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)

Abstract

AimsAn association between antibody deficiency and clozapine use in individuals with schizophrenia has recently been reported. We hypothesised that if clozapine-associated hypogammaglobulinaemia was clinically relevant this would manifest in referral patterns.MethodsRetrospective case note review of patients referred and assessed by Immunology Centre for Wales (ICW) between January 2005 and July 2018 with extraction of clinical and immunological features for individuals with diagnosis of schizophrenia-like illness.Results1791 adult patients were assessed at ICW during this period; 23 patients had a psychiatric diagnosis of schizophrenia or schizoaffective disorder. Principal indications for referral were findings of low calculated globulin and immunoglobulins. Clozapine was the single most commonly prescribed antipsychotic (17/23), disproportionately increased relative to reported use in the general schizophrenia population (OR 6.48, 95% CI: 1.79 to 23.5). Clozapine therapy was noted in 6/7 (86%) of patients subsequently requiring immunoglobulin replacement therapy (IgRT). Marked reduction of class-switched memory B cells (CSMB) and plasmablasts were observed in clozapine-treated individuals relative to healthy age-matched controls. Clozapine duration is associated with CSMB decline. One patient discontinued clozapine, with gradual recovery of IgG levels without use of IgRT.ConclusionsOur findings are consistent with enrichment of clozapine-treatment within schizophrenic individuals referred for ICW assessment over the last 13 years. These individuals displayed clinical patterns closely resembling the primary immunodeficiency common variable immunodeficiency, however appears reversible on drug cessation. This has diagnostic, monitoring and treatment implications for psychiatry and immunology teams and directs prospective studies to address causality and the wider implications for this patient group.

Management of clozapine treatment during the COVID-19 pandemic

“…Early recent research from one research group has found a reduction in immunoglobulin levels in patients taking clozapine, with a greater effect in those taking long-term treatment. 41–43 These studies found clinically significant panhypogammaglobulinaemia and impaired vaccine responses in patients taking clozapine that were not fully explained by smoking or concurrent medication. 41 Reductions in pneumococcal-specific IgA and IgM were also observed.…”

“…41–43 These studies found clinically significant panhypogammaglobulinaemia and impaired vaccine responses in patients taking clozapine that were not fully explained by smoking or concurrent medication. 41 Reductions in pneumococcal-specific IgA and IgM were also observed. 43 A longer duration of clozapine use was associated with a higher risk of hypogammaglobulinaemia (annual decline of 0.15 g/l).…”

Clozapine prescribing in COVID-19 positive medical inpatients: a case series

“… 14 Pneumonia is a significant contributor to mortality in patients taking clozapine, 15 and early data from one group have suggested an effect of clozapine on levels of some immunoglobulins leading to a reversible immunodeficiency-like syndrome, which may correlate with the rate of infections. 16 …”

Epidémie au nouveau coronavirus (SARS-CoV-2) et prescription de la clozapine: quelles mesures? Pourquoi?

“…Cette action passe en partie par une réduction des taux circulants des immunoglobulines (Ig) des trois classes [6]. L'hypogammaglobulinémie observée concerne également les Ig G spécifiques anti-haemophilus influenza et pneumocoques, pathogènes communs du tractus respiratoire.…”

“…L'ampleur de l'action immunosuppressive de la clozapine est comparable à celle de l'association rituximab-methotrexate [7]. Elle est d'autant plus marquée que la durée de traitement par la clozapine est longue et ne semble pas être dose dépendante [6,7]. Il est toutefois important de souligner les nombreux rapports de cas, associant dose élevée de clozapine et infection sévère [8].…”