Clozapine is the only antipsychotic that is effective for the treatment of treatment-resistant schizophrenia. Due to the risk of agranulocytosis, this medicine may only be used in the Netherlands with regular monitoring of the white blood count for the duration of the treatment.
With regard to these blood checks, the Dutch ClozapinePlus Working Group gives the option to discontinue them after six months if a competent and adequately informed clozapine user so wishes. The working group does recommend that the blood count be monitored approximately four times a year to detect slowly progressive leukocyte declines. If agranulocytosis is suspected, the doctor should have the blood count determined immediately.
Due to the fear of agranulocytosis and the mandatory blood tests, clozapine is far too infrequently prescribed worldwide. Peter Schulte (GGZ Noord-Holland-Noord) and his fellow board members of the ClozapinePlus Working Group therefore re-evaluated the scientific evidence for the risk of agranulocytosis and the mandatory blood tests with this effective antipsychotic (Schizophr Res. 2023; online September 26).
In their literature review, the researchers found that the risk of agranulocytosis is highest in the first 18 weeks of treatment. Overall, there is no greater risk of neutropenia with clozapine use than with other antipsychotics. Moreover, frequent blood checks do not demonstrably reduce the risk of agranulocytosis. Patients would even run the risk of having to stop taking clozapine unnecessarily based on abnormal blood values.
Although no RCTs have been conducted comparing mortality between different blood control regimens, based on their findings, the Dutch researchers recommend determining granulocyte counts only during the first 18 weeks of clozapine use. The prescriber and the patient can then determine the further frequency of blood checks in consultation. In accordance with the registration text in the US, clozapine only needs to be discontinued when a granulocyte count is < 1.0 x 109/l and the drug may be restarted if the benefits outweigh the risks.
First author, psychiatrist Peter Schulte, states that the ClozapinePlus Working Group will adopt these suggestions. He expects that this will lead to clozapine being prescribed more often for treatment-resistant schizophrenia, which will reduce mortality among this group of users. This is achieved, among other things, by reducing the number of suicides.
