What medications are used to treat ADHD?
What are the different kind of medications?
How do ADHD medications work?
ADHD diagnoses are becoming more common for children but especially in the adult population. Research tells us that approximately 70% of people with ADHD benefit from stimulant medication. This means that the number of prescriptions for ADHD medications are higher than ever. What impact do these things have on us and our clients? Check out this episode of All Things Substance.
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You’re listening to the All Things Substance podcast, the place for therapists to hear about substance abuse from a mental health perspective. I’m your host, Betsy Byler and I’m a licensed therapist, clinical supervisor, and a substance abuse counselor. It is my mission to help my fellow therapists gain the skills and competence needed to add substance use to their scope of practice. So join me each week as we talk about All Things Substance.
Welcome back to the All Things Substance podcast. At the end of last month, we finished talking about methamphetamine. Meth is something that I think we hear a ton about and I wanted to make sure that we all had good and basic information about what meth does and how it affects people. I also wanted to make sure that we had a chance to understand why someone would use something that’s so incredibly damaging.
I hope you had a chance to listen to the interview that came out the first week of July of a woman in recovery from meth. She was using meth intravenously for many years and ended up getting into recovery, becoming a lawyer, and then a federal judge. It’s a wonderful and inspiring story.
Very closely linked to meth are ADHD medications. For some that might seem like a bit of a surprise. However, ADHD medications have something in common with methamphetamine. In fact, in the meth episodes, we learned that there is a prescription version of meth, Desyoxen, that has been used to treat ADHD in some cases. It’s not a frontline or even necessarily a second line medication.
In order to start looking at these medications, I want to cover a few things about the history of ADHD and the medications that were used to treat it.
How the ADHD diagnosis became what it is today
The first example of an ADHD type diagnosis was actually found in the writings of Scottish physician Sir Alexander Crighton in 1798. In the second book of a trio he wrote, he talked about attention. He stated “when any object of external sense or a thought occupies the mind in such a degree that the person does not receive a clear perception from any other one, he is said to attend to it”. He goes on to say that distraction isn’t necessarily pathological. The rest of the writings don’t sound very complimentary when it comes to people who struggle with attention.
This was one of the first times that someone started talking about mental disorders as diseases, as opposed to moral failings or criminal thought and behavior. In 1844, a German physician Heinrich Hoffman had a little softer touch and seems like a little better way to describe it. He wrote a book called Fidgety Phil. During this time children’s cautionary books were very popular. And in this book, he talks about Fidgety Phil, who is unable to sit still.
It was an illustrated book that became really popular. And the idea of being a Fidgety Phil sort of like a nervous Nellie became a pretty well-known used metaphor. In the story of Fidgety Phil, there’s a conflict at a family dinner caused by the fidgety behavior of the son. In the story the son’s fidgety behavior ends up with him and the table falling over with all the food. In the beginning of the story the father asks in an earnest tone “Let me see if Phillip can be a little gentleman. Let me see if he is able to sit still for once at the table”. Hoffman depicts Phillip’s motor activity as being excessive enough that “ his chair falls over quite. Phillip screams with all his might, catches at the cloth, but then that makes matters worse again, down upon the ground they fall glasses, bread, knives, forks, and all”.
Later, he also wrote a story that translates to Johnny Look-In The-Air. And the story is of a boy who is looking at the clouds and the birds and all of the other things. For those of us, who’ve worked with ADHD. We’re very familiar with the correlation in the DSM for the symptoms, the inability to sit still, being driven by a motor, attending to things that aren’t where the focus should be, among other things.
Through the 1800’s into the 1900s, there were other physicians and scientists who would write about ADHD and it was called a number of different things. None of them are terribly flattering.
The syndrome that we know as ADHD has been called numerous things over the years, like Brain Injured, Brain Damaged Child, Hyperkinetic Impulse Disorder, Hyperexcitability Syndrome, Clumsy Child Syndrome, Minimal Brain Dysfunction, Organic Brain Disease, Nervous Child, Hyper kinetic Reaction of Childhood, and eventually Attention Deficit Disorder and Attention Deficit Hyperactivity Disorder. The final iteration of those would become ADHD in 1987 where it appeared in the DSM for the first time in the third edition. ADHD, while it was something that was being recognized and was beginning to be treated with medication in many cases, wasn’t recognized until the third edition.
