Vortioxetine Significantly Reduces Symptom Severity in Patients With MDD

Jay Fawver, MD, Ambulatory Section Chief, Parkview Behavioral Health Institute, Fort Wayne, IN, answers questions about a study that found vortioxetine significantly reduces depression severity in patients with major depressive disorder (MDD). The study also found vortioxetine improves anxiety, sexual dysfunction, and sleep in patients with MDD. 

Researchers presented the findings in a poster titled "Treatment Patterns and Outcomes in Patients With Major Depressive Disorder Treated With Vortioxetine in a Real-World Setting " at the 2021 Psych Congress.

Question:  What prompted you and your colleagues to investigate the effectiveness of vortioxetine in patients with MDD?

Answer:  Clinicians are often skeptical of the real-world relevance of randomized placebo-controlled antidepressant trials. We wanted to retrospectively examine the charts of adults diagnosed with major depression who had been prescribed vortioxetine in an outpatient practice.  These patients typically previously failed prior antidepressants and exhibited several psychiatric and medical comorbidities that would have led to their being excluded in clinical trials.  Additionally, we wanted to examine the practical utility of patient-rated outcome metrics to measure meaningful treatment progress.

Q:  Please briefly describe the study method.

A:  Charts were reviewed from 1242 outpatients from a single office from 2014 - 2018 with major depressive disorder who had been initiated on vortioxetine and followed over the course of 12 weeks.  This study included almost exclusively patients who had been treatment-refractory, as many were 1) referred from primary care practices or other mental health clinicians and 2) typically required step therapy failures of at least 2 generic medications prior to starting vortioxetine. 

Psychiatric comorbidities were common, as > 40% of patients had 3 or more psychiatric diagnoses, which were expected comorbidities with major depression that you would typically see in a naturalistic outpatient setting.  Patient-rated outcome metrics were utilized in this ambulatory setting to gather information not only for depression, but also for anxiety, cognition, and functional outcomes. 

Additionally, the use of the Patient-Rated Inventory of Side Effects (PRISE) and narrative note review provided additional information concerning insomnia and sexual disturbances.  At the beginning of this 12-week analysis, vortioxetine was typically titrated the first 2 weeks of treatment while simultaneously tapering the previous antidepressant(s).  Augmentation or combination agents may have been continued, but they were also tapered or decreased as patient improvement was evident

Q:  Please summarize the most significant findings.

A: Measures in symptomatic relief, functionality and medication adherence were examined:

1. The primary outcome measure of the PHQ-9 improvement at 12 weeks was achieved with statistical significance.  More practically important, using the guideline of an effect size > 0.5 representing clinical significance, a moderate effect size of 0.728 was shown for the relief of depressive symptoms.

2. Typically, patients experiencing depression with anxious comorbidities would be considered for a sedating antidepressant.  In this analysis, despite vortioxetine typically lacking significant sedation, it had a moderate effect size for improving symptoms of anxiety (assessed by GAD-7).

3. In addition to anxiety relief, other secondary measures having moderate effect sizes included improvement of cognition (assessed by the PDQ-20) and relief of insomnia (assessed by narrative notes).  Consistent with package labeling demonstrating that sexual dysfunction improved upon switching from SSRIs associated with treatment-emergent sexual dysfunction to vortioxetine, this study demonstrated a mild effect size for sexual dysfunction improvement.  This improvement in sexual dysfunction occurred despite this study not recruiting patients with prior sexual disturbances.

4. Improvement in workplace "presenteeism" (based upon narrative notes) demonstrated a moderate effect size, suggesting that patients were more productive at work.

5. Finally, approximately 2 out of 3 patients remained on vortioxetine over the course of 12 weeks.  Those who discontinued may have stopped it not only due to lack of efficacy or intolerability but due to cost prohibition, nonadherence, or merely the desire to trial another medication.  These are reasons commonly evident in a naturalistic setting

Q:  What was the dosing for vortioxetine at 12 weeks?

A: 17% of patients were taking 5 mg daily

53% of patients were taking 10 mg daily

30% of patients were taking 20 mg daily.

Q:  What are the practical applications of your findings for clinicians treating MDD?

A:  This 12-week retrospective, naturalistic study of vortioxetine for major depressive disorder in adults demonstrated not only statistical significance, but clinically meaningful significance in the relief of depressive symptoms.  Secondarily, there was clinically significant relief with anxious symptoms, insomnia, and cognitive disturbances without worsening of sexual functioning.   Patients in this study had typically failed on at least 2 antidepressant trials and exhibited psychiatric and medical comorbidities common in an outpatient setting, such that these patients would have typically been excluded in randomized antidepressant trials.  Very importantly, functionality improvement was demonstrated by improved workplace productivity.  Finally, this study affirms that in a busy outpatient practice, patient-rated outcome metrics can be practically utilized to follow meaningful treatment progress of several symptomatic dimensions.

Jay Fawver, MD, is the Ambulatory Section Chief at the Parkview Behavioral Health Institute which includes Mind-Body Medicine, in Fort Wayne, Indiana. Dr Fawver is a clinical professor of psychiatry at the Indiana University School of Medicine, Indianapolis, Indiana and is board certified by the American Board of Psychiatry and Neurology. Since 1997, he has been the host and producer of the Public Broadcasting System’s Matters of the Mind with Dr. Jay Fawver, a weekly 30-minute live call-in television program addressing mental health topics.