Studies by URI pharmacy professor offer hope to patients with treatment-resistant schizophrenia

Treatment with clozapine can improve lives, reduce costs

KINGSTON, R.I. – August 22, 2016 – Patients with treatment-resistant schizophrenia are not only tormented by their disease, but often receive ineffective treatment. Clozapine, the only effective treatment, is often a last resort because it has unique side effects and risks.

But Jessica Goren, an associate professor of pharmacy practice at the University of Rhode Island, has demonstrated in two studies conducted at the Veterans Affairs (VA) Hospital in Bedford, Mass. that if more veterans with the illness were treated with clozapine they would have better outcomes and the VA health care system would save money.

Goren, whose findings were recently published in the peer-reviewed journal, Psychiatric Services, said that because of the need to monitor patients for side effects, patients are prescribed only one week of medication at a time. Each time, they must be thoroughly evaluated and have a blood test before the prescription can be refilled. Because of this, clinicians are often reluctant to prescribe clozapine, even though it is the only medication that works for treatment-resistant schizophrenia.

Schizophrenia is a chronic and severe mental disorder that affects how a person thinks, feels, and behaves. People with schizophrenia have lost touch with reality, according to the National Institutes of Health.

Even when effectively treated, schizophrenia can be devastating, impairing a person’s social and family life, ability to work and physical health, according to the URI professor. For many it can lead to poverty. For the 20 to 30 percent of treatment-resistant patients – those in whom traditional treatments are ineffective – the prognosis is even worse. In addition it is twice as expensive to treat them if they do not receive clozapine.

“Even though clozapine is a challenge to manage, it can dramatically improve patients’ lives,” Goren said.

In one study, Goren’s team interviewed administrators and clinicians at VA hospitals with high and low clozapine use in different regions across the country to identify facilitators and barriers to clozapine use. The other study was a cost-benefit analysis to see if increased use would save the VA hospitals money.

In the first study, Goren and her colleagues found relatively straightforward changes in how care is provided could help VA expand clozapine use for patients with treatment-resistant schizophrenia. In fact, all of the strategies to improve access to clozapine are being used in at least some VA hospitals. These strategies include: providing transportation to appointments for patients taking clozapine, development of multidisciplinary clinics and having clearly identified processes. They were all were associated with higher clozapine use, Goren said.

In the cost-benefit study, she reported even with additional resource costs to fully monitor treatment, VA hospitals could save $22,444 annually per patient treated with clozapine, primarily through fewer inpatient hospitalizations. If current use was doubled and 50 percent of those veterans remained on clozapine for one year, the VA would save $80 million each year.

While only 1 percent of the U.S. population suffers from schizophrenia, it is an important disease for the VA because its onset usually occurs between 18 and 30. “Which means many people in the military don’t exhibit the symptoms of the disease until after they have joined,” Goren said. “But if the disease surfaces while they are in the service, they remain VA patients for life.

“One patient who went on a clozapine regimen gained a lot of weight (a side effect of the medication), but she told me, “I am happy because I have my life back’,” said Goren, who is also a senior psychiatric pharmacist at Cambridge Health Alliance in Cambridge, Mass. and an instructor in psychiatry at Harvard Medical School. She teaches psychopharmacology, and as a URI pharmacy preceptor, mentors URI doctor of pharmacy students during their psychiatric rotations at her practice in Cambridge.

Goren said evidence-based guidelines and VA policies agree that patients who do not respond to two adequate trials of antipsychotic drugs should be offered clozapine. However, on average, she said, patients receive six antipsychotic trials with multiple drugs, a practice unsupported by research findings. The delay in prescribing clozapine means that patients receive less effective therapies in place of the only treatment proven effective for patients with treatment-resistant schizophrenia, she said.

“This problem is not limited to the VA,” she said, adding that, “research shows this happens in most U.S. treatment settings, so the study findings are important for patients with treatment-resistant schizophrenia receiving care within and outside of the VA.

“This is the only medication that works, but it’s difficult to manage,” Goren said. “It can decrease white blood cell counts, which can lead to infection and death. But, required monitoring programs are quite effective.”

Goren said that with proper monitoring, the rate of agranulocytosis (an acute blood disorder) is 0.38 percent. Given clozapine’s efficacy in decreasing suicide attempts, more lives are saved than harmed with clozapine treatment.

“Our goal is to get more patients treated with clozapine, which is underused because overall, clozapine saves lives, improves patients lives and decreases health care costs,” said Goren.

“This is a tortuous disease, but patients on clozapine will spend less time in the hospital and can reintegrate into daily living. Some patients will even be able to return to work as they are treated with clozapine.”

She also said patients with treatment-resistant schizophrenia have among the highest rates of suicide.

“There are only two drugs to have been shown effective in preventing suicide among this group and one of them is clozapine,” Goren said. “Individuals with schizophrenia die an average of 25 years younger than the general population.

“It breaks my heart to see how poorly these patients are treated in all phases of their lives. This is my population. There are evidence-based treatments that work,” said Goren.