Alice Mao, MD

 We’re going to bring our discussion to a close. Thank you all for this rich and informative discussion. Before we conclude, I’d like to hear final thoughts from each of you. Dr Amann?

 As Andy said, thank you, Mike, for sharing your personal story. Thank you too, Theresa, because you shared what it’s like being a parent of a child with ADHD [attention-deficit/hyperactivity disorder]. We’re appreciative of that as well. We change lives, and I’m ever grateful to all the resources I have to do that. It’s very rewarding to treat this disorder when it’s diagnosed and treated properly. Thank you to everybody for having me join this discussion. I’ve enjoyed it greatly.

 We’ve done a terrific job summarizing some of the issues. I feel so fortunate, like many of you, my colleagues. I’ve been working in this space for over 20 years, and [it’s so rewarding] to see the evolution of the technology and the different options, the understanding of the neuroscience of ADHD. It’s so rewarding to have all these different options.

I always joke that when you’ve seen 1 patient with ADHD, you’ve seen 1 patient with ADHD. We all know that. It’s so variable, the comorbidities and the daily activity. Having these tools and options allow us to do a much better job individualizing, personalizing, and getting better outcomes overall for our patients. I agree with Mike, it’s one of the more rewarding things that we treat in psychiatry. You can really make a difference. One thing that never gets old is helping a child and feeling like you can change the course of someone’s life and put them on a different track. That’s incredible. Mike used the railroad track analogy, which I love. That’s been very rewarding. We have a lot of challenges and a long way to go, but it’s been gratifying to see the progress we’ve made so far.

 For me, as a clinician in both settings, the most positive aspect is seeing self-confidence improve and children who are frequently getting in trouble and getting sent to the principal now getting merit reports saying that they’re the student of the day, and they aren’t getting in trouble anymore. With adults, like my patient who’s an attorney, the joy of watching somebody achieve their goals because they were willing to resume treatment is one of the most gratifying things about being a clinician.

Thank you so much for asking me to be here. It’s an honor to be here with many of my colleagues who are as old as I am, who have also treated folks with ADHD through their life span and have had the pleasure of seeing all the new developments in ADHD emerge and make a difference in people’s lives.

 Twenty years ago, I used to sit in the room with you for different meetings with all the teachers, moderators, and people I looked up to. You guys brought me into the world of validating this stuff and realizing how incredible this stuff was. I’m truly honored to be on the panel with you guys because I’ve always respected you. I might have been a little obnoxious in this [discussion], or a little restless.

 Maybe I interrupted a few times. But my biggest message is that this is a blast, but I hope people watch this and buy into what we’re saying.

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ADHD experts share their final thoughts on the treatment and management of ADHD.

Final Thoughts on Management of ADHD

 Dr Mao, what are the most pressing unmet needs in the treatment and management of pediatric and adult ADHD [attention-deficit/hyperactivity disorder]? We’d love to hear your thoughts on this.

 One unmet need is that despite the efficacy and benefits of all the methylphenidate and amphetamine medications available, there are still a few folks who can’t take stimulants. Perhaps they get ticks or become highly irritable on the stimulants. I treat a specialized population of children with autism and comorbid conditions, such as ADHD. For me, one of the unmet needs has been to have a nonstimulant preparation that doesn’t require being swallowed, because I have a lot of patients who still have difficulty swallowing. I’d like to have a nonstimulant that’s well tolerated and can be administered in a way other than being swallowed.

Viloxazine, which was recently developed, has been helpful in that population because it can be sprinkled. For folks who can’t tolerate stimulants or who have had adverse effects from taking stimulants previously, I’ve been pleased that we have another new option available, such as viloxazine, because it’s a nonstimulant that doesn’t have to be crushed to be taken, as we’ve had to do with immediate-release guanfacine or other compounds. For me, that’s been an unmet need that’s important for clinicians who are treating populations of folks with ADHD who have comorbidities that can be exacerbated, such as anxiety or mood disorders, when taking the stimulant medications.

