Tricyclic antidepressants: contemporary issues for therapeutic practice.

The clinical pharmacology of tricyclic antidepressants is reviewed, with an emphasis on recent findings. These medications have become the treatment of choice for the majority of depressed patients. Their efficacy is limited by lack of vigor and precision in dosage. Pharmacokinetic aspects are addressed which affect the rationale for selective use and interpretation of plasma concentration monitoring. These include nonlinearity, active metabolites, plasma protein binding and age effects. Specific indications for therapeutic drug monitoring occur with patients who fail to respond, those at risk because of age, medical condition or polypharmacy, and to check compliance. Integration of knowledge concerning pharmacokinetics and plasma levels with clinical response will aid in making appropriate pharmacotherapeutic decisions.