The problem of the placebo response in clinical trials for psychiatric disorders: Culprits, possible remedies, and a novel study design approach

Psychotherapy and Psychosomatics

Volumn 72, Issue 3, 2003, Pages 115-127

  Fava, Maurizio ^a   Evins, A Eden ^a   Dorer, David J ^a   Schoenfeld, David A ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

Clinical trials; Novel design; Placebo; Sequential

Indexed keywords

PLACEBO;

ARTICLE; CLINICAL RESEARCH; CLINICAL TRIAL; DIAGNOSTIC ERROR; DOCTOR PATIENT RELATION; INFORMATION PROCESSING; MENTAL DISEASE; METHODOLOGY; OUTCOMES RESEARCH; PRIORITY JOURNAL; RESPONSE TIME; SAMPLE SIZE; SEQUENTIAL PARALLEL COMPARISON DESIGN; STANDARDIZATION;

CLINICAL TRIALS; DOUBLE-BLIND METHOD; HUMANS; MENTAL DISORDERS; PLACEBO EFFECT; REPRODUCIBILITY OF RESULTS; RESEARCH DESIGN;

EID: 0037266035     PISSN: 00333190     EISSN: None     Source Type: Journal    
DOI: 10.1159/000069738     Document Type: Article

References (38)

1. Schatzberg AF, Kraemer HC: Use of placebo control groups in evaluating efficacy of treatment of unipolar major depression. Biol Psychiatry 2000;47:736-744.
2. Demitrack MA, Faries D, Herrera JM, DeBrota D, Potter WZ: The problem of measurement error in multisite clinical trials. Psychopharmacol Bull 1998;34:19-24.
3. Robinson DS, Rickels K: Concern about clinical drug trials. J Clin Psychopharmacol 2000;20:593-596.
4. Otto MW, Nierenberg AA: Assay sensitivity, failed clinical trials and the conduct of science. Psychother Psychosom 2002;71:241-243.
5. Hooper M, Amsterdam JD: Do clinical trials reflect drug potential? A review of FDA evaluation of new antidepressants. 39th Annual NCDEU Meeting, Boca Raton, June 11-14, 1998.
6. NDA 18-936, FDA 1988.
7. Walsh BT, Seidman SN, Sysko R, Gould M: Placebo response in studies of major depression: Variable, substantial and growing. JAMA 2002;287:1840-1847.
8. Jorenby DE, Leischow SJ, Nides MA, Rennard SI, Johnston JA, Hughes AR, Smith SS, Muramoto ML, Daughton DM, Doan K, Fiore MC, Baker TB: A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med 1999;340:685-691.
9. Fiore MC, Smith SS, Jorenby DE, Baker TB: The effectiveness of the nicotine patch for smoking cessation. A meta-analysis. JAMA 1994;271:1940-1947.
10. Niaura R, Spring B, Borrelli B, Hedeker D, Goldstein MG, Keuthen N, DePue J, Kristeller J, Ockene J, Prochazka A, Chiles JA, Abrams DB: Multicenter trial of fluoxetine as an adjunct to behavioral smoking cessation treatment. J Consult Clin Psychol 2002;70:887-896.
11. Quitkin FM, Stewart JW, McGrath PJ, Taylor BP, Tisminetzky MS, Petkova E, Chen Y, Ma G, Klein DF: Are there differences between women's and men's antidepressant responses? Am J Psychiatry 2002;159:1848-1854.
12. Peselow ED, Sanfilipo MP, Difiglia C, Fieve RR: Melancholic/endogenous depression and response to somatic treatment and placebo. Am J Psychiatry 1992;149:1324-1334.
13. Fava M, Rosenbaum JF: How to write a study protocol: A primer for the clinician; in Fava M, Rosenbaum JF (eds): Research Designs and Methods in Psychiatry, Amsterdam, Elsevier Science, 1992, pp 297-305.
14. Fava M, Uebelacker LA, Alpert JE, Nierenberg AA, Pava J, Rosenbaum JF: Major depressive subtypes and treatment response. Biol Psychiatry 1997;42:568-576.
15. Kellner R: The development of sensitive scales for research in therapeutics; in Fava M, Rosenbaum JF (eds): Research Designs and Methods in Psychiatry. Amsterdam, Elsevier Science, 1992, pp 213-222.
16. Gibbons RD, Clark DC, Kupfer DJ: Exactly what does the Hamilton Depression Rating Scale measure? J Psychiatr Res 1993;27:259-273.
