Relationship Between Clozapine Levels and Adverse Effects Evaluated by the GASS‐C in Treatment‐Resistant Schizophrenia
Yui Okubo, Hitoki Hirose, Shohei Nishimon, Hitoshi MaeshimaABSTRACT
Objective
Clozapine is the most effective antipsychotic for treatment‐resistant schizophrenia. However, evidence regarding whether adverse effects are related to the clozapine concentration is insufficient.
Methods
Patients treated with clozapine for at least 6 weeks and maintained on a fixed dose for > 1 week were included ( n = 47). Adverse effects were assessed using the self‐rated Glasgow Antipsychotic Side‐effects Scale for Clozapine (GASS‐C). Plasma concentrations of clozapine and norclozapine were measured, and the relationship between the GASS‐C score and clozapine concentration was analyzed.
Results
Clozapine concentration was significantly associated with both the GASS‐C score (rs = 0.435, p = 0.002) and norclozapine concentration (rs = 0.363 p = 0.012). In addition, significant correlations with large effect sizes were found for GASS‐C sub‐items such as hypersalivation and anticholinergic symptoms. Multiple regression indicated that the GASS‐C total score was associated with both clozapine ( β = 0.374, p = 0.012) and norclozapine ( β = 0.404, p = 0.005) concentrations.
Conclusions
Adverse effects, including subjective ones, of clozapine may be concentration‐related and clinically important. However, monitoring clozapine levels may only have a supplementary role in managing its subjective adverse effects because subjective GASS‐C scores could be influenced by psychological factors and patient perception, which may not always correlate linearly with pharmacokinetic data.