FDA Advisory Committee on Vortioxetine Treatment of Cognitive Dysfunction in Major Depressive Disorder
Thank you for the opportunity to speak today. My name is Dr. Stephanie Fox-Rawlings. I was previously a neuroscientist at Children’s National Medical Center and now am a Senior Fellow at the National Center for Health Research. Our research center analyzes scientific and medical data to provide objective health information to patients, providers and policy makers. We do not accept funding from the drug or medical device industry. I have no conflict of interest.
We want effective treatments to reach patients as quickly as possible. The cognitive dysfunction symptoms of MDD greatly contribute to the difficulties patients face, but most treatments show little improvement on cognitive tests. Patients want treatments for these symptoms, but need to know that a drug marketed to do so is actually effective.
The data discussed today suggests that vortioxetine may ameliorate some cognitive symptoms. However, more evidence is required. In the FOCUS study, the main test that demonstrated improvement was the DSST, which is under debate to determine if it provides a meaningful measure of the diverse domains of cognitive function. If this test is not a comprehensive measure of cognitive function, then we can only rely on the data from the CONNECT study. The improved scores on the tests in this study are encouraging. However, these results need to be replicated. Thus, there is not enough data to fulfill the statutory requirements to state that the drug is effective.
More research is necessary. The cognitive deficits experienced by patients need to be fully described. The cognitive tasks improved by this drug must be clarified. And the extent that treatment influences daily function must be determined. To this last point, a treatment can statistically improve a test score without producing a meaningful improvement in daily life.
There are also concerns over the lack of diversity of participants included in the pivotal studies. There is inadequate racial diversity. Although both studies were conducted in multiple countries, more than 85% of the participants were white. Thus, there were not enough patients to conduct meaningful subgroup analyses to determine the impact of the drug on people of color.
The age of participants is also a concern. Cognitive dysfunction is common in elderly MDD patients. The sponsors even stated that their investigation followed up on the results of a clinical trial in elderly patients. However, the age cutoff for both pivotal studies was 65 years. Furthermore, subgroup analysis by age only showed improvement in DSST scores in only one of the two studies. No subgroup analyses were conducted for any of the other cognitive tests.
Lastly, the time frame for both of these studies was 8 weeks. Cognitive dysfunction can continue to be a problem after a depressive episode is resolved, and depressive episodes can last much longer than 8 weeks. It is important to know whether any improvements would be maintained over a longer term of at least a few months.
In conclusion, based on the data presented and discussed today, I urge you to conclude that there is insufficient data to claim that vortioxetine is effective in providing a meaningful improvement in cognitive dysfunction associated with MDD. Thank you for the opportunity to speak today and for consideration of our views.
UPDATE:
On February 3, 2016, the FDA advisory committee voted 8 to 2 to recommend that the FDA expand approval of vortioxetine (Brintellix) to treat cognitive dysfunction (such as slow or foggy thinking) associated with major depressive disorder. Although vortioxetine is already approved for the treatment of major depression, the recommended labeling would have made this the only drug in the U.S. that could advertise as improving cognitive problems related to depression. However, in late March, the FDA denied approval for the treatment of cognitive problems, because of the lack of evidence – just as we recommended. The press release from the manufacturers is available.