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New Antipsychotic Medications have Little Advantage Over Older Drugs

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 eva luations 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.”


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