Interaction of valproic acid and antidepressant drugs

Introduction and Aims: Valproic acid (VPA) and the antidepressant drugs amitriptyline (AMI), doxepin (DOX) and venlafaxine (VEN) are common psychotropic drugs, which are frequently used in patients with affective disorders. Repeatedly, in the literature an influence of VPA on serum levels of antidepressants is described, although only single smaller studies exist, which focus on AMI and comprise mainly smaller samples or case reports. Methods: We assessed our TDM database of the years 2008 to 2011 for cases receiving a combination of one of these antidepressants and VPA. A control sample of patients with the respective antidepressant drug but without VPA was obtained by matching for gender, age and daily dose. Then both samples were compared by t-tests regarding serum levels of AMI+nortriptyline, DOX+N-DOX, VEN+O-Desmethyl-VEN. Results: The mean serum level of parent compound + metabolite was significantly higher in patients who received the respective antidepressant drug (AMI p<0.001, n=33; DOX p<0.05, n=18; VEN p<0.05, n=48) and co-medication with VPA. Conclusions: If a combination of VPA with an antidepressant drug is administered, cautious dosing is advisable and TDM should be performed since VPA may lead to a striking increase of antidepressants' serum levels.