Major Health Groups Cite Antipsychotic Dangers Psychotropic drugs may be bad for your heart/ Clozaril and Zyprexa
Wed, 23 Mar 2005
Obesity and diabetes are the fastest growing health hazard due to bad nutrition and a sedentary life style. However, diabetes is also caused by a class of widely prescribed drugs. Credible, replicated, peer reviewed scientific evidence shows that the atypical antipsychotic drugs–including Risperdal (risperidone) and Zyprexa (olanzapine) and Clozaril (clozapine)– cause heart attacks (“sudden death”), severe metabolic disorders, hyperglycemia and diabetes. A new Harvard study shows that the risk of diabetes for patients prescribed Clozaril or Zyprexa is highly significant:
“These two drugs appear to be causing insulin resistance, even in nonobese patients, and then there is some sort of impairment in utilization of glucose.”
Psychiatric News reports: “This is perhaps the best cross-sectional study in the literature concerning this issue,” noted Murali Doraiswamy, M.D., an associate professor of psychiatry and head of the Division of Biological Psychiatry at Duke University. “This study shows that even in nonobese subjects, there are demonstrable effects of some antipsychotics on metabolic parameters and supports our original finding that many cases of diabetes occur in people [taking antipsychotics] without weight gain.”
“John Newcomer, M.D., an associate professor of psychiatry at Washington University in St. Louis, added, “This replicates and extends our previous study, using a similar but more rigorous and sensitive approach.” Newcomer said the findings “could serve as a possible explanation for those case reports where people seem to develop some hyperglycemia or diabetes very early in treatment and without any substantial gain in adiposity. Perhaps this represents some evidence for direct drug effect on glucose metabolism.”
The risks of these drugs for many patients for whom the drugs are being prescribed far outweigh any possible benefits. Zyprexa, which was approved for adults with schizophrenia and for short-term use in bi-polar (manic depressive) patients, is Eli Lilly’s best selling drug whose sales exceed $3 billion.
Those sales represent the widespread off-label prescribing of this drug to adults and children–particularly children in foster care. The scientific evidence about the hazards of antipsychotic drugs is overwhelming–the science undermines the rationale of industry-sponsored clinical practice guidelines which were issued by the TMAP (Texas Medication Algorithm Project), and adopted by at least a dozen state mental health agencies. TMAP guidelines recommend the atypicals as first line treatment for schizophrenia.
The fact is, TMAP guidelines which claim to be “evidence based” are not backed by any scientific evidence–they have neither proven to be more effective or safer than older drugs at low doses. TMAP is a marketing expansion scheme initiated by Johnson & Johnson (maker of Rissperdal) and the manufacturers of the other psychotropic drugs. TMAP is promoted by psychiatrists and state mental health officials who are on the take. See: latest in an investigative news series by Nanci Wilson, Money, Influence and Mental Health, Keye TV (a CBS affiliate) http://keyetv.com/investigativevideo/ .
The fact that the President’s New Freedom Commission on Mental Health (NFC) commended the TMAP guidelines stating–without evidence, that the drugs produce better recovery outcomes–leads us to suspect that TMAP and NFC were both influenced by the same pharmaceutical companies.
Contact: Vera Hassner Sharav
Drugs To Help You Can Actually Be Harmful
By Carol Simontacchi, CCN, MS
Special for eDiets
March 23, 2005
Psychotropic drugs may be bad for your heart. According to the American Diabetes Association — the American Psychiatric Association, American Association of Clinical Endocrinologists and North American Association for the Study of Obesity issued a consensus statement cautioning doctors that newer antipsychotic drugs increase the risk for diabetes and related metabolic disorders. The drugs were clozapine (Clozaril) and olanzapine (Zyprexa). The panel came to the conclusion after presentations from 14 experts as well as representatives from pharmaceutical companies and the Food and Drug Administration.
Metabolic disorders include Syndrome X, a cluster of symptoms that include increased obesity, elevated cholesterol and triglycerides, and so on — all significant risk factors in the development of heart disease.
–“Major Health Groups Cite Antipsychotic Dangers,” Autism Res Rev Int, 2004;18(2):2/Psychiatric News, March 5, 2004;39(5). As cited in Clinical Pearls Online.
A study published in the peer-reviewed journal, Archives of Internal Medicine mirrors the concerns of the above panel. In a longitudinal study, there were 554 cases of sudden cardiac death (59 percent male) compared with 4,463 control subjects (60 percent male). Current use of antipsychotics was associated with a threefold increased risk of sudden cardiac death. The risk of death was highest in those using butyrophenone antipsychotics.
–“Antipsychotics and the Risk of Sudden Cardiac Death,” Straus SMJM, Stricker BHC, et al, Arch Intern Med, June 28, 2004;164:1293-1297. As cited in Clinical Pearls Online.
Making It Work For You:
If medications to reduce symptoms of serious mental disorders are required, please show this information to your physician, and ask him to recommend a treatment protocol that ameliorates the possible harmful effects on the heart.
Carol Simontacchi is a certified clinical nutritionist and the author of a number of books on nutrition, including A Woman’s Guide to a Healthy Heart.
© 2005 American Psychiatric Association
Volume 40 Number 3, p. 32
Clinical & Research News
Antipsychotics May Impede Glucose Metabolism
February 4, 2005
Volume 40 Number 3, p. 32
New data support a link between certain antipsychotic medications and altered glucose metabolism, even in patients who do not gain significant amounts of weight. The second-generation antipsychotic medications clozapine (Clozaril) and olanzapine (Zyprexa) are associated with significantly increased insulin resistance, as well as impaired glucose effectiveness, than is risperidone (Risperdal), even in patients with normal body-mass indexes.
