There are several types of attention deficit hyperactivity disorder, or ADHD. According to the DSM-5 [Diagnostic and Statistical Manual of Mental Disorders, 5th edition] criteria, there are 2 categories of symptoms that we look at. The 2 categories are inattention and hyperactivity/impulsivity. There are 9 symptoms in each of these categories.

If you are a child under age 17, you need to have at least 6 of 9 symptoms from 1 or both categories to meet the criteria for diagnosis. If you’re an adult, aged 17 and above, the threshold drops to needing to meet only 5 of the criteria for 1 or both categories. The type of ADHD depends on whether you meet the criteria for 1 or both categories of symptoms.

In DSM-5, instead of calling it types of ADHD they changed it to presentations of ADHD. The most common presentation is called the combined presentation, and that would be somebody meeting the threshold of 5 or 6 symptoms from both of those categories. The next most common presentation is called the predominately inattentive presentation, and that would be somebody with 5 or 6 symptoms from only the inattentive cluster of symptoms, not the hyperactive/impulsive group. The reason it’s called predominately inattentive rather than just inattentive is because you can have some of the hyperactive impulsive symptoms but not enough to meet the threshold criteria. The least common presentation is called predominantly hyperactive/impulsive presentation, and that is seen in less than 5% of patients.

There is 1 other category of ADHD, unspecified ADHD. That includes someone who you really think has ADHD. This type of patient meets several of the criteria required, but they don’t quite meet full criteria across all the categories.

Based on my clinical experience, ADHD is not a uniform disorder. It has many clinical presentations. It’s a very heterogeneous disorder clinically, as far as the way it presents—the pattern of symptoms. We already talked about the different presentations, such as combined or predominantly inattentive or predominately hyperactive/impulsive. Also, it’s heterogeneous in regard to the various comorbidities or associated conditions that can be seen. It varies from individual to individual. This is why a skilled clinician really needs to keep an eye out for this and be aware of the various presentations clinically, as well as the various associated conditions and comorbidities.

It’s very important to realize that ADHD, probably neurobiologically, is a heterogeneous disorder, and that may underlie some of the variability in the way it presents clinically.

Talking about the prevalence and the impact of ADHD, the clinical burden, it does differ between children and adults. Various epidemiological studies have been done estimating the prevalence of ADHD in the United States and around the world. In the United States, a 2016 survey showed that approximately 9% of children had been diagnosed with ADHD. A survey called the National Comorbidity Survey Replication looked at the incidence of ADHD in adults and found the rate to be approximately 4.4%.

This is a neurobiological disorder that starts in childhood. We don’t think you actually outgrow this disorder. We think you might outgrow the symptomatic criteria or the diagnosis but not the disorder, and this is because as our brains age and mature, the symptoms can change and mature. For instance, the hyperactive/impulsive symptoms become less prominent and may occur internally—someone is more restless rather than overtly hyperactive. Also, adults learn coping strategies that make the symptoms less prominent and less impairing.

As far as the clinical burden, we know that ADHD has a significant impact on all phases of a person’s life, including school, work, home function, and social relationships. We know that ADHD can be associated with significant underachievement, behavioral problems in childhood, various comorbidities in adulthood, marital and relationship problems, financial difficulties, and even things such as driving—more speeding tickets and accidents. It can be associated with medical conditions in adulthood as well. There is a significant clinical burden across all phases of a patient’s life. This speaks to the urgency or the importance of doing a careful assessment for all the different conditions and instituting an individualized treatment plan.

Overview of ADHD 

 Many factors predispose children and adults to ADHD [attention-deficit/hyperactivity disorder]. No doubt, the No. 1 factor appears to be genetics. In fact, ADHD is probably the single most genetic neuropsychiatric disorder my colleagues and I take care of. Depending on the study reporting on the disease’s prevalence, the risk is anywhere between 70% and 78%. That’s a great deal of inheritance, and it affects men and women.

But there are other factors. For example, a deprivation environment in childhood can be a risk factor. Maternal cigarette smoking is a risk factor. Nutrition can be a risk factor.

In terms of adult ADHD, this is not an event that all of a sudden magically appears in adulthood. The onset of ADHD symptoms occur before age 12, and the majority of adults we see are ones who’ve had ADHD all their lives but are just being diagnosed.

In terms of ADHD and quality of life, it is very clear that the disorder is not just a collection of symptoms. It profoundly impacts quality of life in a variety of ways.

