Tricyclic antidepressants + St John’s wort (Hypericum perforatum) - Drug Interactions

The plasma levels of amitriptyline can be reduced by St John’swort, but clinical importance of this interaction is unknown.

Twelve depressed patients were given 75mg of amitriptyline twice daily and 900mg of St John’s wort extract (Lichtwer Pharma,Berlin) daily for at least 14 days. The AUC0-12 of amitriptyline was reduced by about 22 % and AUC of nortriptyline (its metabolite) was reduced by about 41 % (See reference number 1).

Not fully understood, but there is evidence that St John’s wort is an enzyme inducer, which can increase liver metabolism by cytochrome P450 isoenzymes, thereby reducing plasma levels of both amitriptyline and its metabolite (nortriptyline). Induction of P-glycoprotein by St John’s wort may also contribute.

The interaction appears to be established,but its clinical importance is uncertain. Both tricyclics and St John’s wort are antidepressants, but whether final sum of this interaction is more or less antidepressant activity is not known. It was not assessed in this study (See reference number 1). Other tricyclics probably interact similarly because they too can be affected by enzyme-inducing drugs. Monitor for antidepressant efficacy and increased adverse effects if St John’s wort is given with any tricyclic. More study is needed.

1. Johne A,Schmider J, Brockmöller J, Stadelmann AM, Störmer E, Bauer S, Scholler G, Langheinrich M, Roots I. Decreased plasma levels of amitriptyline and its metabolites on comedication with an extract from St. John’s wort (Hypericum perforatum). J Clin Psychopharmacol (2002) 22, 46–54.