The real shift in thought that seems to have stuck was in 1922 when a leading expert from Britain suggested that the behavior patterns they were seeing might be from specific brain changes rather than a lack of discipline.
When ADHD medications got their start
In 1936, Benzedrine was approved. One of the first instances of an amphetamine being prescribed. In 1937 Benzedrine was being used experimentally with children living in a home. Benzedrine and Dexedrine, both amphetamine class, are the medications that we see reference to until around 1957, when Ritalin enters the stage. Ritalin is a different kind of medication in the methylphenidate class. In 1961, the FDA approved Ritalin for use in children with behavioral problems.
In the early seventies, the idea of using medication for treating ADHD, which was at the time the Hyperkinetic Impulse Disorder in the DSM II, took a serious hit. There was widespread stimulant abuse and the Congress in the United States passed the Comprehensive Drug Abuse Prevention and Control Act, classing amphetamines and methylphenidate as Schedule Three substances, limiting the number of refills a patient can receive and the length an individual prescription can run. Just a year later, they end up moving into a Schedule Two drug placing more restrictions on it.
In 1975, a media campaign portrays stimulants as being dangerous and that ADHD is a “dubious diagnosis”. There were claims that hyperactivity was caused by a diet, not a brain condition. And there’s public backlash against treating ADHD with stimulant medication, especially Ritalin.
In the eighties, we saw the release of the third DSM and the DSM III- R which listed ADHD, as we know it now, and classified the subtypes that were also present in the fourth edition of the DSM. Those subtypes were the impulsive type, inattentive or the combined type.
In the nineties, we saw an increase in ADHD diagnoses. It’s not possible to know if this was a change in the number of children who had the condition or a change in the awareness of the condition. But by 1991, methylphenidate prescriptions, that’s Ritalin, reached 4 million and amphetamine prescriptions reached 1.3 million.
Stimulant medications are the go-to with ADHD treatment. Up until 2002, we didn’t really have a non-stimulant option. 2002 is when Strattera, Atomoxetine, was approved for use with ADHD.
If you look up medications to treat ADHD, you’re going to see a lot. And some of them might be names that you’ve never heard of. However, there are just a few types of medications and a number of different formulas and release schedules. That’s what accounts for all the different names of the different medications, but their base level is going to typically be either amphetamine or methylphenidate.
How ADHD medications work in the brain
So for our purposes, we need to know how these medications function and why they work the way they do. We start with a little brain science. Don’t worry we won’t go too far into it. As we know our brain is made up of nerve cells called neurons. They’re separated by tiny gaps called synapses. All brain and nervous system functions require that the neurons send messages across the synapse to the other neuron in order to get the information relayed and acted upon.
The chemical messengers are called neuro-transmitters. We’re used to hearing about neurotransmitters like norepinephrine, dopamine, and serotonin. There are a number of other ones, but those are the ones that we end up talking about the most. The neuro-transmitter travels across the space between the two neurons and, if accepted, attaches itself to a receptor on the other neuron.
In order for this to work effectively, the message has to get through. And so the neuron must produce and release the neurotransmitter to push it into the gap. The neuro-transmitter also has to hang out long enough in the gap so that it can bind to the receptor on the next neuron.
Think of it like moving from one train car to another. One train car has a connector in the middle where a person trying to pass a message would have to leave one train car and go through the middle part to connect to the other side. What happens sometimes in individuals with ADHD is that the neurotransmitter gets reabsorbed into the original neuron and so the connection never gets made.
I think of it a little bit like lost packets of information. On the internet when something goes sideways and it doesn’t totally get through and you’ll come up with an error. Sometimes it’s because there were packets of information lost in the transmission of trying to move from one site to another sending information of data from one place to the next.
