Monitoring of antidepressant drug plasma levels: the next ten years.

Future studies of the relationship between plasma level and drug response in depressed patients ought to take the following facts into consideration: 1. Selective drug analytical methods must be used and subjected to quality control. Methods for the major urinary metabolite(s) of the parent drug should also be developed. 2. Each drug has individual pharmacokinetic and pharmacodynamic properties--it is unlikely that one drug will be effective in all patients even under optimal kinetic conditions. 3. The pharmacologic and biochemical effects of hitherto investigated tricyclic antidepressants correlate significantly to the concentrations of parent drug and/or its active metabolite in plasma. 4. It is more likely that a significant correlation will be found between the total tricyclic antidepressant level in plasma and the therapeutic outcome in a patient sample if the range of plasma levels is large--in this case the relatively small interindividual differences in plasma protein binding play a minor role. 5. Concomitant somatic disease may change the kinetics of antidepressant drugs. 6. The clinical methods used for selecting and rating study patients with depressive disorders must be standardized. 7. Novel rapidly acting drugs are desirable because the slow onset of action of tricyclic antidepressant seriously hamper their clinical evaluation. 8. A strong correlation between plasma concentration of an antidepressant drug and clinical outcome is strong evidence that the clinical effect is due to the drug rather than nonpharmacological factors.