Let’s look at someone who is 9 years old. In fact, the last patient I saw, a 9-year-old boy, is affected. But how? His quality of life is impacted at school academically. He’s 9, but he’s already had loss of self-esteem, self-confidence. He wants to drop out of school permanently. He’s 9 years old. That’s a major impact on quality of life. His friends shun him because of his hyperactivity and impulsivity. You can imagine at any age social connectivity is important, but ADHD that has not been treated well took that away from him.

On top of that, he has an older sister whose patience with him has worn thin. His parents—he, by the way, has wonderful parents—are very tired. This is a clear demonstration of how ADHD, even though it’s a symptomatic disorder, can affect quality of life. I’ve seen the same thing with adult ADHD. Work suffers. Marriages suffer. Parent-child relationships can suffer. Self-esteem suffers. Wellness suffers. Social interaction suffers. As far as the eye can see, in most of my patients with ADHD, no matter what their age might be, quality of life takes a rather large hit.

Impact of ADHD on Quality of Life 

There have been some recent updates to the guidelines for the assessment, evaluation, and treatment of attention-deficit/hyperactivity disorder [ADHD] in children and adolescents. The 2 main organizations that have published these guidelines are the American Academy of Pediatrics and the Society for Developmental and Behavioral Pediatrics [SDBP], which specialize in behavioral disorders in children.

In 2019, the American Academy of Pediatrics updated its guidelines. This was an update from the previous guidelines published in 2011. Since then, of course, the DSM-5 [Diagnostic and Statistical Manual of Mental Disorders, 5th edition] criteria have been published. So they were updated to reflect the DSM-5 criteria. Many treatment recommendations stayed the same, including instituting a multimodal treatment plan with stimulants as first-line treatment. However, what was introduced was a new key action statement recognizing the importance of comorbidity and associated conditions.

What the key action statement refers to is, if the primary care provider is trained or experienced in diagnosing comorbid conditions, he or she may initiate treatment of such conditions or may make referral to an appropriate subspecialist. Also, after detecting possible comorbid conditions, if the primary care provider is not trained or experienced or comfortable making the diagnosis or initiating treatment, then the patient, of course, should be referred to an appropriate subspecialist.

The effect of comorbid conditions on ADHD is described as being variable, and the treatment of ADHD may resolve or improve the comorbid condition. They specifically mention, for instance, coexisting aggression, oppositional defiant disorder, depression, or anxiety. The comorbid condition, however, may require treatment, in addition to ADHD treatment.

The Society for Developmental and Behavioral Pediatrics Clinical Practice Guideline was published recently, in 2020. This recognizes the importance of diagnosing and treating comorbidities.

The SDBP guideline refers to this as complex ADHD. What they specify is the clinician, with specialized training or expertise, should initiate a comprehensive assessment and develop an interprofessional multimodal treatment plan for any child or adolescent with suspected or diagnosed complex ADHD upon referral from a primary care clinician. Treatment of complex ADHD should include evidence-based approaches that address ADHD and account for coexisting conditions, while respecting family background and preferences and cultural issues.

They define complex ADHD as including comorbid conditions, but also other complicating factors: moderate to severe functional impairment, diagnostic uncertainty on the part of the clinician, inadequate response to treatment, or uncertainty about treatment planning. Also, ages less than 4 years old or greater than 12 years old at initial presentation of symptoms.

These guideline updates are very helpful and important for clinicians. They raise consciousness on the importance of looking at the whole clinical picture of patients with ADHD. The majority of patients with ADHD have at least 1 comorbid condition. As a matter of fact, only 25% of patients with ADHD have just ADHD, or simple ADHD.

Updates in Diagnostic and Treatment Guidelines for ADHD 

There are certain signs and symptoms that should prompt us to think about ADHD [attention-deficit/hyperactivity disorder], and to think about proactively including it or excluding it. Some of the things I will share with you are not age sensitive. It doesn’t matter how old the person is. If we hear about those symptoms, we must screen for ADHD. We must do so because ADHD, in many ways, is a low-hanging fruit. It’s a very treatable condition, so to not diagnose it becomes a significant error.

For example, if I hear from an individual or their parents or their social system around them report that they’re having a lot of trouble paying attention, particularly to things they don’t want to do but need to do, this would prompt me to conduct an evaluation. If I start hearing a lot about distractibility, or if I hear a lot about forgetfulness—repeat, repeat, repeat, repeat—when that happens, it prompts me to do an evaluation.

