October 03, 2006

Study Suggests Newer Drugs not Better than Older Drugs

A new study, funded by the British government and published in the Archives of General Psychiatry, is the first to compare treatment results from a broad range of older antipsychotic drugs against results from newer ones. The study was requested by Britain's National Health Service to determine whether the newer drugs -- which can cost 10 times as much as the older ones -- are worth the difference in price.

The results of the study suggest that schizophrenia patients do as well, or perhaps even better, on older psychiatric drugs compared with newer and far costlier medications.

Read the full story on the Washington Post web site at the following link:
In Antipsychotics, Newer Isn't Better - Drug Find Shocks Researchers

The Full Research Study is available for your reading here:
Randomized Controlled Trial of the Effect on Quality of Life of Second- vs First-Generation Antipsychotic Drugs in Schizophrenia (Archives of General Psychiatry)

An American Medical Association Press release had this to say:

Among patients with schizophrenia whose medication is changed because of ineffectiveness or harmful side effects, second-generation antipsychotic drugs do not appear to offer significant benefits compared to first-generation antipsychotic drugs, according to a report in the October issue of Archives of General Psychiatry, one of the JAMA/Archives journals. The findings run contrary to the widely held perception that second-generation antipsychotic agents are safer and more effective in treating patients with schizophrenia than the less-expensive first-generation class of medications.

For almost 50 years, antipsychotic medications have been the primary method of treating schizophrenia, a psychiatric disorder that causes a disconnect from reality and severe disturbances in thought, mood and behavior. Patients taking first-generation antipsychotics -- so called because they were developed first -- often relapse or develop severe side effects, including sedation (feeling tranquilized) and involuntary muscle movements, according to background information in the article. The development of second-generation antipsychotics was thought to be a major advance primarily because the drugs reduced such side effects. Claims that second-generation drugs are more effective than first-generation drugs have shifted treatment patterns away from first-generation medications, although research comparing the drug classes has had mixed results.

Peter B. Jones, M.D., Ph.D., University of Cambridge and Cambridgeshire and Peterborough Mental Health NHS Trust, Cambridge, England, and colleagues studied 227 individuals age 18 to 65 with schizophrenia. "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 in people with schizophrenia for whom a change in drug treatment was being considered for clinical reasons, most commonly suboptimal efficacy or adverse effects," the authors write. The participants were randomly assigned to receive one class of drug or the other. Physicians determined which of the many first- or second-generation medications would be best for each patient. Participants were assessed before and 12, 26 and 52 weeks after the change in treatment using a quality of life scale, with higher scores reflecting a better quality of life. The researchers estimated that second-generation antipsychotics would produce a five-point improvement in quality of life scores compared with first-generation antipsychotics. Symptoms, side effects, treatment costs and satisfaction with the drug also were measured.

Of the 227 patients, 118 (52 percent) were randomly assigned to take first-generation medications and 109 (48 percent) to second-generation medications. After 12 weeks, quality of life scores averaged 49.2 for the first-generation group and 46.6 for the second-generation group; after 26 weeks, 49.2 for first-generation and 50.4 for second-generation; and after one year, 53.2 for first-generation and 51.3 for second-generation. "Participants in the first-generation antipsychotic arm showed a trend toward greater improvements in Quality of Life Scale and symptom scores," the authors write. "Participants reported no clear preference for either drug group; costs were similar."

Although surprising, these results align with other recent studies performed in the United States, they continue. "All the data suggest that careful prescribing of first-generation antipsychotics, at least in the context of a trial, is not associated with poorer efficacy or a greater adverse effect burden, both of which would translate into lower quality of life in the medium term," the authors conclude. "This suggests that despite recent policy statements and prescribing patterns, further randomized and other evaluations of second-generation antipsychotics would still be useful in establishing their role in the long-term management of schizophrenia and, likewise, the continued role of older drugs." (Arch Gen Psychiatry. 2006;63:1079-1087. Available pre-embargo to the media at www.jamamedia.org.)

Commentary: New Therapies for Schizophrenia Needed

These and other recent findings suggest that despite their tremendous advantage in market share, second-generation antipsychotic drugs may not be much more effective than first-generation antipsychotic agents, writes Jeffrey A. Lieberman, M.D., College of Physicians and Surgeons, Columbia University, New York, in an accompanying commentary.

An objective view "must lead to the conclusion that with the possible exception of clozapine, the second-generation antipsychotics are not the great breakthrough in therapeutics they were once thought to be; rather, they represent an incremental advance at best," Dr. Lieberman writes. "This underscores the urgent need for greater progress in developing novel therapeutics for schizophrenia and related psychotic disorders." (Arch Gen Psychiatry. 2006;63:1069-1072.

