Changes in immunoglobulin levels during clozapine treatment in schizophrenia

Kira Griffiths, Maria Ruiz Mellado, Raymond Chung, John Lally, Grant McQueen, Kyra-Verena Sendt, Amy Gillespie, Muhammad Ibrahim, Alex Richter, Adrian Shields, Mark Ponsford, Stephen Jolles, John Hodsoll, Thomas A Pollak, Rachel Upthegrove, Alice Egerton, James H MacCabe

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Background and hypothesis: Use of clozapine in treatment-resistant schizophrenia is often limited due to risk of adverse effects. Cross-sectional associations between clozapine treatment and low immunoglobulin levels have been reported, however prospective studies are required to establish temporal relationships. We tested the hypothesis that reductions in immunoglobulin levels would occur over the first 6 months following initiation of clozapine treatment. Relationships between immunoglobulin levels and symptom severity over the course of clozapine treatment were also explored. 

Design: This prospective observational study measured immunoglobulin (Ig) levels (A, M and G) in 56 patients with treatment-resistant schizophrenia at 6-, 12- and 24-weeks following initiation with clozapine. Clinical symptoms were also measured at 12 weeks using the positive and negative syndrome scale (PANSS). 

Results: IgA, IgG and IgM all decreased during clozapine treatment. For IgA and IgG the reduction was significant at 24 weeks (IgA: β = –32.66, 95% CI = -62.38, −2.93, p = 0.03; IgG: β = -63.96, 95% CI = -118.00, −9.31, p = 0.02). For IgM the reduction was significant at 12 and 24 weeks (12 weeks: β = –23.48, 95% CI = -39.56, −7.42, p = 0.004; 24 weeks: β = –33.12, 95 %CI = -50.30, −15.94, p = <0.001). Reductions in IgA and IgG during clozapine treatment were correlated with reductions in PANSS-total over 12 weeks (n = 32, IgA r = 0.59, p = 0.005; IgG r = 0.48, p = 0.03). 

Conclusions: The observed reductions in immunoglobulin levels over six months of clozapine treatment add further evidence linking clozapine to secondary antibody deficiency. Associations between Ig reduction and symptom improvement may however indicate that immune mechanisms contribute to both desirable and undesirable effects of clozapine.

Original languageEnglish
Pages (from-to)223-228
Number of pages6
JournalBrain, Behavior, and Immunity
Early online date11 Oct 2023
Publication statusPublished - Jan 2024


  • Humans
  • Clozapine/therapeutic use
  • Schizophrenia/drug therapy
  • Antipsychotic Agents/adverse effects
  • Cross-Sectional Studies
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin M


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