Patients with schizophrenia are struggling to obtain clozapine. Here's what you can do.
Key Takeaways
The FDA requires some medications to undergo Risk Evaluation and Mitigation Strategy (REMS) programs to ensure that each drug’s benefits outweigh its potential harm.
Treatment-resistant patients with schizophrenia are having difficulty accessing clozapine—considered the gold standard medication for this patient population—due to restrictions placed on it by REMS.
Doctors may choose to treat these patients with typical or atypical antipsychotics, in addition to appropriate therapies and self-management techniques.
Delusions, hallucinations, disorganized thought processes and unusual movements—these are just a handful of symptoms that patients with schizophrenia deal with.
To address these symptoms, doctors often prescribe medications such as clozapine, an atypical antipsychotic that’s considered the gold standard for treatment-resistant patients.
While clozapine can cause dangerous side effects, FDA-mandated REMS programs intended to protect patients may cause more harm by barring them from this potentially life-changing medication.[]
Doctors of patients with schizophrenia may rely on other antipsychotics—coupled with therapy and self-management techniques—for treatment.
Gold standard—for some
When a patient with schizophrenia doesn’t respond well to typical (also known as “first-generation”) antipsychotics or other drugs known to treat this disorder, psychiatrists often rely on clozapine.
Clozapine is a second-generation (also known as “atypical”) antipsychotic—meaning it works by blocking both serotonin and dopamine in the patient’s brain—and has shown to be a successful option for many.
One meta-analysis published by Translational Psychiatry conducted a PRISMA-conforming quantitative meta-review of evidence pertaining to clozapine use in neuropsychiatric disorders.[] The authors spoke highly of the medication’s efficacy.
“Clozapine appears to have superior effects on positive, negative, and overall symptoms and relapse rates in schizophrenia (treatment-resistant and non-treatment-resistant subpopulations) compared to first-generation antipsychotics (FGAs) and to pooled FGAs/second-generation antipsychotics in treatment-resistant schizophrenia,” the authors wrote.
Despite its success in treating schizophrenia and other psychotic disorders, clozapine is subject to harsh regulations imposed under Risk Evaluation and Mitigation Strategy (REMS) programs.
Barring patients from clozapine
REMS programs are intended to protect patients from the potentially dangerous side effects of certain drugs.
For example, to mitigate the risk of post-injection delirium sedation syndrome after use of Zyprexa Relprevv (another antipsychotic used to treat schizophrenia), the FDA requires the drug’s manufacturer to implement a REMS.
The Zyprexa Relprevv REMS states that the drug can only be administered in certified healthcare facilities, and that the patient must be monitored for a minimum 3 hours post-injection to identify and treat any harsh side effects.
What dangerous side effects can clozapine cause that would warrant a REMS? The answer: agranulocytosis, a condition characterized by the absolute neutrophil count falling below 100 neutrophils per microlitre of the patient’s blood.
Agranulocytosis can cause fever, chills, sore throat, and other flu-like symptoms. It can become life-threatening if not treated promptly, as noted in an article published by StatPearls.[]
Clozapine’s REMS therefore requires patients to get blood work done as often as once per week to ensure their neutrophil counts are normal. This has been in place since November 2021.
Since this change went into effect, many patients—including those who have already been using clozapine—have had to jump through hoops to access their medication, potentially paving the way for other adverse effects.
Patients who suddenly discontinue use of clozapine may experience catatonia, rebound psychosis, and delirium, among other undesirable symptoms.
On top of that, only eight of every 1,000 patients who take the drug experience agranulocytosis—and they have a 97% survival rate.
“I see the clozapine REMS system as the biggest barrier to starting patients on this potentially life-saving drug, indirectly causing more harm than good for people with schizophrenia,” wrote Brian Barnett, psychiatrist in an article published by StatNews.[]
He wrote that such severe guidelines only paint an all-too accurate picture of how patients with schizophrenia are marginalized.
“What else could explain why a highly effective antipsychotic is saddled with such cumbersome regulations, while providers routinely prescribe many other medications with similar agranulocytosis risks that have no REMS requirements?” Barnett wrote.
While the American Psychiatric Association and other allies advocate for the suspension and review of clozapine REMS, there are other treatment options available in the meantime.
Actions to take for patients with schizophrenia
If you have patients with schizophrenia who lack access to clozapine, there are other treatment options available.
According to the Cleveland Clinic, schizophrenia can be treated with other antipsychotic medications—both typical (dopamine-blocking) and atypical (dopamine and serotonin-blocking).[]
There are also a handful of therapies to use in tandem with medications. Psychotherapies such as cognitive behavioral therapy, can help patients cope with their illness. Drama and art therapies can increase motivation in patients with schizophrenia, as well as help them identify their symptoms.
Patients with schizophrenia who are treatment-resistant to these therapies and medications may benefit from electroconvulsive therapy (ECT). ECT can save patients from risk of suicide or harming others.
Despite the negative portrayals of ECT in the media, this treatment is effective in kick-starting brain function in patients with the help of a brief seizure.
ECT isn’t painful. Patients who undergo this therapy receive anesthesia during the process.
What this means for you
REMS programs may inhibit your ability to prescribe clozapine, the gold-standard drug for treatment-resistant individuals with schizophrenia. Despite clozapine’s superiority to first-generation antipsychotics and low hospitalization rates, its potential to cause agranulocytosis led to strict REMS requirements. Some psychiatrists may feel REMS harms patients more than helping, by blocking access to this effective, life-saving treatment. If you’re not authorized to prescribe clozapine, look to other therapies like ECT to treat patients with schizophrenia.