Suicides and Suicide Attempts during Long-Term Treatment with Antidepressants: A Meta-Analysis of 29 Placebo-Controlled Studies Including 6,934 Patients with Major Depressive Disorder

Psychotherapy and Psychosomatics

Volumn 85, Issue 3, 2016, Pages 171-179

  Braun, Cora ^a   Bschor, Tom ^c,d   Franklin, Jeremy ^b   Baethge, Christopher ^a,b  

^a Department of Psychiatry and Psychotherapy ^*  (Germany)

^b UNIVERSITY HOSPITAL OF COLOGNE   (Germany)

^c Schlosspark Hospital   (Germany)

^d UNIVERSITY OF DRESDEN MEDICAL SCHOOL   (Germany)

Author keywords

Antidepressants; Maintenance; RCT; Suicidality; Suicide; Suicide attempt

Indexed keywords

ANTIDEPRESSANT AGENT; PLACEBO;

ARTICLE; HUMAN; INCIDENCE; LONG TERM CARE; MAJOR DEPRESSION; MEDLINE; META ANALYSIS; PRIORITY JOURNAL; SUICIDE; SUICIDE ATTEMPT; DEPRESSIVE DISORDER, MAJOR; RANDOMIZED CONTROLLED TRIAL (TOPIC); RISK FACTOR; STATISTICS AND NUMERICAL DATA;

ANTIDEPRESSIVE AGENTS; DEPRESSIVE DISORDER, MAJOR; HUMANS; LONG-TERM CARE; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RISK FACTORS; SUICIDE, ATTEMPTED;

EID: 84968835315     PISSN: 00333190     EISSN: 14230348     Source Type: Journal    
DOI: 10.1159/000442293     Document Type: Article

References (70)

