Over the long haul, skill building; finding the right school or job; finding the right teacher, mentor, or mate; and developing what we call a life rife with positive connections to people, activities, and purpose matter the most, but in the short term nothing gives you the bang for your buck that medication can. Indeed, as long as medications are prescribed and taken properly, they afford by far the most immediate (in some cases within an hour of taking them) and effective benefit of any treatment there is; they are a hugely valuable tool in our therapeutic toolbox.
Whether to prescribe a medication (on the doctor’s part) and whether to take one (on the patient’s part) ought to be based on empirical studies, not on faith or the Internet or a gut feeling. Sure, base the decision on what you hope for, but also on clear evidence you can see. To that end, when one of us prescribes a medication to help a patient with ADHD, we do so as an act of science, a decision rooted in our reading of carefully conducted randomized controlled trials and with confidence that the efficacy of the medication is not in doubt. In 2018, a large study of studies, compiled by Dr. Samuele Cortese from the University of Southampton in the UK, looked at 133 randomized research papers on the effects of medication on ADHD. The results were conclusive that medication for ADHD is effective, not 100 percent of the time, of course (no medication works 100 percent of the time), but on average from 70 to 80 percent of the time.
People who disparage the use of medication or slander those of us who prescribe it have probably never heard the stories of abject human suffering in people of all ages that we hear every day, either in person or from people writing to us from around the world. Nor have they heard a mother or a newly treated adult cry over the amazing benefits the medication has led to in just a matter of days, ending years of needless suffering. To deplore the use of a tool that can not only relieve suffering but actually turn it into success, health, and joy, well, that’s just plain ignorant, as well as cruel to the people whom it scares away from ever trying medication.
Surprisingly, many who warn against ADHD medications—or who are afraid to start one—might be unknowingly self-medicating through a stimulant like caffeine—in their daily coffee order, or in any of the energy drinks on the market (Red Bull, 5-hour Energy, Monster Energy drinks, and others). Many other softly packaged over-the-counter “drugs” (Adrafinil and ginkgo biloba supplements are popular “study drugs”) are used by teens and adults to boost mood, arousal, and cognition. Unlike doctor-prescribed stimulants, these over-the-counter products are not controlled and can have various side effects, and any positive effects are often unsustainable.
Even with assurances that it is powerful and safe, whether to put a child on a medication, or to go on one yourself, is a big, often agonizing decision that impacts the entire family. Which leads to another common question: “Could we try a non-pharmaceutical treatment first and then try medication if the other doesn’t work?” In other words, when is the right time to try medication?
As you saw from our coverage of cerebellar stimulation techniques in chapter 3, we certainly do recognize the distinct merit of non-pharmaceutical treatment, even if the results will not be as immediately seen or felt. But from a strictly pharmacological standpoint, this strategy is sort of like saying “Let’s try a year of squinting before we try eyeglasses.”
That said, we also feel strongly that no one should take a medication, or ask their child to, unless they want to take it. Indeed, any medication works better if you want to take it. This is because of the placebo effect, a proven phenomenon that draws upon your mind’s ability to enhance the efficacy of any intervention, from medication to surgery to acupuncture to exercise to contact lenses to the next meal you eat.
Before you dismiss the placebo effect—or dismiss how you should factor it into your decision about whether to take a medication for ADHD—consider how much better you do on a job you want, or even at a job interview for a job you want; consider how much better care you take of something—a dog, a car, a boat, a house—if you really wanted it; consider how much more you like your meal if you have been looking forward to trying the restaurant in which it is served, or how much more you like the movie if you picked it out, or how much more you like the president if you voted for him or her, or your boss if he or she hired you (or your employee if you did the hiring!).
Not to belabor the obvious, but this is a point most people overlook. It’s really a fundamental principle of a happy and successful life. We do better when we are involved with activities and people we want to be involved with. We do worse, far worse, when forced or coerced. Like doing the right thing for the wrong reason, even the best medication will not work as well as it could if you do not want to take it. So wait as long as it takes for you or your child not only to get comfortable but to want to take medication before you start it.
