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Differences in Adverse Effect Reporting in Placebo Groups in SSRI and Tricyclic Antidepressant Trials

A Systematic Review and Meta-Analysis

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Abstract

Background: Biases in adverse effect reporting in randomized controlled trials (RCTs) [e.g. due to investigator expectations or assessment quality] can be quantified by studying the rates of adverse events reported in the placebo arms of such trials.

Objective: We compared the rates of adverse effects reported in the placebo arms of tricyclic antidepressant (TCA) trials and placebo arms of selective serotonin reuptake inhibitor (SSRI) trials.

Methods: We conducted a literature search for RCTs across PUBMED, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL). Only studies allowing adverse effect analysis were included. Publication year ranged from 1981 to 2007.

Results: Our systematic review and meta-analysis included 143 placebo-controlled RCTs and data from 12 742 patients. Only 21% of studies used structured and systematic adverse effect ascertainment strategies. The way in which trials recorded adverse events influenced the rate of adverse effects substantially. Systematic assessment led to higher rates than less systematic assessment. Far more adverse effects were reported in TCA-placebo groups compared with SSRI-placebo groups, e.g. dry mouth (odds ratio [OR] = 3.5; 95% CI 2.9, 4.2); drowsiness (OR = 2.7; 95% CI 2.2, 3.4); constipation (OR = 2.7; 95% CI 2.1,3.6); sexual problems (OR =2.3; 95% CI 1.5,3.5). Regression analyses controlling for various influencing factors confirmed the results.

Conclusion: Adverse effect profiles reported in clinical trials are strongly influenced by expectations from investigators and patients. This difference cannot be attributed to ascertainment methods. Adverse effect patterns of the drug group are closely related to adverse effects of the placebo group. These results question the validity of the assumption that adverse effects in placebo groups reflect the ‘drug-unspecific effects’.

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Notes

  1. 1The full version of the coding scheme and the quality rating are provided as online Supplemental Digital Content 1, http://links.adisonline.com/DSZ/A17.

  2. 2Sheikh et al.[121] reported two placebo groups, therefore this study was included twice.

References

  1. Cipriani A, Brambilla P, Furukawa TA, et al. Fluoxetine versus other types of pharmacotherapy for depression. Cochrane Database Syst Rev 2005; (4): CD004185

  2. Van Marwijk HWJ, Bijl D, Adegrave HJ, et al. Anti-depressant prescription for depression in general practice in the Netherlands. Pharm World Sci 2001; 23: 46–9

    Article  PubMed  Google Scholar 

  3. Burnier M. Medication adherence and persistence as the cornerstone of effective antihypertensive therapy. Am J Hypertens 2006; 19: 1190–6

    Article  PubMed  Google Scholar 

  4. Ammassari A, Murri R, Pezzotti P, et al. Self-reported symptoms and medication side effects influence adherence to highly active antiretroviral therapy in persons with HIV infection. J Acquir Immune Defic Syndr 2001; 28: 445–9

    PubMed  CAS  Google Scholar 

  5. Barsky AJ, Saintfort R, Rogers MP, et al. Nonspecific medication side effects and the nocebo phenomenon. JAMA 2002; 287: 622–7

    Article  PubMed  Google Scholar 

  6. Rief W, Avorn J, Barsky AJ. Medication-attributed adverse effects in placebo groups: implications for assessment of adverse effects. Arch Intern Med 2006; 166(2): 155–60

    Article  PubMed  Google Scholar 

  7. Sheftell FD, Feleppa M, Tepper SJ, et al. Assessment of adverse events associated with triptans-methods of assessment influence the results. Headache 2004; 44: 978–82

    Article  PubMed  Google Scholar 

  8. Gartlehner G, Thieda P, Hansen R, et al. Comparative risk for harms of second-generation antidepressants: a systematic review and meta-analysis. Drug Saf 2008; 31: 851–65

    Article  PubMed  CAS  Google Scholar 

  9. Moher D, Cook DJ, Eastwood S, et al. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of reporting of meta-analyses. Lancet 1999; 354(9193): 1896–900

    Article  PubMed  CAS  Google Scholar 

  10. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996; 17: 1–12

    Article  PubMed  CAS  Google Scholar 

  11. Kyle CJ, Petersen HEH, Overo KF. Comparison of the tolerability and efficacy of citalopram and amitriptyline in elderly depressed patients treated in general practice. Depress Anxiety 1998; 8: 147–53

    Article  PubMed  CAS  Google Scholar 

  12. Liccardi G, Senna G, Russo M, et al. Evaluation of the nocebo effect during oral challenge in patients with adverse drug reactions. J Investig Allergol Clin Immunol 2004; 14: 104–7

    PubMed  CAS  Google Scholar 

  13. Walsh BT, Seidman SN, Sysko R, et al. Placebo response in studies of major depression: variable, substantial, and growing. JAMA 2002; 287: 1840–7

    Article  PubMed  Google Scholar 

  14. Allgulander C, Dahl AA, Austin C, et al. Efficacy of sertraline in a 12-week trial for generalized anxiety disorder. Am J Psychiatry 2004 Sep; 161(9): 1642–9

    Article  PubMed  Google Scholar 

  15. Clomipramine in the treatment of patients with obsessive-compulsive disorder. The Clomipramine Collaborative Study Group. Arch Gen Psychiatry 1991 Aug; 48(8): 730–8

    Article  Google Scholar 

  16. Asnis GM, Hameedi FA, Goddard AW, et al. Fluvoxamine in the treatment of panic disorder: a multi-center, double-blind, placebo-controlled study in outpatients. Psychiatry Res 2001 Aug 5; 103(1): 1–14

    Article  PubMed  CAS  Google Scholar 

  17. Baldwin D, Bobes J, Stein DJ, et al. Paroxetine in social phobia/social anxiety disorder: randomised, double-blind, placebo-controlled study. Br J Psychiatry 1999; 175: 120–6

    Article  PubMed  CAS  Google Scholar 

  18. Baldwin DS, Huusom AKT, Maehlum E. Escitalopram and paroxetine in the treatment of generalised anxiety disorder: randomised, placebo-controlled, double-blind study. Br J Psychiatry 2006; 189: 264–72

    Article  PubMed  Google Scholar 

  19. Ballenger JC, Wheadon DE, Steiner M, et al. Doubleblind, fixed-dose, placebo-controlled study of paroxetine in the treatment of panic disorder. Am J Psychiatry 1998; 155(1): 36–42

