Implementation of pharmacogenetics in a clozapine treatment resistant patient: a case report

Abstract

We report the case of a young Caucasian male with disorganized chronic schizophrenia, an active smoker and nonresponder to 400 mg of clozapine/day. Therapeutic clozapine monitoring was analyzed revealing a low clozapine:norclozapine ratio. An additional pharmacogenetic test was carried out showing that the patient carried *1F variant (CYP1A2 gene), which has been associated with nonresponse to clozapine in smoker patients. A genetic variation in the SLC6A4 gene was also found, which could be related to the poor response to clozapine. The remainder of the genes analyzed (CYP2D6, ABCB1 and HTR2A) were not directly associated with the patient's phenotype. The dose of clozapine was increased to 600 mg/day, reaching the therapeutic range. This case shows how pharmacogenetics can help in understanding the value of plasma levels to provide clinical improvement.

Keywords: genotype; pharmacodynamics; pharmacokinetics; therapeutic drug monitoring; treatment-resistant schizophrenia.