A man we’ll call Dan approached Dr. Ratey after a speech on ADHD he gave in California. Dan explained that his nine-year-old grandson, Steven, had just been diagnosed as having ADHD. Steven was having frequent outbursts at home; he couldn’t seem to settle down at the dinner table or focus on his homework at night. He was failing in school, had already been held back a year, and was unpopular with kids in the classroom. Dan seemed confident in the clinical diagnosis, but he was also concerned that Steven’s parents didn’t seem to put limits on him. In addition, they were resisting Steven’s doctor’s recommendation to start medication. They feared that it might damage Steven in some way, in addition to further stigmatizing him, setting him apart as having a disorder. What, Dan asked, should I tell them?
A few things stood out in this all-too-common story. First, as Dr. Ratey explained to Dan, setting control and limits is essential by age nine. An adult can more easily create coping and organization mechanisms, hire a coach, and recognize the problems and talk to a therapist. A child with ADHD needs to learn boundaries with the help of a parent. Dr. Ratey also explained that given his symptoms and behaviors, it was that much more important for Steven to get outside to play and exercise. He also explained that good habits around sleep, eating, and screen time were going to be essential for Steven.
On the all-important question of medication, Dr. Ratey suggested that Steven’s parents be encouraged to do a serious risk/benefit analysis. Whether just in casual conversation or more formally by making a pro/con chart together, they needed to consider how ADHD was affecting Steven’s life scholastically, socially, and emotionally. Was Steven at risk of developing a self-image as a failure? Had he already done so? Was his inability to put on the brakes impacting his socialization and efforts to make friends? Did they see other ways to reverse the downward academic trajectory Steven was on, and quickly?
When making your own risk/benefit assessment, we encourage you to answer three important questions:
In addition to consulting my healthcare provider, have I learned as much as I can about this disorder from reputable sources?
Am I doing everything I can in terms of non-medical treatments (e.g., connecting, building structure into my day, getting exercise and quality sleep, eating well, meditating, and other beneficial habits)?
How much is this disorder negatively impacting my life or the life of a loved one?
If the answers to these questions convince you to go the route of medication for yourself or your child, you need to understand the pharmaceutical options. When we first entered the field, the choices were limited. Now they are many: stimulants, stimulant-like drugs, and what we call outlier medications, which include long-acting versions of the others. What follows in this chapter is explanation and commentary on each of these categories.
When it comes to ADHD medication, the important thing to remember is that there is no one-size-fits-all approach. The advice of Paul Wender—who was a professor at the University of Utah Medical School and someone we think of as the father of biological psychiatry—is apt here: “Some drugs work in some people, at some dose, some of the time.”
The key is to be patient with your healthcare provider until you come up with a formula that works. This might entail multiple tries with multiple drugs, and as we do with our patients, combining different drugs at different times. Keep close tabs on any side effects, duration and peak of efficacy, and any shifts in impact, both positive and negative. The more your doctor knows, the easier it is to tailor an effective treatment plan.
Stimulants are the ADHD drug of choice. They have been shown to be the most effective with the fewest side effects; the 70 to 80 percent efficacy rate mentioned above is attributable mostly to the use and study of this category of medications. As with many prescription medications, there is some concern—some of it valid—about becoming addicted to stimulants and/or abusing them, though the issue is rather rare. We will get into these concerns briefly below.
Stimulants can be divided into two main categories: methylphenidate type, commonly packaged as Concerta, Ritalin, Focalin, Metadate, Quillivant, and OROS-MPH), and amphetamine type, which you might recognize as Adderall, Dexedrine, Evekeo, Vyvanse, and Mydayis.
It may seem counterintuitive to use something classified as a stimulant for a brain that already seems in hyperdrive, but that logic discounts the fact that stimulants actually raise the levels of dopamine and norepinephrine—two neurotransmitters that are off-kilter in the ADHD brain. You might say that stimulants stimulate the brain’s brakes, thus giving you more control.
An increase in dopamine helps our nerve cells pass on information more “cleanly” from one to another. It helps to reduce the noise, quiet the chatterbox, and tune your brain to the right channel. If the signals aren’t clear, it’s easy to fall into confusion and anxiety.
