Therapeutic monitoring of antidepressant drugs: current methodology and applications

In the two decades since initial studies demonstrated an association between clinical response and blood levels of tricyclic antidepressants (TCAs), measurement of serum levels of TCAs has become routine in many laboratories and the use of these measurements is rapidly becoming a routine part of psychiatric practice. However, practical therapeutic monitoring of TCAs is complicated by a lack of suitable reference methodology, a diversity of analytic methods, and factors that contribute to difficulties in obtaining useful clinical data. Therapeutic ranges for many antidepressants have still not been firmly established and clinical guidelines for monitoring patients and using therapeutic drug monitoring data for psychoactive drugs are not well understood. Nonetheless, monitoring of antidepressant serum levels has prompted technical advances in methodology. This paper presents an overview of the clinical and pharmacologic issues surrounding the utility of serum level measurements. Technical issues that concern investigators and clinicians in the field are discussed and recent developments and applications in high performance liquid chromatography and immunoassays for the TCAs are reviewed.