That’s the major finding in a study by David Henderson, M.D., an assistant professor of psychiatry at Harvard Medical School and Massachusetts General Hospital, and colleagues and reported in the January Archives of General Psychiatry. The association demonstrates what researchers believe could represent “a one-two punch,” causing abnormalities in two different metabolic pathways that regulate the body’s utilization of glucose. The finding may help explain why around 25 percent of adverse-event reports tying the two “atypical” antipsychotics to treatment-emergent dysfunction in glucose metabolism seem to occur in patients relatively soon after initiating medication therapy and prior to any significant weight gain.
“In our study comparing the three medications in nonobese patients, we found significant differences between the three drugs on a sensitive measure called the insulin sensitivity index [SI],” said Henderson. “Both clozapine and olanzapine were associated with significantly reduced insulin sensitivity compared to risperidone.” The research was funded by grants from the National Institutes of Health General Clinical Research Center and the National Alliance for Research on Schizophrenia and Depression. In addition, Henderson received an investigator-initiated independent research grant from Janssen Pharmaceutica, the maker of the Risperdal brand of risperidone used in the study.
Henderson and his colleagues used the frequently sampled intravenous glucose tolerance test (FSIVGTT) to determine multiple parameters involved in glucose metabolism in 41 nonobese adults with schizophrenia or schizoaffective disorder who were matched for body-mass index, sex, and race. The FSIVGTT is a complex and demanding protocol involving collection of 38 different samples of blood from a patient spanning a period of more than three hours. Blood is first taken 10 minutes and five minutes before administering an IV dose of glucose and then at set intervals over 180 minutes following the glucose challenge dose. Henderson’s team then used the MINMOD computer software program, developed by Richard Bergman, Ph.D., at the University of California at San Diego, to analyze the numerous blood samples for multiple measures of glucose metabolism.
“MINMOD allows us to assess not only how the body is responding to that glucose challenge through the secretion of insulin by beta-cells in the pancreas,” Henderson explained, “but also to look at what is actually happening to the glucose—how the body is utilizing that glucose.”
In most of the measures of glucose metabolism they looked at, Henderson said, patients taking clozapine appeared to have the most significant changes in glucose metabolism, followed by those taking olanzapine. The two groups, however, were not statistically significantly different on any of the measures. Patients taking risperidone showed glucose metabolism that was not significantly different from that reported for normal, healthy adults.
“Now I think for me,” Henderson continued, “the more interesting finding is that there is another parameter that the MINMOD allows you to look at called SG [glucose effectiveness], which is a measure of the uptake and utilization of glucose that is unrelated to insulin action. SG is closely dependent upon the cellular glucose transport system. Surprisingly, we found that there were [statistically significant] reductions in SG in patients taking both clozapine and olanzapine, relative to those on risperidone.”
Henderson noted that normally in patients with a reduced sensitivity to insulin—more commonly referred to as insulin resistance—the body compensates by increasing glucose transport. “Normally, if SI goes down, the system compensates by increasing SG,” he said, the opposite of what he and his team observed.
“This could represent a blocking of glucose transport by the two drugs,” Henderson hypothesized, which, he added, has been shown in vitro with some of the second-generation antipsychotics.
“At any rate, it appears to represent a second hit. These two drugs appear to be causing insulin resistance, even in nonobese patients, and then there is some sort of impairment in utilization of glucose.” “This is perhaps the best cross-sectional study in the literature concerning this issue,” noted Murali Doraiswamy, M.D., an associate professor of psychiatry and head of the Division of Biological Psychiatry at Duke University. “This study shows that even in nonobese subjects, there are demonstrable effects of some antipsychotics on metabolic parameters and supports our original finding that many cases of diabetes occur in people [taking antipsychotics] without weight gain.”
John Newcomer, M.D., an associate professor of psychiatry at Washington University in St. Louis, added, “This replicates and extends our previous study, using a similar but more rigorous and sensitive approach.” Newcomer said the findings “could serve as a possible explanation for those case reports where people seem to develop some hyperglycemia or diabetes very early in treatment and without any substantial gain in adiposity. Perhaps this represents some evidence for direct drug effect on glucose metabolism.”
Henderson, Doraiswamy, and Newcomer cautioned that the results of the study must be taken in context, noting that the study was cross-sectional in design and followed a small number of patients. In addition, many factors could confound the results, such as patients’ exposure to other antipsychotic medications prior to the study, or the use of antidepressants or the mood stabilizers lithium or valproate. “Overall,” concluded Newcomer, “it’s a very nice study, and I think, most importantly, it represents another step in raising the level of the debate on this topic above case reports or large, retrospective database analyses. While there is obvious value in prospective, randomized, clinical trials, this study is an elegant demonstration of how, sometimes, there are experimental questions that cannot be answered by randomization and must be controlled for in some other experimental way.” Henderson said his take-home message is that “the effects of these drugs—at least these two—are concerning, and what this really shows us is that we need to be concerned about glucose metabolism [in patients taking antipsychotic medications] regardless of what the patient looks like—whether they gain a lot of weight or not.” An abstract of “Glucose Metabolism in Patients With Schizophrenia Treated With Atypical Antipsychotic Agents” is posted online at http://archpsyc.ama-assn.org/cgi/content/short/62/1/19. Arch Gen Psychiatry 2005 62 19
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