Impact of patient selection and study characteristics on signal detection in placebo-controlled trials with antidepressants

Journal of Psychiatric Research

Volumn 51, Issue 1, 2014, Pages 21-29

  Mancini, Michele ^a   Wade, Alan G ^b   Perugi, Giulio ^c   Lenox Smith, Alan ^d   Schacht, Alexander ^e  

^a Eli Lilly Italia SpA   (Italy)

^b CPS Research   (United Kingdom)

^c UNIVERSITY OF PISA   (Italy)

^d Medical Department   (United Kingdom)

^e LILLY DEUTSCHLAND GMBH   (Germany)

Author keywords

Duloxetine; Effect size (ES); Hamilton Depression Rating scale (HAM D); Major depressive disorder (MDD); Placebo; Signal detection

Indexed keywords

ANTIDEPRESSANT AGENT; DULOXETINE; PLACEBO;

ANALYSIS OF COVARIANCE; ANALYTIC METHOD; ANTHROPOMETRIC PARAMETERS; ARTICLE; DEPRESSION; DISEASE COURSE; DISEASE SEVERITY; DRUG EFFICACY; DRUG SAFETY; EFFECT SIZE; HAMILTON SCALE; HUMAN; MAJOR DEPRESSION; META ANALYSIS; PATIENT SELECTION; PLACEBO EFFECT; PREVENTION STUDY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); SIGNAL DETECTION; STUDY DESIGN; TREATMENT DURATION; TREATMENT INDICATION; TREATMENT OUTCOME;

DULOXETINE; EFFECT SIZE (ES); HAMILTON DEPRESSION RATING SCALE (HAM-D); MAJOR DEPRESSIVE DISORDER (MDD); PLACEBO; SIGNAL DETECTION;

ADULT; ANALYSIS OF VARIANCE; ANTIDEPRESSIVE AGENTS; DATABASES, FACTUAL; DEPRESSIVE DISORDER, MAJOR; DOUBLE-BLIND METHOD; FEMALE; HUMANS; MALE; MIDDLE AGED; PATIENT SELECTION; PSYCHIATRIC STATUS RATING SCALES; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RESEARCH DESIGN; SIGNAL DETECTION, PSYCHOLOGICAL; THIOPHENES; YOUNG ADULT;

EID: 84893910217     PISSN: 00223956     EISSN: 18791379     Source Type: Journal    
DOI: 10.1016/j.jpsychires.2014.01.001     Document Type: Article

References (49)