So the issue for people who have ADHD is that we want to make sure that the neurons are producing enough of the neurotransmitter and making sure that there’s enough energy getting in across the synapse. So it’s like spark plugs putting off a spark, but it’s not enough to make things run in the engine because it’s not a powerful enough spark. That’s where their medications come in.
So our stimulant medications reduce the symptoms of ADHD by increasing dopamine levels in the brain. It does this by slowing down the dopamine reuptake. Because the re-uptake or the reabsorption is slowed down, the neurotransmitter dopamine has more time to hang out in the synapse and make it to its destination across the way. This means that messages in the brain are being more effectively transmitted and received. This improves activity and communication in the parts of the brain that are responsible for operations.
There’ve been brain imaging studies that show when you’re on a stimulant medication that there’s increased metabolic activity in the prefrontal cortex, the specific subcortical regions and the cerebellum, which are all important centers for executive function.
Even with the explanation, ADHD medication almost seems like it has a paradoxical effect. When we give a kid caffeine or even ourselves caffeine, we feel stimulated and can maybe focus a little better. Well, I read a pediatrician’s description of how this interaction works and why it works, especially in children. She explains that kids with ADHD are self stimulating. They wiggle, they talk out of turn and their mind doesn’t seem to turn off. The thought processes are pretty non-linear. They might be tapping their foot and trying to tie their other shoe at the same time while also talking. They can seem to do everything except follow directions.
She explains that when you give a child a stimulant, it takes care of the need to self stimulate. That the brain has that under control already and so the child is free to manage only what they’re being asked to do rather than attending to the self-stimulation that their brain needs.
Stimulants remain the go-to when it comes to pharmacotherapy for ADHD. It’s estimated that stimulants are helpful for those who have ADHD in approximately 70% of the cases.
Types of ADHD medications
The medications for ADHD are broken down typically into stimulants and non-stimulants. Stimulants like Ritalin or Adderall are pretty familiar to us. And then we have the non-stimulants like Strattera which is atomoxetine, guanfacine and Clonidine. Sometimes non-stimulants are prescribed alongside stimulants to treat the symptoms that the stimulants didn’t alleviate.
There are a staggering number of medications when it comes to ADHD. I thought I had a handle on pretty much all of them. When I went to do research, I didn’t really know much of them at all. I think I was able to name maybe a third of them. Now part of that might be a little unfair for me because a lot of them are different versions of the same thing, but I was going with Adderall Ritalin, Concerta, Vyvanse, Daytrana. And those were the ones that I was mainly coming up with. Of course Strattera as well, but there are a lot of them.
So it took a little bit of digging to kind of find a way that we can think about them that is easier for us to understand and is scientifically accurate. We’re not gonna pay attention to the non-stimulant medications yet. We’re going to talk about the stimulants. It’s easier to think about them in two forms, amphetamines or methylphenidates. The brand name of straight up methylphenidate is Ritalin. For amphetamines the poster child is Adderall.
Methylphenidate aka Ritalin
So we’ll start with methylphenidate. Methylphenidate is a central nervous system stimulant that has become one of the primary drugs in treating ADHD. It’s also been used to treat depression, narcolepsy, brain injury, cancer, pain, cognitive disorders, and to treat patients with the HIV infection. The most impressive effect though has been with ADHD symptoms. The most common side effects are insomnia, stomach ache, headache, and difficulties with appetite.
Methylphenidate was synthesized in 1944 and then patented as Ritalin in 1954. In the 1957 Physician’s Desk Reference it was indicated in chronic fatigue, lethargic and depressed states, including those associated with tranquilizing agents and other drugs, disturbed senile behavior, psycho neurosis, and psychosis associated with depression and indicated for narcolepsy.
The medication does what we want it to in terms of helping dopamine cross the synapse and get to the next neuron. However, the exact mechanism of action is different from amphetamines. Exactly how they differ? That is an incredibly long discussion with a lot more science then I think we need. Suffice to say, that’s why they’re broken into those two categories, because if one doesn’t work, they’re hoping that the other one will.
