CAMBRIDGE, England -- Despite what clinicians generally believe, the newer antipsychotic drugs are no better than earlier medications in improving quality of life for patients, researchers here say.
CAMBRIDGE, England, Oct. 3 -- The newer antipsychotic drugs are no better than earlier medications in improving quality of life for patients, researchers here have found.
The study they conducted had been expected to confirm the conventional wisdom that using the second-generation antipsychotics over a year would result in at least a five-point improvement over the first-generation drugs on a standard quality of life scale, said Peter Jones, M.D., Ph.D., of the University of Cambridge.
"We were surprised to refute the hypothesis," Dr. Jones and colleagues reported in the October issue of Archives of General Psychiatry. If anything, the researchers found in the Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1), quality-of-life results favored the older drugs, although the results did not reach statistical significance.
In an accompanying commentary, Jeffrey Lieberman, M.D., of Columbia in New York said the new study added to the evidence that the second-generation drugs, such as Risperdal (risperidone) and Zyprexa (olanzapine), do not have the dramatic advantages expected by patients and their doctors.
"With the possible exception of clozapine, the second-generation antipsychotics are not the great breakthrough in therapeutics they were once thought to be," Dr. Lieberman said. Dr. Lieberman led the 2005 Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, which had "virtually identical conclusions" to the British study.
"These studies found few differences in effectiveness between first-generation antipsychotics and second-generation antipsychotics in nonrefractory patients-a conclusion that runs counter to the impressions of many clinicians and previous studies suggesting marked superiority of the second-generation antipsychotics and that belies the huge advantage in market share enjoyed by the second-generation antipsychotics in the United States and other parts of the world," said Dr. Lieberman.
Another large government-funded study, the 2003 Department of Veterans' Affairs Co-operative Study, also showed no advantage for a second-generation antipsychotic over an earlier-generation drug.
Dr. Jones and colleagues enrolled 227 patients ages 18 to 65 with schizophrenia who required a change in treatment because their current medications weren't effective or because of side effects.
They were randomly assigned to a first-generation or a second-generation drug (with the exception that Clozaril [clozapine], a second-generation antipsychotics, was not prescribed) and their doctors decided which of the many drugs in each class would be used. Of the 227 patients, 52% were assigned to first-generation medications and 48% to second-generation.
"The key question was whether the additional acquisition costs of second-generation antipsychotics over first-generation antipsychotics would be offset by improvements in health-related quality of life or savings in the use of other health and social care services."
The participants were blindly assessed at baseline and at 12, 26, and 52 weeks after the change in treatment using the standardized Quality of Life Scale (QLS). Symptoms, side effects, treatment costs, and patient satisfaction were also measured.
The study found:
In the end, the researchers said, the expected five-point improvement on the QLS "was excluded at the 95% confidence level." The result was the same at each measurement point and on an intent-to-treat analysis.
Also, there were no significant differences in symptoms scores, preference for either drug group, or costs.
Dr. Jones and colleagues pointed out that the expectation of a five-point difference may have been unrealistically large, although it's a clinically significant endpoint that has been used in other trials.
Equally, they said, the sample size may been too small, although the combination of good follow-up and consistency of the QLS scores and baseline and at the following measurements gave the study 75% power to detect the hypothesized difference.
While each of the three recent studies has limitations, "taken together, they cannot be easily dismissed," said Robert Rosenheck, M.D., of the Department of Veterans' Affairs Connecticut Health Care System in West Haven, Conn., who led the Veterans Affairs' study, in an accompanying commentary.
Dr. Rosenheck noted that one criticism of the British study is that it in effect treated all drugs of each generation as a class, even though they have varied mechanisms of action and side-effect profiles.
On the other hand, he said, physicians tend to think of the drugs in class terms, guidelines treat them as a class, and their "enthusiastic reception" appears to be a class phenomenon, he said, so that the study may reflect the way the drugs are used in clinical practice.