Commentary: Changes to Schizophrenia Treatment Should Be Openly Debated

Newly raised questions about the superiority of second-generation antipsychotics should not be used to justify a large, sudden change in treatment recommendations, warns Robert A. Rosenheck, M.D., Department of Veterans Affairs Connecticut Health Care System, West Haven, in an second related commentary.

Most patients with schizophrenia are unemployed and rely on public assistance; almost 90 percent of schizophrenics currently receive second-generation antipsychotics at a cost of $10 billion annually, 70 percent of which is paid through Medicaid. Although they are more expensive, most expert panels recommend using second-generation medications first in the treatment of schizophrenia, and current health policy supports open access to both first- and second-generation drugs.

This new information should not encourage changes that would mandate the use of less-expensive, first-generation drugs first, Dr. Rosenheck writes. "Data from clinical trials are only one type of information of relevance to public discourse," he continues. "A comprehensive public dialogue is needed prior to policy action and should involve patients, health care professionals, researchers, industry representatives and other stakeholders. Policy change may eventually be warranted, but potentially polarizing decisions are best delayed until thoughtful public deliberation gives a chance for comprehensive review, consensus building and shared understanding."

NAMI Issued the following press release on this topic:

A British study published in the current issue of the Archives of General Psychiatry, comparing old and new antipsychotic medications, has two major implications for federal and state policies, the National Alliance on Mental Illness (NAMI) today advised.

The first involves the nation's science agenda. The second involves individual access to the right medications for treatment under Medicare, Medicaid and the Veterans Administration -- which is expected to fuel ongoing federal and state political battles.

In April 2006, Jeffery Lieberman, M.D., Chairman of the Columbia University Department of Psychiatry -- who heads a series of studies on schizophrenia funded by the National Institute of Mental Health (NIMH) which has made findings similar to those of the British study (and who wrote an editorial that accompanied its publication) -- warned:

"The most important message of the results is the need for better treatments. Until we have those new treatments, given the substantial limitations of current medications and the diversity of patient response, clinicians need a broad range of treatment options, not restrictions on choices."

Science & Medicine

"It is essential that science and access to care not be confused, and that key distinctions, limitations and flaws in the study be overlooked," said NAMI executive director Michael J. Fitzpatrick. "For science and medicine, the study reflects much of NAMI's research agenda and points to the need for the President and Congress to push harder for investment in long-term, independent and comprehensive studies."

"There is a need for a more effective, third generation of medications that can ultimately lead to a cure for schizophrenia, one of the most severe mental illnesses," said NAMI medical director Ken Duckworth, M.D.

Medicare, Medicaid & Veterans Policy

"For Medicare, Medicaid, and the Department of Veterans Affairs, it would be a grave mistake to use the study to restrict access to newer medications, based on general findings that older medications seem to work as well as the newest generation," Duckworth said.

"General findings cannot be substituted for specific choices made in treating individuals with schizophrenia. One size does not fit all. It is critical that the study's limitations be recognized."

For one, the British study relies heavily on an older drug, sulpiride that has never been approved by the Food & Drug Administration (FDA) and is unavailable in the United States. In addition:

- The study's comparisons are limited to classes of drugs, rather than specific medications.

- The study does not include comparison of doses of drugs, either between classes or specific medications.

- Although longer than clinical trials required for FDA approval of specific drugs, the study's one-year test period is still largely inadequate for evaluating treatment outcomes over time. NAMI's own research agenda includes support for life-long studies such as the Framingham Heart Study (see below).

- Many of the newer anti-psychotic medications have been approved by the FDA for both schizophrenia and bipolar disorder. Older ones are approved only for schizophrenia and the study focuses only on schizophrenia.

"It is important to note that the study focuses only on medication," Duckworth said. "This is only one dimension of discussion for policymakers. Treatment of schizophrenia also requires psychosocial interventions, such as supportive counseling, housing and employment."

"Finding the right medication may be the cornerstone in building the right foundation for recovery for an individual. If you don't get the medication right, you run up costs elsewhere. That's another reason that unrestricted access to both old and new medications is a critical factor for budget concerns."

Past Research Comparing Drug Effectiveness

CATIE Phase 2 - Schizophrenia Treatment Study Update

CATIE Study Helps Clinicians Tailor Schizophrenia Treatment

Drs. Torrey & Insel on CATIE Study

CATIE News & Commentary

CATIE Results - Perphenazine almost as good as newer drugs


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