Vortioxetine (Trintellix™, Brintellix™) is a prescription antipsychotic and antidepressant medication used to treat major depressive disorder in adults. Vortioxetine targets the neurotransmitter serotonin, which can affect mood, memory, and other cognitive functions [1]. Vortioxetine appears to improve some aspects of cognitive function in people with depression. Clinical evidence for people with conditions other than depression has been inconclusive. Common adverse events include nausea and diarrhea, and there are some known drug interactions.
Numerous meta-analyses and clinical studies have been carried out, but the clinical evidence for people with conditions other than depression is mixed and inconsistent. Our search identified:
Many clinical trials have examined the effects of vortioxetine on cognitive function; however, the vast majority of studies have been in people with major depressive disorder [2; 3; 4; 5; 6; 7; 8]. Meta-analyses of numerous randomized controlled trials have reported that vortioxetine significantly improves cognitive function compared to placebo or other commonly prescribed antidepressant drugs [3; 4; 6; 8]. Because test performance in people with major depressive disorder tends to indirectly improve with treatment, findings from these studies should not be used to infer potential cognitive benefits in those who do not have this condition.
A human brain imaging study suggested that vortioxetine modulates neural circuitry involved in working memory [9]. These effects were seen across both depressed and healthy subjects, suggesting that vortioxetine may support cognitive function independent of its effects on mood or depression.
Vortioxetine has multiple mechanisms of action. In a randomized controlled trial of depressed patients, vortioxetine treatment increased plasma levels of brain-derived neurotrophic factor (BDNF), a protein that supports the growth and survival of brain cells [10]. Preclinical studies suggest vortioxetine may enhance the release of four pro-cognitive neurotransmitters [11; 12] and may also affect gene expression, neurodevelopment, and neuroplasticity [13].
Based on a Delphi Consensus on the diagnosis and treatment of depression in dementia, experts agree that the gold standard antidepressants for Alzheimer’s patients are those that improve cognitive function and/or have a dual or multimodal mode of action, including vortioxetine, duloxetine, venlafaxine/desvenlafaxine, tianeptine, and mirtazapine [14]. However, antidepressants may be less effective in dementia patients compared to cognitively healthy individuals. In a randomized controlled trial of 100 patients with Alzheimer’s disease and depression, vortioxetine treatment for 12 weeks did not significantly improve depressive symptoms, cognitive functions, or daily functions compared to placebo [15]. Several small open-label clinical studies have reported improvement in cognitive function with vortioxetine in people with Alzheimer’s disease and depression, but because of the open-label design of the studies, placebo effects and practice effects cannot be ruled out [16; 17; 18].
Numerous clinical studies have assessed the safety of vortioxetine in patients with major depressive disorder [7; 8; 19; 20; 21; 22; 23; 24; 25; 26; 27]. The most common adverse effects with vortioxetine (5-20 mg/day) are nausea, headache, dizziness, dry mouth, diarrhea, constipation, vomiting, and itching. However, the label includes a black box warning for suicidal thoughts and behavior in children, adolescents, and young adults [1]. In elderly people, the EU health authorities recommend initiating treatment with a 5 mg/day dose and exercise caution when prescribing at a dose of 10 mg/day, due to higher systemic exposure of vortioxetine in people over 65 years old compared to those aged 45 years old [28].
Vortioxetine can increase the risk of bleeding or bruising when taken with other drugs that cause bleeding, including antiplatelet drugs (e.g., clopidogrel), NSAIDs (e.g., ibuprofen and aspirin), and blood-thinners (e.g., warfarin and dabigatran) [29; 30]. Vortioxetine must not be taken with antidepressants (e.g., fluoxetine, paroxetine, duloxetine, venlafaxine, rasagiline, selegiline) or other drugs that increase serotonin levels, such as MDMA (“ecstasy”) and St. John’s wort, as this can result in “serotonin syndrome”, a serious, possibly fatal, condition. Vortioxetine should not be taken with alcohol.
NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.
Vortioxetine (trade names, Trintellix™, Brintellix™) is a prescription drug used for treating major depressive disorder in adults and is available in oral tablet forms of 5, 10, and 20 mg. Clinical trials that tested the effects of vortioxetine on cognitive functions have used daily doses of 5–20 mg [4; 31]. Vortioxetine is not approved for treating cognitive decline or dementia.
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