Background <p>Electroconvulsive therapy (ECT) is a highly effective treatment option for treatment-resistant psychiatric disorders. Seizure duration and the postictal suppression index (psi) have been suggested as markers for treatment outcome. As concomitant psychopharmacological medication can affect seizure threshold, understanding its effects on seizure quality could help optimize ECT. The aim of the analyses was to investigate associations between serum concentrations of psychopharmacological drugs and seizure duration and psi.</p> Methods <p>A total of 302 ECT sessions in 87 patients were analyzed. Associations between serum concentrations of psychiatric drugs and seizure duration and psi were investigated using multiple linear regression models corrected for age, sex, stimulation side, the interaction number of ECT session:stimulus, as well as seizure-threshold-lowering comedication with clustered standard errors at patient level to account for intra-group correlation.</p> Results <p>Four substances demonstrated effects on ECT quality. Norquetiapine serum concentrations were negatively associated with seizure duration, whereas mirtazapine + N-desmethylmirtazapine serum concentrations showed a positive association. Psi was positively associated with sum serum concentrations of amitriptyline and risperidone. Sensitivity analyses point on robust results for quetiapine and amitriptyline.</p> Conclusion <p>These findings provide first evidence that serum concentrations of amitriptyline and quetiapine may influence seizure quality, suggesting potential for individualized optimization of ECT parameters. For clozapine, despite its seizure threshold-lowering effect, our data indicate that therapeutic-range concentrations do not increase the risk for excessively prolonged seizures.</p> Clinical trial number <p>not applicable.</p>