PLASMA-LEVELS OF TRICYCLIC ANTI-DEPRESSANTS AND CLINICAL EFFICACY - REVIEW OF THE LITERATURE .2.

Abstract

The literature regarding the relationship between plasma levels of tricyclic antidepressants and their clinical efficacy was reviewed. When available, drug-drug interactions, pharmacokinetics and other factors influencing plasma levels of tricyclic antidepressants are discussed. The available evidence suggests a curvilinear relationship between nortriptyline plasma levels and antidepressant efficacy in tricyclic responsive endogenously depressed inpatients, with maximal therapeutic efficacy achieved with nortriptyline plasma levels between 50-175 ng/ml. The evidence for imipramine supports a linear relationship between plasma levels of imipramine plus desmethylimipramine and clinical response in nondelusional endogenously depressed tricyclic responsive inpatients. For amitriptyline, the picture is less clear. With the exception of 1 well-controlled study, the available evidence supports some significant relationship between amitriptyline plus nortriptyline plasma levels and antidepressant efficacy in tricyclic responsive endogenously depressed patients, but it is not clear as to whether this is a linear relationship or a curvilinear one. For the other antidepressants: protriptyline, desmethylimipramine, doxepin, clomipramine, maprotiline and butriptyline, a significant relationship (if any) awaits further elucidation. These plasma level relationships probably do not generalize to other types of depressions (e.g., neurotic, characterological, delusional, acute situational, etc.) and clearly do not apply to every endogenous tricyclic responsive patient. In general, a clinician will obtain best therapeutic efficacy for endogenously depressed patients if these guidelines are followed. Routine monitoring of plasma levels of the tricyclic antidepressants is a useful method to maximize therapeutic efficacy and prevent undue side effects, as well as to insure good medication compliance.