The relationship between antidepressant response and tricyclic antidepressant plasma concentrations. A retrospective analysis of the literature using logistic regression analysis

Abstract

The relationship between the antidepressant effect of the tricyclic antidepressants and their plasma concentrations was reviewed. Logistic regression was utilised as an analytical tool to facilitate the evaluation. The currently available literature allowed the construction of 4 tricyclic data sets of sufficient size to warrant statistical analysis. Inspection of the distribution of the data and the logistic regression analyses resulted in several conclusions regarding the existence of 'therapeutic windows' for these drugs. Firstly, no relationship between amitriptyline plasma concentrations and therapeutic response was apparent. Secondly, curvilinear relationships were apparent for 2 of the other tricyclic antidepressants studied. The currently recommended therapeutic range of 60 to 150 micrograms/L for nortriptyline was found to be the range most likely to produce a positive antidepressant effect. Desipramine concentrations between 108 and 158 micrograms/L were most commonly associated with beneficial therapeutic responses. Finally, a linear relationship was noted for imipramine in which an imipramine therapeutic plasma concentration threshold of 244 micrograms/L and above was most commonly associated with a beneficial response to the drug.