A new study has called into question the safety and effectiveness of four antipsychotic drugs commonly used to treat older adults with schizophrenia, dementia, bipolar disorder and other mental health disorders.
These drugs — aripiprazole (Abilify), olanzapine (Zyprexa), quetiapine (Seroquel) and risperidone (Risperdal) — are approved by the U.S. Food and Drug Administration to treat schizophrenia and bipolar disorders.
Although these drugs aren’t meant for long-term use except in schizophrenia and bipolar disorder, in practice, they tend to be taken off-label for extended periods of time — sometimes years, said study author Dr. Dilip Jeste, president of the American Psychiatric Association.
The study, published in the Journal of Clinical Psychiatry, included 332 patients over 40 years old who had been diagnosed with an indicated mental health condition with psychotic symptoms.
“We wanted to see if these drugs were effective and safe for a long period of time,” said Jeste, professor of psychiatry and neuroscience at the University of California, San Diego. “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.”
Patients and their physicians were given a choice of which of the four antipsychotic drugs they would prefer taking. They had to select at least two so they could be randomly placed into a drug group. Dosing was left up to the clinicians, which could be altered at any time based on the patient’s needs.
The researchers were expecting that one or two of the drugs would come forward as safer and more effective in the long term; instead, patients only stayed on their medication for an average of six months.
The percentage of participants who stopped taking 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 (Seroquel), had to be completely stopped after 3-1/2 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 difficulties with confusion, disorientation and extremely disorganized behavior. Less-serious side effects included restlessness and agitation, drowsiness, and constipation or diarrhea.
Another concern was the greater possibility of developing metabolic syndrome — a collection of symptoms that can raise a person’s risk of developing heart disease and diabetes. In the study, one-third of the patients developed metabolic syndrome within a year.
“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.”
Experts warn 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.
“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,” said Jeste.