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.
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