Effect of Sertraline on Plasma Nortriptyline Levels in Depressed Elderly

Background: Several serotonin selective reuptake inhibitors have been reported to be inhibitors of the cytochrome P450 2D6 (CYP2D6). Thus, they may increase the plasma level of secondary amine tricyclic antidepressants, which are predominantly metabolized through this enzyme. Except for a few case reports, no clinical data document the degree of this drug-drug interaction in elderly depressed patients.

Method: We systematically examined this interaction by determining the change in plasma nortriptyline levels in 14 elderly depressed patients in whom sertraline was added to nortriptyline.

Results: After addition of 50 mg/day of sertraline, the median increase in plasma nortriptyline level over baseline was 2% (range, _26% to 117%; p=.30). In 2 patients (14%), there was an increase of 50% or more. For patients taking higher sertraline doses (N=7; 100 or 150 mg/day), the median increase in plasma nortriptyline level over baseline was 40% (range, _12% to 239%; p=.08).

Conclusion: Overall, a modest effect of sertraline was observed on nortriptyline metabolism in these elderly depressed patients. This is consistent with prior reports of a weak inhibition of CYP2D6 by sertraline in vitro and in young healthy volunteers. However, some patients showed a change in plasma nortriptyline level that would be considered clinically significant. Thus, careful monitoring of plasma nortriptyline levels is recommended in all patients treated with a combination of nortriptyline and sertraline.