Peter J. Weiden, MD, Discusses Clozapine REMS Challenges and Advisory Committees' Recommendations

Peter J. Weiden, MD

Peter J. Weiden, MD, clinical professor of psychiatry at the Renaissance School of Medicine at Stony Brook University in New York, provided critical insights into the challenges posed by the clozapine REMS (Risk Evaluation and Mitigation Strategies) program. His remarks followed a significant FDA joint advisory committee meeting that overwhelmingly recommended the dismantling of the current REMS framework for clozapine. The panel’s 14-1 vote underscores growing concerns about barriers to access and their unintended public health consequences, he remarked.

“The road to hell is paved with good intentions,” Weiden told Psychiatric Times. He highlighted some of the flaws in the monitoring system designed to safeguard against agranulocytosis, a rare but potentially fatal adverse effect of clozapine. Although the system aims to reduce risks, he explained it has created severe obstacles for patients and clinicians alike, resulting in critical gaps in care. “One-third of people with schizophrenia are not getting monitoring because the system is so bad,” Weiden said, “meaning that the public health protection of such a system is already half baked.” Meanwhile, the program fails to fully ensure safety while placing an excessive burden on clinicians.

Weiden also pointed out that the focus on agranulocytosis overshadows other significant adverse events associated with clozapine, and he called for more attention and education on these areas. “Yes, agranulocytosis can be a life-threatening side effect of clozapine, but so is constipation,” he told Psychiatric Times. “And in fact, there's no question that there are more deaths from clozapine-induced constipation than there are agranulocytosis.”

He also warned of the dangers of disrupted clozapine treatment caused by bureaucratic hurdles, which can lead to relapse or even death.

Meanwhile, Weiden noted clozapine’s unique status as the only FDA-approved medication to reduce suicide risk in patients with schizophrenia. “If we don’t use clozapine because of the ‘hassle’ of the phone calls you have to make, of the many family meetings you have to have, of the up titration that makes someone sleepy or complain of orthostasis, and so forth— if that prevents us as health care providers from using a life-saving medicine, that's terrible. Lives will be lost,” he said.

“And in as much as getting to a lab is the right thing, which is very difficult for our patients to do under the best of circumstances, in as much as that lowers the number of people on clozapine, it is a shame,” he added. “It is terrible. We don't know who we lose, but we will definitely lose some.

The FDA now faces the task of deciding whether to adopt the advisory board’s recommendations, which could lead to significant changes including the elimination of the clozapine REMS.

For more from Dr Weiden on the evolving news on the clozapine REMs requirements, see part 2 of this video.