Robert Francis*, a 48-year-old licensed clinical social worker, who lives near Washington, D.C., has been on clozapine for 25 years. When he graduated from college, he started to have trouble sleeping, saying weird things out of context, and behaving strangely.His family sent him to a hospital, where he received an injection of the antipsychotic drug haldol. Forty-five minutes later, his whole body tightened. He said it was like he had cerebral palsy from top to bottom, but it was caused by a severe allergic reaction. Then, the doctors tried an antipsychotic called Zyprexa, which made him feel like a zombie, foggy and tired. He stopped taking it and his symptoms flared up again.“I was nearly catatonic at that time," he said. "I was so paranoid that I pretty much got up and sat down in a chair and watched people all day long because I was just so on edge."At another hospital, Francis was given clozapine. Within three or four days, he said, he felt like himself again. “It was like somebody just wiped the slate clean. You're back to your normal self."
“It was like somebody just wiped the slate clean. You're back to your normal self."
All antipsychotics can have side effects. Clozapine can also cause excess saliva, constipation, drowsiness, weight gain, and in rare cases, inflammation of the heart, or myocarditis. But others can increase the hormone prolactin, which can lead to bone loss, sexual dysfunction, and infertility. Some of the older schizophrenia drugs can cause tardive dyskinesia, an erratic movement disorder and other antipsychotics have a small risk of agranulocytosis, too, Nucifora said.Yet no other psychiatric medication requires the registration and monitoring that clozapine does.Kelly said these restrictions present a narrative that clozapine is impossibly difficult to use, but she doesn't find that to be the case in practice. With her patients, she starts the drug slowly and keeps an eye on their white blood cell counts. She said that many doctors aren't aware of the actual risk of agranulocytosis, which is less than 1 percent. About two thirds of prescribers also don’t know that the biggest risk for agranulocytosis happen within the first six months, and tapers off after that.
"There's no reason you should be waiting for years and years to try clozapine."
Gopal Vyas, an assistant professor at the University of Maryland School of Medicine and a psychiatrist who works with Kelly, said that in 13 years of using clozapine almost exclusively, he’s had only one patient with agranulocytosis. They hospitalized the patient as a precaution, gave him antibiotics and a medication to boost bone marrow—which helps produce white blood cells— and his counts returned to normal. “He didn't even get a runny nose,” Vyas said.It's fair to assume that very sick patients can't handle the upkeep of a weekly blood draw, Nucifora said, but doctors may be overestimating that burden too. In surveys sent to patients and clinicians, most clinicians overestimated how often and how bad clozapine’s side effects were. And only 19 percent of the patents reported they were unhappy about the blood tests compared to 52 percent of the doctors who thought that their patients didn't like them.Nicholas, meanwhile, said that clozapine can make him drowsy, but since he takes it before bed, it actually helps him sleep through the night. He takes a medication to help with related constipation, but has no other side effects. And compared to other drugs he's tried, like Zyprexa, which gave him racing thoughts, or Geodon, which gave him extreme pain in his legs—he said clozapine comes out on top.
"If people haven’t seen someone respond to clozapine, they may not truly appreciate what the drug can do."
Mr. C was a Black 29-year-old who first tried to kill himself at age 11. After being diagnosed with schizophrenia, he tried the antipsychotics risperidone, fluphenazine, and olanzapine, but they either caused severe side effects or didn’t help with his psychotic symptoms. When he went on clozapine, it eased his auditory hallucinations and thought disorders, but after he was discharged, clozapine was discontinued, “allegedly because of a low white blood cell count,” according to a case report from Kelly and her colleagues. He died by suicide 48 hours after stopping the drug.Suicide risk is already extremely high for people with schizophrenia—about half of those diagnosed will attempt suicide and about 5 to 10 percent die by suicide. Clozapine is the only antipsychotic with FDA approval for treating suicidal behaviors. In a study of 88 patients, suicide attempts decreased 86 percent in the two years after they got clozapine, compared the two years prior. Data from more than 12,000 people in the U.K. and Ireland found a four-fold decrease in suicide in the patients who were prescribed clozapine.But if people stop clozapine suddenly, it can cause “super sensitivity psychosis” which is a rapid worsening of delusions and hallucinations in the first couple of days. Nicholas had a friend who died by suicide because he was pulled off clozapine and wasn’t given an alternative fast enough. “He signed himself out of the hospital and shot himself,” Nicholas said. “You can become psychotic very quickly. That's all it takes for the psychosis to step back in.”
Because the FDA’s standards were based on white patients, many Black patients weren’t eligible to even try clozapine.