    PubMed  CAS  Google Scholar 

  20. Benjamin J, Ben Zion IZ, Karbofsky E, et al. Double-blind placebo-controlled pilot study of paroxetine for specific phobia. Psychopharmacology (Berl) 2000 Apr; 149(2): 194–6

    Article  CAS  Google Scholar 

  21. Berard R, Fong R, Carpenter DJ, et al. An international, multicenter, placebo-controlled trial of paroxetine in adolescents with major depressive disorder. J Child Adolesc Psychopharmacol 2006 Feb–Apr; 16(1–2): 59–75

    Article  PubMed  Google Scholar 

  22. Birmaher B, Axelson DA, Monk K, et al. Fluoxetine for the treatment of childhood anxiety disorders. J Am Acad Child Adolesc Psychiatry 2003; 42(4): 415–23

    Article  PubMed  Google Scholar 

  23. Blomhoff S, Haug TT, Hellström K, et al. Randomised controlled general practice trial of sertraline, exposure therapy and combined treatment in generalised social phobia. Br J Psychiatry 2001; 178: 23–30

    Article  Google Scholar 

  24. Blumenfield M, Levy NB, Spinowitz B, et al. Fluoxetine in depressed patients on dialysis. Int J Psychiatry Med 1997; 27(1): 71–80

    Article  PubMed  CAS  Google Scholar 

  25. Brady K, Pearlstein T, Asnis GM, et al. Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial. JAMA 2000; 283(14): 1837–44

    Article  PubMed  CAS  Google Scholar 

  26. Brawman-Mintzer O, Knapp RG, Rynn M, et al. Sertraline treatment for generalized anxiety disorder: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry 2006; 67(6): 874–81

    Article  PubMed  CAS  Google Scholar 

  27. Brown ES, Vigil L, Khan DA, et al. A randomized trial of citalopram versus placebo in outpatients with asthma and major depressive disorder: a proof of concept study. Biol Psychiatry 2005; 58(11): 865–70

    Article  PubMed  CAS  Google Scholar 

  28. Burke WJ, Gergel I, Bose A. Fixed-dose trial of the single isomer SSRI escitalopram in depressed outpatients. J Clin Psychiatry 2002; 63(4): 331–6

    Article  PubMed  CAS  Google Scholar 

  29. Chouinard G, Goodman W, Greist J, et al. Results of a double-blind placebo controlled trial of a new serotonin uptake inhibitor, sertraline, in the treatment of obsessive-compulsive disorder. Psychopharmacol Bull 1990; 26(3): 279–84

    PubMed  CAS  Google Scholar 

  30. Claghorn JL, Kiev A, Rickels K, et al. Paroxetine versus placebo: a double-blind comparison in depressed patients. J Clin Psychiatry 1992; 53(12): 434–8

    PubMed  CAS  Google Scholar 

  31. Davidson J, Kudler H, Smith R, et al. Treatment of post-traumatic stress disorder with amitriptyline and placebo. Arch Gen Psychiatry 1990 Mar; 47(3): 259–66

    Article  PubMed  CAS  Google Scholar 

  32. Davidson J, Yaryura-Tobias J, DuPont R, et al. Fluvoxamine-controlled release formulation for the treatment of generalized social anxiety disorder. J Clin Psychopharmacol 2004 Apr; 24(2): 118–25

    Article  PubMed  CAS  Google Scholar 

  33. Davidson JR, Foa EB, Huppert JD, et al. Fluoxetine, comprehensive cognitive behavioral therapy, and placebo in generalized social phobia. Arch Gen Psychiatry 2004 Oct;61(10): 1005–13

    Article  PubMed  CAS  Google Scholar 

  34. Davidson JRT, Bose A, Korotzer A, et al. Escitalopram in the treatment of generalized anxiety disorder: double-blind, placebo controlled, flexible-dose study. Depress Anxiety 2004; 19(4): 234–40

    Article  PubMed  CAS  Google Scholar 

  35. Davidson JRT, Rothbaum BO, Van der Kolk BA, et al. Multicenter, double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder. Arch Gen Psychiatry 2001; 58(5): 485–92

    Article  PubMed  CAS  Google Scholar 

  36. DeVeaugh Geiss J, Moroz G, Biederman J, et al. Clomi-pramine hydrochloride in childhood and adolescent obsessive-compulsive disorder: a multicenter trial. J Am Acad Child Adolesc Psychiatry 1992 Jan; 31(1): 45–9

    Article  PubMed  CAS  Google Scholar 

  37. Dunlop SR, Dornseif BE, Wernicke JF, et al. Pattern analysis shows beneficial effect of fluoxetine treatment in mild depression. Psychopharmacol Bull 1990; 26(2): 173–80

    PubMed  CAS  Google Scholar 

  38. Edwards JG, Goldie A. Placebo-controlled trial of paroxetine in depressive illness. Hum Psychopharmacol 1993; 8(3): 203–9

    Article  Google Scholar 

  39. Eiser N, Harte R, Spiros K, et al. Effect of treating depression on quality-of-life and exercise tolerance in severe COPD. COPD 2005; 2(2): 233–41

    Article  PubMed  Google Scholar 

  40. Emslie GJ, Wagner KD, Kutcher S, et al. Paroxetine treatment in children and adolescents with major depressive disorder: a randomized, multicenter, double-blind, placebo-controlled trial. J Am Acad Child Adolesc Psychiatry 2006; 45(6): 709–19

    Article  PubMed  Google Scholar 

  41. Evans M, Hammond M, Wilson K, et al. Placebo-controlled treatment trial of depression in elderly physically ill patients. Int J Geriatr Psychiatry 1997; 12(8): 817–24

    Article  PubMed  CAS  Google Scholar 

  42. Fabre LF, Abuzzahab FS, Amin M, et al. Sertraline safety and efficacy in major depression: a double-blind fixed-dose comparison with placebo. Biol Psychiatry 1995; 38(9): 592–602

    Article  PubMed  CAS  Google Scholar 

  43. Fabre LF, Crismon L. Efficacy of fluoxetine in outpatients with major depression. Curr Ther Res 1985 Jan; 37(1): 115–23

