Analgesic and antidepressive effects of low-dose amitriptyline in relation to its metabolism in patients with chronic pain

Abstract

The analgesic and antidepressive effects of amitriptyline (AT) in relation to its kinetics and metabolism were studied in 19 outpatients with chronic pain who received a daily dose of 75 mg AT for at least 6 weeks. Riboflavin was added to the medication to check compliance. On days 0, 4, and 8 and weeks 3, 6, 9, and 12 after the start of dosing, blood samples were drawn from the patients 10 .+-. 1 hours after the first morning dose and a sample of the first morning urine was taken to check riboflavin. Serum levels of AT and its metabolites, especially nortriptyline (NT) and E-10-hydroxy-nortriptyline (E-10-OH-NT), were measured by HPLC. On day 0 and at 3, 6, and 12 weeks the severity of depression was scored by means of a self-rating depression scale and pain intensity scores were measured. In addition, after 6, weeks of dosing patients estimated their percentage of pain in comparison with baseline. Mean (.+-. SD) steady-state concentrations of AT, NT, and E-10-OH-NT were 36 .+-. 23.5, 28 .+-. 14.9, and 52 .+-. 23.7 .mu.g/L, respectively, in male patients (n = 8; age 45 .+-. 7.4 years) and 34 .+-. 14.6, 45 .+-. 25.1, and 40 .+-. 15.6 .mu.g/L, respectively, in female patients (n = 11; age 46 .+-. 6.8 years). There was a significant sex-related difference in the NT/AT ratio, which was higher in women. After 6 weeks of treatment, neither the improvement in the depression score nor the improvement in pain intensity score in comparison with baseline scores correlated significantly with steady-state levels of AT, NT, and E-10-OH-NT and the NT/AT ratio.