 Dr Feld, what are the most unmet needs still remaining for all ages?

 I’ll start at the professional level. There’s an unmet need of having enough providers.

 A lot of nurse practitioners love treating ADHD. It’s on us, the KOLs [key opinion leaders] and leaders, to get people to be passionate about diagnosing ADHD

comfortable treating the comorbidities, and exposed to the new biotechnology. As Andy said earlier, I see some child psychiatry fellows come out of top-level programs in the Midwest, and because of what their exposure is, they don’t even know some of the newer medications. They go into private practice scenarios in which patients come to their office, and they haven’t even used some of these newer medications.

 It’s not only at that level. It’s mostly going to be nonpediatric psychiatrists and neurologists, so how do we get the word out? We need to show that we have enough passion and intelligence to teach primary care doctors who aren’t just teaching about pharmaceuticals to make a company a new medication. We’re here because these medications are changing the treatment, efficacy, and effectiveness of ADHD.

A lot of people are comfortable with 2 or 3 medications and not treating comorbidities. We start by teaching the providers that you have to get comfortable diagnosing correctly, looking for comorbidities, and being open to new treatment options and experiencing them. Because once they experience them, they’re going to understand the differences. A lot of vouchers and co-pay cards don’t require prior authorization, and there’s a maximum amount of money, so you could still use these medications for a vast majority of patients, even if they don’t have a commercial insurance that’s going to potentially cover it too quickly. I’m pretty aggressive that way.

The stigma of psychiatry still exists. It’s up to us to show that we’re valid clinicians who change people’s lives and that we help children, adolescents, and even more so adults by treating ADHD, particularly with comorbidities, and make people’s lives more functional, more effective, more productive, more worthy. For me, treating ADHD is probably the most rewarding disorder to treat in almost any field of medicine. But we have to continue to be reliable, valid, intellectual providers who make the treatment of ADHD truly scientific, because there’s so much stigma, misuse, abuse, and poor prescribing. We should hold our own and stay strong and push the proper treatment and diagnosis of ADHD.

 Well said, Dr Feld. Thanks for sharing all of your professional and personal experience and participating with us. It helps educate the listeners. Hopefully your passion shines through so that people understand that we’re trying to educate because we care. We care about your understanding, the patients, and the clinical outcomes most of all.

 I’d like to share 2 unmet needs. One is that we’re trying to educate primary care prescribers and clinicians about the diagnosis and treatment. But too often, a patient will wait 3 or 4 months to see me. They’re diagnosed, but they’re on the first of the dose in the dose range.

 Now they’ve waited 3 or 4 months for me to simply take the dose to the next step. They’re tolerating it fine, but they aren’t getting any efficacy. An unmet need is to help primary care colleagues feel comfortable going into more of the dose range so that I can tackle the more complex comorbid ADHD. The second thing is that I’m seeing children at younger ages. We could benefit from more available for 3-, 4-, and 5-year-olds. That has come up often in my practice.

 Yes, the preschoolers. Of course, the teaching is that nonpharmacological approaches are first-line therapy for the preschoolers vs school age, where it’s a combination of the pharmacological and nonpharmacological interventions. The little guys are at more risk with the growth delays and…challenges, unfortunately. We don’t have great options for the 3- to 5-year-olds.

 A lot of it is parental guidance in that age range, for sure.

 I’d like to add 1 or 2 more things. First, I appreciate Mike Feld sharing his personal story. You’ve been an inspiration to me, and we’ve all benefited from that and from your bravery. You’re breaking the stigma by normalizing this. It’s a great example for us, for other fields of medicine, and for our patients.

Mike, you also got me thinking in totally different way. When I’m asked, “What are the unmet needs?” I’m thinking, “What new medicine do I need? What does it need to address?” You’re right that we haven’t done a great job educating our peers on how to use the tools that we already have, how to recognize and diagnose this disorder, and the fact that it can be in adults. As we said, 80% of adults are unrecognized and underdiagnosed. As we’ve been talking about, we have all these newer options that allow us to individualize our treatment. Mike, you got me thinking again. We need to help our colleagues and educate. One of the biggest unmet needs is [teaching] how to use the tools we have available and educating around all the complementary therapies in addition to our medications.

