Serum clozapine levels: a review of their clinical utility

Therapeutic drug monitoring (TDM) is frequently utilized in the treatment of psychiatric conditions, but its clinical application concerning the use of clozapine is unclear. We present three case reports of patients taking clozapine, review the relevant literature, and propose guidelines to aid the clinical use of TDM of clozapine. Due to its complex metabolism, there are significant inter- and intra-individual variations in clozapine serum levels, for a given dose. However, the range of serum levels that corresponds with toxicity remains unclear. Although central nervous system side-effects may correlate with serum level, many adverse effects of clozapine appear to be unrelated, including haematological and cardiac events. There are numerous clinically significant interactions between clozapine and other substances, including prescribed medications, nicotine and caffeine. TDM of clozapine may be of clinical value in certain situations, such as poor clinical response; signs of toxicity; onset of seizures; changes in concurrent medication, caffeine or nicotine; liver disease; and suspected non-compliance. The current literature does not support the routine testing of serum clozapine levels in everyday clinical practice.