The Cutting Edge of Medicine: An Interview With Alejandro Alva, MD

CLINICAL CONVERSATIONS

The US Food and Drug Administration (FDA) Advisory Committee Meeting will meet on June 4, 2024, to review investigational MDMA-assisted therapy for posttraumatic stress disorder (PTSD). In our effort to gauge clinician reactions, Psychiatric Times sat down with Alejandro Alva, MD, to learn more on his thoughts about the potential of MDMA, other therapeutic advances, and the future of psychiatry.

PT: Your practice is inclusive, and you are noted as a bicultural clinician. How do you think cultural values and norms will impact patients’ views of MDMA as part of clinical care?

Alejandro Alva, MD: That is a very insightful question. It depends on the parent culture. Traditionally, if you look at Hispanic, Black, and Middle Eastern families, they tend to be very conservative. Adapting to any new modality of treatment is always going to be challenging. We are fighting with this pathos even now, where people do not want to recognize that there is such a thing as mental illness. Number one, there have been cultural challenges, and number two, there are development and research challenges. I think that this is a very exciting time, because patients look to us from a cultural perspective, especially if we have a similar cultural background, for answers. I get this a lot with my Hispanic patients, where they ask me, “Are you sure?” I tell them, “You come here and you pay me to get an opinion. So yes, I am sure.” I think we have a role to play in educating our patients and to make them more aware of the new challenges and technologies that we have available for the treatment of different disease entities.

PT: How do you think this approval/nonapproval will impact the care of patients with PTSD? If approved, do you think you would use MDMA with your own patient population?

Alva: Absolutely. PTSD is by definition an anxiety disorder and it is incredibly difficult to treat. It was once relegated to only veterans, called ‘shell shock,’ and the standard treatment was usually group therapy, psychotherapy, maybe rapid eye movement desensitization. But when it comes to medications, we did not really have a whole lot of anything. We have SSRIs, the prototypical one is sertraline.

We do recognize that when you look at glutaminergic medications, they have been proven to be effective in depression. Now, when you look at depression and anxiety, the pathways are very similar. We know that there is a very close relationship between glutaminergic activity and the hypothalamus, pituitary, adrenal gland axis, and that there is very real evidence that there is not only a serotoninergic dysfunction, but there is also a GABA dysfunction in PTSD. The idea is that we must be on the cutting edge of medicine. Other clinicians may take a very conservative approach. They might say, “I will wait and see what happens. I will wait to see what my colleagues do.” We do not adhere to that principle, because we feel that the patients deserve better. Anything new that comes up, I see it as an opportunity for our patients to improve, as opposed to the possibility of potential lawsuit.

What we have seen so far with glutaminergic medications is that they are incredibly effective and they work in a relatively short period of time. Look at ketamine, for example. Ketamine is incredibly fast, but there is this bias around it. Esketamine is FDA approved, and when patients try it in real life, they realize it works and works quickly. I extrapolate that information into the PTSD area, and I think that MDMA will be extremely beneficial. Obviously, we want to wait and see what the FDA does. Then, if it is approved, yes, we are definitely going to try it out.

PT: Based on your knowledge of its safety and efficacy, how does MDMA-assisted therapy compare with other treatments currently available for patients with PTSD?

Alva: Patients can have some dissociation. That is the drawback with this medication. On the flip side of that, the safety profile is certainly there. We have seen that this medication, when used properly, can work very well.

Once when I was teaching the residents, I said, “Anything can give you side effects, right?” The typical smart aleck raised her hand and said, “Water has no side effects.” Wrong, water can kill you, as evidenced by schizophrenics that drink water because they are compelled to do so because either their hallucinated voices or some other hypothalamic dysregulation exists, and then they become hyponatremic, and then that causes potentially fatal cardiac arrhythmias. Side effects are inherent with the use of medication management, but they are also inherent with the use of any other means by which we treat a certain disease entity. When you are balancing the risk benefit analysis, I think that it is important to recognize that the potential for benefit outweighs the risk for side effects.

PT: Let's say MDMA-assisted therapy gets approved. How do you think this is going to impact the field of psychiatry?

Alva: It is going to be big. There is no question about it. I think it is going to be an adjunct to the therapeutic approach in the realm of the medication management. SSRIs do have a role to play, but it would be very refreshing to have something that has a completely different mechanism of action, because now we are not only hitting serotonin receptors, we are also addressing GABAergic dysfunction that occurs in the hippocampal region in the brain.

PT: Which patients with PTSD would you consider treating with MDMA-assisted therapy?

Alva: Any patient that has a need. Historically, we have seen people that are in the military or first responders. Any type of person that has experienced an event that is outside of the normal human experience, or there has been trauma, or they have symptoms severe enough to cause dysfunctionality—that would be the ideal patient.

PT: What would you say to clinicians who are hesitant about MDMA? Would you have any advice for them?

Alva: I have an advantage: I do clinical research. I have been fortunate enough to work on pretty much every single medication that has come out on the market for the last 15 or 20 years. I get the optic from looking at a patient that has been on standard medications and then trying something completely different and seeing improvement. To my fellow clinicians, I would ask, “If this was a relative, would you not try it?” I believe that, given the option, if a family member was sick, they would be willing to try something they have never tried before. With a reasonable understanding of the medication, most people would want to take a chance.

PT: What do you think the biggest barriers to access to care for patients will be?

Alva: It is going to be financial, 100%. As you know, in the medical realm, we look at getting approval from insurance companies. What it is going to boil down to—extrapolating based on other modalities like TMS or even ketamine, the patient will have to have failed several treatments, have gone through therapy, and have at least 1 SSRI trial and failure. Then maybe they will approve it.

The other barrier is going to be contractual. If there is an indication and the pharmaceutical company cuts a deal with entities, whether they be managed care, or federal, or state, then it may be more readily available.

But I think that the biggest challenge for all of us is education to break the stigma and negative perception. That is where you guys play such a significant role in actually putting this out there for people to consider, you know? It may not be the right fit for everybody, but at least it is another weapon in our armamentaria, that we can bring to the table. Ultimately, that is what it is all about: quality of life for our patients.

PT: Thank you!

Dr Alva is the founder, chief medical officer, and CEO of Pacific Neuropsychiatric Specialists (PNS). He has been practicing psychiatry for more than 20 years.