1. Angst J, Hengartner MP, Gamma A, von Zerssen D, Angst F: Mortality of 403 patients with mood disorders 48 to 52 years after their psychiatric hospitalisation. Eur Arch Psychiatry Clin Neurosci 2013; 263: 425-434.
2. Bradvik L, Mattisson C, Bogren M, Nettelbladt P: Long-term suicide risk of depression in the Lundby cohort 1947-1997-severity and gender. Acta Psychiatr Scand 2008; 117: 185-191.
3. Inskip HM, Harris EC, Barraclough B: Lifetime risk of suicide for affective disorder, alcoholism and schizophrenia. Br J Psychiatry 1998; 172: 35-37.
4. Isometsä E: Suicidal behaviour in mood disorders-who, when, and why? Can J Psychiatry 2014; 59: 120-130.
5. Bschor T, Bauer M, Adli M: Chronic and treatment resistant depression: diagnosis and stepwise therapy. Dtsch Arztebl Int 2014; 111: 766-775.
6. Bauer M, Pfennig A, Severus E, Whybrow PC, Angst J, Moller HJ: World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders. Part 1. Update 2013 on the acute and continuation treatment of unipolar depressive disorders. World J Biol Psychiatry 2013; 14: 334-385.
7. Wasserman D, Rihmer Z, Rujescu D, Sarchiapone M, Sokolowski M, Titelman D, Zalsman G, Zemishlany Z, Carli V: The European Psychiatric Association (EPA) guidance on suicide treatment and prevention. Eur Psychiatry 2012; 27: 129-141.
8. Angst J, Angst F, Gerber-Werder R, Gamma A: Suicide in 406 mood-disorder patients with and without long-term medication: A 40 to 44 years' follow-up. Arch Suicide Res 2005; 9: 279-300.
9. Möller HJ: Is there evidence for negative effects of antidepressants on suicidality in depressive patients? A systematic review. Eur Arch Psychiatry Clin Neurosci 2006; 256: 476-496.
10. Gründer G, Veselinovic T, Paulzen M: Antidepressive agents and suicidal tendencies. Nervenarzt 2014; 85: 1108-1116.
11. Kamat MA, Edgar L, Niblock P, McDowell C, Kelly CB: Association between antidepressant prescribing and suicide rates in OECD countries: an ecological study. Pharmacopsychiatry 2014; 47: 18-21.
12. Oquendo MA, Currier D, Mann JJ: Prospective studies of suicidal behavior in major depressive and bipolar disorders: what is the evidence for predictive risk factors? Acta Psychiatr Scand 2006; 114: 151-158.
13. Schaffer A, Isometsa ET, Tondo L, D HM, Turecki G, Reis C, Cassidy F, Sinyor M, Azorin JM, Kessing LV, Ha K, Goldstein T, Weizman A, Beautrais A, Chou YH, Diazgranados N, Levitt AJ, Zarate CA Jr, Rihmer Z, Yatham LN: International Society for Bipolar Disorders Task Force on Suicide: meta-analyses and meta-regression of correlates of suicide attempts and suicide deaths in bipolar disorder. Bipolar Disord 2015; 17: 1-16.
14. Beghi M, Rosenbaum JF, Cerri C, Cornaggia CM: Risk factors for fatal and nonfatal repetition of suicide attempts: A literature review. Neuropsychiatr Dis Treat 2013; 9: 1725-1736.
15. Baethge C: A bold meta-analysis on suicidality in bipolar disorder. Bipolar Disord 2015; 17: 17-18.
16. de Leon J, Baca-Garcia E, Blasco-Fontecilla H: From the serotonin model of suicide to a mental pain model of suicide. Psychother Psychosom 2015; 84: 323-329.
17. Gibbons RD, Brown CH, Hur K, Davis J, Mann JJ: Suicidal thoughts and behavior with antidepressant treatment: reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine. Arch Gen Psychiatry 2012; 69: 580-587.
18. Gunnell D, Saperia J, Ashby D: Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomised controlled trials submitted to the MHRA's safety review. BMJ 2005; 330: 385.
19. Hammad TA, Laughren TP, Racoosin JA: Suicide rates in short-term randomized controlled trials of newer antidepressants. J Clin Psychopharmacol 2006; 26: 203-207.
20. Khan A, Warner HA, Brown WA: Symptom reduction and suicide risk in patients treated with placebo in antidepressant clinical trials: an analysis of the Food and Drug Administration database. Arch Gen Psychiatry 2000; 57: 311-317.
21. Khan A, Khan SR, Leventhal RM, Brown WA: Symptom reduction and suicide risk in patients treated with placebo in antidepressant clinical trials: A replication analysis of the Food and Drug Administration database. Int J Neuropsychopharmacol 2001; 4: 113-118.
22. 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.
23. Fergusson D, Doucette S, Glass KC, Shapiro S, Healy D, Hebert P, Hutton B: Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials. BMJ 2005; 330: 396.
24. 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.
25. Geddes JR, Carney SM, Davies C, Furukawa TA, Kupfer DJ, Frank E, Goodwin GM: Relapse prevention with antidepressant drug treatment in depressive disorders: A systematic review. Lancet 2003; 361: 653-661.
26. Glue P, Donovan MR, Kolluri S, Emir B: Meta-analysis of relapse prevention antidepressant trials in depressive disorders. Aust NZ J Psychiatry 2010; 44: 697-705.
