A balancing act: Clozapine adjustment in smokers

To the Editor

Smoking is known to alter the metabolism of clozapine, which can have serious consequences. Currently, there are few clinical guidelines to assist in managing clozapine levels that fluctuate due to smoking. We report a case of a man with schizophrenia whose cigarette smoking altered clozapine levels and affected his management.

PT* was a 45-year-old man, with a 25-year-long history of persistent paranoid schizophrenia. (*PT is not the patient’s real initials.) He experienced chronic residual positive symptoms including grandiose and persecutory delusions and auditory hallucinations. He has a history of polysubstance abuse and has smoked up to 40 cigarettes per day. He was started on clozapine in a psychiatry inpatient unit in 2010; however, his symptoms were not completely controlled. While an inpatient in 2012, PT stabbed a co-patient he believed was Satan. Following this incident, he was placed in a secure long-term hospital unit for 1.5 years, where he was unable to smoke. Before leaving this facility, his clozapine level was 597. After he was released into the community, he began smoking again. His clozapine level dropped to 370 and he became symptomatic once more. He was readmitted to hospital and ceased smoking. His clozapine level increased to 1071. An echocardiogram revealed mild cardiomyopathy. From 2012 to 2014, his dose of clozapine was maintained between 500 and 600 mg per day.

Smoking alters the metabolism of several drugs through the production of Polycyclic Aromatic Hydrocarbons (PAHs). PAHs induce the hepatic enzyme CYP1A2, which metabolises clozapine. This alters the level of the drug and may cause it to fall out of its narrow therapeutic range. Clinicians should take a full smoking history from their patients and ascertain how their smoking habits will change in the immediate future. Following this, an adjustment can be made to the clozapine dose if required. If a patient ceases smoking, a reduction of 40% of clozapine dose is advised to achieve pre-cessation dose (Faber and Fuhr, 2004; Lowe, 2010). Faber and Fuhr (2004) recommend a 10% reduction in dose each day for the first 4 days after quitting. De Leon (2004) found that if a patient resumes smoking post admission, clozapine dose should be increased by approximately 50% over 2–4 weeks (De Leon, 2004). More research is required to ascertain how other factors such as sex, other medications and diet would alter these recommendations. Levels should still be closely monitored when adjusting clozapine dose.