Alzheimer’s Patients Linked to Greater Cognitive and Mood Improvements Due to Antidepressant Vortioxetine

Studies on an antidepressant medication that primarily treats major depressive disorder (MDD) in adults showed mixed results in people with Alzheimer’s disease who also experience depressive symptoms.

Vortioxetine has been shown in some clinical trials to reduce depressive orders and improve mood and cognitive function in Alzheimer’s patients. However, the prescription medication did not provide these benefits to participants in other studies.

Vortioxetine targets serotonin, a neurotransmitter that plays a role in regulating mood, memory, and other cognitive functions. Neurotransmitter systems help neurons to communicate with each other throughout the body. However, Alzheimer’s significantly disrupts neurotransmitters in the brain, which results in the disease’s progression and symptoms.

Memory loss is the most common symptom of Alzheimer’s disease, along with confusion, loss of reasoning skills, depression, and changes in mood and personality. As the neurodegenerative disease progresses, the symptoms also progress until they disrupt daily life activities and take away a person’s independence.

According to the Alzheimer’s Association, more than seven million Americans 65 and older are living with Alzheimer’s. While there is no cure for the disease, the symptoms are treated with various medications. Researchers have been developing new drugs to fight different aspects of Alzheimer’s as well as using existing medications to treat the disease. However, studies show that certain antidepressants can increase the rate of cognitive decline, while others improve cognitive function.

Study Shows Vortioxetine Benefits Alzheimer’s Patients

Vortioxetine is primarily used for MDD, but the prescription medication is being tested in clinical trials to evaluate its effectiveness in treating depression in people with Alzheimer’s disease. For example, a 2025 study compared the effects of vortioxetine with other traditional antidepressants in people with Alzheimer’s disease who had depressive symptoms.

The 12-month study conducted by Eduardo Cumbo and Daniela Migliore, researchers at the Neurodegenerative Disorders Unit in Caltanissetta, Italy, involved 108 participants with mild Alzheimer’s disease and depressive symptoms.

Participants were randomly assigned to receive either vortioxetine or one of three other antidepressants—escitalopram, paroxetine, or bupropion. They also continued with their routine treatment of cholinesterase inhibitors or memantine, both of which are used to slow the decline in cognitive functions associated with Alzheimer’s.

Participants were assessed at the start of the study, after six months, and after 12 months. Cognitive functions were measured using several established tests that evaluated overall cognitive ability, non-verbal reasoning, problem-solving, verbal working memory, and depression severity.

At the end of the study, researchers saw some improvement on cognitive tests in participants in all groups. However, the most significant and most consistent improvements came from participants who took vortioxetine. These participants:

• Improved by nearly three points in the test that evaluated overall cognitive ability, including memory, orientation, and language. This was a statistically significant change.

• Showed significant improvements in selective attention and nonverbal reasoning. Participants taking other antidepressants tended to improve less, and in some cases, not significantly.

• Showed a more pronounced reduction in depressive symptoms, even though depressive symptoms decreased in all groups over the 12-month period. On both scales that measured depression, the vortioxetine group’s scores dropped by about seven points from the start of the trial—an improvement considered clinically meaningful.

In comparing each group directly, vortioxetine performed better than the other antidepressants on most cognitive measures. It was the most noticeable when compared to paroxetine, which has properties that can impair cognition in older adults. Escitalopram and bupropion showed moderate improvements in certain attention measures, but not as significant as those of vortioxetine.

Additionally, the participants were able to tolerate vortioxetine, according to the study, which noted that side effects were “relatively uncommon and generally mild.” The two most reported side effects from the medication were nausea and headache. One participant who took paroxetine and another participant who took bupropion stopped taking the medicines due to the side effects. According to the researchers, no serious adverse events or deaths were reported during the study.

Separate Study Shows Vortioxetine Did Not Benefit People With Alzheimer’s

Participants in a 2022 study involving vortioxetine did not see as many benefits as those in the 2025 study. A team of researchers in South Korea carried out a study to examine how effective the medication was at reducing depressive symptoms or cognitive impairment in Alzheimer’s patients with depression. The investigators also wanted to determine whether vortioxetine would help improve cognitive function and activities of daily living (ADL).

The study involved 100 patients with mild to moderate Alzheimer’s disease with depression. The participants were randomly assigned to 12 weeks of daily treatment with either vortioxetine or a placebo. For the most part, participants were able to tolerate vortioxetine. However, nausea and diarrhea were the most commonly reported side effects in both study groups.

At the end of the study, researchers found that the drug was not significantly effective in reducing depression symptoms or cognitive impairment in the participants.

“There was no statistically significant difference between the two groups in terms of depressive symptoms, cognitive functions, and ADL,” the study stated. “Further, the percentage of adverse events and drug discontinuation between the vortioxetine and placebo groups was similar.”

The study concluded that vortioxetine “might not be effective in reducing depressive symptoms or cognitive impairment in AD patients with depression.”

Researchers Discuss Study Results

The South Korean researchers wrote that their results differed from those of other studies that showed vortioxetine improved depressive symptoms. The investigators suggested that one possible explanation is that they included patients with more severe cognitive impairment and depressive symptoms.

“It is possible that the more severe the cognitive impairment in AD patients, the more likely that their response to antidepressant treatment would be poor,” the study stated. “Specifically, clinically more depressed patients could show an increase in severe neurodegeneration.”

Researchers also noted that patients may not have been able to report the effects of vortioxetine because of their severe cognitive decline.

In addition, Cumbo and Migliore discussed limitations in their 2025 study, including:

• The study only included patients with mild Alzheimer’s, so the results may not extend to those with more advanced disease.

• The study could not determine whether the participants’ cognitive improvements were a result of vortioxetine’s pharmacological effects or indirectly through relief of depressive symptoms.

Researchers in both studies concluded that more studies are needed on antidepressant therapy in Alzheimer’s disease patients.

Source Links:

https://www.newsbreak.com/psypost-332799984/4166176789693-antidepressant-vortioxetine-linked-to-greater-cognitive-and-mood-improvements-in-alzheimer-s-patients
https://journals.sagepub.com/doi/10.1177/13872877251340084
https://www.alz.org/alzheimers-dementia/facts-figures
https://pmc.ncbi.nlm.nih.gov/articles/PMC9048008/