Dopamine also increases our motivation. A 2020 study by the Brown University psychologist Andrew Westbrook and colleagues showed that kind of result, which many people report while taking a methylphenidate medication: an increase in the amount of available dopamine in a region deep in the brain involved in motivation (the caudate nucleus) and thus, as a practical matter measured in the study, a desire to tackle a difficult task. Those who were not taking a methylphenidate opted for an easier task.
There are non-pharmaceutical ways to increase dopamine—some healthy, like exercise and engaging your creativity and being connected to others or to a higher goal, and some counterproductive, like bingeing on carbs; using drugs like alcohol, cocaine, marijuana, and Xanax; or engaging in compulsive activities like gambling, shopping, sex, or workaholism. Failing to master the adaptive pursuit of dopamine leads to addictions of all kinds, but mastering it leads to success and joy.
By increasing norepinephrine (NEP) we increase arousal, making us more awake. This improves our ability to take in information from the environment, meaning that our senses are more attuned. We are better able to “read the room” and our audio and visual understanding is clearer.
Both dopamine and NEP stimulate our executive functioning, controlled by the prefrontal cortex (known as the CEO of the brain). This is where planning, sorting, sequencing what’s important, helping with memory, and evaluating consequences are housed. The executive function helps us to put the brakes on: stopping inappropriate responses, impulsive actions, and getting lured into the next internal or external stimulation.
When it comes to the two types of stimulants, the difference is this: methylphenidate type drugs (like Ritalin) raise dopamine levels a little higher than NEP. In the amphetamine type drugs (like Adderall), it’s the reverse. Amphetamine drugs have a greater effect on NEP than on dopamine, though also only by a small amount.
Researchers have also found a small divide in the efficacy of these classifications of drugs based on a person’s age. For kids and teens, methylphenidates were found to be slightly more effective; when it comes to adults, amphetamines got the best results by a hair. Just about all the drugs tested were less well tolerated than placebos, but this is to be expected.
As the name would imply, stimulant-like drugs act like stimulants in that they raise the levels of dopamine and norepinephrine, but they act on those systems in very different ways. Marketed as Wellbutrin, Strattera, and Norpramin, these drugs were developed as antidepressants but soon found their niche in the ADHD world. Longer-acting than stimulants, they can be used morning or night. With no abuse potential, they are a good option for those at risk for substance abuse. They are also an alternative to try for those who have side effects with stimulants. When they work, as they do for a certain segment of the ADHD population (which we cannot predict in advance), they can work beautifully. The downside is that, clinically, they have been shown not to be as effective as the stimulants for most people. Also, these drugs are slower-acting and may take a number of weeks to reach peak efficacy, in addition to having some common side effects like insomnia, agitation, dry mouth, nausea, headache, constipation, and, in the case of Norpramin, cardiac arrhythmias.
Another stimulant-like drug, modafinil (brand name Provigil), works by stimulating both the histamine network and dopamine, which makes us awake and attentive. Originally designed for narcolepsy, and popular with shift workers like night nurses and pilots, it also has benefits for some with ADHD. The pluses include working very smoothly for eight to twelve hours and having minimal side effects. It’s not FDA-approved for ADHD use, so getting insurance approval can be tough, and some who take modafinil do experience anxiety and sleeplessness.
Originally released in 1966 as an antiviral agent, Amantadine is another stimulant-like medication worth mentioning. It was also originally used to help with Parkinson’s symptoms like tremors, stiffness, and attention difficulties. Amantadine has an effect on the dopamine system; it acts weakly like a dopamine surrogate. It also stimulates another neurotransmitter that assists in increasing the actual concentration of dopamine. It has recently been used to treat attention difficulties in Alzheimer’s, in head trauma, and in ADHD with some positive effect. While not yet FDA-approved for ADHD, it is being investigated with an eye toward full approval. The positives of Amantadine include a smooth effect that can last for up to twenty-four hours, with few side effects. It is not addictive and not a controlled substance, which means it can be prescribed with refills.
There are a number of drugs that don’t fit neatly into the stimulant or stimulant-like category. We call these the outliers. Included in the outlier list are clonidine and its sister drug, guanfacine, which is sold and promoted in its long-acting form as Intuniv. These are both old blood pressure medicines that are extremely useful alone or in combination with stimulants. Their major effect is to calm agitation, aggression, and emotional hypersensitivity, along with assisting with focus and attention.
