Studies Weigh Antidepressants Against Herbs and Placebos
January 1, 2003
Kupfer and Frank suggested that clinical trial investigators obtain expert consensus on the level of illness severity and the therapeutic outcomes to assess, in order to provide the study treatment with "a fair opportunity to demonstrate its true therapeutic potential."
In July, a study on placebo trials and related commentaries were published in Prevention & Treatment (Brown, 2002; Kirsch et al., 2002; Thase, 2002). The Kirsch et al. (2002) study, a meta-analysis of 38 placebo-controlled studies of six antidepressants reviewed by the FDA between 1987 and 1999, found that while patients receiving antidepressants achieved a mean 10-point reduction in HAM-D score, patients on placebo did almost as well, achieving an eight-point reduction.
Kirsch et al. argued that the antidepressants may only be responsible for the two-point increment over placebo, rather than the 10-point therapeutic response, and so their effect could be characterized as clinically negligible. This view was shared in some of the commentaries but countered in others (Brown, 2002; Thase, 2002).
Brown (2002) commented, "Placebo is better at alleviating depression than it is at preventing relapse." He also noted that antidepressant effects have been fairly consistent across studies, while placebo effects have varied more depending on patient populations and the severity of illness.
Thase (2002) observed that the Kirsch et al. findings are not revelatory and that similar assessments were made in early studies of fluoxetine(Drug information on fluoxetine) (Prozac) almost a decade earlier (Greenberg et al., 1994). Thase attributed the high placebo response and small relative effects of active antidepressants principally to the study populations with moderate, rather than severe, illness.
"Another problem is that industry has been slow to adapt to the knowledge of relatively small expected effect sizes and continues to conduct conventional underpowered studies," Thase commented.
Brown WA (2002), Are antidepressants as ineffective as they look? Prevention and Treatment 5:Article 25. Available at:http://journals.apa.org/prevention/volumes/pre0050026c.html
. Accessed Sept. 4. 2.
Cott J, Wisner KL (2002), St. John's wort and depression. JAMA 288(4):448 [letter]. 3.
Danish University Antidepressant Group (1990), Paroxetine: a selective serotonin reuptake inhibitor showing better tolerance, but weaker antidepressant effect than clomipramine in a controlled multicenter study. J Affect Disord 18(4):289-299. 4.
Greenberg RP, Bornstein R, Zborowski MJ et al. (1994), A meta-analysis of fluoxetine outcome in the treatment of depression. J Nerv Ment Dis 182(10):547-551. 5.
HDTSG (2002), Effects of Hypericum perforatum (St. John's wort) in major depressive disorder: a randomized controlled trial. JAMA 287(14):1807-1814 [see comment]. 6.
Jonas W (2002), St. John's wort and depression. JAMA 288(4):446 [letter]. 7.
Kirsch I, Moore TJ, Scoboria A, Nicholls SS (2002), The emperor's new drugs: an analysis of antidepressant medication data submitted to the U.S. Food and Drug Administration. Prevention and Treatment 5:Article 23. Available at:journals.apa.org/prevention/volume5/pre0050023a.html
. Accessed Sept. 4. 8.
Kupfer DJ, Frank E (2002a), Placebo in clinical trials for depression: complexity and necessity. [Published erratum JAMA 287(23):3083.] JAMA 287(14):1853-1854 [comment]. 9.
Kupfer DJ, Frank E (2002b), St. John's wort and depression. JAMA 288(4):449 [letter]. 10.
Linde K, Melchart D, Mulrow CD, Berner M (2002), St John's wort and depression. JAMA 288(4):447-448 [letter]. 11.
Linde K, Ramirez G, Mulrow CD et al. (1996), St John's wort for depression-an overview and meta-analysis of randomised clinical trials. BMJ 313(7052):253-258 [see comments]. 12.
Schneider LS, Small GW (2002), The increasing power of placebos in trials of antidepressants. JAMA 288(4):450 [letter]. 13.
Shelton RC, Keller MB, Gelenberg AJ et al. (2001), Effectiveness of St John's wort in major depression: a randomized controlled trial. JAMA 285(15):1978-1986 [see comments]. 14.
Thase ME (2002), Antidepressant effects: the suit may be small, but the fabric is real. Prevention and Treatment 5: Article 32. Available at:journals.apa.org/prevention/volume5/pre0050032c.html
. Accessed Sept. 4. 15.
Walsh BT, Seidman SN, Sysko R, Gould M (2002), Placebo response in studies of major depression: variable, substantial, and growing. JAMA 287(14):1840-1847 [see comment]. 16.
Wheatley D (2002), St John's wort and depression. JAMA 288(4):446 [letter].