Methodological advances in drug assay techniques and their increasing availability have made the measurement of tricyclic antidepressant plasma levels more frequent and even fashionable. Plasma levels of tricyclics have been correlated with diagnosis, prognosis, clinical response, and side effects. But even in the area most extensively examined, the correlation between plasma level and clinical response, the results have been conflicting. Different studies have suggested that there is no relationship between plasma level and clinical response, as well as positive and negative correlations, and even a curvilinear relationship. On the basis of available evidence, it is impossible to define a therapeutic range of plasma levels that will be applicable to depressed patients as a group. For the moment, the problem of finding a suitable therapeutic dose for the individual patient remains of paramount importance. Studies to date suggest the need to take into consideration genetic factors, previous and present use of other drugs, the possibility that therapeutic failure might be a result of too high as well as too low a dose, as well as the possible relationship between high plasma levels and side effects. Also, since for the specific individual, the metabolism of different tricyclic antidepressants is similar, it may be useful to adjust dosages until a therapeutic one is obtained instead of immediately switching to another medication. Finally, although the usefulness of routine plasma level determination remains to be established, this technique may be indicated in cases of intractable depression and remains an important research tool.
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