Despite safety risks, prescribers receive little guidance of monitoring antipsychotic clozapine


Clozapine is an atypical antipsychotic that is often used as a last resort to treat schizophrenia that has not been responsive to other drugs, also known as “treatment-resistant schizophrenia” (TRS), due to its adverse side effects, some of which are life-threatening. A new review published in CNS Drugs analyzes the current available treatment guidelines for monitoring the potential negative side effects of clozapine. Shockingly, based on their inclusion criteria, the authors only found one existing guideline. They offer recommendations for symptom monitoring to be included in the development of future guidelines.

The authors, led by Sarah Smessaert of the Katholieke Universiteit Leuven in Belgium, write:

“Despite the evidence that patients on clozapine have lower mortality and enhanced quality of life, and that no other antipsychotic is as effective for TRS, many psychiatrists remain reluctant to prescribe clozapine due to safety concerns. Clozapine initiation is often delayed by a mean of 4 years, and other antipsychotics are often used instead in ways not recommended by therapeutic guidelines.”

Clozapine is the current standard of care in treating TRS across different guidelines for the treatment of schizophrenia. It is touted to be effective, particularly for people with schizophrenia who are experiencing suicidality or aggression.

However, clozapine is also associated with a number of common adverse effects, such as fever, sedation, gastrointestinal issues, and excessive saliva flow (which in turn can lead to aspiration pneumonia), among others. There are also less common but more severe side effects caused by clozapine, which include myocarditis or inflammation of the heart muscle, convulsions, and neuroleptic malignant syndrome, which, if left untreated, is potentially life-threatening. Due to the number of negative side effects associated with clozapine, prescribers tend to be reluctant to prescribe it.


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Ashley Bobak is a doctoral-level therapist and earned her doctoral degree in Clinical-Community Psychology from Point Park University. She is interested in the intersections of philosophy, history, and psychology and is using this intersection as a lens to examine substance addiction. She hopes to develop and promote alternative approaches to conceptualizing and treating psychopathology that maintain and revere human dignity.