Assessing Adherence to Clozapine: Practical Considerations

Abstract

Background: The clinical assessment of adherence to clozapine may prove difficult.

Method: We studied the incidence of nonadherence (plasma clozapine <0.01 mg L -1 ) in samples submitted to a clozapine therapeutic drug monitoring (TDM) service, 1993-2017.

Results: Clozapine was not detected in 2865 samples from men (2214 patients, 1.1% of all samples from men) and 1068 samples from women (822 patients, 1.0% of all samples from women). Information on the prescribed dose was supplied for 1623 of these samples from men and 492 of these samples from women. Prescribed doses ranged up to 1200 mg d -1 , although most were in the range 100 to 600 mg d -1 . Norclozapine was detected in 260 (9.1%) and 67 (6.3%) of the samples from men and from women, respectively, that did not contain clozapine. While an assay was requested to confirm either a patient history of nonadherence, or to establish that clozapine had been cleared from the circulation after overdosage, for example, in at least 38 instances, in the vast majority of cases the absence of clozapine from the sample was unexpected.

Implications: While adherence to clozapine may be good in general, tolerance to its potentially fatal cardiovascular effects is easily lost. Moreover, in treatment-resistant schizophrenia, the risk of self-harm increases if the drug is not taken regularly. In addition to presently available TDM services, the advent of a clozapine immunoassay for laboratory use should make it easy to institute at least monthly clozapine TDM at minimal extra cost.