2 psychiatric drugs can help improve cognition

Updated 2 years ago on February 04, 2023

  • Researchers at the University of Colorado School of Medicine analyzed drugs that can block the action of the apolipoprotein E4 (APOE4) protein, which is a risk gene for Alzheimer's disease.
  • In selecting various medications that could have this effect, they came across two commonly prescribed psychiatric drugs: imipramine and olanzapine.
  • Researchers observed that the use of these drugs in patients with Alzheimer's disease was associated with a more accurate clinical diagnosis and improved cognition, compared to other antidepressants and antipsychotics.

Alzheimer's disease is a form of dementia that initially causes memory loss and cognitive decline. Eventually, the disease can progress to the point where a person loses cognitive function completely.

According to a study published in Alzheimer's Research & Therapy in June 2022, there are two drugs with Food and Drug Administration (FDA) pre-approval that may be useful for people with Alzheimer's disease. These drugs, imipramine and olanzapine, are already used to treat psychiatric conditions.

The study was led by a team of scientists from the University of Colorado Anschutz Medical Campus in Aurora.

History of Alzheimer's disease

There are several forms of dementia, including mixed dementia, dementia with Lewy bodies, and Alzheimer's disease. According to the Alzheimer's Association, Alzheimer's disease is the most common form of dementia and accounts for 60 to 80% of dementia cases.

Although Alzheimer's disease can affect younger people, including people in their 30s and 40s, it does not happen very often. Alzheimer's disease usually develops in people age 65 and older.

TheNational Institute on Aging (NIA) includes some of the following signs and symptoms of Alzheimer's disease:

  • memory loss
  • confusion
  • mood changes
  • poor judgement
  • language difficulties
  • difficulties in completing tasks consisting of several steps
  • aggression

Scientists don't fully understand what causes Alzheimer's disease, but some believe a combination of genetic and environmental factors may lead to the development of the disease.

There is no cure for Alzheimer's disease, but health care providers may prescribe medications such as donepezil or galantamine to reduce symptoms. In some cases, health care providers may prescribe psychiatric medications to Alzheimer's patients if other treatments have not helped symptoms of aggression, anxiety, and depression.

Psychiatric drugs to treat Alzheimer's disease

A research team from the University of Colorado School of Medicine was primarily interested in finding drugs that could block APOE4, which they hypothesized could reduce the likelihood of developing Alzheimer's disease.

In studying drugs that might have this effect, the team noticed that two were commonly prescribed to treat mental illness. They were imipramine and olanzapine; imipramine is a tricyclic antidepressant and olanzapine is an antipsychotic.

"Then we looked at the huge database of the National Alzheimer's Disease Coordinating Center and asked what happens when someone is prescribed these drugs for a routine indication but they turn out to have Alzheimer's," says Huntington Potter, PhD, professor of neurology and director of the Alzheimer's Disease and Cognitive Disease Center at the University of Colorado Anschutz Medical Center.

Potter and his team observed that patients with Alzheimer's disease taking imipramine and olanzapine, compared with other antidepressants and antipsychotics, showed improvements in cognition that could help reverse the progression of the disease.

"People who took these drugs had improved cognition and actually improved their clinical diagnosis," Potter said. "Compared to those who didn't take these drugs, they went from Alzheimer's disease to mild cognitive impairment or mild cognitive impairment to normal."

Next, the researchers looked at biological sex to see if there was a difference in how men and women responded to the cumulative effect of taking imipramine. The calculations showed that men between 66.5 and 88.5 years of age benefited the most from imipramine administration.

The authors wrote that taking imipramine for an extended period of time "increased the rate of return to a better clinical diagnosis in men." Although improvement was also seen in women, the authors note that it was not "statistically significant" compared to men.

What the experts say

Dr. Tom McLaren, a consulting psychiatrist at Re:Cognition Health, spoke about the findings in an interview with Medical News Today.

"This could be another important step in finding new treatments for dementia," Dr. McLaren commented.

Dr. McLaren acknowledges that more research is needed and notes the positives of using these two drugs in patients with Alzheimer's disease.

"The advantage is that both imipramine and olanzapine have been around for a very long time, so we know they are safe," Dr. McLaren said.

Dr. Clifford Segil, a neurologist at Providence Saint John's Health Center in Santa Monica, California, told MNT that he had some concerns about the study results.

"Most laboratory studies of Alzheimer's dementia have not resulted in real changes or new clinically proven useful drugs for my patients with memory loss. What happens on the calculator does not match what would happen in my office, most often in Alzheimer's dementia," Dr. Segil said.

"In clinical practice, it is still appropriate to use these drugs to treat depressed patients and as antipsychotics, but do not expect them to improve cognition in addition to depression or psychosis."

Limitations of the study

The authors of the study noted that although the data set they reviewed was the largest available, it was still relatively small compared to what they would consider for clinical trials.

In addition, the authors acknowledge that "it is possible that a physician's prescription of a particular antidepressant or antipsychotic was determined by the patient's comorbidities (e.g., diabetes, hypertension, etc.), which may have had independent effects on cognition.

The authors plan to study these drugs further and plan to test imipramine in mice.

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