One of the reasons these outlier drugs are gaining in importance is because of a newly understood disorder called rejection-sensitive dysphoria, or RSD. This is extreme emotional pain triggered by the perception, real or imagined, that a person has been rejected, ridiculed, or criticized by important people in their life. RSD may also be triggered by a sense of falling short, such as failing to meet their own high standards or the expectations of others.
Rejection sensitivity is often a part of ADHD. As discussed in chapter 1, those with ADHD have a tendency to dwell on the “slights” of normal life and amplify their effect. Often, a person with RSD and ADHD is hypervigilant, trying at all costs to diminish these feelings. This can lead to misreading the cues of others, or withdrawing from their lives to avoid the anticipated slights. RSD can also lead to aggressive outbursts and temper tantrums as a person attempts to fight back against imagined threats.
William Dodson, a wonderful psychiatrist who is leading the way in helping us understand the prevalence of this disorder, says that just knowing there is a name for this feeling comforts patients. Whether it is isolated RSD or RSD that coexists with ADHD, it makes a difference to people to realize they are not alone. By naming it, they can actively attempt to tame it, staving off the downward spiral to despair. For those who are deeply affected by RSD, about one in three people feel relief from this despair with a combination of clonidine and guanfacine. While there is no risk of abuse with these medications, they can cause a patient’s blood pressure to drop significantly. And stopping the regime should be done slowly, as otherwise it can cause a significant rise in blood pressure and pulse.
It’s been more than four decades since we entered the field, and while there haven’t been many seismic shifts in ADHD medication in the ensuing years, one game changer has been the concept of “long-acting” stimulants. Our ADHD drugs used to work an average of four hours. Now long-acting versions can help patients remain relatively symptom-free for up to twelve hours. One 2006 study showed that while 40 to 50 percent of those on short-acting medication were satisfied with their treatment, the numbers bump up to 70 percent for those taking the long-acting drugs. As a bonus, those of us with ADHD have a tough time remembering to take pills multiple times a day, so it’s easy to see why long-acting stimulants have quickly become the standard of care.
One uniquely different, relatively new long-acting drug on the market is Vyvanse. Approved in 2008, it is a stimulant that cannot be abused (i.e., snorted or injected). Its delivery system is different in that it is activated by an enzyme in the red blood cells in the gut. Because of this unique delivery system, it also lasts longer. While it advertises twelve to sixteen hours of efficacy, it averages being effective in a concentrated way for about ten hours. It’s become one of the most popular drugs on the market because of its long-acting properties and because it is completely soluble, so it’s easy to administer in beverage form to kids who don’t like to take pills. It can be taken with or without food, giving parents options.
An even newer drug touting a long-acting and novel delivery system has the catchy name of Mydayis. Launched in 2017, this pill boasts a sixteen-hour cycle activated within your body in three steps—morning, noon, and evening.
Long-acting drugs are extremely popular, but when first trying medication it is advisable to use the short-acting stimulants until it can be determined that the drug can be well tolerated.
Spoiler alert! Taking a stimulant or stimulant-like drug early in life helps prevent, not promote, addiction later on. Since 80 percent of addictions get started between the ages of thirteen and twenty-three, and since people with ADHD are far more prone to develop an addiction than the general population, and since taking stimulant medication reduces the risk of addiction later on, it makes a lot of sense to start a child on stimulant medication before age thirteen.
Addiction and abuse are understandably some of the main concerns cited by those reluctant to take an ADHD drug, and the concerns are valid. In fact, ADHD drugs are listed among the top drugs abused by high school and college students. It’s important to note, though, that ADHD stimulant drugs are mainly used inappropriately by those not even diagnosed with ADHD. These “neurotypical” abusers use them to stay up to study, or mix them with other drugs of abuse, like alcohol and marijuana, to intensify the high, among other reasons only teenagers can come up with.
It is less common for those who have ADHD to purposely take far too much of a stimulant medication. Long-term studies found that those with ADHD who are successfully treated with stimulants become addicted to substances far less than the general population, and certainly less than the population who have ADHD and do not take stimulant medication.