    Google Scholar 

  44. Fallon BA, Liebowitz MR, Campeas R, et al. Intravenous clomipramine for obsessive-compulsive disorder refractory to oral clomipramine: a placebo-controlled study. Arch Gen Psychiatry 1998; 55(10): 918–24

    Article  PubMed  CAS  Google Scholar 

  45. Fava M, Amsterdam JD, Deltito JA, et al. A double-blind study of paroxetine, fluoxetine, and placebo in outpatients with major depression. Ann Clin Psychiatry 1998; 10(4): 145–50

    PubMed  CAS  Google Scholar 

  46. Feighner JP, Meridith CH, Dutt JE, et al. A double blind comparison of lofepramine, imipramine and placebo in patients with primary depression. Acta Psychiatr Scand 1982; 66(2): 100–8

    Article  PubMed  CAS  Google Scholar 

  47. Feighner JP, Overo K. Multicenter, placebo-controlled, fixed-dose study of citalopram in moderate-to-severe depression. J Clin Psychiatry 1999 Dec; 60(12): 824–30

    Article  PubMed  CAS  Google Scholar 

  48. Ferguson JM, Mendels J, Manowitz NR. Dothiepin versus doxepin in major depression: results of a multicenter, placebo-controlled trial. J Clin Psychiatry 1994; 55(6): 258–63

    PubMed  CAS  Google Scholar 

  49. Foa EB, Liebowitz MR, Kozak MJ, et al. Randomized, placebo-controlled trial of exposure and ritual prevention, clomipramine, and their combination in the treatment of obsessive-compulsive disorder. Am J Psychiatry 2005 Jan; 162(1): 151–61

    Article  PubMed  Google Scholar 

  50. Geller B, Cooper TB, Graham DL, et al. Double-blind placebo-controlled study of nortriptyline in depressed adolescents using a “fixed plasma level” design. Psychopharmacol Bull 1990; 26(1): 85–90

    PubMed  CAS  Google Scholar 

  51. Geller DA, Hoog SL, Heiligenstein JH, et al. Fluoxetine treatment for obsessive-compulsive disorder in children and adolescents: a placebo-controlled clinical trial. J Am Acad Child Adolesc Psychiatry 2001; 40(7): 773–9

    Article  PubMed  CAS  Google Scholar 

  52. Geller DA, Wagner KD, Emslie G, et al. Paroxetine treatment in children and adolescents with obsessive-compulsive disorder: a randomized, multicenter, double-blind, placebo-controlled trial. J Am Acad Child Adolesc Psychiatry 2004 Nov; 43(11): 1387–96

    Article  PubMed  Google Scholar 

  53. Glassman AH, O’Connor CM, Califf RM, et al. Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA 2002; 288(6): 701–9

    Article  PubMed  CAS  Google Scholar 

  54. Golden RN, Nemeroff CB, McSorley P, et al. Efficacy and tolerability of controlled-release and immediate-release paroxetine in the treatment of depression. J Clin Psychiatry 2002 Jul; 63(7): 577–84

    Article  PubMed  CAS  Google Scholar 

  55. Goodman WK, Bose A, Wang Q. Treatment of generalized anxiety disorder with escitalopram: pooled results from double-blind, placebo-controlled trials. J Affect Disord 2005; 87(2-3): 161–7

    Article  PubMed  CAS  Google Scholar 

  56. Goodman WK, Kozak MJ, Liebowitz M, et al. Treatment of obsessive-compulsive disorder with fluvoxamine: a multicentre, double-blind, placebo-controlled trial. Int Clin Psychopharmacol 1996; 11(1): 21–9

    Article  PubMed  CAS  Google Scholar 

  57. Greist J, Chouinard G, DuBoff E, et al. Double-blind parallel comparison of three dosages of sertraline and placebo in outpatients with obsessive-compulsive disorder. Arch Gen Psychiatry 1995; 52(4): 289–95

    Article  PubMed  CAS  Google Scholar 

  58. Greist JH, Jefferson JW, Rosenfeld R, et al. Clomipramine and obsessive compulsive disorder: a placebo-controlled double-blind study of 32 patients. J Clin Psychiatry 1990; 51(7): 292–7

    PubMed  CAS  Google Scholar 

  59. Heiligenstein JH, Tollefson GD, Faries DE. A double-blind trial of fluoxetine, 20mg, and placebo in out-patients with DSM-III-R major depression and melancholia. Int Clin Psychopharmacol 1993; 8(4): 247–51

    Article  PubMed  CAS  Google Scholar 

  60. Hellerstein DJ, Yanowitch P, Rosenthal J, et al. A randomized double-blind study of fluoxetine versus placebo in the treatment of dysthymia. Am J Psychiatry 1993; 150(8): 1169–75

    PubMed  CAS  Google Scholar 

  61. Hoehn-Saric RM, McLeod DRP, Hipsley PAB. Effect of fluvoxamine on panic disorder. J Clin Psychopharmacol 1993; 13(5): 321–6

    Article  PubMed  CAS  Google Scholar 

  62. Hollander E, Allen A, Steiner M, et al. Acute and long-term treatment and prevention of relapse of obsessive-compulsive disorder with paroxetine. J Clin Psychiatry 2003; 64(9): 1113–21

    Article  PubMed  CAS  Google Scholar 

  63. Jenike MA, Baer L, Summergrad P, et al. Sertraline in obsessive-compulsive disorder: a double-blind compar-ison with placebo. Am J Psychiatry 1990 Jul; 147(7): 923–8

    PubMed  CAS  Google Scholar 

  64. Jenike MA, Baer L, Summergrad P, et al. Obsessive-compulsive disorder: a double-blind, placebo-controlled trial of clomipramine in 27 patients. Am J Psychiatry 1989 Oct; 146(10): 1328–30

    PubMed  CAS  Google Scholar 

  65. Jenike MA, Hyman S, Baer L, et al. A controlled trial of fluvoxamine in obsessive-compulsive disorder: implica-tions for a serotonergic theory. Am J Psychiatry 1990 Sep; 147(9): 1209–15

    PubMed  CAS  Google Scholar 

  66. Johnston DG, Troyer IE, Whitsett SF. Clomipramine treatment of agoraphobic women: an eight-week con-trolled trial. Arch Gen Psychiatry 1988; 45(5): 453–9

    Article  PubMed  CAS  Google Scholar 

  67. Kamijima K, Murasaki M, Asai M, et al. Paroxetine in the treatment of obsessive-compulsive disorder: randomized, double-blind, placebo-controlled study in Japanese pa-tients. Psychiatry Clin Neurosci 2004 Aug; 58(4): 427–33

