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Use of Antipsychotic Drugs Is Common for Parkinson’s Despite Risk

Physicians routinely prescribe antipsychotic drugs to elderly people with Parkinson’s disease (PD) and psychosis, many of whom also have dementia — even though these drugs can worsen Parkinson’s symptoms, and despite warnings that newer antipsychotic medications increase the risk of death in older people with dementia.  This study appears in the July 2011 issue of Archives of Neurology.  In the later stages of PD, people can develop psychosis.  It may be mild — for example, mistaking objects with animals — but it may progress to severe delusions, paranoia and hallucinations.  In addition, individuals may experience dementia.

Led by Daniel Weintraub, M.D., at the University of Pennsylvania, researchers set out to understand how often doctors prescribe antipsychotics to people with Parkinson’s and whether this pattern changed after 2005, when the US Food and Drug Administration (FDA) issued warnings about the risks of atypical antipsychotics.

The researchers analyzed medical records from the Department of Veterans Affairs of about 2,600 people with Parkinson’s and psychosis (800 of whom also experienced dementia).  They compared these to a group of about 6,900 people who had dementia but not PD. Nearly all were men.  Finally, the authors compared rates of prescription of antipsychotics in 2002 and 2008.

Results

  • In 2008, half of people with PD and psychosis, with or without dementia, were prescribed an antipsychotic.
  • Quetiapine (Seroquel®) was the most frequently prescribed drug.
  • Almost 30 percent of people who received an antipsychotic drug received one with limited efficacy known to exacerbate Parkinson’s motor symptoms.
  • Clozapine, the only antipsychotic drug shown to be effective in people with Parkinson’s, accounted for less than two percent of prescriptions.
  • Prescriptions for “atypical” antipsychotics — newer drugs with less impact on motor symptoms — remained steady, despite a warning about the safety of these drugs for elderly people with dementia.    

What Does it Mean?
Most antipsychotic drugs block dopamine, thus worsening the motor symptoms of PD.  Some have been shown to shorten the life span of people with PD who are affected by dementia.  However, the symptoms of psychosis can be so overwhelming that treatment is necessary despite these risks.  The choice is to lower the dosage of anti-parkinsonian medications, or to start an antipsychotic medication. The authors conclude that physicians need to be better educated about the efficacy, side effects and risks of antipsychotic drugs for people with PD, and there is an urgent need for new therapies for psychosis in Parkinson’s.

 

New Genetic Mutation Linked to Parkinson's

Using a new, cutting-edge technology for gene sequencing, researchers funded in part by the Parkinson’s Disease Foundation (PDF) have discovered a new gene, the VPS35 gene, that is linked to Parkinson’s disease (PD) in people with familial PD.  The results appear in the July 14 issue of the American Journal of Human Genetics.  In recent years, researchers have identified about a dozen genes that either cause PD or increase the risk of developing the disease.  A team of researchers led by Carles Vilariño-Güell, Ph.D., and Matthew J. Farrer, Ph.D., at the University of British Columbia (UBC), Vancouver, searched for the new gene by studying a family from Switzerland in which 11 people in three generations were diagnosed with PD.  They compared the DNA of family members with PD to that of unaffected family members to search for differences.  The UBC researchers used a new and efficient technique called “whole exome sequencing,” which focuses on small but important sections of DNA.  These sections govern the production of proteins. Since mutated proteins are most often the cause of genetic diseases, they reasoned that mutations linked to inherited PD would be found here.

Results

  • All 11 members of the Swiss family with PD had a mutation in the VPS35 gene.
  • Among 190 additional families that showed many cases of PD, three were found to have the same mutation (among a total of eight family members).
  • The researchers tested DNA samples from more than 3,000 healthy individuals from several countries and found no mutations in VPS35.
  • People with mutations in the VPS35 were diagnosed with PD around the age of 50.  (Among the people with Parkinson’s who have other gene mutations, symptoms begin at a younger-than-average age.)

What Does it Mean? 
Like most other genetic causes of PD, this newly identified mutation is exceedingly rare, resulting in very few cases of PD.  However, mutations have helped scientists generate key insights into the disease and a broad understanding of why people may develop PD.  These results will need to be replicated in other populations.

More Science News

*The two science stories in this issue of News & Review are abbreviated.  See full stories.