Vortioxetine for the Treatment of Major Depression and Co-morbidities After Traumatic Brain Injury (TBI)
Status:
Withdrawn
Trial end date:
2018-10-01
Target enrollment:
Participant gender:
Summary
Traumatic brain injury (TBI) is a major public health problem with an annual incidence of
about 1.7 million per year. TBI is associated with various long-term morbidities. Among them,
psychiatric disturbances are the major cause of chronic disability and poor quality of life.
Major depression is the common psychiatric sequela post TBI with rates ranging from 13% at 1
year to 60% at 8 years after TBI. Major depression after TBI (henceforth referred to as TBI
depression) is often associated with comorbid neuropsychiatric symptoms (NPS) such as
anxiety, aggression, substance abuse and cognitive deficits that often makes treatment
difficult. Despite increased rates of depression, there is no Food and Drug Administration
(FDA) approved drug/s for its treatment.
The investigators propose to address these limitations by use of a novel serotonergic agent,
vortioxetine, which has a multimodal mechanism of action through serotonin transporter (SERT)
inhibition, 5-hydroxytryptamine (5-HT)3, 7, and 1D receptor antagonism, 1B receptor partial
agonism, and 1A receptor agonism.
Overarching Goal: The overarching goal of the proposed pilot study is to determine the
effectiveness and safety of vortioxetine for the treatment of post-TBI depression and
co-morbid NPS.
Study Design: The study design will include a DBPCT of 30 TBI patients of all severities who
meet the DSM 5 criteria for major depression. A total of 150 will be consented to allow for
screen failures. Written informed consent will be obtained from these patients. Subjects will
be followed for a total of 12 weeks. Subjects will be randomized to either the vortioxetine
arm (N=15) or placebo arm (N=15). The treatment group will receive vortioxetine 10mg per day,
which will be increased to 20 mg or decreased to 5 mg, if deemed clinically necessary, at
week 4 or 8. Subjects will have a total of 4-5 visits: Baseline evaluation (1 or 2 visits)
and follow-up visits at weeks 4, 8 and 12. Well-validated psychiatric instruments will be
used to compare the effectiveness of vortioxetine versus placebo treatment at week 12
compared to baseline Relevance: This study has the potential to provide strong preliminary
evidence for the use of vortioxetine as a safe and novel agent for treatment of TBI
depression and its psychiatric co-morbidities. If found to be effective, results from this
study can be used to design larger studies and also determine brain changes associated with
its use via neuroimaging.