Key Points Regarding Efficacy, Safety of the Co-administration of Psychedelics With Psychiatric Medications

Pharmacy Times interviewed Kelan Thomas, PharmD, MS, associate professor of clinical sciences at Touro University California College of Pharmacy, on his recent presentations at Insight 2021 and the virtual Sana Symposium on psychedelic adverse effects and drug-drug interactions.

Alana Hippensteele: What are some key points to consider regarding co-administration of the psychedelics with psychiatric medications?

Kelan Thomas: Yeah, so the main things to consider are, even though MDMA have these sort of theoretical risks, when they looked at studies of healthy volunteers who were taking MDMA and then previously were given SSRIs or SNRI antidepressants, it actually attenuates the blood pressure effects, which demonstrates to me that there's sort of a pharmacodynamic interaction at play whereby the SSRIs are actually preventing some of the uptake of MDMA into the pre-synapse. So, it's not having as big of an effect on heart rate and blood pressure in co-administration.

From a safety standpoint it actually doesn't seem to be a huge safety risk if they were co-administered. The bigger issue, and this was a theme that was coming up at these conferences, is are we going to lose the benefits and efficacy of it?

So there has been a paper demonstrating, in the analysis of the MDMA phase 2 data, people who recently had to taper and discontinue their antidepressant before they were in the trial didn't respond as well and didn't have as great of a PTSD symptom reduction as people who had just not been taking any antidepressants at all.

There's some really early unpublished preliminary data that I heard about from the Sana Symposium, and some that one of the presenters at Insight 2021 mentioned, that the Imperial College of London is starting to evaluate that in their escitalopram with psilocybin clinical trial, and they're also finding this similar signal regarding people who were recently tapered off, which suggests there's some sort of homeostasis.

We know this that antidepressants take several months to have their benefit, like usually a 1 to 2 months timeline to really see that full benefit unfold. So, there is some neuro-adaptation happening at the receptor level. So, it may take several months of being off of an antidepressant to see MDMA or psilocybin have its benefit for things like depression and PTSD.

So that's an emerging area of research that we really have to understand very well to help predict who's going to respond or how long do we need to stop their antidepressants before they can take this psychedelic-assisted therapy treatment paradigm.

Alana Hippensteele: Right, absolutely. You were discussing antidepressants and their interaction and a little bit regarding potential impact on efficacy—is there any data so far regarding the impact of antidepressants on efficacy in relation to psilocybin, MDMA, and ketamine? I know you touched on that a little bit, but is there anything else to elaborate on there?

Kalen Thomas: Yeah, the most clear data so far is that for MDMA, people who had recently been taking an antidepressant did not seem to have as great of a symptom reduction as people who had stopped. But they didn't get so granular as to where these people stopped, whether 5 years ago or 1 year ago, so that's not really clear. But these are the types of questions we need to do further research on.

Ketamine was approved as an augmentation strategy, so ketamine is routinely given with antidepressants even in all the esketamine phase 3 trials for FDA approval. So, in terms of people having some benefit from existing treatments, ketamine is the most resistant to any issues, whether that's change in efficacy—they were constantly co-administered. But MDMA and psilocybin may actually not be as beneficial if they're co-administered with current antidepressant therapy.

Alana Hippensteele: Yeah, absolutely. Thank you so much for taking the time to speak with me today, Kalen.

Kalen Thomas: Sure, thank you.