title: Treatment discontinuation and tolerability as a function of dose and titration of duloxetine in the treatment of major depressive disorder.
abstract: OBJECTIVE
  We sought to better understand how dose and titration with duloxetine treatment may impact tolerability and treatment discontinuation in patients with major depressive disorder.
  
  
  METHODS
  We investigated Phase III duloxetine trials. Group 1 was a single placebo-controlled study with a 20 mg initial dose and a slow titration to 40 and 60 mg. Group 2 was a single study with a 40 mg initial dose and final "active" doses of 40 and 60 mg (5 mg control group), with 1-week titration. Group 3 consisted of eight placebo-controlled studies with starting doses of 40, 60, and 80 mg/day with minimal titration (final dose 40-120 mg/day). Tolerability was measured by rate of discontinuation due to adverse events (DCAE).
  
  
  RESULTS
  The DCAE in Group 1 were 3.6% in the 60 mg group, 3.3% in the 40 mg group, and 3.2% in the placebo group. In Group 2, the DCAE were 15.0% in the 60 mg group, 8.1% in the 40 mg group, and 4.9% in the 5 mg group. In Group 3, the DCAE were 9.7% and 4.2% in the duloxetine and placebo groups, respectively.
  
  
  CONCLUSIONS
  This study suggests that starting dose and titration may have impacted tolerability and treatment discontinuation. A lower starting dose of duloxetine and slower titration may contribute to improving treatment tolerability for patients with major depressive disorder.
authors.affiliation: Eli Lilly Japan K.K., Medicines Development Unit Japan, Medical Science, Kobe, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Harada
authors.affiliation: Department of Neuropsychiatry, Kinki University Faculty of Medicine, Osakasayama, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Shirakawa
authors.affiliation: Eli Lilly Japan K.K., Medicines Development Unit Japan, Statistical Science, Kobe, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Satoi
authors.affiliation: The University of Texas Health Science Center School of Medicine, Houston, TX, USA.
authors.forename: Lauren B
authors.initials: LB
authors.lastname: Marangell
authors.affiliation: Eli Lilly and Company, Neuroscience, Indianapolis, IN, USA.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Escobar
keywords: antidepressant; dose; duloxetine; major depressive disorder; titration
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