1. Brannan S.K., Mallinckrodt C.H., Brown E.B., Wohlreich M.M., Watkin J.G., Schatzberg A.F. Duloxetine 60mg once-daily in the treatment of painful physical symptoms in patients with major depressive disorder. JPsychiatric Res 2005, 39:43-53.
2. Detke M.J., Lu Y., Goldstein D.J., Hayes J.R., Demitrack M.A. Duloxetine, 60mg once daily, for major depressive disorder: a randomized double-blind placebo controlled trial. JClin Psychiatry 2002, 63:308-315.
3. Detke M.J., Lu Y., Goldstein D.J., McNamara R.K., Demitrack M.A. Duloxetine 60mg once daily dosing vs. placebo in the acute treatment of major depression. JPsychiatric Res 2002, 36:383-390.
4. Detke M.J., Wiltse C.G., Mallinckrodt C.H., McNamara R.K., Demitrack M.A., Bitter I. Duloxetine in the acute and long-term treatment of major depressive disorder: a placebo- and paroxetine-controlled trial. Eur Neuropsychopharmacol 2004, 14:457-470.
5. Dunlop B.W., Thase M.E., Wun C.C., Fayyad R., Guico-Pabia C.J., Musgnung J., et al. Ameta-analysis of factors impacting detection of antidepressant efficacy in clinical trials: the importance of academic sites. Neuropsychopharmacology 2012, 37:2830-2836.
6. Fountoulakis K.N., Möller H.J. Efficacy of antidepressants: a re-analysis and re-interpretation of the Kirsch data. Int J Neuropsychopharmacol 2011, 14(3):405-412.
7. Fountoulakis K.N., Möller H.J. Antidepressant drugs and the response in the placebo group: the real problem lies in our understanding of the issue. JPsychopharmacol 2012, 26(5):744-750.
8. Fournier J.C., DeRubeis R.J., Hollon S.D., Dimidjian S., Amsterdam J.D., Shelton R.C., et al. Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAm Med Assoc 2010, 303:47-53.
9. Gelenberg A.J., Thase M.E., Meyer R.E., Goodwin F.K., Katz M.M., Kraemer H.C., et al. The history and current state of antidepressant clinical trial design: a call to action for proof-of-concept studies. JClin Psychiatry 2008, 69:1513-1528.
10. Goldstein D.J., Mallinckrodt C., Lu Y., Demitrack M.A. Duloxetine in the treatment of major depressive disorder: a double-blind clinical trial. JClin Psychiatry 2002, 63:225-231.
11. Goldstein D.J., Lu Y., Detke M.J., Wiltse C., Mallinckrodt C., Demitrack M.A. Duloxetine in the treatment of depression: a double-blind placebo-controlled comparison with paroxetine. JClin Psychopharmacol 2004, 24:389-399.
12. Gueorguieva R., Mallinckrodt C., Krystal J.H. Trajectories of depression severity in clinical trials of duloxetine: insights into antidepressant and placebo responses. Arch Gen Psychiatry 2011, 68:1227-1237.
13. Höschl C. European perspectives in psychiatry: antidepressants as an example. Acta Psychiatr Scand 2008, 118:89-90.
14. Hudson J.I., Perahia D.G., Gilaberte I., Wang F., Watkin J.G., Detke M.J. Duloxetine in the treatment of major depressive disorder: an open-label study. BMC Psychiatry 2007, 7:43.
15. Khan A., Leventhal R.M., Khan S.R., Brown W.A. Severity of depression and response to antidepressants and placebo: an analysis of the Food and Drug Administration database. JClin Psychopharmacol 2002, 22(1):40-45.
16. Khan A., Detke M., Khan S.R., Mallinckrodt C. Placebo response and antidepressant clinical trial outcome. JNerv Ment Dis 2003, 191:211-218.
17. Khan A., Khan S.R., Walens G., Kolts R.L., Giller E.L. Frequency of positive studies among fixed and flexible dose antidepressant trials: an analysis of the food and drug administration summary basis of approval reports. Neuropsychopharmacology 2003, 28:552-557.
18. Khan A., Kolts R.L., Thase M.E., Krishnan K.R., Brown W. Research design features and patient characteristics associated with the outcome of antidepressant clinical trials. Am J Psychiatry 2004, 161:2045-2049.
19. Khan A., Brodhead A.E., Kolts R.L., Brown W.A. Severity of depressive symptoms and response to antidepressants and placebo in antidepressant trials. JPsychiatric Res 2005, 39:145-150.
20. Khan A., Bhat A., Kolts R., Thase M.E., Brown W. Why has the antidepressant-placebo difference in antidepressant clinical trials diminished over the past three decades?. CNS Neurosci Ther 2010, 16:217-226.
21. Khin N.A., Chen Y.F., Yang Y., Yang P., Laughren T.P. Exploratory analyses of efficacy data from major depressive disorder trials submitted to the US Food and Drug Administration in support of new drug applications. JClin Psychiatry 2011, 72:464-472.
22. Kirsch I., Deacon B.J., Huedo-Medina T.B., Scoboria A., Moore T.J., Johnson B.T. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLOS Med 2008, 5:e45.
23. Kobak K.A., Feiger A.D., Lipsitz J.D. Interview quality and signal detection in clinical trials. Am J Psychiatry 2005, 162:628.
24. Kobak K.A., Leuchter A., DeBrota D., Engelhardt N., Williams J.B., Cook I.A., et al. Site versus centralized raters in a clinical depression trial: impact on patient selection and placebo response. JClin Psychopharmacol 2010, 30:193-197.
25. Kobak K.A., Kane J.M., Thase M.E., Nierenberg A.A. Why do clinical trials fail? The problem of measurement error in clinical trials: time to test new paradigms?. JClin Psychopharmacol 2007, 27:1-5.
