Treatment discontinuation and tolerability as a function of dose and titration of duloxetine in the treatment of major depressive disorder

Purpose: We sought to better understand how dose and titration with duloxetine treatment may impact tolerability and treatment discontinuation in patients with major depressive disorder. Patients and 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. Conclusion: 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.