All seven studies included in these analyses were randomized, multicenter, double-blind, active comparator- and/or placebo-controlled clinical trials. This represented all available data from U.S.-based, placebo-controlled, clinical trials of duloxetine medication in patients with MDD (data from two additional studies carried out in Eastern Europe were not included, since no African-American patients were enrolled). Key design elements of all the studies were similar, since pooling of data from these trials was anticipated during study design. All studies incorporated double-blind, variable-duration placebo lead-in periods to blind patients and investigators to the start of active therapy. All studies were of similar duration (7-9 weeks). Each study included initial weekly assessments followed by biweekly assessments. Study protocols were reviewed and approved by the ethical review board at each center in accordance with the principles of the Declaration of Helsinki, and all patients provided written informed consent prior to the administration of any study procedures or study drug. The numbers of patients randomized in each study are summarized in Table 1. Safety and efficacy results from studies l, 4, 5, 6, and 7 have been published previously. Summaries of data from studies 2 and 3 are available online at (study 2:
Patients were >18 years of age, met criteria for MDD as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), and had a 17-item Hamilton Rating Scale for Depression (HAMDn) total score >15 and a Clinical Global Impression of Severity (CGI-S) score >4 at two screening visits. In study 7, patients were also required to have a Brief Pain Inventory (BPI) average pain score >2 at baseline. Patients were excluded for the following reasons: a current and primary axis-I disorder other than MDD, an axis-II disorder that could interfere with protocol compliance, lack of response of the current depressive episode to two or more adequate courses of canadian antidepressant therapy, a serious medical illness, a serious risk of suicide, a history of substance abuse or dependence within the last year, or a positive urine drug screen.
Table 1. Numbers of randomized patients
60 mg QD
|12 3 4 5 6 7||70 (7, 57) 75 (5, 68) 90 (12, 71) 89 (8, 74) 122 (6, 103) 139 (10, 109) 141 (11, 112)||91 (9, 75) 86 (4, 72)||123 (3, 107) 128 (13, 100) 141 (14, 115)||84 (12, 68) 91 (5, 77)||70 (3, 62) 82 (6, 72)|
|Total||726 (59, 594)||896 (69, 748)|
|1 Data presented in the form T (AA, C), where T=total number of patients, AA: number of African-American patients, C: number of Caucasian patients; a: administered 20 mg twice daily (BID); b: administered 40 mg BID; c: Administered as a forced titration from 20 mg BID to 60 mg BID|
Concomitant medications with primarily central nervous system activity were not permitted, with the exception of episodic use of chloral hydrate or Zolpidem for insomnia. Chronic use of prescription analgesic medications was not allowed; episodic use was permitted at the discretion of the physician in charge of the study. Use of antihypertensive medications was not permitted unless the patient had been on a stable dose for at least three months prior to study entry. Patients were assigned to Caucasian or African-American groups based upon their responses to a question on the Clinical Report Form (CRF), which addressed ethnic origin. Choices of ethnic origin on the CRF were Caucasian (European, Mediterranean, Middle Eastern), African descent, Hispanic, East/Southeast Asian, Western Asian or Other (mixed-racial parentage, American Indian, Eskimo).