What Is the Evidence for Systematic Monitoring of Tricyclic Antidepressant Concentrations?

Surveys of clinical practice suggest that therapeutic drug monitoring (TDM) is not routinely performed for all patients receiving tricyclic antidepressants (TCA) at usual doses. In this report, we explore the hypothesis that a systematic application of TCA TDM would be valuable. We searched the peer-reviewed literature for evidence about TCA TDM. The published evidence suggests that TCA fulfill many criteria for the indication of TDM. Favorable outcomes are concentration-dependent for some TCA. Non-compliance to TCA is frequent and can be assessed with TDM. Neurotoxicity and cardiotoxicity are clearly concentration-dependent with all TCA, and can occur without early symptoms. Subtherapeutic or toxic concentrations can result from usual TCA doses because of the marked interindividual differences in TCA clearance. These differences are due to both endogenous (e.g. metabolic polymorphism, hepatic blood flow, protein binding, etc.) and exogenous factors (e.g. polypharmacy, smoking, diet). There is also the suggestion that systematic TCA TDM reduces overall TCA-related costs. Hence, we suggest that TCA concentrations should be systematically monitored in all patients. The prescription of low TCA doses, e.g. 25mg/d as monotherapy in otherwise healthy adults, could be an exception.