On the flip side, teens who have ADHD and are not treated are five to ten times more likely to become addicted to substances. It is a myth that people come to psychiatrists to get the highest dose and greatest number of pills. Indeed, one of the biggest problems we encounter is that patients do not take the total prescribed dosage for the month. The tough part is keeping them on the medicine, not making sure they aren’t angling for an overabundance of extra-strength medication. That being said, when people do go off stimulant medication, they can experience slight symptoms of withdrawal. This happens every evening, and the symptoms can be so mild as to be missed, or can lead to increasing tiredness, anxiety, aggression, or a variety of other presentations. Which leads us to a discussion of common side effects.
Some of the most frequent side effects associated with ADHD medications are irritability, dry mouth, disruption of sleep, headaches, and a decrease in appetite. There can be an increase in heart rate and blood pressure over time (which are minimal), so some worry about how it will impact the heart in the long term. Recent studies have shown the effects are slim to none, but there are always warnings when taking medication. This is why it is extremely important to be closely monitored by your doctor when on a prescription, especially in the beginning stages.
Last but not least, there is a happy byproduct of treating ADHD with prescription medication: Proper diagnosis and treatment can not only help your ADHD but also be protective against secondary problems like anxiety and/or depression.
The treatment of cancer gained spectacular results from studying patients’ genes, from discovering biomarkers for various forms of cancer, and from planning treatment based upon a patient’s genetic profile. Naturally, researchers started to look at genetic testing for diseases of the mind and the field of psychiatry. Indeed, for some time now, clinicians like us have been able to submit a sample of a patient’s DNA—derived from saliva, blood, skin, or even hair—to a company that will assay the sample and provide a genetic analysis.
Patients and clinicians alike hoped that such an analysis could tell us what drug or medication to use. But in talking to the best experts we know, the verdict has consistently been “It’s promising, but we’re not there yet.” So we do not routinely get genetic testing on our patients to guide our choice of medication unless the patient insists upon it. It certainly does no harm, other than that it can cost anywhere up to $2,000, depending on the test, the company, and the extent of one’s health insurance coverage.
These tests will not tell you or your doctor exactly which drug will work best. This is the “there” we’re not yet at, as much as we all would like to be. But these genetic tests can provide extremely valuable information on how rapidly you will metabolize a certain medication, which can help tremendously in dosing and in some cases prevent a disaster—if you lack a certain enzyme, for example.
We found one company we really like, called Tempus,*2 based in Chicago. The man who founded it in 2015 did so because he was appalled at the lack of genetic data that doctors could draw upon to develop a treatment plan for his wife’s cancer. So he set about building his own company to change that situation.
But then, in 2018, Tempus started looking into psychiatry as well as cancer testing. Most companies offer what’s called “small panel sequencing,” reporting on twelve to fifteen genes and correlating them with medications that might be prescribed.
Tempus stands out from the crowd because it uses what’s called “whole exome sequencing.” A strand of DNA contains exons, which are the coding sites—the sites that dictate the action—as well as introns, whose function is debated. Right now the intron seems to be a spectator to the action, but nature rarely creates spectators, so some essential function will likely be found. But we know for sure the exons matter a lot. Taken together, the exons form an exome.
Whole exome testing is important because in compiling it (coupled with the patient’s personal history and family history, which Tempus also collects) biomarkers can appear in what at first seems like a vast field of irrelevant data. So Tempus wants to collect and test for the whole shebang.
By doing whole exome sequencing rather than the more common small panel sequencing, Tempus is not only laying a foundation for new discoveries, but also giving the patient and the doctor more information to work with.
You’d think that since you’re getting more information, the cost would reflect that. Not so. Tempus seeks reimbursement from insurance companies for their test and has a robust financial assistance program to avoid undue financial burden on the patient. The majority of applicants qualify for a maximum out-of-pocket cost of no more than $100 for the test. So when the maximum you might pay is $100, with zero dollars being a distinct possibility, the risk of financial harm previously associated with testing is eliminated for many patients.
It seems to us that the time has come to at least consider using genetic testing routinely in prescribing medications.
For a more complete rundown of stimulants and non-stimulants and outliers used to treat ADHD, we’ve included this helpful chart, originally printed in, and reprinted with the permission of, ADDitude magazine, a helpful resource for both clinicians and patients.