Nov 28, 2012 9:00 AM by By Mary Brophy Marcus
WEDNESDAY, Nov. 28 (HealthDay News) -- The safety and effectiveness of four drugs commonly used to treat older adults with schizophrenia, dementia, bipolar disorder and other mental health conditions are being called into question by a new study.
The drugs -- aripiprazole (Abilify), olanzapine (Zyprexa), quetiapine (Seroquel) and risperidone (Risperdal) -- are among medications called atypical antipsychotics and are approved by the U.S. Food and Drug Administration to treat schizophrenia and bipolar disorders.
But physicians often pen off-label prescriptions for people with dementia, post-traumatic stress disorder (PTSD) and other mood disorders to help alleviate symptoms of psychosis as well as anxiety, agitation and aggression.
The medications have been in use since the early 1990s.
The new study, published in the Nov. 27 issue of the Journal of Clinical Psychiatry, involved 332 patients older than 40 who had been diagnosed with an indicated mental health condition and had psychotic symptoms.
"We wanted to see if these drugs were effective and safe for a long period of time," said study author Dr. Dilip Jeste, president of the American Psychiatric Association and a distinguished professor of psychiatry and neuroscience at the University of California, San Diego. He said the risk of cardiovascular disease increases in midlife, and previous research has suggested that this class of drugs can up cardiovascular health risks.
"This is a population in which these drugs are commonly used and in whom the risk of cardiovascular disease is high, and there was no long-term data comparing the drugs," Jeste said. Even though the newer drugs aren't indicated for long-term use except in schizophrenia and bipolar disorder, in practice, Jeste said, they tend to be taken off-label for extended periods of time -- sometimes years.
The scientists asked patients and their physicians to choose which of the four antipsychotic drugs they would prefer to take. They had to select at least two so they could be randomly placed into a drug group. The researchers also left dosing up to the clinicians, and doses could be altered at any time based on a patient's needs.
Only about 17 percent of the participants and their doctors agreed to be randomly assigned to all four drugs, with most citing concerns about side effects.
Participants were given medical exams, including waist-circumference measurements, and their health histories, medication use and previous experience with drug side effects were recorded. Follow-up assessments were repeated at six and 12 weeks and then every 12 weeks over a five-year period.
Jeste said they were expecting that one or two drugs would emerge as safer and more effective long term; instead, people stayed on their medication for an average of only six months. The percentage of patients who stopped their medication before the end of the two-year follow-up period ranged from nearly 79 percent on quetiapine to 81.5 percent on aripiprazole.
"We expected the patients to stay on the drugs for two years, but they stopped them due to adverse effects or a lack of improvement," Jeste explained. "That means the antipsychotic to which they were randomized did not work. Significant side effects were often to blame."
The study for one drug, quetiapine, had to be discontinued altogether after three and a half years. "We had twice as many serious adverse side effects midway through the trial with quetiapine," Jeste said.
Serious adverse events included death, hospitalization for pneumonia and other disorders, and emergency room visits for problems such as confusion, disorientation and markedly disorganized behavior. Less-serious side effects included restlessness and agitation, drowsiness, and constipation or diarrhea.
Another concern was the rise in risk for developing metabolic syndrome -- a collection of symptoms that can increase a person's odds of developing heart disease and diabetes. Metabolic syndrome means a person has at least three of these signs: elevated blood fat levels, low "good cholesterol," elevated blood sugar, large waist circumference and high blood pressure.
In the study, one-third of the patients developed metabolic syndrome within a year.
Dr. Lon Schneider, professor of psychiatry, neurology and gerontology at the University of Southern California Keck School of Medicine, was intrigued by the study's findings.
"This was a pragmatic study with good design and the main findings are enlightening about the extensive level of adverse events and the very limited efficacy of these drugs," said Schneider, who wrote a commentary on prescribing antipsychotic medicine in the August issue of the journal Clinical Neurology News.
Schneider said the new study confirms what has been seen in effectiveness trials and in observational studies.
"The important information that it adds is the considerable level of adverse events," he said. "The study shows that when drugs are compared head to head, there is a high level of discontinuation due to intolerability. You don't see this in the pharmaceutical company placebo control trials."
Another expert said the new findings are not surprising.
"There have been concerns about the efficacy of these antipsychotic drugs for a long time," said Dr. Dan Blazer, chairman and professor of psychiatry at the Duke University School of Medicine. He added that this research will "put more pressure on the brakes."
"[But] there are individual patients in whom these types of drugs can make a big difference," Blazer said. "The issue is caution in using them."
Blazer and Schneider both warned that the danger is in using them as a "chemical straitjacket," which can happen in nursing homes and private homes when caregivers aren't always available.
There are no magic bullets to treat agitation and aggressive and threatening behavior, but there are alternatives to prescribing drugs, such as cognitive behavioral therapy, Schneider said.
Jeste concluded: "The practical implication of our research is that we should be very careful in using any of these drugs in people over 40, especially if we are using them off label for any length of time."
The U.S. National Institute of Mental Health has more about mental health medications.