Also, hyperactivity. You might say that’s a childhood problem. No. Adolescence can express it by jumping from task to task. Adults can express it by being unable to sit still in meetings, at church activities, or even during conversations with their spouses. All those symptoms should prompt us to look for ADHD. It’s not to say that any of them is diagnostic by itself. That, of course, requires a full evaluation. But they should serve as red flags so we don’t miss this important diagnosis. 

As far as using tools to diagnose ADHD, it’s always better to start with the screening process. If I conducted a full evaluation for ADHD in every person I see, even though that may sound like an ideal way to go, it will not amount to very much. It’s simply not doable. I suggest the following: a 2-tiered approach. No. 1 is to screen the patient. I’ll tell you more about that in a second. No. 2 in this tiered system is, if the screen is positive, then we can confirm it with the gold standard way to do so.

Let’s first talk about the screening approach. One of my favorite instruments is the ADHD rating scale, although you’re welcome to use the ASRS [Adult ADHD Self-Report Scale] in your adult patients. You can use the Conners Comprehensive Behavior Rating Scale for children, adolescents, or adults, and there’s a host of screening instruments available. Which option you choose isn’t that important, as long as you choose 1 and use it. It’s called screening for a reason. It’s supposed to be given to a lot of people.

If it indicates a potential positivity, then the gold standard tool to use would be the DSM-5 [Diagnostic and Statistical Manual of Mental Disorders, 5th edition] criteria, which by the way, all of us can and should use—psychiatry, child psychiatry, pediatrics, family practice, MDs, NPs [nurse practitioners], PAs [physician assistants], whomever. Nonprescribers? Absolutely. You have an equal responsibility to identify the condition.

The DSM-5 criteria are very elegant. They include a list of 9 symptoms from inattention and 9 from hyperactivity/impulsivity. Once we have at least a certain number from either, then we move on to the next criterion, which is to start having symptoms before age 12. Not a diagnosis, but start having symptoms before age 12. We can then move on to making sure it causes impairment in at least 2 settings. Then we make sure no other condition is fully explaining the patient’s symptoms. When those criteria are met, you can take it to the bank. You can take it to the bank that you have a rock-solid, scientifically valid diagnosis of ADHD, irrespective of the person’s age. That often is the beginning of a wonderful journey for the patient and their family.

 In my experience, a large percentage of adults who I diagnose with ADHD were not diagnosed during childhood. There are not good statistics on this, however. It’s a little difficult to study. There are many reasons for this. Maybe there were attitudes against the diagnosis of ADHD by parents or others around the child, around the adult. Or maybe the person was able to compensate and cope and made it through somehow. Maybe there was some underachievement. Then in adulthood, various stressors and strains and demands can bring out the symptoms or make them more problematic.

As I mentioned earlier, we know that at least 9% of children have been diagnosed with ADHD, so we think that the incidence is in that range—the 8% to 10% range. We think the incidence of actually meeting the criteria for the diagnosis is about 4.4%, or about half in adults. A lot of adults don’t meet the criteria for the diagnosis anymore, but this is a genetic neurobiological disorder. Think of it like a wiring problem in the brain. There’s no other example in clinical medicine of you outgrowing such a disorder, but as I mentioned, you may outgrow the diagnosis.

It’s also very important to realize that the DSM-5 criteria require that symptoms started before age 12. If somebody presents and says to you that their symptoms started recently or only during adulthood, that should prompt you to look for other possible conditions that could cause symptoms that resemble ADHD.

However, what is probably most commonly going on is that the symptoms were not recognized. Or maybe it’s hard for the person to remember when they were in elementary school. Or maybe there were various compensation strategies that were able to be employed during the school years when there was more structure that have not been present as the person moved into adulthood.

Diagnosis and Testing for ADHD 

There are various comorbid conditions that can complicate the diagnosis and treatment of ADHD [attention-deficit/hyperactivity disorder]. These differ from childhood to adulthood. 

During childhood, the most common comorbid conditions include emotional behavioral dysregulation, for which the diagnoses that accompany that are oppositional defiant disorder and conduct disorder. Then we also have anxiety and depression, which are less common in childhood but start to become more prominent during adolescence and adulthood. You can see things like tic disorders, and learning disabilities and learning disorders are often seen in childhood ADHD.

