H. Lundbeck A/S (Lundbeck) has announced results from FOCUS, a new study(1) showing that Brintellix (vortioxetine) 10 mg and 20 mg, met its primary endpoint in demonstrating superiority versus placebo in a composite score of two tests, the Digit Symbol Substitution Test (DSST) and Rey Auditory Verbal Learning Test (RAVLT), that measure cognitive function in adults with major depression.(2)
In this study, Brintellix was shown to improve measures of cognitive domains such as executive function, speed of processing and attention. These data were presented at the 52nd Annual Meeting at the American College of Neuropsychopharmacology (ACNP) in Hollywood, Florida.
FOCUS, a global, eight-week, randomised, double-blind, parallel-group, placebo-controlled, fixed-dose study evaluated the efficacy of Brintellix on cognitive function and major depression across three arms in around 600 patients aged 18-65 with an acute episode of major depression. Cognitive function was measured in a series of validated tests that assessed changes from baseline to week 8 on specific cognitive domains known to be impaired in major depression, including executive function, speed of processing, attention and memory.
On the study’s primary endpoint, Brintellix 10 mg and 20 mg demonstrated a statistically significant improvement in cognitive performance versus placebo (0.36 and 0.33 respectively, p<0.0001),(2) as assessed by a composite score of two validated neuropsychological tests, DSST and RAVLT. The improvement in cognitive performance was shown to include a direct effect of Brintellix and was not solely due to improvement in depressive symptoms (MADRS score). The study also showed significant improvements in cognitive symptoms for both Brintellix 10 mg and 20 mg assessed with a patient-reported outcome questionnaire (PDQ), which supports the clinical relevance of the findings in the neuropsychological tests.
The most commonly observed adverse events in patients treated with Brintellix (incidence ≥5%) were nausea (4.1%, 16.4%, and 20.8%) and headache (7.1%, 8.2%, and 12.6%) for placebo, Brintellix 10 mg and 20 mg, respectively. Overall, the most frequent primary reason for withdrawal was adverse events (AE) for placebo (4.1%), Brintellix 10 mg (3.6%) and Brintellix 20 mg (5.3%).(2)
“Neuropsychological tests are powerful indicators of cognitive function but are not routinely used in everyday, busy clinical practice, so it was equally important to understand how patients reported changes in cognitive symptoms that they experienced,” explained Dr. Roger McIntyre, Professor of Psychiatry and Pharmacology at the University of Toronto. “We are encouraged that Brintellix not only showed benefits in cognitive function in patients with major depression based on the neuropsychological tests, but that patients themselves also reported noticeable improvements in their cognitive symptoms.”
“In addition to the emotional symptoms of major depression, people with depression may also frequently experience a range of cognitive symptoms, including an impaired ability to think, concentrate or make decisions that can affect work, school and family life,” said Dr. McIntyre. “Reducing highly prevalent symptoms beyond mood, including those related to cognition, remains a huge challenge to achieving full disease remission.
While further studies are needed to confirm these findings, it is truly encouraging to have a new treatment option that may target a dimension of major depression that not only is a principal mediator of functional impairment (for example, workforce performance and attendance) but also a domain so highly related to patient reported quality of life and to feeling themselves again.”
Brintellix was recently approved by the US Food and Drug Administration (FDA) for the treatment of adults with Major Depressive Disorder (MDD) and in October 2013 recommended for approval by the Committee for Medicinal Products for Human Use (CHMP) under the European Medicines Agency (EMA) for treatment of adult patients with Major Depressive Episodes.
FOCUS study further builds upon established efficacy and tolerability profile of Brintellix
Brintellix 10 mg and 20 mg significantly improved depressive symptoms as measured by the traditional MADRS scale, with indication of dose response (-4.7 and -6.7 respectively, p<0.0001, MMRM ANCOVA).(2) The study confirmed Brintellix to have a good safety and tolerability profile and well tolerated overall.
These findings also add to previously reported clinical data suggesting Brintellix improved cognitive performance in elderly patients with major depression first presented at the 2012 American Psychiatric Association Annual Meeting.(3)
In addition, these data build upon preclinical in vivo evidence suggesting that the observed improvement in cognitive function in depressed patients of Brintellix may be supported by the pharmacological profile of Brintellix, which has shown positive effects on cognition in animal models through enhanced neurotransmission and synaptic plasticity in brain areas critical for cognitive function. However, the precise contribution of the individual targets to the observed pharmacodynamic profile remains unclear and caution should be applied when extrapolating animal data directly to man.
- ClinicalTrials.gov Identifier: NCT01422213
- McIntyre RS, Lophaven S, Olsen CK. Randomized, double-blind, placebo-controlled study of the efficacy of vortioxetine on cognitive dysfunction in adult patients with major depressive disorder (MDD). Neuropsychopharmacology 2013;38:S380-S381. [Conference abstract] Abstract T160.
- Katona C, Hansen T, Olsen CK. A randomized, double-blind, placebo-controlled, duloxetine-referenced, fixed-dose study comparing the efficacy and safety of Lu AA21004 in elderly patients with major depressive disorder. Int Clin Psychopharmacol. 2012 Jul;27(4):215-23.