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Considering Clozapine for Treatment-Resistant Schizophrenia

May 19, 2019

SAN FRANCISCO—Panels of speakers at 2 American Psychiatric Association (APA) Annual Meeting sessions encouraged clinicians to consider prescribing clozapine in patients with treatment-refractory schizophrenia, despite the many challenges which come with using the drug.

“We’re really undertreating people with treatment-refractory schizophrenia with our best evidence-based treatment,” said Australian psychiatrist Dan Siskind, MD, at a session on strategies to address the underutilization of clozapine.

About 20% to 33% of people with schizophrenia have a treatment-refractory course of the disease, Dr. Siskind said, and it is estimated that, around the world, less than one-third to one-half of them are even offered a trial of clozapine. Among several developed nations, the United States is estimated to have the lowest clozapine prescription rate, approximately 4% to 5%.

Dr. Siskind presented 3 studies to argue why those rates should be higher. A meta-analysis of 25 studies which his team conducted found clozapine to be significantly superior overall in short-term trials, and superior for positive symptoms in both short and long-term trials. The other research found associations between clozapine use and fewer hospital bed days, a reduced risk of rehospitalization, and lower all-cause mortality rates.

Alexander S. Young, MD, MHS
Alexander S. Young, MD, MHS

At the second session, focused on interdisciplinary approaches to clozapine use, psychiatrist and researcher Alexander S. Young, MD, MHS, presented a study from Sweden which found clozapine was more effective than all other antipsychotics, including long-acting injectables, as well as combinations of antipsychotics.

However, Dr. Young admitted, along with being the most effective treatment, clozapine is also the most difficult to use.

Speakers at both sessions reviewed the blood monitoring requirements mandated for patients on clozapine as well as the many possible side effects, ranging from potentially fatal neutropenia to myocarditis, weight gain, and sedation.

Dr. Siskind said lack of knowledge and experience in clozapine management is one of the biggest barriers to clozapine being used more. He encouraged more education for prescribers and trainees, mentorship with experienced prescribers, and integrated clozapine community clinics.

Clinicians can learn about the drug through, which Dr. Young said has a “very robust” section on clozapine. The website is part of the Clinical Support System for Serious Mental Illness (CSS-SMI), a $14.2 million multidisciplinary initiative funded by the Substance Abuse and Mental Health Services Administration and administered by the APA.

Henry A. Nasrallah, MD, presenting at the first session, said about 40% to 45% of people who take clozapine have a very good response to it. He spoke of a female patient who finished college and authored a book after starting clozapine, following 4 years which she spent homeless and suffering from schizophrenia with no treatment.

“It’s really worth it because it gives people their life back. And we can manage those side effects. They’re manageable,” he said. “We can’t succeed with everybody with clozapine but it’s mandatory that you give patients with severe treatment-refractory psychotic symptoms a trial. Give them a chance”

—Terri Airov


“Innovative strategies to address clozapine underutilization.” Presented at: the American Psychiatric Association Annual Meeting; San Francisco, CA; May 19, 2019.

“It takes a village: interdisciplinary approaches to the use of clozapine.” Presented at: the American Psychiatric Association Annual Meeting; San Francisco, CA; May 19, 2019.

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