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Antidepressant may slow Alzheimer's disease
Myriam
Posted: Friday, May 16, 2014 5:17 PM
Joined: 12/6/2011
Posts: 3326


A commonly prescribed antidepressant can reduce production of the main ingredient in Alzheimer's brain plaques, according to new research at Washington University School of Medicine in St. Louis and the University of Pennsylvania.  

 
 

 

The findings, in mice and people, are published May 14 in Science Translational Medicine. They support preliminary mouse studies that evaluated a variety of antidepressants. 

 

Brain plaques are tied closely to memory problems and other cognitive impairments caused by Alzheimer's disease. Stopping plaque buildup may halt the disastrous mental decline caused by the disorder. 

 

The scientists found that the antidepressant citalopram stopped the growth of plaques in a mouse model of Alzheimer's disease. And in young adults who were cognitively healthy, a single dose of the antidepressant lowered by 37 percent the production of amyloid beta, the primary ingredient in plaques. 

 

Although the findings are encouraging, the scientists caution that it would be premature for people to take antidepressants solely to slow the development of Alzheimer's disease. 

 

"Antidepressants appear to be significantly reducing amyloid beta production, and that's exciting," said senior author John Cirrito, PhD, assistant professor of neurology at Washington University. "But while antidepressants generally are well tolerated, they have risks and side effects. Until we can more definitively prove that these drugs help slow or stop Alzheimer's in humans, the risks aren't worth it. There is still much more work to do." 

 

Amyloid beta is a protein produced by normal brain activity. Levels of this protein rise in the brains of patients with Alzheimer's, causing it to clump together into plaques. Plaques also are sometimes present in cognitively normal brains. 

 

Cirrito's earlier research had shown that serotonin, a chemical messenger in the brain, reduces amyloid beta production. First author Yvette Sheline, MD, also has linked treatment with antidepressants to reduced plaque levels in cognitively healthy individuals. 

 

Most antidepressants keep serotonin circulating in the brain, so this led Cirrito and Sheline to wonder whether the drugs block the increase of amyloid beta levels and slow the progression of Alzheimer's. 

 

In 2011, the researchers tested several antidepressants in young mice genetically altered to develop Alzheimer's disease as they aged. In these mice, which had not yet developed brain plaques, antidepressants reduced amyloid beta production by an average of 25 percent after 24 hours. 

 

For the new study, the team gave citalopram to older mice with brain plaques. Jin-Moo Lee, MD, PhD, professor of neurology, used a technique called two-photon imaging to track the growth of Alzheimer's-like plaques in the mice for 28 days. Giving the mice the antidepressant stopped the growth of existing plaques and reduced the formation of new plaques by 78 percent. 

 

In a second experiment, the scientists gave a single dose of citalopram to 23 people ages 18 to 50 who were not cognitively impaired or depressed. Samples of spinal fluid taken from the participants over the next 24 hours showed a 37 percent drop in amyloid beta production. 

 

Now the researchers are trying to learn the molecular details of how serotonin affects amyloid beta production in mouse models. 

 

"We also plan to study older adults who will be treated for two weeks with antidepressants," said Sheline, who is now at the University of Pennsylvannia. "If we see a drop in levels of amyloid beta in their spinal fluid after two weeks, then we will know that this beneficial reduction in amyloid beta is sustainable."  

 

The above story is based on materials provided by Washington University in St. Louis. The original article was written by Michael C. Purdy. 


Vita99
Posted: Saturday, May 17, 2014 5:37 AM
Joined: 9/4/2012
Posts: 469


This is great information Myriam.  This is the antidepressant that my mother is on and lately I have been noticing that she is quite stable in spite of not following a good diet and in general has bad health habits.  She has been prescribed this medicine for years but neglected to take it because it made her sleepy.  She has been taking it for the last several months due to anxiety  and I noticed that her reading concentration is also improved.  She was able to finish reading 2 books which she has not done since last summer.   
Lane Simonian
Posted: Saturday, May 17, 2014 9:46 AM
Joined: 12/12/2011
Posts: 4855


Here is some information of the positive and negative effects of citalopram.


Alzheimer’s disease can make patients disruptive and aggressive, leaving distraught caregivers with little option but to place their loved ones in nursing homes. Clinicians have few choices for treating these behavioral disorders. No drug has been approved to mitigate these symptoms in AD patients, and drugs used off-label have serious health risks. Several research groups are searching for alternatives. In the February 19 Journal of the American Medical Association, researchers led by Anton Porsteinsson at the University of Rochester, New York, report mixed results from a clinical trial of one such medication. They found that the antidepressant citalopram calms Alzheimer’s patients, which reduces stress for caregivers. However, at the tested dose of 30 mg daily, citalopram comes with safety risks of its own, including abnormal heart rhythms. The Food and Drug Administration now recommends that elderly patients take no more than 20 mg citalopram daily for any indication. Further study will have to sort out whether this lower dose will be equally effective at quieting agitation, the authors note.

Commentators agreed that citalopram shows promise for treating agitation in AD, but said more research is needed and urged clinicians to use the drug with caution. “Although the results from this study support a role for citalopram in the management of agitation in dementia, when and how to prescribe the drug so that benefits are optimized and risks minimized are not straightforward,” wrote Gary Small at the University of California, Los Angeles, in an accompanying editorial.

With no FDA-approved treatment for agitation in Alzheimer’s, clinicians frequently fall back on atypical antipsychotics, a newer class of drugs that are believed to have fewer side effects than first-generation antipsychotics. Atypical antipsychotics carry a “black box” warning from the FDA because they increase the risk of death in people with dementia and can have other negative consequences such as sleepiness and parkinsonism (see Oct 2005 news storyJan 2009 news story). Moreover, some studies have questioned how well these drugs work (see Oct 2006 news story). Other alternatives tested so far, such as donepezil and antiepileptics like valproate, have failed to show a benefit (see Oct 2007 news storyNov 2009 conference story).

http://www.alzforum.org/news/research-news/citalopram-calms-agitation-alzheimers-carries-risks