27. Kok RM, Heeren TJ, Nolen WA: Continuing treatment of depression in the elderly: A systematic review and meta-analysis of doubleblinded randomized controlled trials with antidepressants. Am J Geriatr Psychiatry 2011; 19: 249-255.
28. Williams N, Simpson AN, Simpson K, Nahas Z: Relapse rates with long-term antidepressant drug therapy: A meta-analysis. Hum Psychopharmacol 2009; 24: 401-408.
29. Lane PW: Meta-analysis of incidence of rare events. Stat Methods Med Res 2013; 22: 117-132.
30. Blumenthal JA, Babyak MA, Doraiswamy PM, Watkins L, Hoffman BM, Barbour KA, Herman S, Craighead WE, Brosse AL, Waugh R, Hinderliter A, Sherwood A: Exercise and pharmacotherapy in the treatment of major depressive disorder. Psychosom Med 2007; 69: 587-596.
31. Cheung A, Kusumakar V, Kutcher S, Dubo E, Garland J, Weiss M, Kiss A, Levitt A: Maintenance study for adolescent depression. J Child Adolesc Psychopharmacol 2008; 18: 389-394.
32. Doogan DP, Caillard V: Sertraline in the prevention of depression. Br J Psychiatry 1992; 160: 217-222.
33. Emslie GJ, Kennard BD, Mayes TL, Nightingale-Teresi J, Carmody T, Hughes CW, Rush AJ, Tao R, Rintelmann JW: Fluoxetine versus placebo in preventing relapse of major depression in children and adolescents. Am J Psychiatry 2008; 165: 459-467.
34. Feiger AD, Bielski RJ, Bremner J, Heiser JF, Trivedi M, Wilcox CS, Roberts DL, Kensler TT, McQuade RD, Kaplita SB, Archibald DG: Double-blind, placebo-substitution study of nefazodone in the prevention of relapse during continuation treatment of outpatients with major depression. Int Clin Psychopharmacol 1999; 14: 19-28.
35. Goodwin GM, Emsley R, Rembry S, Rouillon F: Agomelatine prevents relapse in patients with major depressive disorder without evidence of a discontinuation syndrome: A 24-week randomized, double-blind, placebocontrolled trial. J Clin Psychiatry 2009; 70: 1128-1137.
36. Kamijima K, Burt T, Cohen G, Arano I, Hamasaki T: A placebo-controlled, randomized withdrawal study of sertraline for major depressive disorder in Japan. Int Clin Psychopharmacol 2006; 21: 1-9.
37. Kishimoto A, Mizukawa R, Matsuzaki F, Hazama H, Kamase H, Tanaka K, Kunimoto N: Prophylactic effect of mianserin on recurrent depression. Acta Psychiatr Scand 1994; 89: 46-51.
38. Klysner R, Bent-Hansen J, Hansen HL, Lunde M, Pleidrup E, Poulsen DL, Andersen M, Petersen HE: Efficacy of citalopram in the prevention of recurrent depression in elderly patients: placebo-controlled study of maintenance therapy. Br J Psychiatry 2002; 181: 29-35.
39. Kornstein SG, Bose A, Li D, Saikali KG, Gandhi C: Escitalopram maintenance treatment for prevention of recurrent depression: A randomized, placebo-controlled trial. J Clin Psychiatry 2006; 67: 1767-1775.
40. Lepine JP, Caillard V, Bisserbe JC, Troy S, Hotton JM, Boyer P: A randomized, placebocontrolled trial of sertraline for prophylactic treatment of highly recurrent major depressive disorder. Am J Psychiatry 2004; 161: 836-842.
41. Licht RW: Is it possible to evaluate true prophylactic efficacy of antidepressants in severely ill patients with recurrent depression? Lessons from a placebo-controlled trial. The fifth trial of the Danish University Antidepressant Group (DUAG-5). J Affect Disord 2013; 148: 286-290.
42. Lustman PJ, Clouse RE, Nix BD, Freedland KE, Rubin EH, McGill JB, Williams MM, Gelenberg AJ, Ciechanowski PS, Hirsch IB: Sertraline for prevention of depression recurrence in diabetes mellitus: A randomized, double-blind, placebo-controlled trial. Arch Gen Psychiatry 2006; 63: 521-529.
43. McGrath PJ, Stewart JW, Quitkin FM, Chen Y, Alpert JE, Nierenberg AA, Fava M, Cheng J, Petkova E: Predictors of relapse in a prospective study of fluoxetine treatment of major depression. Am J Psychiatry 2006; 163: 1542-1548.
44. Montgomery SA, Rasmussen JG, Tanghoj P: A 24-week study of 20 mg citalopram, 40 mg citalopram, and placebo in the prevention of relapse of major depression. Int Clin Psychopharmacol 1993; 8: 181-188.
45. Montgomery SA, Dunbar G: Paroxetine is better than placebo in relapse prevention and the prophylaxis of recurrent depression. Int Clin Psychopharmacol 1993; 8: 189-195.
46. Group OADI: How long should the elderly take antidepressants? A double-blind placebo-controlled study of continuation/prophylaxis therapy with dothiepin. Br J Psychiatry 1993; 162: 175-182.
47. Perahia DG, Gilaberte I, Wang F, Wiltse CG, Huckins SA, Clemens JW, Montgomery SA, Montejo AL, Detke MJ: Duloxetine in the prevention of relapse of major depressive disorder: A double-blind placebo-controlled study. Br J Psychiatry 2006; 188: 346-353.
