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In this retrospective observational study, supratherapeutic vortioxetine was associated with improved clinical severity scores over 8 weeks in patients with treatment-resistant depression. Clinical Global Impressions scores improved from 4.45 b1 0.74 at baseline to 2.63 b1 1.05 at follow-up, with a statistically significant change (P < .001). The study included 56 adults with major depressive disorder who had failed to respond to 2 or more antidepressants and were treated with vortioxetine 30 mg/day or 40 mg/day.

The study included adults with major depressive disorder and treatment-resistant depression, defined as failure to respond to 2 or more different oral antidepressants given at an adequate dose and for a sufficiently long period. Patients also had to have a Montgomery-Asberg Depression Rating Scale score of at least 20 and be treated with vortioxetine 30 mg/day or 40 mg/day. Fifty-six patients were enrolled, with a mean age of 51.1 b1 9.3 years; 32 were female and 24 were male.

Patients were treated with vortioxetine 30 mg/day or 40 mg/day after escalation above the usual maximum recommended dose of 20 mg/day. Of the 56 patients, 37 received 30 mg/day and 19 received 40 mg/day. Slow titration was used for all patients, and outcomes were assessed from the first day the dose exceeded 20 mg/day to 8 weeks later, or earlier if the dose had to be reduced.

The main reported adverse effects were nausea and weight gain, while no serious adverse events were observed during the 8-week observation period. Nausea occurred in 22 patients (39.3%), and weight gain, defined as more than 5% above baseline weight, occurred in 6 patients (10.7%). The authors also reported that no symptoms or signs of serotonin syndrome were observed or recorded.

Dose reduction to 20 mg/day or less was common in this cohort. Thirty-five of 56 patients had their dose reduced before 8 weeks, including 22 because of nausea and 13 because of lack of improvement. In this study, if dose reduction occurred early, the endpoint assessment was taken on the day vortioxetine was discontinued or reduced to 20 mg/day or less.

No serious adverse events were reported during the observation period, and no symptoms or signs of serotonin syndrome were observed or recorded. The authors also stated that no worsening of suicidal ideation or suicidal behaviors was recorded during the study.

This study suggests potential benefit, but the evidence is preliminary and should not be interpreted as definitive proof of efficacy. The authors found a significant improvement in CGI scores over 8 weeks, but the study was retrospective, observational, nonrandomized, lacked a placebo arm, and included a small sample. They also noted possible Berkson bias, meaning the sample may have included patients with more severe illness than the average patient with treatment-resistant depression.

The main limitations were the small sample size, retrospective design, lack of randomization, and lack of a placebo arm. The authors also cited Berkson bias, because the study may have selected patients with more severe illness than the average patient with treatment-resistant depression. For that reason, they stated that the results should be considered very preliminary.