This article was published on August 1, 2022.
Please read this article carefully even if you don’t prescribe clozapine yourself.
Patients with schizophrenia or schizoaffective disorder who are candidates for clozapine are often not referred for clozapine treatment or referred only after a long delay.
All of us can help by referring patients with schizophrenia/ schizoaffective disorder who are either “treatment-resistant” OR at high risk of suicide for treatment with clozapine more often and earlier than is currently being done.
On this page, let’s look at the reasons why clozapine is such a big deal.
Clozapine and “treatment-resistant” schizophrenia
1. “Treatment-resistant” schizophrenia is very common
It occurs in somewhere between 1/4th and 1/3rd of patients with schizophrenia (Siskind et al., 2017).
2. Clozapine is more effective than other antipsychotics
Clozapine is a unique and very important treatment because it is the only antipsychotic that has been clearly shown in meta-analyses of studies to be more effective than others for the treatment of schizophrenia (Mizuno et al., 2020; Siskind et al., 2016).
This becomes especially important in so-called “treatment-resistant” schizophrenia, defined as a lack of an adequate response despite sequential trials of at least two different antipsychotics—at adequate doses, for adequate durations, and with adequate adherence (Correll et al., 2022).
3. Clozapine helps a high proportion of patients
Of course, clozapine doesn’t work for all patients in this very difficult-to-treat population. But, it works in a considerable percentage of these patients. In different reviews of studies, roughly 40% to 60%, that is, about half of patients with “treatment-resistant” schizophrenia had a clinically meaningful improvement when treated with clozapine (Siskind et al., 2017).
Clozapine reduces the risk of suicidal behavior in schizophrenia/ schizoaffective disorder
Clozapine is the only antipsychotic that has been shown to have a specific effect in reducing the risk of suicidal behavior in patients with psychosis.
A review of 35 comparisons of antipsychotic drugs to comparators used for the treatment of psychosis found that (Forte et al., 2021):
– Clozapine DID reduce the risk of suicidal behavior (death by suicide or suicide attempts) in these patients.
– The reduction in suicidal behavior was a LARGE reduction; not just a little bit.
– This reduction in suicidal behavior was found in ALL 7 studies in which clozapine was used.
– On the other hand, a statistically significant reduction in suicidal behavior was NOT found with other antipsychotics— risperidone, olanzapine, aripiprazole, and so on.
An important, large, randomized clinical trial in patients with schizophrenia or schizoaffective disorder who were considered to be at high risk for suicide because of previous suicide attempts or current suicidal ideation (Meltzer et al., 2003). Over 2 years of follow-up, the study found that clozapine was more efficacious than olanzapine in terms of less/ fewer:
– Suicidal behavior
– Suicide attempts
– Need for hospitalizations.
Since we usually think of clozapine in treatment-resistant patients, we should note that these patients were enrolled due to a high risk of suicide and only 27% had not benefited from treatment in the past.
Since you may see this study mentioned elsewhere, I will add that this study was called the International Suicide Prevention Trial (InterSePT).
I hope that you, dear Colleague, are now even clearer than before about why clozapine is a unique and very important treatment option for patients with schizophrenia or schizoaffective disorder.
Optional to read:
Clozapine seems to reduce the risk of hospitalization: A meta-analysis of studies found that, even though patients treated with clozapine were more seriously ill, they had a lower risk of being hospitalized compared to treatment with other second-generation antipsychotics (Masuda et al., 2019). But, the studies in this meta-analysis were non-randomized cohort studies. So, could the close follow-up and careful monitoring in patients on clozapine have been the real reason why
Clozapine (Clozaril®): Basic Information
Why we must refer more patients for clozapine treatment
What can we do about the underutilization of clozapine and delays in starting it?
Where can I find someone who prescribes clozapine?
Clozapine for schizophrenia in children?
Changes in rules about clozapine
How to check and interpret clozapine levels
Are the clozapine-norclozapine ratio and norclozapine level useful?
Can oral contraceptives affect clozapine levels?
Caffeine can significantly change serum clozapine levels
Potential side effects of clozapine (Clozaril®) handout
Key information about seizures with clozapine
Clozapine-induced hypersalivation (sialorrhea)
Clozapine-induced hypersalivation (sialorrhea): Treatment
Benign ethnic neutropenia (BEN)
Let’s explicitly identify patients with “treatment-resistant” schizophrenia
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