Pharmacokinetics and pharmacodynamics of amitriptyline in depression.

1. The therapeutic effect and pharmacokinetics of amitriptyline were assessed in thirty-five patients suffering from primary depressive illness during inpatient treatment. 2. Contrary to our previous study, no significant correlation was obtained between the plasma concentrations of amitriptyline, nortriptyline or total tricyclics with Hamilton rating score at 6 weeks or percentage improvement after 6 weeks treatment. 3. There was also no correlation with the plasma concentrations of tricyclics with the corrected subjective side-effects score. 4. A linear correlation (rs = 0.80; p less than 0.001) was observed between the plasma concentration of nortriptyline and decreased tyramine sensitivity, an index of noradrenaline reuptake blocking effect. 5. The corrected side-effect score during the trial correlated (r = 0.64; p less than 0.001) with Hamilton rating score at week 6, i.e. the patients who complained of more side-effects had less clinical benefit during amitriptyline therapy.