As we move into adolescence and adulthood, we still have some behavioral issues. However, these issues become more prominent as anxiety and depression. We think up to half of adults with ADHD have anxiety, and about 40% to half of adults will have comorbid depression. This is often how they present to clinicians—with treatment-resistant anxiety and depression. That’s the tip of the iceberg, and then the ADHD is subsequently recognized.

What also comes into the picture is substance abuse, which is a common comorbid condition. Then there are medical conditions such as sexually transmitted diseases, unwanted pregnancies, and cardiovascular disease. There’s an association of smoking with ADHD. Also, ADHD is associated with traffic accidents and driving problems. These are some of the common comorbidities that can be seen.

I failed to mention bipolar disorder as a common comorbidity. It’s been estimated that anywhere from 15% to 40% of patients with ADHD will also meet criteria for bipolar disorder.

 Based on my clinical experience, there are many unmet needs in the world of ADHD in children, adolescents, and adults. Perhaps I can highlight for you 4 that I run into repeatedly. First, ADHD and sometimes the treatment of ADHD can have a rather negative impact on sleep. Sleep architecture is often abnormal to begin with. Undoubtedly, many individuals with ADHD have trouble falling asleep.

Second, not everybody gets adequate, full, and necessary coverage of symptoms. That doesn’t happen. That does happen for a fairly large number of people, but I would not say it happens for everybody. So that’s an unmet need.

Third is rebounding of symptoms. By that I mean things are quite well for a certain number of hours, but once the medication fades out, instead of coming back to baseline gently, some individuals actually go above baseline in terms of their difficulties. They are often very irritable, moody, and dysphoric. That’s a rebound. That’s an unmet need.

Then with some medications we have challenges with rather slow onset of action. It may take sometimes weeks while you are engaging in the medication for it to produce full results. Those are the 4 current and often-encountered unmet needs in the world of ADHD treatment.

Unmet Needs in ADHD 

 There are various nonpharmacological treatments that have been documented to have efficacy in the treatment and management of ADHD [attention-deficit/hyperactivity disorder]. Cognitive behavioral therapy [CBT] is 1 of the most extensively studied and has some of the best evidence for efficacy. Cognitive behavioral therapy—a lot of the work has been done on this at Massachusetts General Hospital at Harvard Medical School—includes various manuals and videos to help with training and to help with the administration of CBT. I’ve even seen some CBT programs online that allow someone to participate in individually.

Basically, this involves psychoeducation and training in concrete skills such as organization and planning. There is an emphasis on practice and maintenance of strategies. CBT can be delivered either with or without medication. It has been shown to be effective in either situation. There are certainly many patients for whom medication is contraindicated or who you’re treating with medicine and there are still residual symptoms and impairments.

CBT has been best studied in adults. CBT has been shown to improve not only self-ratings of the symptoms of the illness but also clinician-administered ratings, not only for the core symptoms of ADHD but also for associated anxiety and depression. As we mentioned, these are common comorbidities associated with ADHD. CBT has the best evidence for use, but there’s also evidence for other modalities including group therapy, mindfulness and relaxation, and coaching. 

There is another nonpharmacological intervention that has an extensive and growing database with very convincing evidence for efficacy, and that’s exercise. Exercise has been shown to improve not only the core symptoms of ADHD but also executive function, which can often be a problem. That includes organization and planning. Also, there is good evidence that this can improve depression, anxiety, and a sense of well-being. This has been demonstrated not only in adults but also in children. This is a modality that I recommend for all patients with ADHD. 

Biologically, we think exercise increases blood flow to various parts of the brain, so it makes the blood flow and probably makes the function of various parts of the brain more efficient. It also increases levels of dopamine and norepinephrine in the brain. That’s interesting because we know there are abnormalities of dopamine and norepinephrine neurotransmission and we know there are effective approved medications to treat ADHD, increasing norepinephrine and dopamine. We also believe exercise can improve neuroplasticity, which means neurogenesis, growth factors, synaptogenesis, the connections between nerve cells, and things like that.

We also have evidence that exercise can improve functioning in certain key areas of the brain that are related to ADHD, including the prefrontal cortex, the basal ganglia, or striatum, the cerebellum, as well as the amygdalae. Exercise is a very low-tech, very easy-to-implement strategy that I recommend for all patients. It doesn’t have to be high-intensity, serious weight lifting. It can be any form of exercise, including walking, dancing, martial arts, sports, and other training. There are various forms of exercise.