17. Faries D, Herrera J, Rayamajhi J, DeBrota D, Demitrack M, Potter WZ: The responsiveness of the Hamilton Depression Rating Scale. J Psychiatr Res 2000;34:3-10.
18. Bech P, Allerup P, Gram LF, Reisby N, Rosenberg R, Jacobsen O, Nagy A: The Hamilton Depression Scale. Evaluation of objectivity using logistic models. Acta Psychiatr Scand 1981;63:290-299.
19. O'Sullivan RL, Fava M, Agustin C, Baer L, Rosenbaum JF: Sensitivity of the six-item Hamilton Depression Rating Scale. Acta Psychiatr Scand 1997;95:379-384.
20. Simpson GM, Lee HJ, Cuculic Z, Kellner R: Two dosages of imipramine in hospitalized endogenous and neurotic depressives. Arch Gen Psychiatry 1976;33:1093-1102.
21. Chmura-Kraemer H, Pruyn JP, Gibbons RD, Greenhouse JB, Grochocinski VJ, Waternaux C, Kupfer DJ: Methodology in psychiatric research. Arch Gen Psychiatry 1987;44:1100-1106.
22. Hrobjartsson A, Gotzsche PC: Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment. N Engl J Med 2001;344:1594-1602.
23. Laird N: Estimating rates of change in clinical studies; in Fava M, Rosenbaum JF (eds): Research Designs and Methods in Psychiatry. Amsterdam, Elsevier Science, 1992, pp 185-193.
24. Campbell DT, Kenny DA, Reichardt, CS: A Primer on Regression Artifacts. Guilford, New York, 1999.
25. Shelton RC, Keller MB, Gelenberg A, Dunner DL, Hirschfeld R, Thase ME, Russell J, Lydiard RB, Crits-Cristoph P, Gallop R, Todd L, Hellerstein D, Goodnick P, Keitner G, Stahl SM, Halbreich U: Effectiveness of St. John's wort in major depression: A randomized controlled trial. JAMA 2001;285:1978-1986.
26. Chassan JB: Intensive design: Statistics and the single case; in Fava M, Rosenbaum JF (eds): Research Designs and Methods in Psychiatry. Amsterdam, Elsevier Science, 1992, pp 173-183.
27. Uhlenhuth EH, Turner DA, Purchaske G, Gift T, Chassan JB: Intensive design in evaluating anxiolytic agents. Psychopharmacology 1977;52:79-85.
28. Fava M: Traditional and alternative research designs and methods in clinical pediatric psychopharmacology. J Am Acad Child Adolesc Psychiatry 1996;35:1292-1303.
29. Myers ED, Calvert EJ: Information, compliance and side-effects: A study of patients on antidepressant medication. Br J Clin Pharmacol 1984;17:21-25.
30. Hypericum Depression Trial Study Group: Effect of Hypericum perforatum (St. John's wort) in major depressive disorder: A randomized controlled trial. JAMA 2002;287:1807-1814.
31. Kobak KA, Greist JH, Jefferson JW, Mundt JC, Katzelnick DJ: Computerized assessment of depression and anxiety over the telephone using interactive voice response. MD Comput 1999;16:64-68.
32. Rush AJ, Carmody T, Reimitz, PE: The Inventory of Depressive Symptomatology (IDS): Clinician (IDS-C) and Self-Report (IDS-SR) ratings of depressive symptoms. Int J Methods Psychiatr Res 2000;9:49-59.
33. DeBrota DJ, Gelwicks SC, Potter WZ: Same rater versus different raters in depression clinical trials. 42nd Annual NCDEU Meeting, Boca Raton, June 10-13 2002.
34. Trivedi MH, Rush AJ: Does a placebo run-in or a placebo treatment cell affect the efficacy of antidepressant medications? Neuropsychopharmacology 1994;11:33-43.
35. Faries DE, Heiligenstein JH, Tollefson GD, Potter WZ: The double-blind variable placebo lead-in period: Results from two antidepressant clinical trials. J Clin Psychopharmacol 2001;21:561-568.
36. Quitkin FM, Rabkin JG, Ross D, Stewart JW: Identification of true drug response to antidepressants: Use pattern analysis. Arch Gen Psychiatry 1984;41:782-786.
37. Quitkin FM: Methodology of measuring the efficacy of antidepressants. Psychopharmacology (Berl) 1992;106(suppl):S87-S89.
38. Rao CR: Linear Statistical Inference and Its Applications. New York, Wiley, 1973, pp 1-441.