title: Elevated clozapine levels associated with infection: A systematic review.
abstract: Clozapine is the most effective anti-psychotic medication for treatment refractory schizophrenia. A growing number of case reports have linked infection to high clozapine levels and associated adverse outcomes. We present a systematic review of published cases to clarify the relationship between infection and elevated clozapine levels. The case reports were located through PubMed and Embase. In addition, 8 new cases from two Australian states were included. Demographics, psychiatric diagnoses and medical morbidities, medications, clinical symptoms, clozapine levels, inflammatory markers and final clinical outcome were extracted. 40 cases were identified in 23 publications that demonstrated elevated clozapine levels associated with infection. Infections were commonly respiratory in origin. Adverse events, typically sedation, were associated with raised clozapine levels during infection. In many cases the signs of infection such as fever and white blood cell count were reduced. Severe adverse effects were uncommon, with one case each of seizure, myocarditis and neutropenia. The relationship between infection, clozapine levels and adverse events is complex and multi-factorial. Monitoring of clozapine levels is essential during hospitalisation for infection and consideration should be given to gradual dose reduction to minimise dose related side effects.
authors.affiliation: University of Adelaide, Department of Psychiatry, Adelaide, SA 5005, Australia.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Clark
authors.affiliation: Metro South Addiction and Mental Health Service, Brisbane, QLD 4012, Australia; University of Queensland, School of Medicine, Brisbane, QLD 4072, Australia. Electronic address: n.warren@uq.edu.au.
authors.forename: Nicola S
authors.initials: NS
authors.lastname: Warren
authors.affiliation: University of Adelaide, Department of Psychiatry, Adelaide, SA 5005, Australia.
authors.forename: Gajin
authors.initials: G
authors.lastname: Kim
authors.affiliation: Southern Adelaide Local Health Network, Adelaide, South Australia 5042, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Jankowiak
authors.affiliation: University of Adelaide, Department of Psychiatry, Adelaide, SA 5005, Australia; Northern Adelaide Local Health Network, Adelaide, South Australia 5112, Australia.
authors.forename: Klaus Oliver
authors.initials: KO
authors.lastname: Schubert
authors.affiliation: Metro South Addiction and Mental Health Service, Brisbane, QLD 4012, Australia; University of Queensland, School of Medicine, Brisbane, QLD 4072, Australia.
authors.forename: Steve
authors.initials: S
authors.lastname: Kisely
authors.affiliation: Princess Alexandra Hospital, Brisbane, QLD 4012, Australia.
authors.forename: Tori
authors.initials: T
authors.lastname: Forrester
authors.affiliation: University of Adelaide, Department of Psychiatry, Adelaide, SA 5005, Australia.
authors.forename: Bernhard T
authors.initials: BT
authors.lastname: Baune
authors.affiliation: Metro South Addiction and Mental Health Service, Brisbane, QLD 4012, Australia; University of Queensland, School of Medicine, Brisbane, QLD 4072, Australia.
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Siskind
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D003024:Clozapine / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D007239:Infections / Q000453:epidemiology* / Q000276:immunology; D012559:Schizophrenia / Q000188:drug therapy* / Q000453:epidemiology* / Q000276:immunology
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine
keywords: Clozapine; Infection; Inflammation; Levels; Schizophrenia; Toxicity