Andrew J. Cutler, MD, SUNY Upstate Medical University

COVID-19 has obviously presented significant challenges in our clinical work, particularly in the evaluation, diagnosis, and treatment of patients with ADHD [attention-deficit/hyperactivity disorder] of all ages. What we’ve all done, of course, is acclimate to this, largely through the use of telemedicine, telepsychiatry for a lot of our patients. Although more recently, I’ve gone back to more of a hybrid model where I am seeing some patients live and some via telepsychiatry. 

There are significant challenges. Some of those challenges include the fact that it’s a little more difficult to do an evaluation and to collect all the nonverbal information that you might get from being in the room with a person. Part of the problem is you may be seeing only a portion of the patient’s body. You may not be seeing the lower half of the body if you’re on a virtual call. You might not see some of the fidgeting or hyperactivity, for instance.

Also, what I find is patients either do really well with virtual telepsychiatry or don’t. They have trouble focusing. They get distracted. It’s really important to try to individualize care for our patients. Some people try to do in-person meetings. Ideally, this may be helpful for the initial evaluation so we can collect as much information as possible. When you’re dealing with children, you’d like to have collateral information, so you’d like to have parents and caregivers involved. That can be a little harder too, although it can be done virtually.

As far as prescribing medications, that can present a challenge. Although now, states are going to e-prescribing. In Florida, we now have to e-prescribe all controlled substances. That makes it easier, not having to handwrite a prescription and somehow get it to the patient in a COVID-19 environment.

The other thing I find is that sometimes children do a little better in this virtual environment, but many with ADHD struggle more. There’s a lot more stress and difficulty in school. Obviously, there’s more isolation, so fewer social relationships, fewer extracurricular activities, and maybe less access to exercise, which has been shown to be very beneficial for ADHD. These are some of the challenges that we’re trying to negotiate in the era of COVID-19.

Tele-prescribing of stimulants presents some unique challenges in the era of COVID-19. Part of the challenge is making sure you can e-prescribe appropriately. Most of us have figured out how to do that. Also, you want to make sure the pharmacy is available and shows up on your e-prescribing software. It is required, when we prescribe stimulants, that we monitor certain things. This can be more challenging in this environment, particularly when assessing vital signs, height, and weight. Blood pressure, heart rate, height, and weight can be a challenge in the virtual environment. This is when I may sometimes have the patient come to the office, just for the vital signs and height and weight checks. Or the patient can get 1 of the home monitoring devices, which you can get at many pharmacies. These devices can monitor blood pressure and heart rate. Your patients can check those periodically and report the results to you. Or you can certainly have them email that to you or communicate electronically.

As far as monitoring for abuse and possibility of diversion, this is something we also need to keep our eyes on. We can do this in various ways, including by checking prescribing databases, which can certainly be done online.

As far as monitoring for other issues and problems, such as the emergence of psychotic or manic symptoms or the possibility of vasoconstriction or cardiovascular issues, this is where taking a very careful history and evaluation and trying to look at the patient and evaluate them as best you can on camera really seems to help.

It’s important to understand that when evaluating and treating ADHD, comorbidity is the rule. Three-quarters of patients with ADHD will have a least 1 other comorbid condition. This is important because sometimes our core treatments for ADHD can help alleviate these other conditions. For instance, secondary anxiety or secondary depression. Sometimes, however, we do have to institute specific treatment in addition to the ADHD treatment to address a comorbid condition.

Rakesh Jain, MD, MPH: When parents and their children first come to see me for an evaluation for ADHD, there’s often a lot of confusion. We have a lot of myths in our heads. “Is this bad parenting?” “Was this just because one of us got divorced?” Is it because I had too many Diet Cokes when I was pregnant?” 

My first job is to offer parents and children a combination of sympathy and encouragement. I offer sympathy for the suffering they have gone through and encouragement that, if we do the right thing, we can make a pretty significant difference in all the challenges your child is having and you’re having as parents and caregivers. I have found that injection of enthusiasm, support, and knowledge to be as useful as anything I do.