Typically methylphenidate dosage ranges a bit for kids. For adults it tends to be about 20 to 30 milligrams a day. Most texts recommend that the dose should not exceed 60 milligrams. Although some people might require higher doses. So the way these medications are put together has to do with how quickly they act and how long they stick around. So typically the basic form of Ritalin has been short acting so it starts to work pretty quickly within 30 to 60 minutes and lasts for about three to four hours.
We’ll often find with kids that they need to take it before school, sometimes at lunch and after school. What a lot of parents have found is that their child might be okay at school, but by the time they get home, the medication has worn off. And holy cow, it is a whole different world. It’s a little tricky with timing though, because if you have a kid who’s taking methylphenidate, you have to make sure you’re not giving it to them to the point that they’re going to be amped up when it’s time for bedtime.
Types of methylphenidates are Ritalin, Focalin, methylene, metadata and Concerta. There are a lot of different types within there. There is a sustained release, there’s extended release. There’s even ones that have a 30% immediate release and a 70% delayed release or 50/50 immediate and delayed. In order to best help the person with what they need, whether they need a dose of it immediately and then need to slow down later, or if they need it to be a different percentage.
You can imagine how difficult it can be to get the right medication for the right person. 50/50 might be great for one person, but someone else might need it to last a little longer. And so the 30/70 might work better.
I should note that it’s not just dopamine that plays a role here. The neurotransmitter norepinephrine is also at play. Methylphenidate also slows the reuptake of norepinephrine in addition to dopamine, with the same goal of helping it get across the synapse and attach appropriately.
Methylphenidate has warnings, just like all the other stimulants that there can be some cardiac issues. There have been cases of sudden death in both children and adults with pre existing structural cardiac abnormalities. Typically they avoid giving methylphenidate and amphetamines for that matter to people who have structural cardiac abnormalities, cardiomyopathy, or arrhythmias.
As you would expect, overdose is absolutely possible. Doses that exceed 60 milligrams of the immediate release or 120 milligrams of extended release formulations can be considered toxic. We’re looking for signs like tremors, hyperreflexia, convulsions, confusion, hallucinations, delirium, flushing, and fever. This definitely needs medical attention and immediately so in order to treat.
There are some indications that methylphenidate has trouble interacting with acid reflux medication. Like antacids, H2 blockers and proton pump inhibitors. Or with serotonergic drugs, which for us is really important because taking methylphenidate with some of the serotonergic drugs could increase the risk of serotonin syndrome, which can be fatal. So we’re talking about SSRIs like fluoxetine and sertraline or SNRI, like duloxetine and venlafaxine, which are Cymbalta and Effexor, respectively.
Other substances that might interfere are opioids like fentanyl and Tramadol Buspirone, Lithium, and St. John’s Wort. Of course, we imagine that blood pressure medications also might have an issue. In addition, anti-psychotics, seizure medications, and warfarin, which is a blood thinner.
It sounds like methylphenidate might be pretty dangerous and that’s not what I’m saying. There’s just a lot of contraindications for people who are able to use methylphenidate to treat ADHD symptoms. It has been a huge deal for them. It just seems like how can this little pill and this even small amount of it cause such a huge difference.
It is a stimulant and therefore seems like it would amp you up. However, the difference here is in how it’s taken for both methylphenidate and amphetamines, it’s the way you take it that changes whether or not it’s going to get you high and you’re going to experience euphoria or not. We’ll get to that in a little bit.
Adderall and other amphetamines
Next we’re going to move on to talking about the amphetamine class. Under the amphetamine class, they further break it down to amphetamine, dextroamphetamine and lisdexamfetamine, which specifically is the generic name of Vyvanse. You don’t have to remember the breakdowns only that they fall under the amphetamine category.
Examples of amphetamines for ADHD are Dexedrine Adderall. Pro Sentra, Zenzedei, desoxyn Dyanavel and Evekeo. Amphetamines are also a central nervous stimulant, and are a first line medication for ADHD. Lisdexamfetamine, that’s the Vyvanse, has been approved for treating binge eating disorder. These amphetamines work in a similar way, increasing the amount of dopamine and norepinephrine and somewhat serotonin to a lesser extent in the synaptic cleft through a variety of mechanisms.