    Article  PubMed  CAS  Google Scholar 

  68. Kasper S, de Swart H, Friis Andersen H. Escitalopram in the treatment of depressed elderly patients. Am J Geriatr Psychiatry 2005; 13(10): 884–91

    PubMed  Google Scholar 

  69. Kasper S, Stein DJ, Loft H, et al. Escitalopram in the treat-ment of social anxiety disorder: randomised, placebo-controlled, flexible-dosage study. Br J Psychiatry 2005 Mar; 186: 222–6

    Article  PubMed  Google Scholar 

  70. Katz RJ, DeVeaugh-Geiss J, Landau P. Clomipramine in obsessive-compulsive disorder. Biol Psychiatry 1990 Sep 1; 28(5): 401–14

    Article  PubMed  CAS  Google Scholar 

  71. Kiev A. A double-blind, placebo-controlled study of par-oxetine in depressed outpatients. J Clin Psychiatry 1992; 53 (2 Suppl.): 27–9

    PubMed  Google Scholar 

  72. Klein RG, Koplewicz HS, Kanner A. Imipramine treat-ment of children with separation anxiety disorder. J Am Acad Child Adolesc Psychiatry 1992; 31(1): 21–8

    Article  PubMed  CAS  Google Scholar 

  73. Klein RG, Mannuzza S, Koplewicz HS, et al. Adolescent depression: controlled desipramine treatment and atypical features. Depress Anxiety 1998; 7(1): 15–31

    Article  PubMed  CAS  Google Scholar 

  74. Kobak KA, Greist JH, Jefferson JW, et al. Fluoxetine in social phobia: a double-blind, placebo-controlled pilot study. J Clin Psychopharmacol 2002; 22(3): 257–62

    Article  PubMed  CAS  Google Scholar 

  75. Kronig MH, Apter J, Asnis G, et al. Placebo-controlled, multicenter study of sertraline treatment for obsessive-compulsive disorder. J Clin Psychopharmacol 1999 Apr; 19(2): 172–6

    Article  PubMed  CAS  Google Scholar 

  76. Kutcher S, Boulos C, Ward B, et al. Response to desipra-mine treatment in adolescent depression: a fixed-dose, placebo-controlled trial. J Am Acad Child Adolesc Psychiatry Jun 1994; 33(5): 686–94

    Article  CAS  Google Scholar 

  77. Lader M, Stender K, Bürger V, et al. Efficacy and toler-ability of escitalopram in 12-and 24-week treatment of social anxiety disorder: randomised, double-blind, placebo-controlled, fixed-dose study. Depress Anxiety 2004; 19(4): 241–8

    Article  PubMed  CAS  Google Scholar 

  78. Lenze EJ, Mulsant BH, Shear MK, et al. Efficacy and tol-erability of citalopram in the treatment of late-life anxiety disorders: results from an 8-week randomized, placebo-controlled trial. Am J Psychiatry 2005 Jan; 162(1): 146–50

    Article  PubMed  Google Scholar 

  79. Lepola U, Bergtholdt B, St Lambert J, et al. Controlled-release paroxetine in the treatment of patients with social anxiety disorder. J Clin Psychiatry 2004 Feb; 65(2): 222–9

    Article  PubMed  CAS  Google Scholar 

  80. Lepola UM, Loft H, Reines EH. Escitalopram (10-20mg/day) is effective and well tolerated in a placebo-controlled study in depression in primary care. Int Clin Psychopharmacol 2003 Jul; 18(4): 211–7

    Article  PubMed  Google Scholar 

  81. Lespérance F, Frasure-Smith N, Koszycki D, et al. Effects of citalopram and interpersonal psychotherapy on de-pression in patients with coronary artery disease. The Canadian Cardiac Randomized Evaluation of Anti-depressant and Psychotherapy Efficacy (CREATE) trial. JAMA 2007; 297(4): 367–79

    Article  PubMed  Google Scholar 

  82. Liebowitz MR, DeMartinis NA, Weihs K, et al. Efficacy of sertraline in severe generalized social anxiety disorder: results of a double-blind, placebo-controlled study. J Clin Psychiatry 2003 Jul; 64(7): 785–92

    Article  PubMed  CAS  Google Scholar 

  83. Liebowitz MR, Stein MB, Tancer M, et al. A randomized, double-blind, fixed-dose comparison of paroxetine and placebo in the treatment of generalized social anxiety disorder. J Clin Psychiatry 2002 Jan; 63(1): 66–74

    Article  PubMed  CAS  Google Scholar 

  84. Liebowitz MR, Turner SM, Piacentini J, et al. Fluoxetine in children and adolescents with OCD: a placebo-controlled trial. J Am Acad Child Adolesc Psychiatry 2002; 41(12): 1431–8

    Article  PubMed  Google Scholar 

  85. Londborg PD, Wolkow R, Smith WT, et al. Sertraline in the treatment of panic disorder: a multi-site, double-blind, placebo-controlled, fixed-dose investigation. Br J Psy-chiatry 1998 Jul; 173: 54–60

    Article  CAS  Google Scholar 

  86. Lyketsos CG, DelCampo L, Steinberg M, et al. Treating depression in Alzheimer disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction. The DIADS. Arch Gen Psychiatry 2003; 60(7): 737–46

    Article  PubMed  CAS  Google Scholar 

  87. Mallya G-K, White K, Waternaux C, et al. Short-and long-term treatment of obsessive-compulsive disorder with fluvoxamine. Ann Clin Psychiatry 1992 Jun; 4(2): 77–80

    Article  Google Scholar 

  88. March J, Silva S, Petrycki S, et al. Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial. JAMA 2004 Aug 18; 292(7): 807–20

    Article  PubMed  CAS  Google Scholar 

  89. March JS, Biederman J, Wolkow R, et al. Sertraline in children and adolescents with obsessive-compulsive disorder: a multicenter randomized controlled trial. JAMA 1998; 280(20): 1752–6

    Article  PubMed  CAS  Google Scholar 

  90. Martenyi F, Brown EB, Zhang H, et al. Fluoxetine versus placebo in posttraumatic stress disorder. J Clin Psychiatry 2002 Mar; 63(3): 199–206