The second step is really a pretty quick but accurate increase in knowledge base about the disease. Most people are quite surprised to know that it is a neurobiologically active condition. It is an inherited condition. It is a brain-based condition. Even though behavior is what they might see, the child is not being a “bad” child. 

Finally, we need to give an explanation of why interventions work or why a combination of nonpharmacological and pharmacological interventions is best explained in the context of neurobiology. 

When I offer that whole package of information, from sympathy to increasing their enthusiasm and encouragement to disease-state knowledge and then finally medication and nonmedication knowledge, you can see the parents and the child breathe a sigh of relief. “I’ve got a direction. There’s something I can do. I feel empowered.” That is precious. As a clinician, once I see that, I know I have established a solid therapeutic relationship that will lead to good outcomes.

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Optimizing care and managing challenges for patients with ADHD during the COVID-19 pandemic and advice for clinicians educating patients and families on disease management. 

Optimizing Care for ADHD During COVID-19 

Very often, parents approach me, or sometimes even patients approach me and say, “What do you think about drug holidays?” You have to ask them, “Are you wanting to take your drug to a holiday? What exactly do you mean?” Of course, I’m teasing them. What they mean by that is taking a break from their medications.

Perhaps you know, in years gone by that used to be recommended by many clinicians, until we realized that was not a good recommendation. If you think about it, if ADHD [attention-deficit/hyperactivity disorder] is a newer psychiatric disorder, which we know it is. If it is a disorder that causes impairment in every aspect of human life, which it does, then why would you want to take a holiday from covering those symptoms, particularly younger individuals who are shaping their lives on a daily basis? You would not.

Therefore, the conversation in the field has changed quite a bit to walking away from drug holidays. But instead of telling people, “Bad idea; don’t do it,” it is so much wiser to understand what their motivation is. Did they hear that from their neighbor? Is the medication causing adverse effects? Is there another issue? Is it cost, perhaps? Maybe they’re trying to minimize how many pills they’re taking per month? The only way to find out is to find out. Once I do, then I can educate them. If they’re afraid of growth suppression, which many parents are, I sympathize with them. Then I show them if their child was in the 45th percentile and is still at the 45th percentile, there’s no challenge. But if there is, then I would agree with them and look for another treatment option. I might offer to switch them to a nonstimulant. What if the patient is reporting rebound symptoms? I can work with them to address that so they can overcome their challenges without resorting to a drug holiday. 

In summation, what I would say is the following: A request for a drug holiday is very common. No. 2, I always try to approach it with respect and sympathy and curiosity. Why? What is your belief system about drug holidays, and why are you requesting 1? The final step I take is I offer psychoeducation and, if appropriate, a medication switch. I will almost always find a way to meet the patient in the middle in such a way that while they feel listened to, I’m still able to make sure they get as near a continuous coverage of symptoms as possible.

During these very challenging COVID-19 times, many parents wonder, “Is this a good time to take a drug holiday?” I have often said to them, “If there was a worse time than now, I have never met that time.” I tell them, “No, it just doesn’t make any sense. You are now the teacher. The child doesn’t even have the advantage of being in front of their teachers and with their peers to help some with organization. This is the worst time, in many ways, to think about a drug holiday.” 

One more time, I would urge every colleague online to appreciate the following: If a parent is asking for a drug holiday, it may be a very good idea to explore why. There may be other reasons. There may be a spouse with a difference of opinion. It may be the child is having insomnia and the parent is noticing it, or there’s irritability. Those are fixable problems. But a drug holiday solves nothing. Often, it compounds the difficulties the child and the family are having. So I would not support drug holidays, but I will very respectfully explore why the conversation is being brought up and do my best to address it.

Remote schooling is common in Texas, as I suspect it is in very many places. That places a tremendous burden on the child, or the adolescent, as well as the family. It is psychologically distressing. Exercise is reduced. The weather doesn’t always cooperate in letting kids run around to get physical exercise. There are a whole bunch of challenges. If there ever was a time where 100% adherence to pharmacotherapy for ADHD was a necessity, this is it, folks. 

