Pharmacodynamic Drug Interactions in Bipolar Disorder Treatment Transcript

Hi, I'm Paul Sarkowski. My day job is at Sound Community Mental Health Center, where I am a senior psychiatric supervisor. I also do work at the University of Washington, where I am a clinical assistant professor.

In considering the effect of pharmacodynamic interactions for specific disorders, the most important thing is really these drugs are very well tested one at a time. They're tested much more frequently one at a time than in combination. And because of that, as long as clinicians stick to monotherapy for indications and for efficacy-based results, they're usually free of pharmacodynamic issues, obviously with monotherapy, but even for combination therapy.

In the case of major depression, our biggest combination study was in the STAR-D trial in which there was a trial of monotherapy leading to augmenting agents. And in each case, the response was what we might call an additive, in that there was another 30% when another agent was added. And that 30% increase in response for the patient population could be predicted from that drug's response alone.

So even though the agents, the augmenting agents were selected in the STAR-D trial to not carry a pharmacodynamic interaction, it had a different mechanism of action. It turned out to be in effect additive in their interactions in which we saw an increasing chunk of the patient population respond. And the situation with major depression is actually different than the situation with bipolar disorder with the multiple phases of bipolar disorder.

And this is another area in which medications have been studied in combination because of its relevance in treating bipolar depression, which is the agents that are effective in bipolar depression are different than the agents that are effective in unipolar depression in that, in the step BD trial, they found that the addition of antidepressants to mood stabilizing agents did not improve efficacy, it did not improve time to recovery, and it tended to cause a relapse at three months into mania.

So we could say then that would be a pharmacodynamic interaction possibly due to the function of the drugs where even though the mechanism of action of say an antidepressant and mood-stabilizing agent are different, the proven efficacy is different for each classification of each medication. And because of using a medicine that's not tested in a specific class, it leads to inferior results.