    Article  PubMed  CAS  Google Scholar 

  91. Martenyi F, Soldatenkova V. Fluoxetine in the acute treatment and relapse prevention of combat-related post-traumatic stress disorder: analysis of the veteran group of a placebo-controlled, randomized clinical trial. Eur Neuropsychopharmacol 2006 Jul; 16(5): 340–9

    Article  PubMed  CAS  Google Scholar 

  92. Mendels J, Kiev A, Fabre LF. Double-blind comparison of citalopram and placebo in depressed outpatients with melancholia. Depress Anxiety 1999; 9(2): 54–60

    Article  PubMed  CAS  Google Scholar 

  93. Michelson D, Allgulander C, Dantendorfer K, et al. Efficacy of usual antidepressant dosing regimens of fluoxetine in panic disorder: randomised, placebo-controlled trial. Br J Psychiatry 2001 Dec; 179: 514–8

    Article  PubMed  CAS  Google Scholar 

  94. Modigh K, Westberg P, Eriksson E. Superiority of clomi-pramine over imipramine in the treatment of panic disorder: a placebo-controlled trial. J Clin Psychopharmacol 1992 Aug; 12(4): 251–61

    Article  PubMed  CAS  Google Scholar 

  95. Montgomery SA, Kasper S, Stein DJ, et al. Citalopram 20 mg, 40 mg and 60 mg are all effective and well tolerated compared with placebo in obsessive-compulsive disorder. Int Clin Psychopharmacol 2001 Mar; 16(2): 75–86

    Article  PubMed  CAS  Google Scholar 

  96. Montgomery SA, McIntyre A, Osterheider M, et al. A double-blind, placebo-controlled study of fluoxetine in patients with DSM-III-R obsessive-compulsive disorder. Eur Neuropsychopharmacol 1993 Jun; 3(2): 143–52

    Article  PubMed  CAS  Google Scholar 

  97. Moscovitch A, Blashko CA, Eagles JM, et al. A placebo-controlled study of sertraline in the treatment of outpatients with seasonal affective disorder. Psychopharmacology (Berl) 2004 Feb; 171(4): 390–7

    Article  CAS  Google Scholar 

  98. Murray V, Von Arbin M, Bartfai A, et al. Double-blind comparison of sertraline and placebo in stroke patients with minor depression and less severe major depression. J Clin Psychiatry 2005; 66(6): 708–16

    Article  PubMed  CAS  Google Scholar 

  99. Nyth AL, Gottfries CG, Lyby K, et al. A controlled multicenter clinical study of citalopram and placebo in elderly depressed patients with and without concomitant dementia. Acta Psychiatr Scand 1992 Aug; 86(2): 138–45

    Article  PubMed  CAS  Google Scholar 

  100. Oehrberg S, Christiansen PE, Behnke K, et al. Paroxetine in the treatment of panic disorder: a randomised, double-blind, placebo-controlled study. Br J Psychiatry 1995 Sep; 167(3): 374–9

    Article  PubMed  CAS  Google Scholar 

  101. Paile Hyvarinen M, Wahlbeck K, Eriksson JG. Quality of life and metabolic status in mildly depressed women with type 2 diabetes treated with paroxetine: a single-blind randomised placebo controlled trial. BMC Fam Pract 2003 May 14; 4: 7

    Article  PubMed  Google Scholar 

  102. Pediatric OCD Treatment Study (POTS) Team. Cognitive-behavior therapy, sertraline, and their combination for children and adolescents with obsessive-compulsive disorder: the Pediatric OCD Treatment Study (POTS) randomized controlled trial. JAMA 2004; 292: 1969–76

    Article  Google Scholar 

  103. Petracca G, Tesón A, Chemerinski E, et al. A double-blind placebo-controlled study of clomipramine in depressed patients with Alzheimer’s disease. J Neuropsychiatry Clin Neurosci 1996; 8(3): 270–5

    PubMed  CAS  Google Scholar 

  104. Petracca GM, Chemerinski E, Starkstein SE. A double-blind, placebo-controlled study of fluoxetine in depressed patients with Alzheimer’s disease. Int Psychogeriatr 2001 Jun; 13(2): 233–40

    Article  PubMed  CAS  Google Scholar 

  105. Pine DS. Fluvoxamine for the treatment of anxiety disorders in children and adolescents. N Engl J Med 2001; 344(17): 1279–85

    Article  Google Scholar 

  106. Pohl RB, Wolkow RM, Clary CM. Sertraline in the treatment of panic disorder: a double-blind multicenter trial. Am J Psychiatry 1998 Sep; 155(9): 1189–95

    PubMed  CAS  Google Scholar 

  107. Pollack MH, Otto MW, Worthington JJ, et al. Sertraline in the treatment of panic disorder: a flexible-dose multicenter trial. Arch Gen Psychiatry 1998 Nov; 55(11): 1010–6

    Article  PubMed  CAS  Google Scholar 

  108. Pollack MH, Zaninelli R, Goddard A, et al. Paroxetine in the treatment of generalized anxiety disorder: results of a placebo-controlled, flexible-dosage trial. J Clin Psychiatry 2001 May; 62(5): 350–7

    Article  PubMed  CAS  Google Scholar 

  109. Pomara N, Shao B, Choi SJ, et al. Sex-related differences in nortriptyline-induced side-effects among depressed patients. Prog Neuropsychopharmacol Biol Psychiatry 2001 Jul; 25(5): 1035–48

    Article  PubMed  CAS  Google Scholar 

  110. Ravindran AV, Guelfi JD, Lane RM, et al. Treatment of dysthymia with sertraline: a double-blind, placebo-controlled trial in dysthymic patients without major depression. J Clin Psychiatry 2000 Nov; 61(11): 821–7

    Article  PubMed  CAS  Google Scholar 

  111. Rickels K, Amsterdam J, Clary C, et al. A placebo-controlled, double-blind, clinical trial of paroxetine in depressed outpatients. Acta Psychiatr Scand Suppl 1989; 350: 117–23

    Article  PubMed  CAS  Google Scholar 

  112. Rickels K, Amsterdam JD, Avallone MF. Fluoxetine in major depression: a controlled study. Curr Ther Res 1986 Apr; 39(4): 559–63

    Google Scholar 

  113. Rickels K, Zaninelli R, McCafferty J, et al. Paroxetine treatment of generalized anxiety disorder: a double-blind, placebo-controlled study. Am J Psychiatry 2003 Apr; 160(4): 749–56