It’s difficult to go through each of these medications and talk about why they’re different. The way the amphetamine functions is slightly different than the way the methylphenidate functions. So in the amphetamine class, the way that it’s put together and synthesized as a medication has a lot to do with how it acts, how fast it acts, how slow it drains away and each has a different formulation in order to make it produce different results. For our purposes. I think we’ll focus on Adderall because that’s the main medication that we’re all pretty familiar with.
When it comes to Adderall a starting dose is typically for a short acting tablet around five to 10 milligrams in the morning and given five to 10 milligram increments later in the day, up to a level of 30 milligrams. The short acting tablets start in about 30 to 60 minutes and they last from four to five hours.
If you get an extended release, of course, we’re talking about a little bit longer onset because of the extended release. That’s the 60 to 90 minute window and they can last from 10 to 12 hours. There are versions of these amphetamine medications that have the 50/50 immediate release beads and the delayed release beads. But it sorta depends on which one you’re going for. And what is needed.
Common side effects are just like methylphenidate: headache, upset stomach, trouble sleeping, decreased appetite. There could also be nervousness, dizziness, sexual dysfunction, gastrointestinal problems and potential mood swings. There are serious side effects, just like with methylphenidate. Overdose, heart problems and other cardiac issues have strong warnings. There’s also interaction with stomach acid medications as we talked about before. Some of the SSRIs, antipsychotic drugs and blood pressure medication.
How ADHD medications are different than meth
Amphetamine is the main ingredient in Adderall. And it is extremely similar to methamphetamine. Meth is simply amphetamine with an added methyl group at the N position. The addition of this methyl group has two consequences that make methamphetamine a more powerful drug than amphetamines. The addition of that methyl group is a very large difference between methamphetamine and amphetamine.
The methyl of methamphetamine makes the molecule more lipophilic, which is fat soluble and fat soluble compounds go across the blood-brain barrier much more quickly and at higher concentrations. This pushes a more powerful rush and euphoric high, because it goes into the brand that much more quickly.
The meth in methamphetamine also has an effect on metabolism. As soon as meth goes into the system, the methyl group is cleaved away and the molecule is metabolized into amphetamine. That increases the duration of the drug’s effect by a large percentage because not only does methamphetamine have to go through its elimination half-life before it’s cleared from the body. But methamphetamine is also metabolized into amphetamine, which is active on its own and has to go through its own half-life just as if someone had taken an amphetamine alone. So meth is innately stronger and more euphoric/addictive then the drug amphetamine because of those medicinal chemistry properties.
The reason this is important is because some people struggle with the idea of “isn’t taking Adderall just next to taking meth?” And the truth is it’s not. It’s not for those who need Adderall for their ADHD. The difference comes when someone who’s been taking meth wants to, or has been taking Adderall. Those two things become very similar for a meth addict.
Abuse of ADHD medications
The use of prescription stimulants by people addicted to meth is really common. Sometimes it’s used as a stop gap measure when they’re not able to find meth. Sometimes it’s used in conjunction for whichever reason that the person feels it’s important.
Sometimes the use of pills like Adderall and Ritalin can lead to someone choosing to move on to meth. Certainly just like everything else it’s not the stimulants fault that the person moved on to meth. Rather it’s an indication of tolerance and dependence.
Research tells us that abuse of prescription stimulants has grown continually over the last two decades. A lot of the research though has been focused on underage college students. And whether or not they’re using it to help with their studying. I think that’s a really narrow field and not even the place where I’ve seen it be the worst.
I’ve seen stimulant use in high school, down to the middle school age, as well as it being diverted from parents who are supposed to have it for their children. But instead they were using it for themselves or were selling it. Prescription pills like opiates are not the only ones that are being abused as this class of drugs is really popular.
