Clozapine 'Vastly' Underutilized for Resistant Schizophrenia

Megan Brooks

February 12, 2014

Many patients with treatment-resistant schizophrenia who could benefit from clozapine are not getting it, new research suggests.

A retrospective study shows a "low" initiation rate of clozapine among patients who warrant a trial of the atypical antipsychotic.

"Clozapine is the treatment of choice for someone diagnosed with schizophrenia who isn't responding to other antipsychotics. Lots of people who might benefit from clozapine never try it," Scott Stroup, MD, MPH, of Columbia University Medical Center in New York City, told Medscape Medical News.

"Doctors should prescribe clozapine when indicated or refer to someone who will. The needs and preferences of patients rather than those of doctors should determine treatments," he added.

The study was published in the February issue of Psychiatric Services.

"Vastly Underused"

Dr. Stroup and colleagues analyzed Medicaid claims data in 45 states for 326,119 individuals with a schizophrenia spectrum disorder who initiated 1 or more antipsychotic treatment episodes during a 4-year period (January 2002 to December 2005).

Among 629,809 unique antipsychotic treatment episodes, 79,934 met the criteria for treatment resistance.

Clozapine accounted for just 2.5% of new antipsychotic starts overall and 5.5% of new starts among patients with treatment-refractory illness who would be candidates for a trial of the drug.

"This is far below expectations, given the estimated proportion of individuals who would warrant a clozapine trial," Martha Sajatovic, MD, of the Department of Psychiatry, Case Western Reserve University School of Medicine in Cleveland, Ohio, writes in an accompanying editorial.

These findings are "in line with other reports suggesting that clozapine is vastly underused," she points out.

Although the precise proportion of people with schizophrenia who warrant a trial of clozapine is unknown, most estimates suggest a figure ranging from 20% to 30%, Dr. Stroup and colleagues note.

Consistent with prior studies, African Americans were less likely than their white counterparts to initiate clozapine treatment, whereas male patients and younger patients were more apt to start the drug.

Those with more frequent outpatient service use for schizophrenia and those with greater prior-year hospital use for mental health were also more likely to initiate clozapine, findings that reflect "sound clinical decision making," the researchers say.

Living in a county with historically high rates of clozapine use was also a strong predictor of clozapine use, suggesting that local practice pattens "greatly" influence clozapine use, they add.

Low Comfort Levels a Factor?

Why is clozapine rarely used to treat patients who might benefit? Multiple factors are at play, Dr. Stroup said.

"Some patients may not want clozapine because of medical risks and frequent blood draws. They may not understand that clozapine's risks can be managed. But more likely is that patients aren't made aware of its potential benefits," he said.

On the other hand, "some doctors don't offer clozapine because they aren't comfortable using it or because of the close clinical monitoring and paperwork that clozapine requires," Dr. Stroup said.

"Unfortunately, this means that instead, they use other treatment strategies that are unproven, for example, combinations of antipsychotics or switching to a different standard antipsychotic."

Dr. Sajatovic notes that clozapine no longer has patent protection, "and lack of commercial promotion may affect clinical use in relation to other patent-protected drugs."

"Unless something changes it is likely that clozapine will continue to be underused. As Stroup and colleagues point out, it is up to our entire health community (clinicians, care systems, policy makers, and consumers) to consider this pattern and implement ways to reverse it," writes Dr. Sajatovic.

One author of the study reports receiving honoraria from Boehringer Ingelheim. The other authors report no relevant financial relationships. Dr. Sajatovic is a member of the editorial board of Psychiatric Services, a monthly publication of the American Psychiatric Association.

Psychiatr Serv. 2014;65:186-192. Abstract, Editorial

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