The Impact of Therapeutic Drug Monitoring on Clozapine Dosing and Clinical Outcome in a Tertiary Care Center in India: A Retrospective Study.

Background: There are significant interindividual and interethnic variations in serum clozapine levels achieved for a particular dose of clozapine. Therapeutic drug monitoring (TDM) helps optimize the clozapine dosing. We studied the impact of TDM on clozapine dosing and clinical outcomes in subjects with treatment-resistant schizophrenia.

Methods: We compared clozapine dose and clinical outcomes before and after the TDM service implementation in our center, a tertiary care psychiatric facility in India. A retrospective file review of inpatients diagnosed with treatment-resistant schizophrenia and started on clozapine between 2016-2017 (pre-TDM arm; n = 45) and 2021-23 (post-TDM arm; n = 45) was conducted. Clozapine dose in milligrams per day (mg/d), Clinical Global Impression-Improvement scores, and adverse event profile were compared between these groups after 3 months of therapeutic clozapine dose.

Results: The median clozapine dose reduced by 100 mg/day after introducing TDM (mean ± SD [median] mg, pre-TDM arm: 276.66 ± 118 [250] mg vs post-TDM arm: 167.22 ± 68 [150] mg, P ≤ 0.0001). However, there was no significant difference in Clinical Global Impression-Improvement score between the 2 groups (pre-TDM arm = median 2; post-TDM arm = median 2, P = 0.33). The incidence of hypersalivation (P = 0.026, odds ratio (95% confidence interval) = 3.06 [1.2-7.6]) and weight gain (P = 0.04, odds ratio [95% CI] = 4.5 [1.1-17.5]) were higher in the pre-TDM group. The median serum clozapine concentration/dose (C/D) ratio was 3 ng/mL/mg in our post-TDM sample of 35, where serum clozapine levels were done.

Conclusions: After introducing TDM, there was a significant reduction in clozapine dosage while the magnitude of clinical improvement was comparable.