What is it about?

The introduction of clozapine in the 1950s was a major therapeutic advance in the treatment of schizophrenia. It remains the gold standard therapy for approximately 3/10 individuals who fail to respond to initial management. Overall, clozapine improves symptoms and saves lives. Our recent studies have suggested that clozapine therapy may be associated with a block in antibody production (causing antibody deficiency). This would predict patients receiving this therapy to be more likely to experience infections (such as pneumonia). This work examines patients referred to a major immunology centre since 2005, with focus on those receiving antipsychotic medicines (including clozapine). As predicted by our hypothesis (but against the normal pattern of prescribing), clozapine was the most common antipsychotic used by patients referred with antibody deficiency. We go on to define the clinical and immunological features of this group, highlighting a close similarity to individuals without a known cause of antibody deficiency. Several clozapine-treated patients went on to receive antibody replacement therapy, successfully reducing their infection rate. By following these patients over time, we also saw that in one patient who stopped clozapine treatment this was associated with a gradual return in their major antibody (IgG). This adds to the suggestion that clozapine therapy is associated with a drug-related (secondary) antibody deficiency.

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Why is it important?

These finding add to the body of evidence that individuals with schizophrenia receiving clozapine therapy are at greater risk of antibody deficiency than the general population. Currently, antibody testing is not included in existing clozapine monitoring programs. Diagnosis of antibody deficiency may be therefore be missed or delayed, placing them at risk of infection. This is also an important finding for immunologists around the world, who could easily confuse a drug-related cause of antibody deficiency with an inherited (primary) case.


The disease processes underlying both schizophrenia and primary antibody deficiency remain largely unknown: meaning there could be important shared mechanisms linking both conditions. We remain cautious and suggest further studies are needed to confirm these findings, including those with greater size and following patients as they start antipsychotic therapy.

Mark Ponsford
Cardiff University

Read the Original

This page is a summary of: Clinical and laboratory characteristics of clozapine-treated patients with schizophrenia referred to a national immunodeficiency clinic reveals a B-cell signature resembling common variable immunodeficiency (CVID), Journal of Clinical Pathology, February 2020, BMJ,
DOI: 10.1136/jclinpath-2019-206235.
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