    Article  PubMed  Google Scholar 

  114. Riddle MA, Reeve EA, Yaryura-Tobias JA, et al. Fluvox-amine for children and adolescents with obsessive-compulsive disorder: a randomized, controlled, multicenter trial. J Am Acad Child Adolesc Psychiatry 2001; 40(2): 222–9

    Article  PubMed  CAS  Google Scholar 

  115. Riddle MA, Scahill L, King RA, et al. Double-blind, crossover trial of fluoxetine and placebo in children and adolescents with obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry 1992 Nov; 31(6): 1062–9

    Article  PubMed  CAS  Google Scholar 

  116. Rifkin A, Reardon G, Siris S. Trimipramine in physical illness with depression. J Clin Psychiatry 1985; 46 (2 Pt 2): 4–8

    PubMed  CAS  Google Scholar 

  117. Roose SP, Sackeim HA, Krishnan KR, et al. Antidepressant pharmacotherapy in the treatment of depression in the very old: a randomized, placebo-controlled trial. Am J Psychiatry 2004 Nov; 161(11): 2050–9

    Article  PubMed  Google Scholar 

  118. Rynn MA, Siqueland L, Rickels K. Placebo-controlled trial of sertraline in the treatment of children with generalized anxiety disorder. Am J Psychiatry 2001 Dec; 158(12): 2008–14

    Article  PubMed  CAS  Google Scholar 

  119. Schneider LS, Nelson JC, Clary CM, et al. An 8-week multicenter, parallel-group, double-blind, placebo-controlled study of sertraline in elderly outpatients with major depression. Am J Psychiatry 2003; 160(7): 1277–85

    Article  PubMed  Google Scholar 

  120. Sheehan DV, Burnham DB, Iyengar MK, et al. Efficacy and tolerability of controlled-release paroxetine in the treatment of panic disorder. J Clin Psychiatry 2005 Jan; 66(1): 34–40

    Article  PubMed  CAS  Google Scholar 

  121. Sheikh JI, Cassidy EL, Doraiswamy PM, et al. Efficacy, safety, and tolerability of sertraline in patients with late-life depression and comorbid medical illness. J Am Geriatr Soc 2004 Jan; 52(1): 86–92

    Article  PubMed  Google Scholar 

  122. Sheikh JI, Londborg P, Clary CM, et al. The efficacy of sertraline in panic disorder: combined results from two fixed-dose studies. Int Clin Psychopharmacol 2000 Nov; 15(6): 335–42

    Article  PubMed  CAS  Google Scholar 

  123. Smith WT, Glaudin V. A placebo-controlled trial of paroxetine in the treatment of major depression. J Clin Psychiatry 1992 Feb; 53 Suppl.: 36–9

    PubMed  Google Scholar 

  124. Stahl SM, Gergel I, Li D. Escitalopram in the treatment of panic disorder: a randomized, double-blind, placebocontrolled trial. J Clin Psychiatry 2003 Nov; 64(11): 1322–7

    Article  PubMed  CAS  Google Scholar 

  125. Stein DJ, Andersen EW, Tonnoir B, et al. Escitalopram in obsessive-compulsive disorder: a randomized, placebo-controlled, paroxetine-referenced, fixed-dose, 24-week study. Curr Med Res Opin 2007 Apr; 23(4): 701–11

    Article  PubMed  CAS  Google Scholar 

  126. Stein DJ, Westenberg HGM, Yang H, et al. Fluvoxamine CR in the long-term treatment of social anxiety disorder: the 12-to 24-week extension phase of a multicentre, randomized, placebo-controlled trial. Int J Neuropsycho-pharmacol 2003; 6(4): 317–23

    Article  CAS  Google Scholar 

  127. Stein MB, Fyer AJ, Davidson JRT, et al. Fluvoxamine treatment of social phobia (social anxiety disorder): a double-blind, placebo-controlled study. Am J Psychiatry 1999; 156(5): 756–60

    PubMed  CAS  Google Scholar 

  128. Stein MB, Liebowitz MR, Lydiard RB, et al. Paroxetine treatment of generalized social phobia (social anxiety disorder): a randomized controlled trial. JAMA 1998 Aug 26; 280(8): 708–13

    Article  PubMed  CAS  Google Scholar 

  129. Stocchi F, Nordera G, Jokinen RH, et al. Efficacy and tolerability of paroxetine for the long-term treatment of generalized anxiety disorder. J Clin Psychiatry 2003 Mar; 64(3): 250–8

    Article  PubMed  CAS  Google Scholar 

  130. Strik JJMH, Honig A, Lousberg R, et al. Efficacy and safety of fluoxetine in the treatment of patients with major depression after first myocardial infarction: findings from a double-blind, placebo-controlled trial. Psychosomc Med 2000; 62(6): 783–9

    CAS  Google Scholar 

  131. Tan RS, Barlow RJ, Abel C, et al. The effect of low dose lofepramine in depressed elderly patients in general medical wards. Br J Clin Pharmacol 1994 Apr; 37(4): 321–4

    Article  PubMed  CAS  Google Scholar 

  132. Tollefson GD, Bosomworth JC, Heiligenstein JH, et al. A double-blind, placebo-controlled clinical trial of fluoxetine in geriatric patients with major depression. The Fluoxetine Collaborative Study Group. Int Psychogeriatr 1995; 7(1): 89–104

    Article  PubMed  CAS  Google Scholar 

  133. Tollefson GD, Rampey Jr AH, Potvin JH, et al. A multi-center investigation of fixed-dose fluoxetine in the treatment of obsessive-compulsive disorder. Arch Gen Psychiatry 1994; 51(7): 559–67

    Article  PubMed  CAS  Google Scholar 

  134. Trivedi MH, Pigotti TA, Perera P, et al. Effectiveness of low doses of paroxetine controlled release in the treatment of major depressive disorder. J Clin Psychiatry 2004 Oct; 65(10): 1356–64

    Article  PubMed  CAS  Google Scholar 

  135. Tucker P, Potter Kimball R, Wyatt DB, et al. Can physiologic assessment and side effects tease out differences in PTSD trials? A double-blind comparison of citalopram, sertraline, and placebo. Psychopharmacol Bull 2003; 37(3): 135–49