48. Reynolds CF, 3rd, Frank E, Perel JM, Imber SD, Cornes C, Miller MD, Mazumdar S, Houck PR, Dew MA, Stack JA, Pollock BG, Kupfer DJ: Nortriptyline and interpersonal psychotherapy as maintenance therapies for recurrent major depression: A randomized controlled trial in patients older than 59 years. JAMA 1999; 281: 39-45.
49. Robinson M, Oakes TM, Raskin J, Liu P, Shoemaker S, Nelson JC: Acute and longterm treatment of late-life major depressive disorder: duloxetine versus placebo. Am J Geriatr Psychiatry 2014; 22: 34-45.
50. Rosenthal JZ, Boyer P, Vialet C, Hwang E, Tourian KA: Efficacy and safety of desvenlafaxine 50 mg/d for prevention of relapse in major depressive disorder: A randomized controlled trial. J Clin Psychiatry 2013; 74: 158-166.
51. Rouillon F, Phillips R, Serrurier D, Ansart E, Gerard MJ: Recurrence of unipolar depression and efficacy of maprotiline. Encephale 1989; 15: 527-534.
52. Schmidt ME, Fava M, Robinson JM, Judge R: The efficacy and safety of a new enteric-coated formulation of fluoxetine given once weekly during the continuation treatment of major depressive disorder. J Clin Psychiatry 2000; 61: 851-857.
53. Shiovitz T, Greenberg WM, Chen C, Forero G, Gommoll CP: A randomized, doubleblind, placebo-controlled trial of the efficacy and safety of levomilnacipran ER 40-120 mg/day for prevention of relapse in patients with major depressive disorder. Innov Clin Neurosci 2014; 11: 10-22.
54. Stewart JW, Tricamo E, McGrath PJ, Quitkin FM: Prophylactic efficacy of phenelzine and imipramine in chronic atypical depression: likelihood of recurrence on discontinuation after 6 months' remission. Am J Psychiatry 1997; 154: 31-36.
55. Terra JL, Montgomery SA: Fluvoxamine prevents recurrence of depression: results of a long-term, double-blind, placebo-controlled study. Int Clin Psychopharmacol 1998; 13: 55-62.
56. Thase ME, Nierenberg AA, Keller MB, Panagides J: Efficacy of mirtazapine for prevention of depressive relapse: A placebo-controlled double-blind trial of recently remitted highrisk patients. J Clin Psychiatry 2001; 62: 782-788.
57. Versiani M, Mehilane L, Gaszner P, Arnaud-Castiglioni R: Reboxetine, a unique selective NRI, prevents relapse and recurrence in longterm treatment of major depressive disorder. J Clin Psychiatry 1999; 60: 400-406.
58. Weihs KL, Houser TL, Batey SR, Ascher JA, Bolden-Watson C, Donahue RM, Metz A: Continuation phase treatment with bupropion SR effectively decreases the risk for relapse of depression. Biol Psychiatry 2002; 51: 753-761.
59. Maund E, Tendal B, Hrobjartsson A, Jorgensen KJ, Lundh A, Schroll J, Gotzsche PC: Benefits and harms in clinical trials of duloxetine for treatment of major depressive disorder: comparison of clinical study reports, trial registries, and publications. BMJ 2014; 348:g3510.
60. Hughes S, Cohen D, Jaggi R: Differences in reporting serious adverse events in industry sponsored clinical trial registries and journal articles on antidepressant and antipsychotic drugs: A cross-sectional study. BMJ Open 2014; 4:e005535.
61. Rouillon F, Serrurier D, Miller HD, Gerard MJ: Prophylactic efficacy of maprotiline on unipolar depression relapse. J Clin Psychiatry 1991; 52: 423-431.
62. White N, Litovitz T, Clancy C: Suicidal antidepressant overdoses: A comparative analysis by antidepressant type. J Med Toxicol 2008; 4: 238-250.
63. Henry JA, Antao CA: Suicide and fatal antidepressant poisoning. Eur J Med 1992; 1: 343-348.
64. Michel K, Arestegui G, Spuhler T: Suicide with psychotropic drugs in Switzerland. Pharmacopsychiatry 1994; 27: 114-118.
65. Stone M, Laughren T, Jones ML, Levenson M, Holland PC, Hughes A, Hammad TA, Temple R, Rochester G: Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to us food and drug administration. BMJ 2009; 339:b2880.
66. Carpenter DJ, Fong R, Kraus JE, Davies JT, Moore C, Thase ME: Meta-analysis of efficacy and treatment-emergent suicidality in adults by psychiatric indication and age subgroup following initiation of paroxetine therapy: A complete set of randomized placebo-controlled trials. J Clin Psychiatry 2011; 72: 1503-1514.
67. Fava GA: Rational use of antidepressant drugs. Psychother Psychosom 2014; 83: 197-204.
68. El-Mallakh RS, Briscoe B: Studies of longterm use of antidepressants: how should the data from them be interpreted? CNS Drugs 2012; 26: 97-109.
69. Fava GA, Guidi J, Rafanelli C, Sonino N: The clinical inadequacy of evidence-based medicine and the need for a conceptual framework based on clinical judgment. Psychother Psychosom 2015; 84: 1-3.
70. Lewitzka U, Severus E, Bauer R, Ritter P, Muller-Oerlinghausen B, Bauer M: The suicide prevention effect of lithium: more than 20 years of evidence-A narrative review. Int J Bipolar Disord 2015; 3: 32.