26. Mallinckrodt C.H., Goldstein D.J., Detke M.J., Lu Y., Watkin J.G., Tran P.V. Duloxetine: a new treatment for the emotional and physical symptoms of depression. Prim Care Companion - J Clin Psychiatry 2003, 5:19-28.
27. Mallinckrodt C.H., Meyers A.L., Prakash A., Faries D.E., Detke M.J. Simple options for improving signal detection in antidepressant clinical trials. Psychopharmacol Bull 2007, 40:101-114.
28. Mallinckrodt C.H., Zhang L., Prucka W.R., Millen B.A. Signal detection and placebo response in schizophrenia: parallels with depression. Psychopharmacol Bull 2010, 43:53-72.
29. Mundt J.C., Greist J.H., Jefferson J.W., Katzelnick D.J., DeBrota D.J., Chappell P.B., et al. Is it easier to find what you are looking for if you think you know what it looks like?. JClin Psychopharmacol 2007, 27:121-125.
30. Mundt J.C., Debrota D.J., Greist J.H. Anchoring perceptions of clinical change on accurate recollection of the past: memory enhanced retrospective evaluation of treatment (MERET). Psychiatry 2007, 4:39-45.
31. Oakes T.M., Myers A.L., Marangell L.B., Ahl J., Prakash A., Thase M.E., et al. Assessment of depressive symptoms and functional outcomes in patients with major depressive disorder treated with duloxetine versus placebo: primary outcomes from two trials conducted under the same protocol. Hum Psychopharmacol Clin Exp 2012, 27:47-56.
32. Nemeroff C.B., Schatzberg A.F., Goldstein D.J., Detke M.J., Mallinckrodt C., Lu Y., et al. Duloxetine for the treatment of major depressive disorder. Psychopharmacol Bull 2002, 36:106-132.
33. Nierenberg A.A., Greist J.H., Mallinckrodt C.H., Prakash A., Sambunaris A., Tollefson G.D., et al. Duloxetine versus escitalopram and placebo in the treatment of patients with major depressive disorder: onset of antidepressant action, a non-inferiority study. Curr Med Res Opin 2007, 23(2):401-416.
34. Papakostas G.I., Fava M. Does the probability of receiving placebo influence clinical trial outcome? A meta-regression of double-blind, randomized clinical trials in MDD. Eur Neuropsychopharmacol 2009, 19:34-40.
35. Perahia D.G., Wang F., Mallinckrodt C.H., Walker D.J., Detke M.J. Duloxetine in the treatment of major depressive disorder: a placebo- and paroxetine-controlled trial. Eur Psychiatry 2006, 21:367-378.
36. Perahia D.G., Maina G., Thase M.E., Spann M.E., Wang F., Walker D.J., et al. Duloxetine in the prevention of depressive recurrences: a randomized, double-blind, placebo-controlled trial. JClin Psychiatry 2009, 70:706-716.
37. Posternak M.A., Zimmerman M., Keitner G.I., Miller I.W. Areevaluation of the exclusion criteria used in antidepressant efficacy trials. Am J Psychiatry 2002, 159:191-200.
38. Raskin J., Wiltse C.G., Siegal A., et al. Efficacy of duloxetine on cognition, depression, and pain in elderly patients with major depressive disorder: an 8-week, double-blind, placebo-controlled trial. Am J Psychiatry 2007, 164:900-909.
39. Raskin J., Wiltse C.G., Dinkel J.J., Walker D.J., Desaiah D., Katona C. Safety and tolerability of duloxetine at 60mg once daily in elderly patients with major depressive disorder. JClin Psychopharmacol 2008, 28:32-38.
40. Raskin J., Xu J.Y., Kajdasz D.K. Time to response for duloxetine 60mg once daily versus placebo in elderly patients with major depressive disorder. Int Psychogeriatrics 2008, 20(2):309-327.
41. Robinson M., Oakes T.M., Raskin J., Liu P., Shoemakers S., Nelson J.C. Acute and long-term treatment of late-life major depressive disorder: duloxetine versus placebo. Am J Geriatric Psychiatry 2014, 22(1):34-45.
42. Rutherford B.R., Roose S.R. Amodel of placebo response in antidepressant clinical trials. Am J Psychiatry 2013, 170(7):723-733.
43. Schacht A., Dyachkova Y., Walton R.J. Critical evaluation of mixed treatment comparison meta-analyses using examples assessing antidepressants and opioid detoxification treatments. Int J Methods Psychiatric Res 2013, 22:166-174.
44. Simon G.E. Evidence review: efficacy and effectiveness of antidepressant treatment in primary care. Gen Hosp Psychiatry 2002, 24:213-224.
45. Turner E.H., Matthews A.M., Linardatos E., Tell R.A., Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. New Engl J Med 2008, 358:252-260.
46. Turner E.H., Rosenthal R. Efficacy of antidepressants. Br Med J 2008, 336(7643):516-517.
47. Wise T.N., Wiltse C.G., Losifescu D.V., Sheridan M., Xu J.Y., Raskin J. The safety and tolerability of duloxetine in depressed elderly patients with and without medical comorbidity. Int J Clin Pract 2007, 61:1283-1293.
48. Zimmerman M., Posternak M.A., Chelminski I. Symptom severity and exclusion from antidepressant efficacy trials. JClin Psychopharmacol 2002, 22:610-614.
49. Zimmerman M., Chelminski I., Posternak M.A. Generalizability of antidepressant efficacy trials: differences between depressed psychiatric outpatients who would or would not qualify for an efficacy trial. Am J Psychiatry 2005, 162:1370-1372.