Why Clozapine is Still an Essential Antipsychotic

by Staff Writer
August 16, 2023 at 4:05 PM UTC

Why clozapine is till an essential antipsychotic.

Clozapine was originally synthesized in the 1950s, but languished on the shelves due to associated adverse effects. However, its unique efficacy for treatment-resistant schizophrenia sparked interest beginning in the 1970s. Emerging as a game-changer for that disorder, the drug’s unparalleled impact on treatment-resistant cases cemented its position as a last-resort beacon of hope for those failed by conventional therapies.

Brain J. Lee, MD, a resident at the Johns Hopkins University School of Medicine, told Psychiatrist.com that there’s still a lot of hesitation for prescribing clozapine among psychiatrists. Lee is the author a new The Journal of Clinical Psychiatry paper on the protective effect of clozapine for suicide. In a series of videos, he asked psychiatrists to reconsider this reticence, given the drug’s substantial benefits.

When to Prescribe Clozapine

Lee said he can understand why psychiatrists don’t usually consider clozapine as a first-line treatment. Its serious side effects, including agranulocytosis, a severe condition characterized by a dangerous drop in white blood cell count, are well established. But when other antipsychotics fall short, clozapine may offer a patient a good response.


Clozapine’s exceptional efficacy as an antipsychotic lies in its unique receptor profile. By engaging serotonin and dopamine receptors with precision, it addresses symptoms that often elude other medications. This distinct pharmacological action enables clozapine to provide relief when other antipsychotics have proven ineffective. This cements its status as a go-to option in complex cases of mental illness.

Side Effects

Lee doesn’t deny clozapine’s risks. Patients have to be monitored carefully and submit to regular blood tests to guard against a precipitous drop in white blood cells known as agranulocytosis. Taking a cautious prescribing approach makes sense to Lee. Clinicians always need a balance therapeutic benefits with vigilant safety measures, he cautioned, which is why many reserve the drug for cases where other treatments have proven inadequate.

Then, there is clozapine’s potential for metabolic side effects. Patients can experience sudden, substantial weight gain, with some individuals packing on 20 to 30 pounds or more over just a few months of treatment. Lee also advised being on the look out for myocarditis, an inflammation of the heart muscle that causes chest pain and shortness of breath.

Mitigating Side Effects

Lee said a focused care team can manage the negative symptoms of clozapine use with careful monitoring and by getting on top of them early. For example, if a patient shows signs of myocarditis, consider pausing clozapine until the condition is under control. A patient can restart medication once the danger has passed.


For more information, you’ll find bonus videos on this topic on our YouTube channel.


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