On the relationship of nortriptyline: amitriptyline ratio to clinical improvement of amitriptyline treated depressive patients.

The antidepressant effect of amitriptyline was studied in 28 endogenous depressive patients. They received 150 mg amitriptyline once nightly in a sustained release form for 4 weeks. Blood samples were drawn 12 hrs. after medication. Amitriptyline concentrations were between 35--300 ng/ml Nortriptyline concentrations were between 20--330 ng/ml. No correlations were found between plasma concentrations of amitriptyline, nortriptyline, or their sum, and the clinical outcome of treatment. Plasma levels of amitriptyline depended on neither the age nor the sex of the patients. A significant correlation was found between the ratio of nortriptyline to amitriptyline concentrations in serum (demethylation ratio) and clinical improvement. The demethylation ratio appeared to be relatively constant after a few days of treatment. The results suggest that monitoring the demethylation ratio of endogenous depressive patients treated with amitriptyline may predict therapeutic effects of the treatment. They also suggest that a balance between noradrenergic and serotonergic mechanisms is necessary to improve antidepressant treatment with amitriptyline.