I do have to work with my parents, who themselves might have ADHD. If you recall, this is 1 of the most common inheritable conditions. I have to make sure that we create a system of reminders. Sure, you’re starting school at 10 o’clock now because it’s home based. That doesn’t mean we change the time the medication has been taken previously—7:30 or 8 AM. Two or 3 hours later could be a small but important thing to consider. 

We should be frowning upon drug holidays and asking our parents to reconsider if they’re requesting 1. I may even have to adjust medications. I may have to switch medications. That’s all OK, as long as I remember the final goal, which is to help the child not fall behind academically and help the child not fall behind emotionally in terms of confidence and self-respect. By whatever means necessary in these times of crisis, we should employ every tool we have. If not now, we might have to ask ourselves when we will bring our A game to the table.

Rakesh Jain, MD, MPH, shares his thoughts on whether drug holidays are appropriate for children taking medication for ADHD. 

Addressing Drug Holidays for ADHD Medication

There is a new investigational medication called SPN-812, which may represent a very important advancement in the treatment of ADHD [attention-deficit/hyperactivity disorder]. This is a nonstimulant that has a unique mechanism of action. It has some efficacy as a norepinephrine reuptake inhibitor, but it also binds to certain specific serotonin receptors. This is important because our other available medications to treat ADHD are all working through norepinephrine and dopamine. This medication works through serotonin, which has been a bit of a neglected neurotransmitter in the treatment of ADHD.

SPN-812 has been studied in children and adolescents from the ages of 6 to 17, and it now has 4 clinical trials—2 in children and 2 in adolescents—that demonstrate clear evidence of efficacy for the total symptoms of ADHD using the standard ADHD rating scale and a subset of symptoms of inattention and hyperactivity or impulsivity. 

One of the other qualities that makes it unique is it demonstrated efficacy as early as the first 1 to 2 weeks of treatment. Also, it has a much more straightforward dosing regimen with less complicated titration. We believe this could be an important addition to our treatment armamentarium.

Also, it’s a capsule. Its extended release. If you open the capsule, there are pellets that can be sprinkled on foods like applesauce or yogurt. For those patients who can’t or prefer not to swallow pills, this is the first nonstimulant to have that property.

The safety database has been very impressive. It has been very well tolerated. The most common adverse effects seen were fatigue and nausea. It didn’t cause much in the way of insomnia or decreased appetite. It didn’t seem to cause a lot of irritability, agitation, or anxiety. As a matter of fact, it is derived from a medication called viloxazine that was approved for many years outside the United States as an antidepressant, so it might be effective in treating some of the associated comorbid conditions such as depression and anxiety.

 One of the more interesting and exciting recent developments in the world of ADHD is the study of a new chemical entity called SPN-812. This is a new chemical entity for us in the United States. The study design is straightforward and elegant. It is a randomized, placebo-controlled, multicenter study of individuals who have significant ADHD symptoms. Our goal is to see, through this study, how quickly and how strongly SPN-812 affects the core symptoms of ADHD. The core symptoms are the 18 items that are part of the DSM-5 [Diagnostic and Statistical Manual of Mental Disorders, 5th edition] criteria. Of course, the scale that is most commonly used for studies is the ADHD rating scale. 

In terms of adverse effects, the medication has been well tolerated. We shall see what happens in this study, in this evaluation. On occasion, mild degrees of sleep difficulties and mild difficulties of nausea have been noted. But generally speaking, the medication has been well tolerated. Of course, phase 3 data studied in rigorous double-blind fashion tell us the full story. I excitedly look forward to seeing the final results of this study.