Sometimes the risk of abusing stimulant medications is overshadowed by the positive therapeutic effect that they have. I think part of that is because there isn’t the overdose rate that there is with opiates. Opiates are also prescriptions and also have a really positive therapeutic effect and we’re all really aware of how much that’s being abused. With these medications though that risk is somewhat pushed aside because the overdose rate isn’t high. It is a possibility. And I want to make sure, just like with everything we talk about, that I mention whether or not there’s the addiction potential, what the risks are, et cetera.
So I want to be clear. Stimulant prescription medications can be dangerous when abused. There is an overdose potential. There can be cardiac problems. There is a risk of sudden death in certain cases. And of course, that goes up when we’re talking about the abuse of these medications.
Tolerance in ADHD medications
There has been some controversy over whether or not stimulants can cause tolerance. However, it is recognized in literature by the American Academy of Child and Adolescent Psychiatry that most children will require dose adjustment upward as treatment progresses. Additionally the largest ADHD treatment study in existence, called the Multimodal Treatment Study of Children With ADHD, found that stimulants may have less efficacy over time.
There are a few ways that tolerance is believed to happen with these medications. Could be the changes in the pharmacokinetics, having to do with the size of the child and the changes in the body over time. Could be that there’s a progression of the disorder and not necessarily that the medication itself has lost efficacy. Could be there’s environmental changes and that the child could be placed in a new environment with more attention demands, which unmasked hidden symptoms up until that point.
And there’s a suggestion of paradoxical decompensation, where the idea is that the medication itself has worsened the ADHD because tolerance and dependence have caused the paradoxical decompensation. If this is the case, then an increase in the dose may help temporarily, but lead to worsened decompensation in the long term.
The studies in general, looking at efficacy of stimulants over time are lacking. The FDA, the Food and Drug Administration does have risks listed for these medications for tolerance and dependence with long-term use. While the research isn’t totally clear, the consensus seems to be that there is the risk for tolerance and dependence. Stimulants act to directly increase dopamine activity in the brain, which has a similar mechanism to many addictive drugs of abuse.
The theory and evidence does support that using stimulants, even in an appropriate way, can lead to tolerance and dependence. Remember with dependence, we’re talking about physiological dependence rather than abuse. The guidance for prescribers is that they should use stimulants as long as symptoms appear and limit their use when possible.
How ADHD medications get people high
So earlier, I told you that using stimulant medication as prescribed and orally, isn’t going to get you high and so we’ll talk about that. When we’re talking about oral use, you certainly could use enough to create a high. Remember though that we’re talking about something that’s breaking down in the stomach and that in order to achieve the high that people want, they have to use it in a way that gets it to the blood more quickly.
There are reports of patients taking upwards of a hundred methylphenidate tablets daily and experiencing the euphoria along with hallucinations, paranoia, and delusions. It’s not very efficient and it ends up being really expensive. The best way to do that in this case is using it nasally or intravenously. These are the ways that people typically use to get these medications into their systems so they can get a high from it. The mechanism of course is similar to meth and so there is going to be a dopamine rush, but as we just discussed it’s not going to be as powerful.
Intranasal abuse of stimulant medications hasn’t been as highly studied as intravenous use. So there isn’t going to be as much information. What we know is that crushing and snorting pills intranasally is going to get into the bloodstream faster, of course, than using it orally. And for people who haven’t graduated to using needles, this is typically the way it’s going to go. There are reports of patients taking up to 200 milligrams intranasally and in the beginning there’s euphoria, but it ends in the way that stimulants typically do when abused in paranoia, delusions, agitation and the like.
The most effective way of course, is intravenously. Using these pills intravenously is done the same way that people use opiates. Crush it up, dissolve it in water, heat it up, draw it up into a syringe and then use it that way. Now the step between taking something and snorting it and taking something and putting a needle in your vein is quite a step. For some people it’s a while before they’re willing to cross that line. For others, it may not be, but it totally depends on a number of factors, internal and external.
Next week we’ll talk about people in recovery and how they can deal with ADHD symptoms.
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