Study: Atypical antipsychotics not worth the risks in those over 40

[Altostrata]

Low efficacy and high incidence of metabolic syndrome within a year caused researchers to warn against use of atypical antipsychotics for older patients.

 

Dilip Jeste is the current president of the American Psychiatric Association.

 

http://www.medpagetoday.com/Psychiatry/Schizophrenia/36126

 

Atypicals May Not Work in Older Patients

By Kristina Fiore, Staff Writer, MedPage Today

Published: November 27, 2012

• This study was designed to evaluate the safety and effectiveness of the four most commonly used atypical antipsychotics in patients ages >40 years who had psychosis associated with schizophrenia, mood disorders, PTSD, or dementia.
• Note that the study found a lack of effectiveness and a high incidence of side effects with all four atypical antipsychotics across diagnostic groups.

Atypical antipsychotics may not work in older patients, and they carry a high risk of adverse events, researchers found.

 

In a randomized trial, there was a lack of significant improvement in psychopathology and a high cumulative incidence of metabolic syndrome (36.5% in 1 year) and of serious and nonserious adverse events (23.7% and 50.8%, respectively), Dilip Jeste, MD, of the University of California San Diego, and colleagues reported.

 

....

The investigators called the findings "sobering" and "worrisome," especially given the fact that the trial was designed to closely resemble real-world use, and patients were able to have some choice in selection of their medications.

 

Currently, most atypical antipsychotics are approved for schizophrenia and bipolar disorder, but they're commonly used off-label for other disorders, including dementia and post-traumatic stress disorder (PTSD).

 

But there's been growing concern about cardiovascular and metabolic issues with these drugs -- particularly olanzapine (Zyprexa) -- and the FDA has issued a warning about cerebrovascular adverse events and a boxed warning about increased mortality with their use in dementia-related psychosis.

 

There also are few data on longer-term use of these drugs.

 

So to compare the long-term safety and efficacy of the four most commonly used atypical antipsychotics -- aripiprazole (Abilify), olanzapine, quetiapine (Seroquel), and risperidone (Risperdal) -- the researchers assessed 332 patients over age 40 who had schizophrenia, mood disorders, PTSD, or dementia.

 

They used Equipoise-Stratified Randomization to best achieve a pragmatic, real-world trial, allowing patients to have some say in selection of their drugs.

 

Patients were followed for up to 2 years and the researchers looked at several outcomes, including primary metabolic markers -- such as body mass index, blood pressure, fasting blood glucose, cholesterol, and triglycerides -- as well as adherence, psychopathology, and adverse events.

 

Overall, they found a higher incidence of serious adverse events with quetiapine (38.5% versus 19% for the other three drugs, P=0.002), so it was discontinued halfway through the trial. The proportion of patients who discontinued their medication before the end of the 2-year follow-up ranged from 78.6% of those on quetiapine to 81.5% of those on aripiprazole.

 

The early discontinuation could reflect "significant clinical improvement or at least adherence to treatment guidelines for using atypical antipsychotics for as short a period as possible, especially in patients with dementia," they wrote.

 

Reasons for discontinuation included:

• Side effects (51.6%)
• Lack of effectiveness (26.9%)
• Other reasons (21.5%)

It appeared that patients likely to have a greater risk of developing metabolic syndrome tended to exclude olanzapine as a treatment option, they found. Still, the groups didn't differ in longitudinal changes on metabolic parameters.

 

"The reported metabolic advantages of aripiprazole compared to olanzapine were not borne out in this study," they wrote. In fact, a slightly higher incidence of metabolic syndrome with aripiprazole "was likely related to the fact that the patients who included that drug in their list of acceptable medications were at a greater risk of developing the metabolic syndrome at baseline than those who opted for olanzapine."

 

Jeste and colleagues also saw a lack of significant improvement in psychopathology, as well as a high cumulative incidence of metabolic syndrome (36.5% in 1 year) and of serious and nonserious adverse events (23.7% and 50.8%, respectively).

 

"Caution in the use of these drugs is warranted in middle-age and older patients," they wrote.

 

The study was limited because it may not be generalizable to younger patients, may not apply to newer antipsychotics such as lurasidone or iloperidone, and because it's not possible to conclude that every adverse event was causally related to the drug, the researchers said.

 

Still, they concluded that the results suggest there are "currently no safe and effective treatment alternatives" in older patients with psychotic disorders. If the drugs must be used, they wrote, they are to be given in low doses, for as short duration as possible, and side effects must be monitored closely.

 

In addition, psychosocial treatments should be used whenever possible, they wrote.

 

The study was supported in part by the National Institutes of Health and the Department of Veterans Affairs.

 

AstraZeneca, Bristol-Myers Squibb, Eli Lilly, and Janssen donated drugs for the study.

 

The researchers reported relationships with AstraZeneca and Bristol-Myers Squibb.

 

Primary source: Journal of Clinical Psychiatry

Source reference:

Jin H, et al "Comparison of longer-term safety and effectiveness of four atypical antipsychotics in patients over age 40: A trial using equipoise-stratified randomization" J Clin Psychiatry 2012; DOI: 10.4088/JCP.12m08001.

[Jemima]

Wish I knew how to spell a long, low whistle.

[Skyler]

Nursing homes have been using antipsychotics as mental straight jackets for the last one or two decades. Hopefully this sort of research will expose the real reasons they are administered to that population..

[Barbarannamated]

This is a terrible situation with psychosis in dementia, particularly in Nursing Home residents. I have some familiarity with this and agree with the conclusion that there really are no treatments that offer an better risk/benefit profile. I've seen some very creative psychosocial interventions that are no doubt underutilized in favor of pharmacologic treatments. However, when those psychosocial interventions fail and a NH resident with dementia is combative, psychotic and at risk of going into other residents' rooms and attacking them, stealing their belongings, disrobing in public areas, etc., the options come down to physical or chemical restraints (after a locked facility, of course). Most admissions to Nursing Homes happen when the family/caretakers can't physically control them in a home environment or they are wandering away and getting lost. I've picked up a few elderly demented people wandering in streets in their bedclothes. Fortunately, they hadn't gotten far.

 

Prior to atypical neuroleptics, Haldol was used most often prior to Risperdal coming to market. Benzos often turn paradoxical in the elderly. Tegretol, Depakote, SSRIs, sleepers and lithium are used, but no agents have been studied or approved in aggression related to dementia.

 

I don't know if individual locked rooms are ever used but I am aware of electronic monitoring devices to notify staff if a resident has left their room (or fallen).

 

I wouldnt wish this choice on my worst enemy. Often these people are in strong physical shape, but are extremely combative. I've asked myself which is the lesser of the evils: physical or chemical restraints, usually permanent due to the neurodegenerative condition. There are times of day when some symptoms flare ("sundowning"). This is when "humane euthanasia" enters my mind.

 

Not everyone with dementia becomes aggressive or combative. Some become very withdrawn, depending on area of brain effected and subtype of dementia. Alzheimers is most known, but Frontotemporal, Vascular, Picks, Lewy bodies, Parkinson's are a few other types. Some have younger onset, in 50-60 age range, compared to 70-80 age range of Alzheimers.