A discussion on the widespread abuse of stimulants amongst pediatrics with ADHD (attention deficit hyperactivity disorder), with special consideration to ongoing substance abuse liability trials.
Tim Wilens, MD: Ann, when we first started talking about the unmet needs, 1 of the first things you commented on was to come up with a medicine for ADHD [attention deficit hyperactivity disorder] that doesn’t have the abuse liability, that doesn’t have that abuse potential. If I went across and polled everybody on the panel, people would say that that is a concern, either their own concern or a concern for their patients who they sit across from.
It does beget the whole issue about the stimulants and abuse liability. In fact, the only black box that stimulants have is concerns about addiction, and it’s a big black box right there in the package insert, and there are some real concerns.
When you talk about nonmedical use of stimulants, you’re either using them if you’re prescribed, not using them appropriately, or you don’t have a prescription and you’re using them. We know overall that about 10% of high school kids and older adults have experimented with stimulants or other prescription pain medications. Stimulants are now No. 1. It used to be opioids, but it just shifted. Up to about a third of college students have used stimulants nonmedically. That’s a big number. It aggregates in college students, that’s the group who do it the most. If you look at similarly aged individuals and vocations, as Harlan was just talking about, or in the military, that’s not the issue.
We also know that those who use stimulants nonmedically have high rates of ADHD. Not all of them have ADHD, and they have more neuropsychological dysfunction and high rates of substance abuse. Where do they get it? They get it from friends and family, and they get it from reservoirs of pills.
The other disturbing fact that’s emerged—and this has been seen in multiple studies—is that it turns out that about 40% of stimulant misuse is intranasal, which is a huge concern. There’s an NIH [National Institutes of Health] study on this. We’ve studied a lot around nonmedical use of stimulants, and I’ve also collaborated with Sean McCabe [of the University of Michigan School of Nursing] and Ty Schepis [of Texas State University], and they do a lot of work in this area. I saw Mark flinch there because you don’t expect it to be that high. It’s a much smaller percentage of intravenous. Why is that important? Because Stephen Faraone and I just published a paper looking at poison control data. We found that if you use intranasal or intravenously, you have 20-fold likelihood that you’re going to have some serious medical morbidity or even death, and that is 1 of the things we worry about with intranasal misuse of these compounds. That is occurring in up to 40% of kids using stimulants nonmedically.
I’d be interested in having the panel talk about the different trial designs being used for abuse liability. Some of them are using people who are what we call connoisseurs of stimulants, who have experience with that. Some are in normal controls.
Ann, do you want to us give a sense? You’ve been involved with or looked at some of the abuse liability trial designs that are ongoing.
Ann Childress, MD: There are several drugs too. Just last week the FDA had an advisory board looking at what they’re going to do with these medications that people are developing. Really, we can’t call them abuse deterrent, because people could still misuse them, but they’re manipulation-resistant formulations.
I was disappointed, somewhat exasperated, at the end of the meeting because the advisers didn’t see what a big deal all this was. There’s a lot of education not only of physicians and patients and families, but we have to educate our friends in the government in so many areas.
Tim Wilens, MD: Mark, what patients are you worried about as a pediatrician? What have you taught your residents? What do you teach other pediatricians? When you were practicing, what do you worry about? What patient populations do you focus on when you’re thinking about the abuse liability?
Mark Wolraich, MD: When there is substance abuse in the family or some history of it. The other thing I do is with the kids who have done well on stimulants and are planning to go off to college. We talk about taking their senior year, when their grades aren’t as important, and trying 1 of the nonstimulants to see if they can get as good benefit. Because if they’re going to college out of state, they’re going to have to get another physician to take care of them. Also, if they’re caught giving the medication to their friends, they can get into trouble for dispensing controlled substances. I try to, where possible, see if there’s an alternative when they’re in college, and that’s worked for some. Also, educating them that it is an addictive drug and that they need to be careful.
Tim Wilens, MD: Bob, are there prevention strategies or groups you worry about or things you talk to parents or groups about to potentially obviate this from happening?
