A Randomized, Double-Blind Study of Increasing or Maintaining Duloxetine Dose in Patients Without Remission of Major Depressive Disorder After Initial Duloxetine Therapy

Objective: To compare efficacy of remaining on duloxetine 60 mg to increasing to 120 mg q.d. in patients without remission of major depressive disorder (MDD) after 6 weeks at 60 mg.

Method: This double-blind, parallel study was conducted in adults with MDD (DSM-IV-TR criteria). Patients initially randomly assigned to duloxetine 60 mg for 6 weeks with a 17-item Hamilton Rating Scale for Depression (HAM-D-17) score > 7 (nonremitters) were randomly reassigned to 60 mg or 120 mg duloxetine for 8 weeks. Patients with a HAM-D-17 score <= 7 (remitters) continued on duloxetine 60 mg. The primary objective was to compare time to remission (HAM-D-17 score <= 7) between rerandomized groups. Secondary objectives included evaluation of HAM-D-17 and Inventory of Depressive Symptomatology assessments and safety and tolerability evaluations in nonremitters and remitters. Patients were enrolled from November 2004 to January 2006.

Results: Nonremitters randomly reassigned to 60 mg and 120 mg achieved similar time to remission and similar improvements on efficacy measures. Remission was achieved in 30.0% and 30.5% in the 60-mg and 120-mg groups, respectively. Of the remitters, 85.5% continued to be in remission at study end. Other than a greater incidence of hyperhidrosis and chest pain in the 120-mg group, adverse events were similar between groups, as were discontinuations due to adverse events.

Conclusion: Nonremitters to 60 mg of duloxetine for 6 weeks randomly reassigned to 60 mg or 120 mg of duloxetine demonstrated continued symptom improvement in the 8-week extension. Patients randomly reassigned to 120 mg showed no advantage over those who continued on 60 mg. Duloxetine was well tolerated at both doses and had similar safety profiles.

Trial Registration: clinicaltrials.gov Identifier: NCT00191061