Are there any documented interactions between aripiprazole and sertraline or clonazepam

Fråga: Are there any documented interactions between aripiprazole and sertraline or clonazepam that could result in increased aripiprazole exposure (1-2 times above the therapeutic range)?

Sammanfattning: In conclusion no convincing evidence can be found on clinically significant effects of sertraline or clonazepam on aripiprazole concentration in the literature. Sertraline is a moderate CYP2D6 inhibitor but does not affect other drugs through CYP3A4. It does not appear to have a significant effect on the aripiprazole concentration based on comparison of aripiprazole concentrations in patients on monotherapy and those with concomitant sertraline. An interaction in individual patients cannot, however, be excluded. For it to be reasonable to consider an interaction effect as the reason for the increase in aripiprazole concentration in this specific patient case, sertraline should have been added or increased between the two aripiprazole sampling dates.

Svar: A study compared dose adjusted concentrations of aripiprazole in patients treated with aripiprazole with or without other drugs in a therapeutic drug monitoring database. Concomitant treatment with sertraline (n=14) had no statistically significant effect on the dose adjusted aripiprazole concentration compared to patients that had only aripiprazole (n=79) (1). One case report on akathisia and one on dystonia associated with the combination of aripiprazole and sertraline have been found (2,3). In the later case the authors speculate on the possibility that the aripiprazole concentration might have increased because of an interaction with sertraline through CYP2D6 (3). There are no measured concentrations described in the report though.

A search of PubMed and the interaction databases SFINX and Stockley´s Drug Interactions did not reveal any documented interaction effect of clonazepam on aripiprazole.

Aripiprazole is metabolized by CYP2D6 and CYP3A4 (4,5). Strong CYP2D6 or CYP3A4 inhibitors have been shown to increase aripiprazole exposure (5). Sertraline is a moderate CYP2D6 inhibitor but does not appear to affect other drugs significantly through CYP3A4 (4,6). Clonazepam does not appear to affect other drugs significantly through CYP2D6 or CYP3A4 (4,7).