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Clinical and Research News
 DOI: 10.1176/appi.pn.2013.12b2
Multiple Factors Affect Use of Clozapine for Schizophrenia
Psychiatric News
Volume 49 Number 02 page 1

Abstract

A recent study searches for explanations for the low use of clozapine—the only approved drug for treatment-resistant schizophrenia.

Abstract Teaser

Clozapine is the only medication approved by the Food and Drug Administration (FDA) for treatment-resistant schizophrenia, which accounts for about 30 percent of schizophrenia diagnoses. Although the atypical antipsychotic is highly effective in treating symptoms associated with schizophrenia, it is rarely used. Researchers from the New York State Psychiatric Institute and Columbia University have shown how demographic and geographic factors influence the use of clozapine in the United States.

Clozapine was introduced in Europe in 1971, but was withdrawn four years later by its manufacturer after multiple deaths associated with agranulocytosis, a condition that causes a drastic loss of white blood cells. After a series of clinical trials showed that clozapine was effective for treatment-resistant schizophrenia, it was later approved by the FDA solely for such use and with a strict white blood cell monitoring protocol.

Though clozapine was heavily marketed and widely prescribed in the United States in the 1990s, it quickly lost its appeal as new antipsychotics emerged that promised similar benefits without the risk for agranulocytosis. However, recent clinical-trials data suggest that clozapine is more efficacious than newer options.

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T. Scott Stroup, M.D., M.P.H.: Switching or combining standard antipsychotics is not supported by research for patients do not respond to standard antipsychotics.

Columbia University (Scott)

“Some patients may not understand the potential benefits of using clozapine and may not want it because of medical risks and frequent blood draws,” said T. Scott Stroup, M.D., M.P.H., a professor of psychiatry at Columbia University and lead author of the study, which was published November 15, 2013, in Psychiatric Services in Advance. “They may not understand that the risks can be managed.”

In Stroup’s study, data were collected from more than 320,000 Americans aged 18 to 64 with a schizophrenia spectrum disorder diagnosed according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Participants had to have initiated one or more antipsychotic medication treatments for episodes from January 2002 to December 2005. Initiation of clozapine and other antipsychotic treatment was compared with respect to patients’ geographic, sociodemographic, and clinical characteristics. Data were obtained from 45 states using Medicaid Analytics Extracts and were supplemented by county-level data.

Of approximately 630,000 treatment episodes among the patients in the sample, 13 percent were consistent with patterns of treatment resistance. Clozapine accounted for 2.5 percent of initiations of antipsychotic medication and 5.5 percent of initiations among patients with treatment-resistant schizophrenia. Therapy initiation with clozapine was significantly associated with younger age, male gender, and Caucasian race, in addition to more-frequent outpatient schizophrenia services and greater prior-year hospital use for mental illness reasons.

Also, clozapine was more likely to be prescribed in regions where there were at least 15 psychiatrists per 100,000 residents. In addition to treatment resistance, living in a county with historically high rates of clozapine use was among the strongest predictors that patients will be prescribed clozapine.

The authors noted that the findings regarding rates of clozapine use among adults with schizophrenia fell far below their expectations. They told Psychiatric News that though patients and caregivers may opt not to use clozapine, it is most likely not the sole reason for regional differences that were observed in the current study.

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Ira Glick, M.D., says that clozapine may not be widely prescribed by clinicians because of tedious work demands that come with the medication.

Stanford University (Glick)

Ira Glick, M.D., a professor emeritus of psychiatry and behavioral sciences at Stanford University, agreed. “I have had several patients use clozapine. . . . It demands a lot from the doctor—increasing paperwork and routinely sending samples to a lab. Clozapine is definitely more labor intensive than other antipsychotics, and some physicians may feel that they are too busy or intimidated by those work demands,” Glick told Psychiatric News.

Both Glick and Stroup emphasized that when treatment options are approved and readily available to remedy a particular condition, those options should be used.

“When someone diagnosed with schizophrenia does not respond to standard antipsychotics, using combinations of antipsychotics or switching to a different standard antipsychotic are not strategies supported by research,” stated Stroup.

“The characteristics of patients, and not doctors, should determine treatments, especially for a condition that can be as disabling as schizophrenia. I strongly believe that individuals with treatment-resistant schizophrenia should have an opportunity to try clozapine no matter where they happen to live,” Stroup concluded.

The study was funded by the Agency for Healthcare Research and Quality. σ

“Geographic and Clinical Variation in Clozapine Use in the United States” is posted at http://ps.psychiatryonline.org/data/Journals/PSS/0/appi.ps.201300180.pdf.

Anchor for JumpAnchor for Jump

T. Scott Stroup, M.D., M.P.H.: Switching or combining standard antipsychotics is not supported by research for patients do not respond to standard antipsychotics.

Columbia University (Scott)
Anchor for JumpAnchor for Jump

Ira Glick, M.D., says that clozapine may not be widely prescribed by clinicians because of tedious work demands that come with the medication.

Stanford University (Glick)

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