    PubMed  Google Scholar 

  136. Tucker P, Zaninelli R, Yehuda R, et al. Paroxetine in the treatment of chronic posttraumatic stress disorder: results of a placebo-controlled, flexible-dosage trial. J Clin Psychiatry 2001 Nov; 62(11): 860–8

    Article  PubMed  CAS  Google Scholar 

  137. Van Ameringen MA, Lane RM, Walker JR, et al. Sertraline treatment of generalized social phobia: a 20-week, double-blind, placebo-controlled study. Am J Psychiatry 2001 Feb; 158(2): 275–81

    Article  PubMed  Google Scholar 

  138. van der Kolk BA, Dreyfuss D, Michaels M, et al. Fluoxetine in posttraumatic stress disorder. J Clin Psychiatry 1994 Dec; 55(12): 517–22

    PubMed  Google Scholar 

  139. van Vliet IM, den Boer JA, Westenberg HGM. Psycho-pharmacological treatment of social phobia: a double blind placebo controlled study with fluvoxamine. Psychopharmacology 1994 Jun; 115(1–2): 128–34

    Article  PubMed  Google Scholar 

  140. Vanelle JM, Attar-Levy D, Poirier MF, et al. Controlled efficacy study of fluoxetine in dysthymia. Br J Psychiatry 1997 Apr; 170: 345–50

    Article  PubMed  CAS  Google Scholar 

  141. Veith RC, Raskind MA, Caldwell JH, et al. Cardiovascular effects of tricyclic antidepressants in depressed patients with chronic heart disease. N Engl J Med 1982 Apr 22; 306(16): 954–9

    Article  PubMed  CAS  Google Scholar 

  142. Von Knorring AL, Olsson GI, Thomsen PH, et al. A randomized, double-blind, placebo-controlled study of citalopram in adolescents with major depressive disorder. J Clin Psychopharmacol 2006; 26(3): 311–15

    Article  CAS  Google Scholar 

  143. Wade A, Lemming OM, Bang Hedegaard K. Escitalopram 10mg/day is effective and well tolerated in a placebo-controlled study in depression in primary care. Int Clin Psychopharmacol 2002; 17(3): 95–102

    Article  PubMed  CAS  Google Scholar 

  144. Wagner KD, Ambrosini P, Rynn M, et al. Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: two randomized controlled trials. JAMA 2003 Aug 27; 290(8): 1033–41

    Article  PubMed  CAS  Google Scholar 

  145. Wagner KD, Berard R, Stein MB, et al. A multicenter, randomized, double-blind, placebo-controlled trial of paroxetine in children and adolescents with social anxiety disorder. Arch Gen Psychiatry 2004 Nov; 61(11): 1153–62

    Article  PubMed  CAS  Google Scholar 

  146. Wagner KD, Jonas J, Findling RL, et al. A double-blind, randomized, placebo-controlled trial of escitalopram in the treatment of pediatric depression. J Am Acad Child Adolesc Psychiatry 2006 Mar; 45(3): 280–8

    Article  PubMed  Google Scholar 

  147. Walczak DD, Apter JT, Halikas JA, et al. The oral dose-effect relationship for fluvoxamine: a fixed-dose comparison against placebo in depressed outpatients. Ann Clin Psychiatry 1996 Sep; 8(3): 139–51

    Article  PubMed  CAS  Google Scholar 

  148. Wernicke JF, Dunlop SR, Dornseif BE, et al. Low-dose fluoxetine therapy for depression. Psychopharmacol Bull 1988; 24(1): 183–8

    PubMed  CAS  Google Scholar 

  149. Wernicke JF, Dunlop SR, Dornseif BE, et al. Fixed-dose fluoxetine therapy for depression. Psychopharmacol Bull 1987; 23(1): 164–8

    PubMed  CAS  Google Scholar 

  150. Westenberg HGM, Stein DJ, Yang H, et al. A double-blind placebo-controlled study of controlled release fluvoxamine for the treatment of generalized social anxiety disorder. J Clin Psychopharmacol 2004; 24(1): 49–55

    Article  PubMed  CAS  Google Scholar 

  151. Wiart L, Petit H, Joseph PA, et al. Fluoxetine in early poststroke depression: a double-blind placebo-controlled study. Stroke 2000 Aug; 31(8): 1829–32

    Article  PubMed  CAS  Google Scholar 

  152. Zisook S, Peterkin J, Goggin KJ, et al. Treatment of major depression in HIV-seropositive men. J Clin Psychiatry 1998; 59(5): 217–24

    Article  PubMed  CAS  Google Scholar 

  153. Zohar J, Amital D, Miodownik C, et al. Double-blind placebo-controlled pilot study of sertraline in military veterans with posttraumatic stress disorder. J Clin Psychopharmacol 2002 Apr; 22(2): 190–5

    Article  PubMed  CAS  Google Scholar 

  154. Amin M, Lehmann H, Mirmiran J. A double-blind, placebo-controlled dose-finding study with sertraline. Psychopharmacol Bull 1989; 25(2): 164–7

    PubMed  CAS  Google Scholar 

  155. Hollander E, Allen A, Steiner M, et al. Acute and long-term treatment and prevention of relapse of obsessive-compulsive disorder with paroxetine. J Clin Psychiatry 2003; 64(96): 640–7

    Article  PubMed  CAS  Google Scholar 

  156. Trindade E, Menon D, Topfer L-A, et al. Adverse effects associated with selective serotonin reuptake inhibitors and tricyclic antidepressants: a meta-analysis. CMAJ 1998; 159(10): 1245–52

    PubMed  CAS  Google Scholar 

  157. Wilson K, Mottram P. A comparison of side effects of selective serotonin reuptake inhibitors and tricyclic anti-depressants in older depressed patients: a meta-analysis. Int J Geriatr Psychiatry 2004; 19: 754–62

    Article  PubMed  Google Scholar 

  158. Justice AC, Rabeneck L, Hays RD, et al. Sensitivity, specificity, reliability, and clinical validity of provider-reported symptoms: a comparison with self-reported symptoms. J Acquir Immune Defic Syndr 1999; 21: 126–33

    PubMed  CAS  Google Scholar 

  159. Brinkhaus B, Pach D, Lüdtke R, et al. Who controls the placebo? Introducing a placebo quality checklist for pharmacological trials. Contemp Clin Trials 2008; 29: 149–56