 What Birgit said was maximally on target, because when I make a dose change, I look like a genius.

 I make a quick medication change, and people say, “How did you do that?” I’m not going to pat myself on the back. It wasn’t even intellectually challenging. They realize it was a step that wasn’t taken.

 Exactly what you said, Birgit. These people wait so long, they remain untreated or they drop out of treatment because they didn’t think it was efficacious. There’s a disservice being done, and we end up looking as though we’re that good—and hopefully we are—but half those patients don’t need to come to us.

 It’s how to use the tools we already have. If you’re going to use the drug, commit to it. The 2 times I look like a genius are exactly that: I raise the dose, or I switch from one MOA [mechanism of action] to the other, like methylphenidate to amphetamine or vice versa. It keeps us employed, but I wish more of our colleagues knew this stuff and could do a better job treating.

 If a medication is on label to 100 mg, why wouldn’t you feel safe prescribing it up to 100 mg?

 I still teach with the residents at Harvard University, and the old saying “Start low and go slow” is still prevalent. There’s still fear around how to dose.

 But if you have an adverse effect with a stimulant, you could stop it that day, so going slow doesn’t make sense to me.

 I don’t agree with starting low and going slow. That’s just what they’re used to hearing.

Drs Feld, Cutler, Mao, and Amann discuss unmet needs in the management of ADHD.

Unmet Needs in Management of ADHD

 After we get things through the FDA and they’re approved, there’s always the challenge of access.

 Birgit, you’re in the trenches on the front line. Access to newly approved medications can be challenging. What advice do you have for other physicians who want to get these in the hands of the patients?

 To take it to the patient level, in my practice, when a new medication comes out, I talk with all of my families, patients, and parents about it. I give them some information about it. If somebody is doing well on what they’re on, it isn’t ethical to change them. But I like to give them that information so that if not now, maybe in the future they’ll know that they could call to talk about it.

From the standpoint of physicians, clinicians, or prescribers, on the whole, it’s important to understand new options and what they can offer to patients over what we’ve had before. If it seems as though a new medication would offer longer duration, better tolerability, or something about it would be suitable for the patient they’re treating, it’s important to prescribe it. It’s important to make noise. I’m not afraid to do a prior authorization. Usually, the patients who come into our offices have plenty of ammunition, if you will, regarding past medications that they’ve been on, and we can try to have that go through. They may not be able to use these newer medications in patients who have never been on anything. But with patients who have had a few different medication trials, we need to prescribe these medications for them if we think they’re appropriate.

 In my experience, these companies with newer medications have gotten very sophisticated with copay card access and giving us information on what we have to do to get one of their medications. I certainly suggest talking to the company’s representatives and letting them help you.

 How nice is that with viloxazine XR [extended release], not just copay cards.

 It’s a noncontrolled substance. We can provide samples to the patients. Talk to your representative about getting samples for your practice.

 Yes. How long has it been since we’ve had ADHD [attention-deficit/hyperactivity disorder] samples in our closets? It’s unbelievable.

 We certainly can’t do this with a stimulant.

 But with viloxazine XR, it’s been a nice way to get folks started while you’re trying to work on the copay card and prior authorizations. Sometimes it also takes the assistance in working with the pharmacies to make sure they’re comfortable using the cards.

 Your representative may be able to assist with that as well. The pharmacists don’t always try too hard. The copay cards work, but they need to be properly utilized.

 Sometimes the independent mom-and-pop pharmacies do a better job with that. Maybe cultivate a relationship with some of those pharmacies.

ADHD experts discuss strategies for improving access to ADHD medications for their patients.

Access to ADHD Treatments

 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.

 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.

ADHD experts discuss novel treatments and unmet needs in pediatric and adult patients.

Alice Mao, MD

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