FDA updates Trintellix® (vortioxetine) label to include data showing improvement in processing speed, an important aspect of cognitive function in acute Major Depressive Disorder (MDD)
- Category: Small Molecules
- Published on Thursday, 03 May 2018 10:29
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- Trintellix® (vortioxetine) is the first FDA-approved treatment for MDD to have data in the U.S. Prescribing Information showing a positive effect on processing speed, an aspect of cognitive function that is impaired in many patients with MDD
- Depression is the leading cause of disability worldwide, and is a major contributor to the overall global burden of diseasei
VALBY, Denmark I May 2, 2018 I H. Lundbeck A/S (Lundbeck) today announced the U.S. Food and Drug Administration (FDA) approved a supplemental new drug application for Trintellix® (vortioxetine). The clinical trials section of the U.S. label now includes data from the largest replicated clinical studies on an important aspect of cognitive function in acute major depressive disorder (MDD, depression). The FOCUS and CONNECT studies show Trintellix has a positive effect on processing speed, an important aspect of cognitive function observed in some patients with MDD.
Depression is a complex disorder that is more than just sadness. This condition has a wide range of symptoms, including depressed mood or loss of interest, physical symptoms such as sleep deprivation, and cognitive symptoms, like difficulty concentrating, slowed thinking or trouble thinkingii. Cognitive impairment is highly prevalent in depressioniii.
“Many of my MDD patients recognize the mood and physical attributes of depression, but do not often recognize that their cognitive symptoms may also be part of their depression. As part of a comprehensive treatment approach, it’s important for clinicians to talk to patients about all symptoms associated with depression. This updated Trintellix labelling regarding improvements in processing speed provides important information to improve discussions between healthcare providers and patients about their depression,” said Dr. Gregory Mattingly, Associate Clinical Professor, Department of Psychiatry, Washington University School of Medicine.
“With my depression, I felt like my thoughts slowed down. It was as if my brain just couldn’t keep up. After speaking with my doctor, I was surprised to learn that this could be part of my depression,” said David, a patient who spoke about his experience with depression at a FDA Advisory Committee meeting in 2016.
The new data in the label are from the FOCUS and CONNECT studies, which were specifically designed to assess the effect of Trintellix on certain aspects of cognitive dysfunction in adult patients (18-65 years) with depressioniv,[v]. These two eight-week, randomized, double-blind, placebo-controlled studies of Trintellix 10 and 20 mg/day used a neuropsychological measure, known as the Digit Symbol Substitution Test (DSST). The DSST is a neuropsychological test that most specifically measures processing speed, an aspect of cognitive function that may be impaired in MDD. The effects observed on DSST may reflect improvements in depression. Comparative studies have not been conducted to demonstrate a therapeutic advantage over other antidepressants on the DSST.
The FDA approved Trintellix on 30 September 2013 for the treatment of MDD in adults. Vortioxetine is furthermore approved in 77 countries (including Europe, Canada, Chile, China, Mexico, Argentina, South Korea, Turkey, Australia, Hong Kong, Singapore and South Africa). It is available in more than 60 countries to date. Outside North America, vortioxetine is recognized as Brintellix®.
About Major Depressive Disorder (MDD)
MDD is a complex mental health illness that affects approximately 14 million people annuallyvi. Depression is the leading cause of disability worldwide, and is a major contributor to the overall global burden of diseasei. MDD may trigger emotional, cognitive and physical symptoms, which includes depressed mood, loss of interest or pleasure, significant weight loss or gain or change in appetite, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue or loss of energy, feelings of worthlessness or excessive guilt, diminished ability to think or concentrate, or indecisiveness, and recurrent suicidal ideation. Despite treatment, many symptoms of depression may not be addressed.vii
About Trintellix (vortioxetine)
The mechanism of the antidepressant effect of Trintellix is not fully understood. It is an inhibitor of serotonin (5-HT) reuptake and that is thought to be a mechanism of its action. It is also an agonist at 5-HT1A receptors, a partial agonist at 5-HT1B receptors and an antagonist at 5-HT3, 5-HT1D and 5-HT7 receptors. The contribution of each of these activities to Trintellix’s antidepressant effect has not been established. It is considered to be the first and only compound with this combination of pharmacodynamic activity. The clinical relevance of this is unknown.
Trintellix was discovered by Lundbeck researchers in Copenhagen, Denmark. The clinical trial program in the U.S. was conducted jointly by Lundbeck and Takeda, and Takeda holds the new drug application for the U.S. market. Trintellix is a trademark of H. Lundbeck A/S and is used under license by Takeda Pharmaceuticals U.S.A., Inc.
The World Health Organization has issued an Anatomical Therapeutic Chemical (ATC) code for Trintellix that places it in the category of “Other” antidepressants.
The most commonly observed adverse events in MDD patients treated with Trintellix in 6-8-week placebo-controlled studies (incidence greater than or equal to 5 percent and at least twice the rate of placebo) were nausea, constipation and vomiting. Overall, 5 to 8 percent of the patients who received Trintellix 5 to 20 mg/day in short-term trials discontinued treatment due to an adverse reaction, the most common being nausea, compared with 4 percent of placebo-treated patients in these studies. Trintellix and other antidepressants may cause serious side effects. See Important Safety Information below.
In clinical studies, Trintellix had no significant effect on body weight as measured by the mean change from baseline in 6-8-week placebo-controlled studies. In the 6-month, double-blind, placebo-controlled phase of a long-term study in patients who had responded to Trintellix during the initial 12-week, open-label phase, there was no significant effect on body weight between Trintellix and placebo-treated patients. Trintellix has not been associated with any clinically significant effects on vital signs, including systolic and diastolic blood pressure and heart rate, as measured in placebo-controlled studies.
The recommended starting dose of Trintellix is 10 mg once daily without regard to meals. The dose should then be increased to 20 mg/day, as tolerated, because higher doses demonstrated better treatment effects in trials conducted in the U.S. A dose decrease down to 5 mg/day may be considered for patients who do not tolerate higher doses. The available doses provide important flexibility for physicians to help address the variability of patient needs.
Trintellix is available as 5 mg, 10 mg and 20 mg tablets.
About H. Lundbeck A/S
H. Lundbeck A/S (LUN.CO, LUN DC, HLUYY) is a global pharmaceutical company specialized in psychiatric and neurological disorders. For more than 70 years, we have been at the forefront of research within neuroscience. Our key areas of focus are Alzheimer's disease, depression, Parkinson's disease and schizophrenia.
Our approximately 5,000 employees in 55 countries are engaged in the entire value chain throughout research, development, manufacturing, marketing and sales. Our pipeline consists of several late-stage development programmes and our products are available in more than 100 countries. We have production facilities in Denmark, France and Italy. Lundbeck generated revenue of DKK 17.2 billion in 2017 (EUR 2.3 billion; USD 2.6 billion).