    Article  PubMed  Google Scholar 

  160. Golomb BA, McGraw JJ, Evans MA, et al. Physician response to patient reports of adverse drug effects. Drug Saf 2007; 80: 669–78

    Article  Google Scholar 

  161. Rosenthal R. Experimenter effects in behavioral research. New York: Appleton Century Crofts, 1966

    Google Scholar 

  162. Mulant BH, Pollock BG, Nebes R, et al. A twelve-week, double-blind, randomized comparison of nortriptyline and paroxetine in older depressed inpatients and outpatients. Am J Geriatr Psychiatry 2001; 9: 406–14

    Google Scholar 

  163. Preston RA, Materson BJ, Reda DJ, et al. Placebo-associated blood pressure response and advers effects in the treatment of hypertension. Arch Intern Med 2000; 160: 1449–54

    Article  PubMed  CAS  Google Scholar 

  164. Levine ME, Stern RM, Koch KL. The effects of manipulating expectations through placebo and nocebo administration on gastric tachyarrhythmia and motion-induced nausea. Psychosom Med 2006; 68: 478–86

    Article  PubMed  Google Scholar 

  165. Flaten MA, Simonsen T, Olsen H. Drug-related information generates placebo and nocebo responses that modify the drug response. Psychosom Med 1999; 61: 250–5

    PubMed  CAS  Google Scholar 

  166. Link J, Haggard R, Kelly KE, et al. Placebo/nocebo symptom reporting in a sham herbal supplement trial. Eval Health Prof 2006; 29: 394–406

    Article  PubMed  Google Scholar 

  167. Vase L, Robinson ME, Verne GN, et al. The contribution of suggestion, desire, and expectation to placebo effects in irritable bowel syndrome patients: an empirical investigation. Pain 2003; 105: 17–25

    Article  PubMed  Google Scholar 

  168. Lorenz J, Hauck M, Paur RC, et al. Cortical correlates of false expectations during pain intensity judgments: a possible manifestation of placebo/nocebo cognitions. Brain Behav Immun 2005; 19: 283–95

    Article  PubMed  Google Scholar 

  169. Benedetti F, Amanzio M, Casadio C, et al. Blockade of nocebo hyperalgesia by the cholecystokinin antagonist proglumide. Pain 2006; 71: 135–40

    Article  Google Scholar 

  170. Sauro MD, Greenberg RP. Endogenous opiates and the placebo effect: a meta-analytic review. J Psychosom Res 2005; 58: 115–20

    Article  PubMed  Google Scholar 

  171. Johansen O, Brox J, Flaten MA. Placebo and nocebo responses, cortisol, and circulating beta-endorphin. Psychosom Med 2003; 65: 786–90

    Article  PubMed  CAS  Google Scholar 

  172. Benedetti F, Amanzio M, Vighetti S, et al. The biochemical and neuroendocrine bases of the hyperalgesic nocebo effect. J Neurosci 2006; 26: 12014–22

    Article  PubMed  CAS  Google Scholar 

  173. Benedetti F, Lanotte M, Lopiano L, et al. When words are painful: unraveling the mechanisms of the nocebo effect. Neuroscience 2007; 147: 260–71

    Article  PubMed  CAS  Google Scholar 

  174. Rief W, Hessel A, Braehler E. Somatization symptoms and hypochondriacal features in the general population. Psychosom Med 2001; 63: 595–602

    PubMed  CAS  Google Scholar 

  175. Hiller W, Rief W, Brähler E. Somatization in the population: from mild bodily misperceptions to disabling symptoms. Soc Psychiatry Psychiatr Epidemiol 2006; 41: 704–12

    Article  PubMed  Google Scholar 

  176. Rief W, Nestoriuc AY, Hofmann SG. The power of expectation: understanding the placebo and nocebo phenomenon. Soc Pers Psychol Compass 2008; 2: 1–14

    Article  Google Scholar 

  177. Staats PS, Staats A, Hekmat H. The additive impact of anxiety and a placebo on pain. Pain Med 2001; 2(4): 267–79

    Article  PubMed  CAS  Google Scholar 

  178. Geers AL, Helfer SG, Kosbab K, et al. Reconsidering the role of personality in placebo effects: dispositional optimism, situational expectations, and the placebo response. J Psychosom Res 2005; 58: 121–7

    Article  PubMed  Google Scholar 

  179. Colloca L, Benedetti F. How prior experience shapes placebo analgesia. Pain 2006; 124: 126–33

    Article  PubMed  Google Scholar 

  180. Price DD, Craggs J, Verne GN, et al. Placebo analgesia is accompanied by large reductions in pain-related brain activity in irritable bowel syndrome patients. Pain 2006; 124: 238–9

    Article  PubMed  CAS  Google Scholar 

  181. Colloca L, Sigaudo M, Benedetti F. The role of learning in nocebo and placebo effects. Pain 2008; 136: 211–8

    Article  PubMed  CAS  Google Scholar 

  182. Kirsch I, Deacon BJ, Huedo-Medina TB, et al. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the food an drug administration. PLoS Med 2008; 5: 260–8

    Article  Google Scholar 

  183. Turner EH, Matthews AM, Linardatos E, et al. Selective publication of antidepressant trials and its influence on apparent efficacy. New Engl J Med 2008; 358: 252–60

    Article  PubMed  CAS  Google Scholar 

  184. Geddes JR, Carney SM, Davies C, et al. Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet 2003; 361: 653–61

    Article  PubMed  CAS  Google Scholar 

  185. Brambilla F, Cipriani A, Hotopf M, et al. Side-effect profile of fluoxetine in comparison with other SSRIs, tricyclic and newer antidepressants: a meta-analysis of clinical trial data. Pharmacopsychiatry 2005; 38: 69–77

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

Financial support for this study came from the University of Marburg, Germany. This funding source had no involvement on study design, results, this manuscript or its content. Dr Winfried Rief declares that he had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. ## Dr Hofmann is a paid consultant to Organon (Schering-Plough) for studies unrelated to the content of this manuscript. The other authors have no conflicts of interest to declare that might potentially bias this study.

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Rief, W., Nestoriuc, Y., von Lilienfeld-Toal, A. et al. Differences in Adverse Effect Reporting in Placebo Groups in SSRI and Tricyclic Antidepressant Trials. Drug-Safety 32, 1041–1056 (2009). https://doi.org/10.2165/11316580-000000000-00000

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