Pharmacometabolomics-guided clozapine therapy in treatment resistant schizophrenia: Preliminary exploration of future too near

Aim: To study the association of clozapine pharmacometabolomics and clozapine response in Asian patients with treatment-resistant schizophrenia (TRS). Method: A cross-sectional study was performed on 50 consecutive TRS patients following up in psychiatry department of the tertiary care hospital. Demographic details, response assessment, were collected on the case record form. A blood sample was also collected for trough concentration assessment of drug and its metabolites. Clozapine (CLZ) the parent drug and its two major metabolites - Clozapine N oxide (CNO) and N-Desmethyl clozapine (N-DSMC) levels were assessed using a high-performance liquid chromatography method. Clozapine responders and nonresponders patients were classified based upon Andreasen criteria. Results: The average trough concentration of CNO, N-DSMC, and CLZ were 123 +/- 76.04, 171.93 +/- 93.24, 229.27 +/- 124.25 ng/ml, respectively. The two patient subgroups did not differ for CLZ, CNO, and N-DSMC concentrations statistically. However, clozapine nonresponse was associated with a higher CLZ/N-DSMC ratio (p = 0.03) and clozapine dose (p = 0.01). The receiver operator characteristic curve showed that the cut-off CLZ/N-DSMC ratio of 1.54 with a sensitivity of 85% and a positive predictive value of 84% for identifying nonresponders. Conclusion: CLZ/N-DSMC ratio and clozapine dose were identified as significant variables for future dose optimization algorithms. Pharmacometabolomics-guided clozapine therapy has the potential to revolutionize TRS management.

Automated summary

The study revealed that the CLZ/N-DSMC ratio and clozapine dose are significant variables for future dose optimization algorithms. This research opens up possibilities for pharmacometabolomics-guided clozapine therapy to revolutionize TRS management.