Case Presentation: 64-year-old man with history of schizoaffective disorder, hypertension, cigarette smoker (quit recently) was admitted to the hospital with acute onset recurrent falls in the last 2 weeks. Medications include buspirone 10mg, amlodipine 2.5 mg, metoprolol 50 mg, clozapine 450 mg. He had hypotension on presentation, which improved with fluids. Symptomatic orthostatic hypotension persisted even after stopping his antihypertensives. We ruled out adrenal insufficiency, neurodegenerative diseases and cardiac causes of orthostatic hypotension. Salt tablets, compression stockings, midodrine and fludrocortisone were ineffective. Attention turned to medication reconciliation: He was found to have toxic clozapine levels (1,486 ng/mL) despite stable dosing for 20 years. Clozapine was tapered safely which led to resolution of orthostasis.
Discussion: Clozapine (strong dopaminergic, serotonergic, noradrenergic, and anticholinergic agent) is an effective but underutilized antipsychotic for resistant schizophrenia in US. Clozapine REMS program is effective in 30-60% patients. Tobacco smoking tends to decrease the levels by inducing CYP1A2; by corollary – smoking cessation may led to elevated blood levels. Clozapine can also cause orthostatic hypotension in about 9% of patients during initial 4-6 weeks (Patel 2019). Clozapine toxicity (target levels 350-450 ng/ml ) can cause arrhythmias, myocarditis (0.2-3%), cardiomyopathy (<0.1%), autonomic dysfunction, seizures, altered mental status, blood dyscrasias, and hepatitis (Yuen 2019). CNS adverse effects are common with levels above 1000 ng/ml. Management options include dose reduction, interrupting the medication and re-challenging later. Shared decision making including the patient and the psychiatrist is central in the management of toxicity of clozapine.
Conclusions: 1. Clozapine is a very effective for treatment of resistant schizophrenia. 2. The utilization of clozapine is expected to increase .3. As hospitalists, we are providing care to patients with mental health disease. It is imperative we identify the safety profile and interactions of Clozapine.4. Smoking cessation can increase the levels of clozapine to toxic levels.