Antidepressant treatment history and drug-placebo separation in a placebo-controlled trial in major depressive disorder

作者：Hunter Aimee M^*; Cook Ian A; Tartter Molly; Sharma Simi K; Disse Gregory D; Leuchter Andrew F

来源：Psychopharmacology, 2015, 232(20): 3833-3840.

DOI：10.1007/s00213-015-4047-2

• Antidepressant treatment history
• Tachyphylaxis
• Tolerance
• Placebo response
• Antidepressant medication
• Randomized clinical trial
• Treatment-resistant depression
• Expectations

A history of antidepressant treatment may predispose subjects toward placebo nonresponse in randomized controlled trials (RCTs) in major depressive disorder (MDD).
The objective of this study is to examine self-reported prior antidepressant treatment and response in relationship to clinical outcome in an 8-week randomized trial of reuptake inhibitor antidepressant medication (MED) versus placebo (PBO) administered along with limited supportive care.
Chi-square and MMRM analyses examined MED vs. PBO outcomes in antidepressant-na < ve vs. antidepressant-experienced subjects. Linear regression models examined treatment history along with covariates as predictors of clinical improvement.
Among completers (n = 56), there was no significant difference in response rate between MED (53.3 %) and PBO (42.3 %) (chi (2) = 0.33, p = 0.28, 1-tailed). The antidepressant-experienced subgroup (n = 37), however, showed a significantly greater response rate to MED (52.4 %) than PBO (25.0 %) (chi (2) = 2.82, p = 0.047, 1-tailed). The full intent-to-treat (ITT) sample (n = 69) did not show a significant difference between MED and PBO group improvement over time, but in the treatment-experienced subgroup (n = 46), MED showed significantly greater improvement than PBO (coefficient = .39, SE = .23, p = .045, 1-tailed). A history of prior antidepressant treatment predicted poorer overall response independent of pretreatment symptom severity, number or length of previous episodes, subject expectations, or family history of MDD.
Treatment history appears to constitute a factor that is distinct from other commonly studied illness characteristics or expectancy measures, and that impacts overall response as well as drug-placebo separation in RCTs.

• 出版日期2015-10