Collaborative Effort Among Stakeholders Can Reduce Barriers to Clozapine Use

To reduce barriers to clozapine use, prescribers should collaborate with primary care physicians to manage side effects that could emerge during treatment of patients with schizophrenia.

Additionally, prescribers should continually seek to improve their own knowledge base with lifelong learning on clozapine treatment. Less experienced prescribers should establish links with more experienced prescribers who can assist them in addressing issues that arise during clozapine treatment.

These were among the recommendations outlined in a recent white paper on the underuse of clozapine—an antipsychotic that remains underprescribed, despite proven efficacy for the treatment of refractory schizophrenia. The report, a publication of the National Association of State Mental Health Program Directors (NASMHPD), was presented as a poster at the International Congress on Schizophrenia Research in San Diego in March.

It is the result of a collaboration of multiple stakeholders and includes recommendations for psychiatric training programs and academic health centers, acute care and psychiatric hospitals, academic scientists and pharmaceutical research programs, local and state health authorities, payers, correctional systems, and providers of continuing education for health professionals.

“Our report provides recommendations to different key stakeholders about what they should be doing at a minimum,” co-author Deanna Kelly, Pharm. D., of the Maryland Psychiatric Research Center, told Psychiatric News. “The barriers to use are related to side effects associated with the drug and a lack of provider education. If everyone plays their part, these barriers are not as significant as they may seem. If access to clozapine is improved, millions of patients could benefit. In turn, their improved care would result in substantial cost savings to the entire health care system.”

Prescriber knowledge and comfort around the decision to use clozapine remains a significant barrier to care. In an interview with Psychiatric News, Brian Hepburn, M.D., executive director of NASMHPD, said individual clinicians may be intimidated by the challenges associated with using clozapine, especially the requirement for routine blood monitoring for the risk of neutropenia (a severe reduction in a type of white blood cell).

Individual clinicians tend to overestimate patients’ unhappiness with many side effects of clozapine, including the frequency of blood draws and sedation, when in fact patients report less concern about these disadvantages. “[P]eople with schizophrenia have more favorable attitudes toward clozapine treatment than prescribers expect,” the report stated.

Additionally, clinicians tend to overestimate the risk of neutropenia. “[O]ne study reports that about one-quarter of physicians think the risk is greater than 1 percent, when it is actually estimated to occur less than 0.8 percent of the time,” according to the paper. “Furthermore, approximately two-thirds of prescribers do not realize that the greatest risk for severe neutropenia occurs in the first 6 months of clozapine treatment.”

Hepburn said a principle recommendation for clinicians is the need to work together—those who are new to prescribing clozapine, or have little experience with it, collaborating with clinicians more comfortable using the medication. Telepsychiatry, for instance, can link clinicians working in rural, isolated areas to urban clozapine clinics where physicians have more experience with clozapine. “What’s important is to provide support to individual practitioners so that they don’t feel as though they are alone dealing with someone who is on clozapine,” he said.

Physicians report that a significant barrier to more widespread use of clozapine is the lack of experience during residency training. “This is critical, as physicians who have never prescribed clozapine are more likely to overestimate the significance of these challenges than current prescribers,” according to the report. “Incorporating clozapine education in residency training to increase the knowledge of clozapine and comfort level of future prescribers would create a generation of future psychiatrists who have at least had some exposure to real-world clozapine prescribing.”

The NASMHPD white paper recommends that psychiatric residency and training programs include didactic instruction on the use of clozapine, a requirement to become certified under the FDA Clozapine REMS Program, clinical experience in treating and monitoring patients receiving clozapine, and participation in interdisciplinary teams that manage patients receiving clozapine.

Among other recommendations in the report are the following:

• All acute care and psychiatric hospitals should have clozapine on their formularies as an essential medication and have policies and procedures to facilitate its safe and appropriate use.

• Clozapine should be a preferred medication on the pharmacy drug lists of all state Medicaid programs and pharmacy benefit/managed care programs contracting with state Medicaid programs, and on the formularies of Medicare prescription drug programs and other payers of pharmacy benefits.

• Academic centers, in consultation with state or local mental health authorities, should encourage interdisciplinary consultation centers for community providers such as psychiatric pharmacists or nurse practitioners involved in the management of patients receiving clozapine.

• Every public health system of care should have a system that provides ready access to clozapine, provides appropriate safety monitoring of patients receiving it, and encourages prescribers to consider its use when appropriate.

• Mental health authorities should consider establishing model programs for the initiation and monitoring of clozapine patients, and consider offering evidence-based recommendations for addressing metabolic and other emergent side effects. ■