In 2008, clozapine accounted for only 4.4% of antipsychotic prescriptions in the United States.3 In our state forensic facility, only 10% of patients on an antipsychotic received clozapine in 2011. Despite the CATIE trial, there were no significant increases in clozapine prescribing after the results were published4 and patients often experience a substantial delay before clozapine is initiated.5 In the last several years, we have looked at methods to increase clozapine use in our hospital and have described some of our experiences. Despite enthusiasm for, and good experience with, clozapine, barriers limit the use of this medication (Table 1). One significant barrier is patient acceptance. Although most of our patients taking an atypical antipsychotic will accept a blood draws every 6 months for metabolic monitoring, many will reject clozapine because of the initial weekly blood draw. Other patients will reject a trial of clozapine because of fears of serious adverse reactions.
Clinicians may be reluctant to initiate clozapine treatment because of increased time demands to obtain and document informed consent, complete initial paperwork, initiate a clozapine titration protocol, and order laboratory work. Clinicians also may fear more serious adverse reactions with clozapine such as agranulocytosis, acute diabetes, severe constipation, and myocarditis. With close monitoring, however, these outcomes can be avoided, and clozapine therapy can decrease mortality.6 With the increasing availability and decreasing cost of genetic analysis, in the near future we may be able to better predict clozapine responders and the risk of agranulocytosis before initiating clozapine.7,8
Overcoming barriers
When initiating clozapine, it is helpful to reduce barriers to treatment. One strategy to improve patient acceptance of blood testing is to use fingerstick hematology profiles rather than the typical venipuncture technique. The Micros 60 analyzer can provide a complete blood count and granulocyte count from a blood specimen collected in a mini capillary tube.
National clozapine registries accept results derived from this method of blood analysis. Using preprinted medication and treatment orders can ease the paperwork burden for the psychiatrist. To help ensure safe use of clozapine, clinical pharmacists can help interface with the clozapine registry (see this article at CurrentPsychiatry. com for a list of clozapine registry Web sites), assist with monitoring laboratory and medication orders, and anticipate drug interactions and side effects. Staff members directly involved in the patient’s care can try to improve the patient’s insight of his (her) illness. Nursing staff can provide medication education.
Many efforts have been made to educate medical staff to reduce adverse effects and improve patients’ experience with clozapine. Employing agents such as polyethylene glycol, desmopressin, terazosin, and topiramate can help to manage adverse effects of clozapine such as constipation, nocturnal enuresis, drooling, and weight gain, respectively. Lithium can help boost a low neutrophil count9; a lithium level >0.4 mEq/L may be needed to achieve this response. Although generally well tolerated, adding lithium can increase the risk of seizures with clozapine. A final hurdle has been the dilemma of an unwilling, but obviously ill and suffering, patient who has failed several medication trials and other therapeutic interventions.