What is the use of Clozaril (Clozapine)?

From the Guidelines

Clozaril (clozapine) is a powerful antipsychotic medication that should be used to treat treatment-resistant schizophrenia, as recommended by the American Psychiatric Association (APA) 1.

Key Points

• Clozaril is typically started at a low dose of 12.5-25mg once or twice daily, gradually increasing to an effective dose range of 300-450mg daily, with some patients requiring up to 900mg daily.
• The medication works differently from other antipsychotics by affecting multiple neurotransmitter systems, particularly dopamine and serotonin receptors, which explains its effectiveness in treatment-resistant cases.
• However, Clozaril requires strict monitoring due to potentially serious side effects, most notably agranulocytosis (dangerous decrease in white blood cells), as noted in the practice parameter for the assessment and treatment of children and adolescents with schizophrenia 1.

Monitoring and Side Effects

• Patients must enroll in a monitoring program with weekly blood tests for the first six months, then biweekly for the next six months, and monthly thereafter if counts remain stable.
• Other significant side effects include seizures, myocarditis, metabolic changes, sedation, hypersalivation, and constipation, as reported in the practice parameter for the assessment and treatment of children and adolescents with schizophrenia 1.

Recommendation

The APA recommends (1B) that patients with treatment-resistant schizophrenia be treated with clozapine 1.

Considerations

• Despite the risks associated with Clozaril, it remains an important option for patients who haven't responded to other treatments, often dramatically improving symptoms and quality of life when other medications have failed.
• The use of Clozaril should be carefully considered, taking into account the potential benefits and risks, as well as the need for strict monitoring and management of side effects.

From the FDA Drug Label

INDICATIONS AND USAGE Clozapine tablets are an atypical antipsychotic indicated for: Treatment-resistant schizophrenia. Efficacy was established in an active-controlled study. (1.1,14.1) Reducing suicidal behavior in patients with schizophrenia or schizoaffective disorder. Efficacy was established in an active-controlled study. (1.2,14.2) The main use of Clozaril is for:

• Treatment-resistant schizophrenia
• Reducing suicidal behavior in patients with schizophrenia or schizoaffective disorder 2

From the Research

Overview of Clozaril

• Clozaril, also known as clozapine, is a medication used to treat treatment-resistant schizophrenia 3.
• It is the only approved strategy for treatment-resistant schizophrenia, but its use is highly underutilized due to various barriers 3, 4.

Efficacy and Safety

• A consistent body of evidence supports the efficacy of clozapine in reducing morbidity and mortality in schizophrenia 3.
• However, clozapine can cause agranulocytosis, a potentially life-threatening condition, in up to 0.8% of patients 5.
• Other side effects include granulocytopenia, which can lead to a prolonged low white blood cell count 6.

Barriers to Prescribing Clozaril

• The main obstacles to the use of clozapine are the lack of experience by prescribers and perceived treatment burden 3.
• Other barriers include concern about side effects, poor adherence, prescriber-perceived barriers, administrative barriers, and other healthcare systems-related barriers 4.
• Providers' lack of knowledge and training is a significant barrier to prescribing clozapine 4.

Management and Treatment

• Systematic screening of eligibility, utilization of available resources for consultation, and developing a professional network with other stakeholders can help overcome barriers to clozapine use 3.
• Specific evidence-based recommendations for initiation, maintenance, and safety monitoring with clozapine are available 3.
• In cases of clozapine-associated granulocytopenia, switching to another antipsychotic may not always solve the problem, and close monitoring of white blood cell count is necessary 6.
• Newer treatment approaches, such as augmentation with long-acting antipsychotic injections or multi-component psychosocial interventions, may be considered for patients with clozapine-resistant schizophrenia 7.