Antipsychotics Used for Parkinson’s Despite Warnings
WebMD Health News
July 11, 2011 — Doctors continue to prescribe antipsychotic drugs to their patients with Parkinson’s disease and psychosis, despite “black box” warnings from the FDA linking them to increased risk of death among patients with dementia, a study shows.
A black box warning is the strongest drug warning issued by the FDA.
“My sense is that the black box warnings don’t factor into decision making,” says study researcher Daniel Weintraub, MD, an associate professor of psychiatry at the University of Pennsylvania.
The study is published in the Archives of Neurology.
The black box warning for antipsychotics says the drugs are associated with an increased risk of death for those with dementia, which is common among people diagnosed with Parkinson’s. Some commonly prescribed antipsychotics also worsen symptoms of Parkinson’s.
Risperdal (risperidone) and Zyprexa (olanzapine), for example, are two such drugs, and neither has been shown to be very effective. Yet according to the study, nearly 30% of patients with Parkinson’s and psychosis take them.
Clozaril (clozapine), the only drug known to be both effective and well-tolerated for treating psychosis in Parkinson’s patients, is prescribed to less than 2% of those with the disease.
“The gold standard treatment is also one of the most impractical treatments,” says neurologist Hubert Fernandez, MD, a Parkinson’s specialist at the Cleveland Clinic’s Center for Neurological Restoration.
Because of a rare but potentially deadly side effect of the drug, patients on clozapine must have their blood monitored at regular intervals. That burden discourages many doctors from prescribing the medication.
The alternatives, however, are far from ideal. Abilify (aripiprazole), the third most commonly prescribed antipsychotic, is poorly tolerated by Parkinson’s patients. And the most popular drug, Seroquel (quetiapine), has failed to show positive results in three studies.
“Quetiapine is the No. 1 choice without clear evidence that it’s effective,” says Weintraub.
Lack of Treatment Alternatives
The researchers examined Department of Veterans Affairs patient records from fiscal year 2008, comparing the rates of antipsychotic drug prescriptions among two groups: 2,597 patients with Parkinson’s disease and psychosis with and without dementia and 6,907 patients with dementia and psychosis but without Parkinson’s disease; 97.3% of the patients studied were men.
“More men are diagnosed with Parkinson’s, and men are more likely to develop dementia,” says Weintraub.
An estimated 60% of Parkinson’s patients will experience some form of psychosis during their illness, according to the study. Weintraub and colleagues found that half of all patients with Parkinson’s and psychosis were treated with antipsychotic medications.
Perhaps their most striking finding was that overall prescription rates had not decreased compared to 2002, despite the black box warning that was issued in 2005. To Fernandez, the reason is simple: doctors have few options to offer.
“This study is very important because it highlights the problem that clinicians face,” says Fernandez. “The problem is it’s not very easy to treat, and few patients will be completely treated.”
Weintraub agrees that treatment choices are quite limited, but he hopes that his study will encourage doctors to make greater use of clozapine and to be more conservative in prescribing other antipsychotics.
“If they are to be used, they should be used only for a period of time rather than indefinitely, as negative effects may accrue from exposure,” says Weintraub.
with Michael Breus, PhD, ABSM
Sleep disorders include a range of problems — from insomnia to narcolepsy — and affect millions of Americans. Dr. Michael Breus shares information and advice on sleep disorder and insomnia treatments and causes.
Maybe That’s Why We Sleep?
Here’s a fact that might surprise you: we really do not know why we sleep. Of course, we sleep because our bodies demand it; we know we require sleep for our survival. But we’ve yet to discover the why of sleep, to determine the physiological purpose sleep serves. Sleep is one of our most elemental functions, essential to life, and the purpose of sleep remains something of a mystery. That’s why this news is so exciting, and potentially important: a new study has found a direct link between sleep and the creation of long-term memories.
Scientists at Washington University School of Medicine have discovered a cluster of cells in the fruit-fly brain that controls sleep. By manipulating those cells, scientists were able to establish long-term memories in fruit flies by controlling their sleep habits. How did they accomplish this? First, the researchers bred genetically-modified fruit flies to sleep on demand. Using their ability to control the fruit flies’ sleep, the scientists tested the insects’ ability to learn — and retain — information. Here’s how they did it, and what they found:
- As a test of learning, researchers exposed male fruit flies to other male flies that had been engineered to smell like female fruit flies.
- After a few unsuccessful mating attempts, the flies learned not to court these female-in-disguise flies.
- Without sleep, the fruit flies retained this knowledge of the pretend-female flies for a short period of time, amounting to a few hours.
