A recent study found two-thirds of homeless people have a mental illness, with more than three-quarters of them having experienced it during their lifetimes. Between 10 and 20 percent of the homeless have schizophrenia, one of the most debilitating of all mental health disorders. For people with such a severe condition, it is crucial that they have easy access to effective antipsychotic medications.
Unfortunately, an FDA policy — specifically the Risk Evaluation and Mitigation Strategies (REMS) program — has been largely responsible for the underprescribing and underuse of clozapine, the only FDA-approved drug for treatment-resistant schizophrenia, the most severe form of the disorder.
The FDA established REMS in 2007 to ensure safety precautions for certain drugs with potentially dangerous side effects. While ensuring drug safety is essential, 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.
Tragic stories abound of stable patients who lost access to clozapine and had catastrophic relapses. Kevin Keith Langemeier missed the REMS window to refill his clozapine prescription, leading to delusions that caused him to brandish a toy rifle at police, who then shot and killed him. Andrew M.’s delusions and threatening voices returned when he was cut off from clozapine after missing a routine blood test. He pulled out his right eye with his fingers and even managed to sever the optic nerve.
The FDA approved clozapine, which is classified as an “atypical” antipsychotic drug, for treatment-resistant schizophrenia in 1990. In 2002, the FDA announced clozapine was effective in reducing the risk of suicide in people with schizophrenia and associated disorders. Atypical antipsychotics are preferred over so-called “typical” antipsychotics due to fewer movement-related side effects, like tremors, stiffness, uncontrollable muscle movements (tardive dyskinesia) and restlessness. A 2024 Brazilian study found patients taking non-clozapine atypical antipsychotics had a 21 percent greater chance of death than those taking clozapine. The World Health Organization includes clozapine on its List of Essential Medicines.
Clozapine was included in 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. We believe this policy is overly cautious since 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.
It is now 34 years after the FDA approved this essential antipsychotic drug. Yet, the agency still requires all prescribers to enroll and be certified in the Clozapine REMS program, all pharmacists who dispense it to be Clozapine REMS-certified, and all patients to enroll in the program.
The Clozapine REMS mandates regular lab tests for people taking the drug, with results reviewed by the prescriber and pharmacy before patients receive a seven-day supply. These requirements, burdensome even for healthy people, have discouraged doctors from prescribing, pharmacies from dispensing and patients from obtaining clozapine. 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 United States.
Government-imposed REMS programs are unnecessary. After the FDA approves a drug for marketing, it requires drug makers to monitor it for unforeseen long-term risks. Concerns about reputation and liability are other motivators. Furthermore, when doctors prescribe medications that may have serious side effects, they, too, monitor their patients — it’s malpractice not to do so.
For example, widely prescribed statin drugs can cause liver abnormalities in some patients. Doctors routinely check for this, especially in statin-naïve patients, and then relax surveillance as circumstances warrant. Doctors frequently prescribe drugs that can cause severe blood abnormalities for a variety of conditions. These include other antipsychotic drugs such as Seroquel, which, unlike clozapine, is unconstrained by a regimented, complex, top-down program overseen by a federal bureaucracy.
Although uncommon, the FDA has eliminated REMS requirements for certain drugs in the past. But in this case, there is no incentive for the makers of off-patent generic clozapine to petition the FDA to remove the Clozapine REMS, particularly if they profit from patented alternatives that doctors can prescribe more easily. And clozapine treatment would cost less without the weekly blood monitoring expenses.
The FDA’s Clozapine REMS program is a good example of how overemphasizing safety can do more harm than good. By imposing a one-size-fits-all monitoring regime on drug makers, doctors and pharmacists, the government blocks them from independently using the more tailored and innovative monitoring methods they would otherwise employ. The FDA barriers to clozapine access are preventing thousands of people with schizophrenia from receiving proper treatment.
There are an estimated 653,000 homeless people in the U.S. today. Some 60,000-120,000 of them, who are further straining already-drained resources for homeless people, could benefit from easier access to a long-used, effective drug. The Clozapine REMS program stands in the way. It should be eliminated.
Jeffrey A. Singer, M.D., practices general surgery in Phoenix and is a senior fellow at the Cato Institute. Josh Bloom, Ph.D., is director of chemical and pharmaceutical science at the American Council on Science and Health.
