Hence, this in Health Affairs...
Bethesda, MD -- Are drugs known as "second-generation antipsychotics" (SGAs) being overused and misused? What steps can be taken to make sure that medications are used correctly? Those questions are addressed in a trio of articles published today on the Health Affairs Web site.
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SGAs, also known as "atypical antipsychotics," have largely replaced older, less expensive first-generation (or typical) antipsychotics in the treatment of schizophrenia. SGAs are increasingly being used for a wide range of other clinical conditions as well.
The cost of SGAs is typically from ten to 100 times the cost of "first-generation" antipsychotics, and domestic U.S. sales of SGAs have reached $13 billion a year. However, based on recent research, some experts believe that the overall risk-benefit profiles of SGAs may be no better than those of some of the older and cheaper medications they have displaced, although important questions remain to be addressed through further research, and considerable variation exists in treatment response across individual antipsychotic drugs. While SGAs appear to cause fewer "extrapyramidal" side effects, including serious movement disorders, they bring increased risk of weight gain and blood-lipid abnormalities that may increase the risk of heart disease and diabetes.
Other researchers believe that SGAs can offer important new benefits for patients with schizophrenia and other serious mental conditions, but that the broadened use of these drugs for a more clinically diverse population of patients may have outstripped the evidence base for such use.
Examining The Use Of SGAs Among Youth and Elderly. In "Broadened Use of Atypical Antipsychotics: Safety, Effectiveness, and Policy Challenges" Stephen Crystal and coauthors document the increased use of SGAs on the two ends of the age spectrum, the nation’s youth and the elderly in nursing homes. When the researchers examined youth in seven state Medicaid programs, they found that 4.2 percent of enrollees ages 6-17 filled at least one prescription for an antipsychotic medication in 2004, up from 2.7 percent in 2001. Virtually all of the antipsychotics used were SGAs.
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Clinical indications approved by the Food and Drug Administration for antipsychotics in young people are limited to schizophrenia, behavioral symptoms in autism, Tourette’s disorder, and mixed or manic bipolar episodes. But in 2004, one-third of the youth in the seven Medicaid programs studied were being treated for attention deficit hyperactivity disorder without diagnostic codes for more-serious diagnoses such as schizophrenia, autism or bipolar disorder, according to Crystal, director of the Center for Education and Research on Mental Health Therapeutics in the Center for Pharmacotherapy at Rutgers University, and colleagues. Overall, almost three-quarters of Medicaid youth receiving antipsychotics were being treated only for conditions for which no FDA clinical indication existed. The results were similar among privately insured youth.
Likewise, among elderly nursing home residents, most use was for residents without an FDA diagnostic indication, and use increased from 1999 to 2006 despite new safety concerns including FDA warnings of increased mortality associated with use among elderly with dementia. Among nursing home residents in 2006, 27.6 percent were receiving antipsychotics, up from 20.2 percent in 1999.
Increasing Information To Ease Resistance To Practice Changes. In "Developing A Policy For Second-Generation Antipsychotic Drugs," Robert Rosenheck and Michael Sernyak report that many SGAs were prescribed for questionable reasons at one university-affiliated Veterans Affairs health center caring for veterans with serious mental illness. "The most frequent reasons given for prescribing SGAs … were greater efficacy, followed by patient preference and sedation/sleep, none of which is well-supported by current research. In contrast, prevention of neurological side effects – the reason for using SGAs with the strongest research support – was the least frequently cited reason for starting a new SGA," say Rosenheck, codirector of the New England Mental Illness Research, Education, and Clinical Center at the VA Connecticut Health Care System, and Sernyak, chief of the Mental Health Service at the VA Connecticut Health Care System.
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Rosenheck and Sernyak suggest that the most appropriate policy would be "stepped therapy," in which patients would have to start on first-generation antipsychotics and would only be allowed to try the SGAs with the most risk of side effects if other drugs had failed to help them. However, this policy would be likely to meet resistance, the authors acknowledge. They suggest that "counter-detailing, with its emphasis on individualized education and direct feedback, may be crucial in garnering the understanding and needed support for successful implementation of meaningful practice change."
Notice, no measure of individual response or outcomes..
Whereas David Meltzer and co. note what happens when individual responses to individual drugs are counted...
The Need For More Comparative Effectiveness Research. In "Comparative Effectiveness Research for Antipsychotic Medications: How Much Is Enough?" David Meltzer and coauthors examine a high-profile study funded by the National Institutes of Health that has been used to argue for restricting coverage of SGAs. In 2006, a cost-effectiveness analysis based on this study – known as the Clinical Antipsychotic Trials of Intervention Effectiveness study, or CATIE – found that "treatment with perphenazine [a first-generation antipsychotic] was less costly than treatment with second-generation antipsychotics with no significant differences in measures of effectiveness."
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However, there are a number of concerns about CATIE’s design that create "great uncertainty about the extent to which CATIE findings should be used to make coverage policy," write Meltzer, Director of the Center for Health and the Social Sciences at the University of Chicago, and colleagues. The authors present a model that they say indicates that additional comparative effective research involving SGAs would be of immense value – exceeding $300 billion – to those who have schizophrenia today and to those who will develop it over the next 20 years. The model also suggests that it would be worthwhile to perform studies of the effectiveness of SGAs with much larger sample sizes than CATIE, on the order of 8,300 patients in each treatment group as opposed to the 400 patients per group in CATIE. The model indicates that studies of cost-effectiveness should be even larger and would offer the greatest value.
Larger? I don't think so. I think spending money developing/testing predictive and biomarker based tools in observational settings would be a lot cheaper.
What are people thinking?
After the embargo lifts, you can read the article by Crystal and coauthors at http://content.healthaffairs.org/cgi/content/abstract/hlthaff.28.5.w770
After the embargo lifts, you can read the article by Rosenheck and Sernyak at http://content.healthaffairs.org/cgi/content/abstract/hlthaff.28.5.w782
After the embargo lifts, you can read the article by Meltzer and coauthors at http://content.healthaffairs.org/cgi/content/abstract/hlthaff.28.5.w794
