Serum levels of amitriptyline and therapeutic effect in non-delusional moderately to severely depressed in-patients: a therapeutic window relationship

In a prospective, open clinical study, the relationship between serum level s of amitriptyline (At) and nortriptyline (Nt) and the therapeutic effect a fter 6 weeks of treatment was investigated. Serum levels were measured by g as-liquid chromatography and the therapeutic effect was assessed by the Ham ilton Depression Rating Scale (HAMD) and the Clinical Global Impression Sca le (CGI). A number of 25 non-delusional, moderate to severely depressed inp atients were included. A therapeutic window relationship was detected by me ans of regression analysis (quadratic model). Low and high serum levels wer e associated with low therapeutic effect. In an intermediate range, the pro bability of good therapeutic effect was increased. This relationship reache d significance for the serum levels of At (p < 0.05) and a trend for the su m of serum levels of At and Nt (p < 0.1). As expressed by the regression co efficient r(2), about 25% to 35% of the variability of therapeutic effect w as explained by serum levels. Dichotomized data sets according to limits of final values of HAMD and CC;I as well as limits of a therapeutic window of 70 ng/ml and 200 ng/ml (sum of At and Nt) revealed significant differences by means of Fisher's exact test (p < 0.05). Furthermore, increased ratios of serum level of Nt per serum level of At were found to be associated with decreased therapeutic effect. Thus, the present data support the existence of a therapeutic window of serum levels of At in depression. Also taking i nto account other reports, this therapeutic window can be defined as being between about 70 and 220 ng/ml. The assay of serum levels of At can be used to lower the risk of unsatisfactory therapeutic outcome.