Emerging Treatments for Adults With ADHD

Theresa R. Cerulli, MD: The last thing we’re going to talk about is emerging treatments and unmet needs. I’d like to start with this one. What are some of the studies in pediatric and adult ADHD [attention-deficit/hyperactivity disorder] that we’re most excited about? I’d like to take this because I attended a program on centanafadine, and I was very excited to hear that centanafadine is now a pipeline product for ADHD. It’s a triple reuptake inhibitor with all 3 neurotransmitters: dopamine, norepinephrine, and serotonin reuptake inhibition. I was excited. This is something new and different in the pipeline. Feel free to weigh in. We don’t have a lot of time on this topic. Andy, if you could, help with some of the other options.

Andrew Cutler, MD: As you know, I’m a researcher. I do clinical trials. I’ve been doing ADHD clinical trials for over 20 years. I’ve studied every product that’s on the market and some that didn’t make it to the market. I also consult with companies. I’m very familiar with a bunch of new medicines that are in development. You mentioned centanafadine. The very first study of centanafadine in people was done at my site. We studied it in adults as a pilot study.

Centanafadine is an SNDRI [serotonin–norepinephrine–dopamine reuptake inhibitor]. It’s triple, but it has highest affinity for the norepinephrine transporter, then dopamine, and right behind that is serotonin. Right away, it looks like it would be effective for ADHD and, as we said with viloxazine XR [extended-release], for comorbidities such as depression and anxiety. It’s very exciting to have another option here. Some patients may do better with one than the other.

One that I’m particularly excited about, and that I have a historic relationship with, is a compound called solriamfetol. Solriamfetol is on the market. It’s FDA approved for excessive daytime sleepiness [EDS] associated with obstructive sleep apnea or narcolepsy. It’s a DNRI [dopamine-norepinephrine reuptake inhibitor]. That might make you think of bupropion. This has way more potent binding to those transporters, and it has higher affinity and activity at the dopamine transporter vs the norepinephrine transporter. Right away, on paper, that sounds like an ADHD medicine as well.

Twenty years ago, I studied this medicine for depression. We did studies for major depression with this medicine. In my hands, it worked very well. Unfortunately, the phase 2 overall study failed to distinguish the drug from placebo. That was because there were 2 sites. The highest enrolling sites had very high placebo response. Unfortunately, that killed the signal. This drug bounced around and then finally was introduced for EDS. The company that now has it told me that we’re going to be doing ADHD with this drug, and I’m consulting with them on this. I’m thrilled to have another nonstimulant option.

Also, there’s a really interesting medication being developed based on a Chinese herb. This Chinese herb has a multimodal action, and there are a number of different active substances within this herb. It does things, such as neuroprotection. It binds to NMDA [N-methyl-D-aspartate] receptors, it appears to bind to some alpha norepinephrine receptors, and it affects the immune system. There’s some preliminary evidence being looked at for both major depression and ADHD.

Some existing medications are being looked at in various ways. We mentioned that viloxazine XR is approved as monotherapy. It’s being studied now in combination with stimulants, such as the alpha-2 agonists, which are approved. The methylphenidate extended-release liquid is being looked at for children with ADHD and Down syndrome. That comorbidity is understudied and very important. Most of our ADHD medicines are approved for only ADHD. And yet, as we said, ADHD is a comorbid disease. The majority of the time, there are comorbidities, so we don’t have a lot of guidance on whether it works for ADHD with comorbidities. Is it safe? How do I dose it? Those studies are also important, not just studies of new mechanisms of action. I’ll stop there. There are some other things. For instance, there are some non-medication therapies being studied. There are some prescription digital therapies and devices being looked at. But that’s a little beyond the scope of our discussion.

Transcript edited for clarity