Schizophrenia Research Forum - A Catalyst for Creative Thinking
Home Profile Membership/Get Newsletter Log In Contact Us
 For Patients & Families
What's New
Recent Updates
SRF Papers
Current Papers
Search All Papers
Search Comments
News
Research News
Conference News
Plain English
Forums
Current Hypotheses
Idea Lab
Online Discussions
Virtual Conferences
Interviews
Resources
What We Know
SchizophreniaGene
Animal Models
Drugs in Trials
Research Tools
Grants
Jobs
Conferences
Journals
Community Calendar
General Information
Community
Member Directory
Researcher Profiles
Institutes and Labs
About the Site
Mission
History
SRF Team
Advisory Board
Support Us
How to Cite
Fan (E)Mail
The Schizophrenia Research Forum web site is sponsored by the Brain and Behavior Research Foundation and was created with funding from the U.S. National Institute of Mental Health.
Research News
back to News Search
Antipsychotics on Trial Again—DART-AD Confirms Increased Mortality
View related comments: Alzheimer Research Forum

Adapted from a story that originally appeared on the Alzheimer Research Forum.

13 January 2009. Antipsychotics are getting pushback as a treatment for behavioral symptoms in AD patients. While at first blush it may seem reasonable to use these drugs to control psychiatric symptoms in moderate and advanced dementia, prior studies have warned of serious side , and in short-term (8-12 week) trials even increased mortality in AD patients taking second-generation. That deadly risk is now confirmed by results from the much longer dementia antipsychotic withdrawal trial (DART-AD), published in today’s Lancet Neurology online. Led by Clive Ballard at King’s College London, DART-AD investigators found that over a period of 12 months, patients continuing on drug instead of placebo had a significantly increased rate of mortality. The authors write that “...the accumulating safety concerns, including the substantial increase in long-term mortality, emphasise the urgent need to put an end to unnecessary and prolonged prescribing.”

Ballard and colleagues randomized 165 AD patients living in care facilities in the U.K. to either continue their use of antipsychotic treatment (at enrollment patients had to have been taking such a drug for three months) or to take a placebo for 12 months. At the end of the randomized period, the probability of survival in the drug group was 90 percent, compared to 97 percent in the placebo group. The researchers also followed patients for up to three and a half years after the trial, finding even more pronounced differences in mortality. At 24 months, survival was 46 and 71 percent in drug and placebo groups, respectively, and the differences were even greater at 36 and 54 months. The authors write that it is not clear why the biggest differences in mortality occur after the 12-month trial. One plausible explanation is that the frailest patients are most likely to die within the first 12 months regardless of medication status. Another possibility is that the close monitoring of patients during the trial helped prevent fatalities. Whatever the reason, the hazard ratio for survival over the full study (54 months) was 0.58 in the drug group compared to placebo, meaning people were a little over half as likely to still be alive if they had been on antipsychotic drugs than if they had been on placebo.

“This work further emphasises the clinical imperative to review antipsychotic medication that is regularly prescribed, and to avoid a protracted period of treatment with antipsychotic drugs in people with dementia,” write the authors. In fact, the U.S. Food and Drug Administration is aware of the increased mortality in AD patients treated with antipsychotics and has issued a black box warning to that effect, also noting that the drugs are not approved for AD (see FDA public health advisory). Nevertheless, some clinicians see antipsychotics as an important part and parcel of AD management and are not convinced that the clinical trial data capture the full story. John (Wes) Ashford, a psychiatrist at Stanford University, California, has reported that AD patients are the most violent of all psychiatric patients (see Paveza et al., 1992) and he wrote ARF via e-mail, “the most agitated patients need to be managed acutely and cannot participate in such trials.” For this reason he believes that real-life, placebo-controlled trials of antipsychotic medications cannot be conducted (see full comment below). In fact, Ballard and colleagues concede that this is a limitation of their study. Enrollment required a Mini-Mental State Exam score of 6 or more and a Severe Impairment Battery score of 30 or more, effectively eliminating the most severely affected patients.

And even if there is increased risk of mortality, might these drugs offer some relief for this terminal illness over the short term if managed properly? As Ashford wrote, “…isn't there the issue of allowing patients to die with dignity? These drugs, just like morphine for cancer patients, will provide some measure of better end-of-life care.” A better scenario might be to have drugs that relieve psychotic symptoms without dangerous side effects. Both Ballard and colleagues and Ashford note that other drugs, such as memantine, antidepressants, selective serotonin reuptake inhibitors, and even low doses of certain antipsychotics may fit the bill, but more research is needed.—Tom Fagan.

Reference:
Ballard C, Hanney ML, Theodoulou M, Douglas S, McShane R, Kossakowski K, Gill R, Juszczak E, Yu L-M, Jacoby R, for the DART-AD investigators. Lancet. 2009, January 9; online publication.

 
Submit a Comment on this News Article
Make a comment on this news article. 

If you already are a member, please login.
Not sure if you are a member? Search our member database.

*First Name  
*Last Name  
Affiliation  
Country or Territory  
*Login Email Address  
*Confirm Email Address  
*Password  
*Confirm Password  
Remember my Login and Password?  
Get SRF newsletter with recent commentary?  
 
Enter the code as it is shown below:
This code helps prevent automated registrations.

Please note: A member needs to be both registered and logged in to submit a comment.

Comment:

(If coauthors exist for this comment, please enter their names and email addresses at the end of the comment.)

References:


SRF News
SRF Comments
Text Size
Reset Text Size
Email this pageEmail this page

Share/Bookmark
Copyright © 2005- 2014 Schizophrenia Research Forum Privacy Policy Disclaimer Disclosure Copyright