Amitriptyline plasma levels and clinical response in primary depression.

Sixteen patients with primary depression were treated for 4 wk with amitriptyline. After clinical diagnoses were determined, patients entered a double-blind protocol (amitriptyline or placebo) and their clinical status was determined with the Hamilton Depression Rating Scale by raters blind to the drug type, its dosage and plasma levels. Amitriptyline (AT) and nortriptyline (NT) plasma levels were assayed twice weekly by gas chromatography-mass spectrometry. In the 16 patients, a negative correlation between the Hamilton Score and the mean total tricyclic level (p less than 0.01), as well as with individual plasma levels, was found at the end of the treatment period. When the group was divided into clinical responders and nonresponders, the mean total tricyclic (AT + NT) levels discriminated the two groups by day 12 (p less than 0.001) as well as at the end of the protocol (day 26, 88% of the patients were classified correctly if an arbitrary level of 200 ng/ml total tricyclic plasma level was chosen). These results strongly suggest the presence of a positive correlation between plasma levels and clinical improvement in patients with primary depression.