Abstract

It has been shown that up to one third of patients with schizophrenia do not respond to antipsychotic therapy. Thus, treatment-resistant schizophrenia (TRS) remains a major mental health care challenge.

Clozapine has been shown to provide superior therapeutic benefits and is approved as first-line therapy for TRS. These benefits include improvement in both positive and negative symptoms, and reduction of suicidal behavior in patients with schizophrenia. Clozapine, however, remains significantly underused for TRS. A major reason for clozapine's underuse is its substantial adverse effect profile, mainly the risk of life-threatening agranulocytosis which necessitates regular hematologic monitoring. Another factor contributing to reduced clozapine prescribing is the increased use of other second-generation antipsychotics. In TRS patients, there is often a considerable delay in clozapine use, which is prescribed only after other unsuccessful second-generation antipsychotic trials. To combat this trend, there is a push for increased awareness to optimize clozapine prescribing. An important aspect in improving the use of clozapine therapy is physician and patient education. Furthermore, pharmacist involvement can improve clozapine prescription trends in TRS.

Abstract

Treatment refractory schizophrenia is a serious issue affecting at least 30% of all patients with schizophrenia despite the continued emergence of new agents aimed at treating this disease. Clozapine therapy remains the most efficacious treatment for patients with schizophrenia who have failed two prior antipsychotics or those deemed an imminent harm to themselves or others. Because data are lacking on how to proceed if a patient should prove nonresponsive to clozapine therapy, the utmost care should be taken to ensure the optimization of clozapine. Therapeutic drug monitoring (TDM) is used with many other psychoactive agents to ensure the optimal therapeutic efficacy while minimizing adverse effects. The unique pharmacology of clozapine and the inter- and intraindividual variations in its pharmacokinetics make it a difficult agent with which to use TDM. The consensus is that 350 ng/mL is the lower threshold of therapeutic efficacy to define an adequate trial of clozapine. As of this writing, no clearly defined threshold exists for the upper limit of therapeutic efficacy or toxicity. TDM of clozapine can be useful in the following circumstances: when a clozapine-induced central nervous system toxicity is suspected, a medication that can inhibit or induce the metabolism of clozapine is being added or withdrawn, a change in smoking status has occurred, concerns for medication nonadherence are present, or decompensation while on a previously effective clozapine dosage is observed. The psychiatric pharmacist may play a crucial role in the interpretation and effective utilization of serum clozapine and norclozapine levels. This review will examine the current evidence for the clinical utility of monitoring serum levels of clozapine and its metabolites.

Abstract

Since its initial landmark trial against chlorpromazine in 1988, clozapine has been the drug of choice for the treatment of refractory schizophrenia. However, variability in clinical response to clozapine treatment is unequivocal. In an effort to preselect patients who are most likely to benefit from clozapine, a number of patient and disease variables and select genetic differences have been studied for their association with positive treatment response to clozapine. Because of small trial sizes and the heterogeneity of study design, findings have resulted in no generalizable conclusion. Future pharmacogenetic studies hold the promise of antipsychotic treatment personalization.

Abstract

Abstract

Abstract

Neuroleptic malignant syndrome (NMS) is a potential life-threatening adverse effect of antipsychotics. Characteristic signs and symptoms of NMS include hyperthermia, muscle rigidity, altered mental status, and autonomic instability. Treatment of NMS includes discontinuation of any antipsychotic or other potentially offending agents. This report describes the details of a patient diagnosed with NMS induced by clozapine with subsequent successful rechallenge. Given limited therapeutic options for patients with treatment-resistant schizophrenia, clinicians should be cognizant of potential risks but aware of the possibility of successful rechallenge with clozapine.