Clinical Summary
Clinical Summary: Effectiveness and Tolerability of Supratherapeutic Dosing of Vortioxetine in Patients With Treatment-Resistant Depression
Patients with treatment-resistant depression often remain symptomatic after multiple antidepressant trials, and standard next-step options are not always available or feasible. This article addresses a practical question for such patients: whether increasing vortioxetine above the approved 20 mg/d maximum can improve depressive severity without introducing serious tolerability problems.
Design
This retrospective observational naturalistic study
N
Fifty-six patients
Population
patients with MDD who experienced an episode of treatment-resistant depression
Duration
after 8 weeks of treatment with supratherapeutic doses
Key Findings
- Clinical Global Impressions scores significantly improved from T0 to T1, from 4.45 ± 0.74 to 2.63 ± 1.05 (P < .001).
- Thirty-seven patients received vortioxetine 30 mg/d, and the remaining 19 patients were treated with vortioxetine 40 mg/d.
- A dose reduction to a daily dose of ≤ 20 mg was made before 8 weeks of treatment for 35 patients because of nausea (22 patients) or lack of improvement (13 patients).
- Weight gain (defined as weight increased by more than 5% from baseline) and nausea were observed in 6 (10.7%) and 22 (39.3%) of the patients treated with vortioxetine 30 and 40 mg, respectively.
- No serious adverse events emerged during the observation period, and no symptoms or signs of serotonin syndrome were observed or recorded.
Clinical Bottom Line
In treatment-resistant depression, vortioxetine 30-40 mg/d was associated with a significant reduction in CGI severity over 8 weeks and no serious adverse events. The main practical limitation was tolerability, with nausea driving many dose reductions back to ≤ 20 mg/d.
Practice Implications
- Consider supratherapeutic vortioxetine only in patients with treatment-resistant depression who have failed 2 or more different oral antidepressants given at an adequate dose and for a sufficiently long period.
- Use slow titration and reassess early, because 35 patients required dose reduction before 8 weeks, including 22 for nausea.
- Counsel patients that nausea was the most common adverse effect and that weight gain occurred in 6 (10.7%) patients; discuss the possibility of returning to ≤ 20 mg/d if tolerability is poor or improvement is lacking.
- Monitor closely when patients are taking concomitant medications, since 38 patients were receiving concomitant medications when vortioxetine was administered.
