Baseline patient characteristics associated with placebo remission and their impact on remission with duloxetine and selected SSRI antidepressants

Abstract

Objective:

We examined whether identification of patients with placebo-remitter characteristics and placebo-nonremitter characteristics enhances the ability to identify drug–placebo treatment differences and, perhaps, differences between agents in major depressive disorder (MDD). We hypothesized: 1) that drug–placebo differences in remission rates would be greater for both duloxetine and selective serotonin reuptake inhibitors (SSRIs) among placebo nonremitters than placebo remitters and: 2) that the difference between active treatments would also be greater in placebo nonremitters than placebo remitters.

Data and methods:

Data were obtained from seven randomized, parallel, double-blind MDD studies which compared the effects of duloxetine (N = 795), placebo (N = 510), and SSRIs (N = 551). The 17-item Hamilton depression rating scale (HAMD) was used to assess depression severity. The classification of participants as having placebo-remitter or placebo-nonremitter characteristics was based on age, duration of current MDD episode, HAMD anxiety score, and HAMD core score. Odds ratios (ORs) for remission comparing active treatment and placebo were obtained from logistic regression models. Tests of homogeneity were used for between-group comparisons.

Results:

For placebo nonremitters, both duloxetine (OR = 3.52 [95% CI: 2.21, 5.62; P < 0.0001]) and SSRIs (OR = 2.38 [95% CI: 1.45, 3.89; P = 0.0006]) showed significantly higher remission rates compared to placebo. Drug–placebo differences in remission were significantly greater for placebo nonremitters than for placebo remitters for both duloxetine (P = 0.02) and SSRIs (P = 0.049). For placebo remitters, remission with duloxetine (OR = 1.83 [95% CI: 1.35, 2.47; P = 0.0001]), but not the SSRIs selected for this study (OR = 1.31 [95% CI: 0.93, 1.84; P = 0.12]), was significantly greater than placebo. Contrary to expectation, the advantage of duloxetine over the SSRIs was not greater in placebo nonremitters. However, the fact that our analysis required patient-level data limited the number of agents studied, compromising generalization.

Conclusions:

Our study suggests that drug–placebo differences in remission rates will be greater in subjects with placebo-nonremitter than with placebo-remitter characteristics.

Keywords::

• Duloxetine
• Major depressive disorder (MDD)
• Placebo
• SSRIs

Transparency

Declaration of funding

This research was supported by Eli Lilly and Company.

Declaration of financial/other relationships

During the past 12 months J.C.N. has served as an advisor or consultant for Avanir, Bristol Myers Squibb, Cenestra Health, Corcept, Dey Pharma, Eli Lilly, Forest, Labopharm, Lundbeck, Medtronic, Merck, Otsuka, Pfizer, Sunovion; he has received lecture honoraria from Eli Lilly Global, Lundbeck, Otsuka Asia, Merck Asia; he is not on a US Speakers Bureau; he receives research support from NIMH and HRSA; and owns stock in Atossa. E.E. has received research grants from Lundbeck and has been advisor for and/or received speaker honoraria from Lundbeck, Lilly, JanssenCilag, AstraZeneca and BayerSchering. M.B. has received Grant/Research Support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Organon, Novartis, Mayne Pharma and Servier, has been a speaker for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, Solvayand Wyeth, and served as a consultant to Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck and Servier. Q.Z., K.K., and W.D. are employees of and minor stockholders in Eli Lilly and Company.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors thank Rodney Moore PhD of inVentiv Health Clinical, a company which received funding from Eli Lilly and Company, for his assistance in drafting the manuscript.