💊 Clozapine

Clozapine is an atypical antipsychotic, unique in its efficacy for treatment-resistant schizophrenia. It is considered a 'gold standard' for this indication, despite its significant side effect profile.

Clozapine has a complex pharmacological profile, acting as an antagonist at multiple dopamine (D1, D2, D3, D4) and serotonin (5-HT2A, 5-HT2C, 5-HT1A) receptors. It also has significant affinity for alpha-adrenergic, histamine H1, and muscarinic cholinergic receptors. Its unique efficacy is thought to stem from its relatively weak D2 antagonism and potent 5-HT2A antagonism.

Clozapine is exclusively indicated for treatment-resistant schizophrenia, defined as inadequate response to at least two other antipsychotics, including one atypical. It is also used for reducing the risk of recurrent suicidal behaviour in patients with schizophrenia or schizoaffective disorder. It can be considered for psychosis in Parkinson's disease.

Absolute contraindications include a history of clozapine-induced agranulocytosis or severe neutropenia, uncontrolled epilepsy, and severe cardiac, renal, or hepatic disease. It is also contraindicated in paralytic ileus and conditions associated with bone marrow suppression. Regular blood monitoring is mandatory for its safe use.

The most serious adverse effect is agranulocytosis, requiring mandatory haematological monitoring. Other serious effects include myocarditis, cardiomyopathy, seizures, and paralytic ileus. Common side effects include sedation, hypersalivation, weight gain, constipation, orthostatic hypotension, and tachycardia.

Strict haematological monitoring is mandatory, with weekly full blood counts (FBC) for the first 18 weeks, then fortnightly, and then monthly for as long as the patient is on clozapine. ECG is recommended before initiation and periodically. Regular monitoring for metabolic parameters, blood pressure, and signs of myocarditis is also crucial.

Prescribing clozapine requires registration with a specific monitoring service. Always confirm the patient's FBC results are within acceptable limits before prescribing each supply. Counsel patients extensively on the need for regular blood tests, the symptoms of agranulocytosis (e.g., fever, sore throat), and other serious side effects like constipation and myocarditis.

High-yield facts include clozapine's role as the only effective treatment for treatment-resistant schizophrenia. The mandatory FBC monitoring and the risk of agranulocytosis are paramount. Recognition of myocarditis symptoms (e.g., chest pain, dyspnoea, tachycardia) is also a key learning point. Its unique side effect profile, including hypersalivation and constipation, is often tested.

SBAs will almost certainly focus on the mandatory haematological monitoring requirements for clozapine and the management of neutropenia. Questions may also test the specific indications for clozapine (treatment-resistant schizophrenia) and its unique side effects like myocarditis and hypersalivation. Differentiating clozapine's side effect profile from other antipsychotics is common.