Family therapy is another nonpharmacological intervention that has a very good database and is highly recommended as part of the multimodal treatment plan for patients with ADHD and their families. Family therapy is delivered by a therapist, typically as 8 or more sessions, and can be done with 1 family or with groups of parents without the children. Family therapy entails education and structure, working on various problematic behaviors, and teaching coping skills to help decrease the stress involved with having a family member with ADHD. The idea is to build and strengthen positive relationships and to emphasize positive ways of interacting. This can help with arguing, blame, and negative attitudes that are so common in families with ADHD. Also, it provides a safe environment to discuss various problematic and stressful behaviors. It offers practical solutions and a behavior modification plan and focuses not only on positive attitudes but on positive methods of communication and positive ways to reinforce certain behaviors.

The communication can be emphasized as parent to parent, because there’s often very real stress in the parental relationship, and also parent to child. The evidence base, as I mentioned, is very good and certainly can be part of the multimodal treatment plan for ADHD.

Non-Pharmacological Therapy in ADHD 

The classic treatment of ADHD [attention-deficit/hyperactivity disorder] has been pharmacotherapy. That’s appropriate, but it should never be offered in isolation. No matter how old the person is, no matter what subtype of ADHD they might have, it should never be recommended alone. Often, we offer school-based interventions if they’re appropriate, maybe even workplace setting adjustments. But I do think there’s 1 other emerging form of therapy worthy of our thought, and that is coaching. 

Coaching is different from psychotherapy. Coaching is very much goal setting, tracking progress, and encouraging. It doesn’t necessarily follow a CBT [cognitive behavioral therapy] model. It follows much more a model that often works well with individuals with ADHD, particularly those who are adolescents and older. Often, time management is such a big challenge. Coaching can address that. Very often, being late to pay bills or being present at appointments is a problem. Coaching can be very helpful. Shaming or blaming doesn’t go very far.

These are all executive function deficits. Of course, optimized treatment of ADHD does help, but it’s OK to offer additional treatment modalities like coaching to help our patients. I really do hope you will consider that as a valid option for appropriate patients.

The management of ADHD is always a combination of strategies. It could be 2 or more nonpharmacological techniques. It could be a pharmacological intervention with a nonpharmacological intervention. The combination doesn’t matter per se, as long as we never allow ourselves, as clinicians, to be monolithic in our approach, offering just 1 thing at a time. That is not logical. That is not supported by guidelines. That is not supported by the package insert for medications they’re unfamiliar with. They should be used in combination. But why? Because it’s politically correct, or is there evidence 1 plus 1 may actually equal 3 in some patients, metaphorically speaking? 

The evidence is for the full restoration of a person’s functioning and the restoration of their self-confidence. For the reinsertion of optimum functioning in a person’s life, rarely does 1 intervention do it all for most people. Therefore, I recommend a combination approach. It could be something as simple as physical exercise plus school-based interventions and academic adaptation to the child’s needs and a medication. If you remove even 1 of these 3 pillars, things come crashing down. Those 3 options end up supporting one another. It could be sleep hygiene. It could be cognitive behavioral therapy. It could even be family-centric psychotherapy, in which coaching is offered not to the patient—the patient may be too young—but to the parents.

The upshot of my recommendation is to resist the temptation to offer 1 intervention at a time. Resist it. It’s better to think of a multimodal approach for every single patient with ADHD.

Benefits of a Multimodal Treatment Approach to ADHD 

The American Academy of Pediatrics has published treatment guidelines for children and adolescents from the ages of 6 to 18 for ADHD [attention-deficit/hyperactivity disorder]. The class of medications that is recommended as first-line therapy is stimulants. Stimulants have the most extensive and best evidence for efficacy, with some of the highest effect sizes or measures of efficacy of any treatment we have in clinical medicine. The guidelines don’t specify which of the stimulants to start with, and the stimulants are divided into 2 categories. There are methylphenidates and amphetamines.

It’s interesting that there are some patients who preferentially respond to or tolerate 1 of them better than the other. We think as many as 30% of patients will respond better to a methylphenidate or an amphetamine or tolerate 1 better than the other, so it’s important to be comfortable prescribing both of these categories of medication.

There are also some nonstimulant medications that are FDA approved, and the treatment guidelines do recommend FDA-approved medications as first-line treatment. Currently, only 3 nonstimulant medications are FDA approved. One is called atomoxetine, and the other 2 are extended-release versions of alpha-2 agonists. These bind to alpha-2 norepinephrine receptors and stimulate them, whereas atomoxetine is a norepinephrine reuptake inhibitor.

