Using TDM data to study treatment failure

Introduction Psychotropic drug treatments are associated with frequent ‘trial-and-error’ events reflecting insufficient clinical responses or serious side effects. The term treatment failure is in this context defined as an unsuccessful outcome of the medical intervention. Accordingly, indirect endpoints of treatment failure comprise drug discontinuation (1), drug switch (2), hospitalization or nonadherence during drug treatment (3), serum concentrations outside the target range (4), and treatment-resistance (5). Use of therapeutic drug monitoring (TDM) data in research projects offers unique possibilities of providing rates of such endpoints and also relate their occurrence to patient factors, including pharmacogenetics.

Methods The talk will in more detail present how endpoints of psychotropic drug treatment failure could be drawn from TDM databases. In addition, examples of research projects at the Center for Psychopharmacology in Oslo, Norway, using this methodology are presented.

Results By using longitudinal TDM data coupled to pharmacogenetic profiles, studies have been able to investigate the relationship between genotypes and switch rates, along with genotypes and serum concentrations, both for antidepressants and antipsychotics. Further, nonadherence rates have been measured by studying the occurrence of undetectable serum concentrations of antipsychotics during prescribing of recommended doses in schizophrenia. Another example is characterization of longitudinal TDM profiles of antipsychotic drugs preceding initiation of clozapine, as an endpoint of treatment-resistant schizophrenia.

Conclusions TDM data have the potential to study different measures of treatment failure. Longitudinal TDM profiles are often necessary, which requires that TDM data from different laboratories are merged at a national level.

Publication History

Article published online:
16 May 2022