Issues in methodology and applications for therapeutic monitoring of antidepressant drugs.

Measurement of antidepressant drugs in serum provides a useful indicator of optimal dosage and can enable the clinician, in certain circumstances, to easily adjust dosages for individual differences in drug metabolism, alterations in the concentration in serum owing to drug interactions, or failure to achieve an adequate concentration in serum because of noncompliance. Practical therapeutic monitoring of antidepressants, however, is still complicated by a lack of suitable reference methodology or established assay-performance criteria and the diversity of analytical techniques. We review here several contemporary methods of analysis for the tricyclic antidepressant drugs--including gas chromatography with a nitrogen-specific detector, HPLC, and immunoassays--that are available for toxicology screening or for quantifying the most widely monitored tricyclic drugs. We also present an overview of current laboratory issues and practical considerations facing those who analyze for antidepressant drugs.