 The medications for ADHD have been looked at for the possibility of disease modification. Unfortunately, we don’t have great evidence that any of them are disease modifying, although there is evidence that appropriate medication in childhood can head off some of the problems later on, such as depression, anxiety, and bipolar disorder, and may improve subsequent functioning. I don’t believe SPN-812 will necessarily be what we call disease modifying. When you stop using medications for ADHD, symptoms come right back. So we’re not necessarily curing patients. We’re managing the condition. I do believe SPN-812 has the potential to be a significant addition to our armamentarium because of this documented efficacy and safety that I mentioned.

I certainly welcome the approval and addition of SPN-812 to my clinical practice, and I see it as an option for patients for whom either a stimulant is not appropriate or contraindicated or if we have a case of parental or patient preference to not use a stimulant. This would probably be 1 of my go-to medications for that situation; or for a patients who I’ve tried a stimulant and they don’t have a good result, a good outcome from an efficacy point of view, or they have trouble with tolerability. One of the big tolerability problems in children is anorexia, or decreased appetite and suppression in growth. I see this as a good addition for patients who have trouble swallowing pills. This would be 1 of my considerations as a go-to medication because it is a capsule that you can open and sprinkle its pellets on soft foods.

I also see this as a potential option for a patient who has ADHD with comorbidities. As I mentioned, the chemical in SPN-812, which is viloxazine, was proven to be efficacious as an antidepressant. It was actually approved for use as an antidepressant around the world. The mechanism of action predicts potential efficacy for anxiety. Also, it does not appear to have potential for worsening tics, which is another issue that can be seen with stimulants.

A discussion on the recent development of investigational serotonin norepinephrine modulating agent (SNMA), SPN-812, for the treatment of ADHD in adults. 

Emerging Treatments for ADHD 

 Let’s address the issue of the evidence-based recommendation hierarchy in the choice of medications for adult patients who have ADHD [attention-deficit/hyperactivity disorder]. The treatment guidelines are elegant and helpful. They recommend, I think appropriately so, that a stimulant might be the appropriate first choice for the vast majority of patients.

However, there may be some patients for whom such an approach might be reserved as second- or third-line therapy. Those patients may have significant anxiety, significant depression, significant sleep difficulties, or significant and worrisome substance misuse disorders. In such situations, a nonstimulant may be the preferred first therapy. But it does appear that the greatest efficacy and appropriateness for most patients does tend to be with the use of stimulants. 

I will add 1 further word of advice for you. If you don’t receive all that your patient deserves from that intervention, it’s OK. Let’s not get frustrated. It’s OK to sometimes switch to another release mechanism, or maybe another medication of the same class of stimulants, or maybe switch to a nonstimulant medication. It’s OK to consider a long-acting version there. Of course, as I said before, let’s always combine our medication interventions with other interventions—the nonpharmacological interventions. That is what is recommended by our treatment guidelines, and I very much follow that in my own clinical practice.

Let’s now talk about the pediatric population and treatment paradigms for addressing ADHD. Very similar to adult ADHD, stimulants do tend to be recommended as first-line treatment by the vast majority of guidelines. I fully support that approach. Let’s never, however, ignore the specific populations for which nonstimulants may well be first-line options. For example, maybe a patient has a tic disorder, or the patient has significant anxiety or comorbidity. You know for a fact that’s rather common. What if the patient is significantly underweight to begin with and can’t afford to lose much weight right off the bat? Those may all be reasons to consider nonstimulants.

It’s better not to put it as a stimulant versus nonstimulant. It’s better to think of it as we have 2 different classes. Each class has many members in it, and I need to know their strengths. It’s not a matter of, “It must be this. It must be that.” It’s more a matter of customizing treatment to the patient. The patient might be pretty complex or might be highly comorbid or might be relatively straightforward. You may have a family member who responded very well to a certain class of medications. All those factors should influence our final decision as to what medication to choose to help our pediatric patients.

Rakesh Jain, MD, MPH, considers the evidence-based recommended hierarchy in the choice of medications for the treatment of pediatric and adult ADHD. 

Andrew J. Cutler, MD, SUNY Upstate Medical University

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