Clozapine remains the
drug of choice for
treatment resistant schizophrenia, but is associated with potentially life threatening side effects, including
agranulocytosis and
myocarditis. Immunological mechanisms may be involved in the development of these side effects or in the unique
antipsychotic efficacy in subgroups of
schizophrenia patients. This systematic review presents the immunomodulatory effects of
clozapine from human in vitro and in vivo studies and relates these findings to the developments of adverse and
therapeutic effects of
clozapine. Several studies confirm the immunomodulatory actions of
clozapine, but only few studies investigated their relationship to the unique adverse and
therapeutic effects of
clozapine. During the first month of
clozapine treatment, up to 50% of patients develop
fever and flu like symptoms, which is seemingly driven by increased
cytokines. Within the same time period, the risk of side-effects with a suspected immunological mechanism peaks. Patients developing
fever during the first weeks of treatment should have a thorough physical examination, and measurements of white blood cell count, absolute neutrophil count, ECG,
C-reactive protein,
creatinine kinase, and
troponin to exclude
infection,
agranulocytosis,
myocarditis and
neuroleptic malignant syndrome. To what degree the unique
antipsychotic efficacy of
clozapine in subgroups of
schizophrenia patients is related to its immunomodulatory effects has not been studied. Research relating the immunomodulatory actions of
clozapine and its early markers to clinically relevant adverse and therapeutic outcomes is hoped to provide new leads for the understanding of the pathophysiology of
schizophrenia and aid the development of novel treatment targets.