As far as the pros and cons, stimulants are very effective, but there are issues with certain warnings and precautions. For instance, there’s a warning about the potential for abuse and diversion and dependence. There is a warning about cardiovascular risk. There’s a warning about the precipitation of psychosis or mania. There’s a warning about vasoconstriction and Raynaud disease. Also, not everybody can tolerate a stimulant. There are some negative attitudes out there about stimulants, and some people are hesitant to prescribe stimulants. Some people are hesitant to accept a stimulant as a choice for their child.

Also, the problem with stimulants is they only work for a certain portion of the day. When you take them in the morning, there’s a delay until they kick in and start working. Of course, they wear off at some point. They have to wear off at some point. They can’t last around the clock or the child would never sleep. There is a problem with what we call the “bookend” times in the morning and evening.

There are also some practical issues with stimulants, such as prescribing regulations and restrictions that can make it more difficult to prescribe stimulants. We also have to keep track of our records. We often have to check prescribing databases to make sure the patient is not abusing the medication.

As far as the nonstimulants, their efficacy may not be as robust, but when they work, they can certainly work. With atomoxetine there are issues with titration. You have to titrate the medicine, which is slower in onset of efficacy. There are some warnings, particularly around hepatic or liver function. There are some adverse effects that we can see, including things like nausea, fatigue, urinary retention, constipation.

The predominant problem with alpha-2 agonists is sedation, so when used by themselves they can be quite sedating. There’s also a risk of some other adverse effects, but they can be effective, and they do cover more around the clock. They are approved for monotherapy, but I also commonly use them in combination with a stimulant, which is how they’re also FDA approved.

One of the other problems with the nonstimulants, besides the fact that there can be a little lag—you have to titrate them and there’s a little lag in the onset of efficacy—is that you have to be able to swallow a pill, a tablet, or a capsule. There’s not a way to open the package and sprinkle the treatment into a liquid or onto food. There’s not a dissolvable form or a chewable form. That’s certainly an unmet medical need.

As far as efficacy and safety of the various FDA-approved medications to treat ADHD, the best evidence we have for efficacy is with the stimulants. Stimulants have effect sizes in the range of 0.8 to 1.0, which is very high, very strong, and these are some of the highest effect sizes we have in clinical medicine. They work best for some of the core symptoms of ADHD, particularly some of the inattentive symptoms. However, they don’t completely address all the symptoms. They might not always address some of the executive function issues. They may induce anxiety or agitation, and may worsen dysphoria in some patients. There are also adverse effects such as irritability, decreased appetite, and insomnia. Those are some of the most common adverse effects. They may not be tolerated or appropriate for every patient.

As far as the nonstimulants, the effect sizes for the nonstimulants have ranged from about 0.4 to 0.6, which we consider medium-effect sizes. These are certainly very good and effective. What we find, though, is they may not be as universally effective for as many patients. Stimulants seem to work in up to 80% to 90% of patients, whereas nonstimulants may not be quite as effective for as many patients. They also have been shown to work on the core inattentive and hyperactive impulsive symptoms. They may not be as prone to inducing anxiety, agitation, or irritability. They’re less likely to decrease appetite, and they’re less likely to induce insomnia.

FDA-Approved Medications 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.

Approaching ADHD Treatment Selection in Children and Adults 

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.

Emerging Treatments for ADHD 

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.

Addressing Drug Holidays for ADHD Medication

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.

Optimizing Care for ADHD During COVID-19 

Optimal Management of ADHD

Andrew J. Cutler, MD, and Rakesh Jain, MD, MPH, discuss current and emerging therapies for the management of attention deficit hyperactivity disorders (ADHD).

Optimal Management of ADHD

EP 1: Overview of ADHD

EP 2: Impact of ADHD on Quality of Life

EP 3: Updates in Diagnostic and Treatment Guidelines for ADHD

EP 4: Diagnosis and Testing for ADHD

EP 5: Unmet Needs in ADHD

EP 6: Non-Pharmacological Therapy in ADHD

EP 7: Benefits of a Multimodal Treatment Approach to ADHD

EP 8: FDA-Approved Medications for ADHD

EP 9: Approaching ADHD Treatment Selection in Children and Adults

EP 10: Emerging Treatments for ADHD

EP 11: Addressing Drug Holidays for ADHD Medication

EP 12: Optimizing Care for ADHD During COVID-19