- Scientists put their fruit-fly subjects to sleep after the courtship training. With sleep, the fruit flies were able to retain the same information for several days. Sleep enabled the fruit flies to convert short-term knowledge into long-term memory.
We’ve long known that there was a relationship between sleep, memory and learning. You don’t have to be a scientist to have a sense of this. Think about your typical state of mind — and your inclination to retain new information — at the end of a long, busy day.
The science behind your end-of-day brain fatigue is also what the results of this new research appear to confirm: a theory called synaptic homeostasis. Like all animals, fruit flies included, our brains are engaged in processing information every moment we’re awake. A key component of this process are the synapses in our brains. Synapses create communication pathways in the brain that enable us to retain information. The theory of synaptic homeostasis suggests that sleep functions like a filter, to help us weed out and relax the synapses we develop over the course of a day, in order to start fresh the next day. Our brains use sleep as the time to determine what information can be discarded, and what is useful enough that it should be stored as longer-term memories.
In their fruit-fly subjects, researchers discovered:
- Flies in stimulating, learning-rich environments created more synapses than flies kept in isolation.
- During sleep, these synapses were reduced in size and number, essentially clearing out the clutter in the brain to prepare for another round of learning.
So, what are the implications for us humans? A sleep-inducing switch for our brains sounds like the stuff of science fiction, and its safe to say we’re awhile away from this. But this is a dramatic step toward developing an answer to that elusive question of why we sleep. The more we understand about the underlying reasons for sleep, the better able we’ll be to explore and develop safe, natural solutions to sleep problems.
Michael J. Breus, PhD
The Sleep Doctor™
New Genetic Clues to Cause of Parkinson’s
WebMD Health News
June 24, 2011 — Researchers have identified two new genetic variants linked to Parkinson’s disease and say they now know how big a role heredity plays in the neurodegenerative disorder.
About a dozen genetic associations with Parkinson’s have been confirmed, and many more remain to be discovered, says researcher Nicholas Eriksson, PhD, of the California-based direct-to-consumer gene testing company 23andMe.
In their new study, published this week in the journal PLoS Genetics, Eriksson and colleagues estimated that about a quarter of the variation in susceptibility to the disease is due to genetic factors.
“Each new genetic variant we find gets us a little bit closer to being able to see the full picture of how genes impact this disease,” Eriksson tells WebMD. “Roughly 10 genetic variants that contribute to Parkinson’s had been found and we added another two to the list.”
Role of Genes in Parkinson’s
The exact causes of Parkinson’s disease are not known, but researchers now believe that both environmental triggers and genetic influences play a role.
Genetic variants have been implicated in the small percentage of cases that occur in people under the age of 50, known as early-onset Parkinson’s. But much less is known about the role of genes in late-onset disease.
In an effort to better understand genetic influences in both early- and late-onset Parkinson’s, Eriksson, study researcher Chuong B. Do, PhD, and colleagues conducted a novel genome-wide study involving around 3,400 Parkinson’s patients and close to 30,000 people without the disease who were 23and Me clients.
The Parkinson’s patients were recruited with the help of the Michael J. Fox Foundation, the Parkinson’s Institute, and the National Parkinson’s Foundation. The study was funded solely by the genetic testing company, however.
Genome-wide association studies became possible following the completion of the Human Genome Project and other landmark projects around the middle of the decade, which provided tools that allow researchers to look for genetic contributions to common diseases.
These tools include computerized human genome sequence databases, human genetic variation mapping, and continuously evolving technologies that simplify the analysis of genetic variations that contribute to disease.
Identifying Genetic Variants
The newly published study included the largest Parkinson’s patient group ever recruited for a genome-wide association study.
One of the newly identified genetic variants, SCARB2, is associated with a known Parkinson’s disease pathway involving protein degradation.
The other, SREBF1, is not associated with any known Parkinson’s pathway.
“This variant is involved in lipid metabolism,” Do tells WebMD. “Its association with Parkinson’s is not really clear, which is what makes it exciting because it highlights a new area to look at.”
Based on their own predictive model, the researchers estimate that around 7% of the genetic variants associated with Parkinson’s disease have been identified. That means that more than 90% have not.
While the genetic variants, or mutations, identified to date explain only a small percentage of Parkinson’s cases, the gene studies have provided clinically relevant information, Do says.
He points out that one identified mutation is associated with a 50% lifetime risk for developing the disease.
“This one variant accounts for a very small percentage of the total disease burden, but for people who do have the variant it is quite significant,” he says.
It is a fast test and I can’t take my morning meds. I love, getting blood tests done. They have kitties and puppies, above where you get your blood taken.