Compliance with SSRI medication during 6 months of treatment for major depression: an evaluation by determination of repeated serum drug concentrations

Background: A recent estimation in a psychiatric cohort showed numbers of noncompliance between 10% and 60%. Therapeutic drug monitoring (TDM) is one method assessing compliance by analysis of drug concentration in the blood. Method: During a 24-week phase IV clinical trial, five repeated serum samples of sertraline (SERT) and N-desmethylsertraline (DSERT), trough values in steady state, were collected per patient. Previous results show that the intraindividual variation over time of the ratio DSERT/SERT is low. Hence, we hypothesized that significant partial noncompliance could be scrutinized further by an assessment of the DSERT/SERT ratio. The main aim was to test the applicability of a novel type of TDM procedure based on repeated metabolite/parent compound ratio measurements. Result: 9.4% of the per-protocol population in the trial (n=96) were in either hidden total (n=4) or hidden partial (n=5) noncompliance. Only by using the novel TDM ratio screening method could a majority of these patients be identified.