipolar Disord 2003;56:421–433.

    External Resources

  39. Lepine JP, Chignon JM, Teherani M: Suicidal behavior and onset of panic disorder. Arch Gen Psychiatry 1991;487:668–669.
  40. Placidi GP, Oquendo MA, Malone KM, Brodsky B, Ellis SP, Mann JJ: Anxiety in major depression: relationship to suicide attempts. Am J Psychiatry 2000;15710:1614–1618.

    External Resources

  41. Mann JJ, Waternaux C, Haas GL, Malone KM: Toward a clinical model of suicidal behavior in psychiatric patients. Am J Psychiatry 1999;1562:181–189.
  42. Grant BF, Hasin DS: Suicidal ideation among the United States drinking population: results from the National Longitudinal Alcohol Epidemiologic Survey. J Stud Alcohol 1999;603:422–429.
  43. Reynolds WM: Psychometric characteristics of the Adult Suicidal Ideation Questionnaire in college students. J Pers Assess 1991;562:289–307.

    External Resources

  44. Beck AT, Brown GK, Steer RA: Psychometric characteristics of the Scale for Suicide Ideation with psychiatric outpatients. Behav Res Ther 1997;3511:1039–1046.

    External Resources

  45. Brown GK, Beck AT, Steer RA, Grisham JR: Risk factors for suicide in psychiatric outpatients: a 20-year prospective study. J Consult Clin Psychol 2000;683:371–377.
  46. Brown GK: A review of suicide assessment measures for intervention research with adults and older adults. 2000. http://www.nih.gov/suicideresearch/adultsuicide.pdf
  47. Goodwin FK, Fireman B, Simon GE, Hunkeler EM, Lee J, Revicki D: Suicide risk in bipolar disorder during treatment with lithium and divalproex. JAMA 2003;290:1467–1473.
  48. Jick SS, Dean AD, Jick H: Antidepressants and suicide. BMJ 1995;310:215–218.
  49. Hu XH, Bull SA, Hunkeler EM, Ming E, Lee JY, Fireman B, Markson LE: Incidence and duration of side effects and those rated as bothersome with selective serotonin reuptake inhibitor treatment for depression: patient report versus physician estimate. J Clin Psychiatry 2004;65:959–965.
  50. Matthews JD, Fava M: Risk of suicidality in depression with serotonergic antidepressants. Ann Clin Psychiatry 2000;12:43–50.


Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50