Clinical Chemistry, Vol 34, 841-847, Copyright © 1988 by American Association for Clinical Chemistry

Is there a practical alternative to therapeutic drug monitoring in therapy with tricyclic antidepressants?

S Dawling
Poisons Unit, New Cross Hospital, London, U.K.

Optimization of tricyclic antidepressant (TCA) therapy by dosage adjustments made in response to inappropriate concentrations in plasma or side effects can be extremely slow owing to the long half-lives of these drugs. I examine the practicality of alternative methods of arriving quickly and reliably at an adequate starting dosage. The clearance of a single test dose from plasma has been used to select individualized dosages before commencing therapy, but this takes several days and requires computer-assisted calculation of clearance. A simpler technique is to measure the concentration in a single timed plasma sample as an index of metabolism, and to infer the required dosage directly from a nomogram. Ideally, the nomograms should be interchangeable between patient populations and independent of the analytical method used, and the drug must have linear kinetics. Furthermore, TCAs are metabolized by common routes--demethylation and hydroxylation--so one might apply a single tolerance test for the entire class of drugs. Hydroxylation of TCAs can also be correlated with that of debrisoquine. The debrisoquine clearance test is non- invasive, faster, and analytically less demanding than TCA measurements. In the absence of rigid therapeutic ranges, tests that identify abnormally slow metabolizers may well be invaluable in preventing iatrogenic poisoning. Despite the usefulness of these methods in establishing effective initial dosages, their continued success depends upon good compliance, the maintenance of the patient's concurrent drug therapy, and a stable physical condition. In the non- ideal world, therefore, TDM cannot be dispensed with, but must be seen as an essential part of effective TCA treatment, based ultimately of course on sound clinical judgement.