FDA Policy Worsens Homelessness by Limiting Access to Antipsychotics

Clozapine is the only drug approved for treatment-resistant schizophrenia. So why does the FDA make it so hard to prescribe?

Homelessness, sadly, is a pervasive problem that persists even in developed countries like the U.S. Two experts say a policy enforced by the Food and Drug Administration (FDA) is making it worse.

Jeffrey Singer, a physician and a senior fellow at the Cato Institute, and Josh Bloom, director of chemical and pharmaceutical science at the American Council on Science and Health, wrote an article this week about the Risk Evaluation and Management Strategies (REMS) program, which the FDA can enforce "for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks."

REMS, write Singer and Bloom, "has been largely responsible for the underprescription and underuse of clozapine, the only FDA-approved drug for treatment-resistant schizophrenia, the most severe form of the disorder." The FDA approved clozapine for use in 1989.

There are many reasons a person could find themselves homeless, but severe mental illness is a major contributor. Last month, Esquire ran a first-person account of Patrick Fealey, an award-winning journalist who found himself unable to hold a job after he was diagnosed with Bipolar I disorder in 1997; after struggling for years, he became homeless in October 2023. While admitting that his particular cocktail of drugs is not ideal and negatively affects other parts of his body, Fealey writes that it also "enables me to function and has kept me alive for twenty-seven years."

A 2019 meta analysis of 31 studies, encompassing nearly 52,000 homeless people in both developed and developing countries, found that more than 10 percent had schizophrenia or related disorders.

"While ensuring drug safety is essential," Singer and Bloom write, "the REMS program has unintentionally created barriers that disproportionately affect individuals with severe mental illnesses like schizophrenia, further compounding the significant challenges they already face, including unemployment, substance abuse, heightened suicide risk and homelessness."

Schizophrenia is a mental disorder characterized by delusions and hallucinations. It is primarily treated with antipsychotic medications like haloperidol, fluphenazine, and chlorpromazine. But these "typical" antipsychotics also carry the risk of side effects, like tremors or involuntary muscle movements.

Clozapine, an "atypical" antipsychotic, "is sometimes prescribed when people do not respond adequately to other antipsychotic medications. However, it may cause additional side effects, such as kidney or bladder problems," according to New York University's Langone Health. "For this reason, the doctor conducts frequent blood testing to monitor health and prevent serious complications."

Singer and Bloom acknowledge that the FDA added clozapine to the REMS program in 2015 "because of a rare side effect (less than 3 percent frequency) called agranulocytosis, a reversible but life-threatening drop in the white blood cell count." But, they note, "the risk of agranulocytosis drops sharply within months of beginning treatment while the risk of untreated patients falling through the cracks, unable or unwilling to go for weekly REMS-mandated blood tests, is considerable. Furthermore, research shows that, within a year, the risk of blood abnormalities caused by clozapine is similar to that of other antipsychotic drugs for which no weekly blood tests are required."

And yet for those who take clozapine, REMS requires "weekly blood tests for the first 6 months" on the drug, testing "every 2 weeks for the next 6 months" if tests are normal, and "monthly after the first year" if results remain normal, for the rest of the patient's life or until they stop taking the drug.

"These requirements, burdensome even for healthy people, have discouraged doctors from prescribing, pharmacies from dispensing and patients from obtaining clozapine" write Singer and Bloom. "With an estimated 30 percent of schizophrenic patients not responding to first-line antipsychotic drugs, it is a travesty that clozapine is only prescribed to 4 percent of schizophrenic patients in the U.S."

Singer and Bloom say the REMS clozapine rules are not just unnecessary but redundant: "After the FDA approves a drug for marketing, it requires drug makers to monitor it for unforeseen long-term risks," they write. "Furthermore, when doctors prescribe medications that may have serious side effects, they, too, monitor their patients—it's malpractice not to do so."

They're not alone: "Advocates…argue that the REMS are harmful for patients whose lives could be saved if the FDA made the REMS requirements less demanding and more similar to the evidence-based clozapine monitoring policies of countries like the United Kingdom, the Netherlands, Denmark, New Zealand, and Romania," according to the Treatment Advocacy Center, a nonprofit that advocates on behalf of those with severe mental illness.

There may be a bright spot: In November, President-elect Donald Trump announced his intention to nominate Marty Makary, a surgeon and Johns Hopkins University professor, to become the new FDA commissioner. Makary's pick drew a mixed response from health officials based on his prior advocacy against COVID-19 lockdowns and vaccine mandates. But in a June 2020 Soho Forum debate, Makary took the position that lockdowns had saved countless lives, before noting, in September 2022, the "mental health crisis" and "lifelong learning loss" that the lockdowns caused among school-aged children. Rather than an antiscience zealot, this suggests Makary is open to changing his mind when presented with countervailing information.

"The Food and Drug Administration Amendments Act of 2007 (FDAAA)," the agency notes, "established FDA's authority to require Risk Evaluation and Mitigation Strategies (REMS) for prescription drug and biological products when it determines that such a strategy is necessary to ensure that the benefits of a drug outweigh the risks." Under a new commissioner, then, the agency should have the authority to relax the rules on clozapine and expand access to those on the margins of society who could benefit from it.