An Interesting Drug-Drug Interaction
A case and comment are reported in Currents in Affective Medicine Nov 2007 which reflect an interesting drug-drug interaction. A child with OCD was well treated with clomipramine 150mg/day. A diagnosis of bipolar disorder while he was in the hospital was treated with oxcarbazepine 600mg bid. The treater states that the child's sleep improved as well as agitation, but his OCD symptoms worsened. Dr. Rosenblatt discusses the case and correctly cites a case reported by P Baird in J Clin Psychopharm 23:419, 2003 in which the addition of oxcarbazepine shifted the metabolitic ratio of clomipramine and desmethylclomipramine from levels of 49/60 ng/ml to no detectble clomipramine and a desmethylclomipramine level of 98ng/ ml. He rightly points out that although oxcarbazepine is less CYP- inducing than carbazepine, it is likely that oxcarbazepine induced CYP3A4 and shifted the decreased the levels of parent and increased the levels of the metabolite. However, Dr Rosenblatt fails to appreciate the difference in neurotransmitter activity of the serotonergic parent clomipramine and noradrenaline metabolite desmethylclomipramine. This is the basis of the reduction of OCD activity. If the child had ADHD, his symptoms would likely have improved because of the increase in desmethylclomipramine at the expense of clomipramine. A more complete discussion of these factors can be found in: Oesterheld J, Kallepalli BR:Grapefruit juice andclomipramine: shifting metabolitic ratios.
J Clin Psychopharmacol.1997 Feb;17(1):62-3. PMID: 9004067 Jessica Oesterheld, M.D.