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Drug Treatment of Schizophrenia Patients Sounds Alarms

15 January 2010. Two studies in the January Archives of General Psychiatry sound alarms about the treatment provided to psychiatric patients. In a study contracted by Pfizer, Inc., Elaine Morrato of the University of Colorado, Denver, and colleagues report that, despite warnings about the need to check blood glucose levels in patients who are taking antipsychotic drugs and who are at risk for diabetes, metabolic testing rates remain stubbornly low. However, the warnings apparently changed which drugs patients received. In the same issue, Ramin Mojtabai of Johns Hopkins University, Baltimore, Maryland, and Mark Olfson of Columbia University, New York, report that, from 1996 to 2006, visits to psychiatrists led to increasing prescriptions for psychotropic medication, including drug combinations of unknown safety and efficacy.

Patients with schizophrenia show increased rates of cardiovascular disease (see Mitchell and Malone, 2006 for a review of physical health in schizophrenia). This may stem from their tendency to develop metabolic syndrome, with its high insulin levels, hypertension, lipid abnormalities, and excess abdominal fat (Meyer and Stahl, 2009). Unhealthy behaviors, such as smoking, eating poorly, and inactivity, surely contribute, but the drugs that help people with schizophrenia function also tax their health. Patients taking second-generation antipsychotics (SGAs), in particular, are likely to gain excess weight and to develop ominous changes in glucose and lipid metabolism (see SRF related news story). In fact, a 2006 study (Basu and Meltzer, 2006) tied the emergence of these drugs to rising rates of diabetes in patients with schizophrenia (see SRF related news story).

Back in 2003, evidence of the adverse metabolic effects of SGAs spurred the United States Food and Drug Administration to order labeling changes for all drugs in the class. The revisions warn prescribers to check fasting blood glucose levels at the start of treatment in patients with diabetes or its risk factors and to watch for symptoms of hyperglycemia in all patients. The agency also told drug makers to send letters to healthcare professionals to inform them about the warning. Around the same time, the American Diabetes Association and other organizations issued a consensus statement that underscored the risks and the need to monitor all patients who are taking SGAs.

A partial response?
After the warnings, rates of lipid and glucose testing remained low in SGA users who had private insurance, according to prior studies (Morrato et al., 2009; Haupt et al., 2009). However, Medicaid recipients account for a large fraction of psychotropic drug use and costs (Zuvekas and Cohen, 2007), and Morrato and colleagues wondered whether the warnings had any effect on their care. In a study with an unusually big sample, the researchers examined medical, laboratory, and pharmacy claims from the years 2002 to 2005 for two groups of fee-for-service Medicaid patients.

One group consisted of 109,451 patients who started taking an SGA for a variety of disorders in addition to schizophrenia. The study excluded those on clozapine, due to the extra monitoring needed to detect a white blood cell disorder caused by the drug. The control group of 203,527 patients had started treatment with albuterol, an asthma treatment, but were not taking antipsychotic drugs.

Before the FDA warning, 27 percent of patients with a new SGA prescription received baseline testing of their blood glucose levels. Only 10 percent underwent baseline lipid testing. However, during and after the nine-month warning period, blood glucose testing rates remained unchanged. Lipid testing rose by a statistically significant 1.7 percent during the warning period, but improved no further in the subsequent 16 months.

The warnings may have changed patient care in another way, however. During the warning period, new prescription claims for olanzapine, an SGA with relatively severe metabolic effects, decreased by about 20 percent per year. Meanwhile, those for aripiprazole, which causes less metabolic mayhem, rose; however, this may reflect a policy change that eased access to the drug in one of the states studied. Use of quetiapine, risperidone, and ziprasidone remained unchanged. Analyses limited to SGA users with schizophrenia revealed a similar, but less pronounced, prescribing shift (see SRF related news story).

The study did not explore the reasons for the lack of metabolic testing. However, the researchers point out that surveys of psychiatrists (e.g., Newcomer et al., 2004) suggest that they knew about the warnings. Morrato and colleagues speculate that prescribers may find it easier to switch drugs than to change their monitoring habits. They recall that the number of antidepressant prescriptions for children dropped after warnings about a possible drug-linked rise in suicidal thoughts and behavior, but the recommended stepped-up monitoring for suicidal tendencies or worsening depression did not occur. Even so, in the present study, the researchers could not say whether the behavior of prescribers, patients, or both explained the lack of metabolic monitoring.

More reasons to monitor
Treatment of serious mental illness often involves more than one medication at a time. Sometimes, this reflects a need to treat comorbid conditions or to improve upon a disappointing response to one drug. Patients with schizophrenia, in particular, often receive combinations of antipsychotic drugs, with the idea of targeting complementary receptors and symptoms. In reality, though, these combinations may work no better than a single antipsychotic (see SRF related news story).

The study by Mojtabai and Olfson examined recent trends in the prescribing of psychotropic drugs and especially multidrug regimens. Using data from the 1996 to 2006 National Ambulatory Medical Care Survey, they examined patient visits to a nationally representative sample of office-based psychiatrists. Specifically, they focused on 13,079 visits in which adult patients received a psychiatric diagnosis. The psychiatrist or a member of the psychiatrist’s staff supplied data on the psychotropic drugs prescribed or given during the visit.

Results showed that from 1996 to 2006, the percentage of visits in which any psychotropic drug was prescribed increased from 73 percent to 86 percent. Visits involving prescriptions for two or more psychotropics rose from 43 percent to 60 percent, while those for three or more jumped from 17 percent to 33 percent. The most common drug combos consisted of antidepressants given with sedative-hypnotics, antipsychotics, or other antidepressants. During the study period, the fraction of visits resulting in prescriptions for two or more antidepressants, two or more antipsychotics, and antidepressants plus antipsychotics increased.

Multivariate analyses assessed prescribing trends over time, while controlling for such factors as patient demographic characteristics, the kind and number of psychiatric diagnoses, payment source, practice type, and location. They showed that visits for schizophrenia, bipolar disorder, or major depression were especially likely to involve prescriptions for antidepressant-antipsychotic combos. Patients with schizophrenia or bipolar disorder were particularly likely to receive treatment that combined antidepressants with mood stabilizers, antipsychotics with mood stabilizers, antipsychotics with sedative-hypnotics, or mood stabilizers with sedative-hypnotics.

Mojtabai and Olfson acknowledge that certain drug combinations have some empirical basis, but many lack evidence of benefits beyond those bestowed by a single drug. Moreover, multidrug regimens may increase the risk of adverse drug interactions, such as metabolic side effects from treatment with two or more antipsychotics (Suzuki et al., 2008). As Mojtabai and Olfson write, “These data call for more careful monitoring of metabolic parameters in patients taking more than one antipsychotic medication.”—Victoria L. Wilcox.

Mojtabai R, Olfson M. National trends in psychotropic medication polypharmacy in office-based psychiatry. Arch Gen Psychiatry. 2010 January;67(1):26-36. Abstract

Morrato EH, Druss B, Hartung DM, Valuck RJ, Allen R, Campagna E, Newcomer JW. Metabolic testing rates in 3 state Medicaid programs after FDA warnings and ADA/APA recommendations for second-generation antipsychotic drugs. Arch Gen Psychiatry. 2010 January;67(1):17-24. Abstract

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