January 6, 2010 (Updated January 7, 2010) — When it comes to monitoring metabolic effects of second-generation antipsychotics (SGAs), it appears that physicians are not heeding recommendations by government or leading professional organizations. New research suggests that less than one-third of patients treated with these medications, which can have significant and serious adverse metabolic effects, undergo blood glucose or lipid testing.
"We studied a 3 state population of Medicaid recipients and found diabetes and dyslipidemia screening among patients receiving SGAs was low and did not increase following the FDA [Food and Drug Administration] warnings or recommendations from the American Diabetes and American Psychiatric Associations, which called for increased metabolic monitoring of patients taking these agents," study investigator Elaine H. Morrato, DrPH, MPH, University of Colorado, Denver, told Medscape Psychiatry.
The retrospective analysis is published in the January issue of Archives of General Psychiatry.
Prompted by research showing a strong link between SGAs and an increased risk for hyperglycemia and diabetes, starting in 2003 the FDA began requiring warning labels on SGAs, including olanzapine, risperidone, quetiapine, ziprasidone, clozapine and aripriprazole.
"In some cases the hyperglycemia was extreme and associated with ketoacidosis, hyperosmolar coma, or death," the study authors note.
As part of the FDA initiative, manufacturers of SGAs were required to send letters to neuropsychiatric health care professionals informing them of the warnings and advising them of the need for glucose testing in patients with a diagnosis of diabetes, risk factors for diabetes, or symptoms of hyperglycemia.
At the same time, the American Diabetes Association and the American Psychiatric Association published a consensus statement describing the metabolic risks associated with atypical antipsychotics and specifying a monitoring protocol for all patients receiving these medications.
Low Rates of Metabolic Testing
To assess the impact of these warnings and recommendations on glucose and lipid testing and drug selection of SGAs, the investigators examined laboratory claims data from the Medicaid population of 3 states — California, Missouri, and Oregon — between 2002 and 2005.
They compared rates of metabolic monitoring between a group of 109,451 patients receiving SGAs and a control group of 203,527 patients who began taking albuterol but who did not receive antipsychotic medication. Rates were also compared before and after the FDA warning.
Baseline glucose and lipid testing rates for SGA-treated patients were low at 27% and 10%, respectively. However, the FDA warning was not associated with an increase in glucose testing among SGA-treated patients, and lipid testing rates only increased by a marginal 1.7%.
In addition, testing rates and trends among SGA-treated patients were no different from those in the albuterol control group.
This finding was unexpected, said Dr. Morrato. "Glucose and lipid monitoring rates were no different for patients on SGAs than for the control group. I thought that given the increased risk that monitoring would be higher for patients taking antipsychotics, but this was not the case."
Intent to Reduce Risk
However, the researchers found that the number of new prescriptions for olanzapine, which has a higher metabolic risk than other SGAs, decreased. In addition, the number of new prescriptions for aripiprazole, which carries a lower metabolic risk, increased.
However, the study authors note that it is not clear whether this finding is attributable to the elimination of prior approval of the drug in California during the same time frame.
"We observed a significant change in SGA medication selection. Specifically, we saw a decrease in drugs with higher metabolic risk and an increased use of lower-risk agents.
"Often times we see in the published literature that black box warnings have little or no effect on clinical practice. But here we have a scenario where doctors are aware of the risk and are showing intent to decrease it, but not through increased monitoring. To me, this suggests there may be larger system issues that are inhibiting the adoption of the recommendations," said Dr. Morrato.
Path of Least Resistance?
She speculated that it may be simpler for physicians to lower their patients' metabolic risk by choosing lower-risk agents than for them to integrate regular metabolic monitoring into their practice.
"It is a lot easier to change your drug choice than it is to add in a whole new level of complexity to your practice, particularly since the mental health system and the medical health system are so fragmented. It's not like you can go to your psychiatrist and get your blood drawn; mental health practices generally just aren't set up that way," she said.
Anecdotally, she added, some clinicians have successfully integrated such changes into their practices, but widespread systemic changes are needed to address this growing problem.
She pointed out that use of SGAs, both for approved and off-label indications, is on the rise. Furthermore, the agents' target patient populations are expanding to include adjunctive treatment of antidepressant-resistant depression and use in an increasing number of children who, recent research suggests, are as vulnerable to the agents' adverse metabolic effects as their adult counterparts.
Commenting on the findings, Christoph U. Correll, MD, who helped develop the American Diabetes Association/American Psychiatric Association consensus statement, described the low rate of lipid and glucose monitoring as "alarming."
"Since the initial FDA warning, there have been more and more data produced about the use of these drugs in mentally ill patients and the link between metabolic syndrome and poor cardiac outcomes. It is really shocking how little psychiatrists and other prescribers of antipsychotics have responded to the need for [metabolic] monitoring," Dr. Correll, director of the Adverse Events Assessment and Prevention Unit, Zucker Hillside Hospital, North Shore–Long Island Jewish Health System, Glen Oaks, and the Feinstein Institute for Medical Research, Manhasset, New York, told Medscape Psychiatry.
Like Dr. Morrato, Dr. Correll speculated that low rates of testing may be a resourcing issue and that busy psychiatrists are simply opting for a lower-risk agent instead of taking the time to test and vigilantly monitor their patients.
It is also possible, he said, that patient nonadherence is playing a role and that even though testing is ordered mentally ill patients do not follow through on referrals to a laboratory or primary care physician.
Dr. Correll also agreed that fragmentation between medical and psychiatric practices may play a role in poor rates of metabolic monitoring.
"It may be that what needs to happen is that large mental health clinics need to be attached to medical clinics so they can provide patients with a one-stop shop," he said.
Dr. Correll added that further studies are needed to look at the potential barriers to metabolic testing and find out why physicians are not either able or willing to carry it out.
"Once we know the answers to these questions, we can develop strategies to address the problem," said Dr. Correll.
The study was supported by Pfizer Inc. Dr. Morrato is an employee of the University of Colorado, Denver, which was contracted by Pfizer Inc for this study. Dr. Morrato reports that she has received research funding from Eli Lilly and the National Institutes of Health and is a consultant to the FDA. The disclosures of the other study authors are available in the original article. Dr. Correll has disclosed being a consultant or receiving honoraria from AstraZeneca, Bristol Myers Squibb, Cephalon, Eli Lilly, Intra-Cellular Therapeutics, Medicure, Ortho-McNeill-Janssen, Otsuka, Organon, Pfizer, Schering-Plough, Solvay, Supernus, Vanda, and Wyeth. He has also disclosed that he has served on the speaker’s bureaus of AstraZeneca, Bristol-Myers Squibb/Otsuka, and Pfizer.
Arch Gen Psychiatry. 2010;67:17-24.
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Cite this: Metabolic Monitoring in Patients Taking Second-Generation Antipsychotics Remains Poor - Medscape - Jan 05, 2010.