Robert L. Findling, MD, MBA: Certainly Mark has talked a lot about patients you need to worry about or family members you need to worry about. But at the end of the day, what is also important is that you’ve got to take the medicine as prescribed. That means you’ve got to make sure the medicine goes where it’s supposed to, to whom it’s supposed to. I always love the, “Well, they’re old enough to do this, so I just left the pills out on the counter.” I hear that all the time. You’re all shaking your heads, but tell me who hasn’t heard that repeatedly. Then you have to remind the parents and not just take it out and leave it on the counter or put it next to the toothbrush.
Remember, the hard part is having many of these parents—who themselves may struggle with being unorganized—do it so they can remember and make sure the youngster does it. Because of this abuse about concern, you could stockpile stuff not even intentionally. Then all of a sudden, look what you got here: a medicine that could be really quite detrimental in multiple ways. Own the medicine. The medicine must go to the right place, at the right time, into the right person.
Ann Childress, MD: You don’t find out until they get caught. I’m careful: I do all the things that you all talk about. I tell people not to give it to their friends; it’s a felony. A few months ago, I had a young man who wound up in the emergency department. He was taking fluoxetine, which I prescribed. And I’m like, “He has ADHD but didn’t want to take medicine for it.” He just turned 18. I’m like, “How can that give you dystonia? How can the fluoxetine do that?” I’m looking it up, but I didn’t see it. I come to find out—he finally fessed up—that he had gotten into his little brother’s IR [immediate release] methylphenidate. He had crushed it up and snorted it, and sure enough it gave him a dystonia. This was a 5-mg tablet. A lot of our patients out there, I am sorry to say, are doing things they shouldn’t be doing, even though we’re educating them and we don’t know until they get caught.
Tim Wilens, MD: That’s an important point. If I could summarize what I heard, because this is a lot of wisdom that people just got. We’re talking about when you’re talking to parents of kids growing up and that age that Ann was talking about, everybody from young to old. You’re talking about misuse and the importance, as Mark was saying, of knowing that these can be abused. Take them as prescribed, as Bob said. Encourage the supervision of adolescents who are taking these medicines. I would also add safe storage if you’re talking to college students. Don’t keep your controlled substances in medicine cabinets. That’s where people look.
The other thing I would add to it is—and we’ll hear more about the new meds— extended release, when you have high-risk situations. Use the extended release, and we’ll talk more about the immediate release, some potentially new versions of immediate release that don’t have quite the abuse liability. at least from the intranasal perspective.
Then, as Bob was saying, monitor your pill counts. Get the pill counts right. Don’t give people a reservoir of pills. Don’t write for 120 when 30 is what they really need, especially because you can do e-prescriptions now, so write size it so you don’t have reservoirs from which people can sell or give their medication.
-Dr. Findling receives or has received research support, acted as a consultant and/or has received honoraria from Acadia, Adamas, Aevi, Afecta, Akili, Alkermes, Allergan, American Academy of Child & Adolescent Psychiatry, American Psychiatric Press, Arbor, Axsome, Daiichi-Sankyo, Emelex, Gedeon Richter, Genentech, Idorsia, Intra-Cellular Therapies, Kempharm, Luminopia, Lundbeck, MedAvante-ProPhase, Merck, MJH Life Sciences,NIH, Neurim, Otsuka, PaxMedica, PCORI, Pfizer, Physicians Postgraduate Press, Q BioMed, Receptor Life Sciences, Roche, Sage, Signant Health, Sunovion, Supernus Pharmaceuticals, Syneos, Syneurx, Takeda, Teva, Tris, and Validus.
-Dr Gephart is retired from the practice of medicine. He is on the faculty of the REACH Institute for a course entitled “Patient Centered Mental Health in Primary Care.” He receives a stipend for serving as a virtual consultant to Course graduates who call in and present difficult cases. He has no other financial contracts to report.
-Dr Childress reports receipt of research or writing support, participation on advisory boards, and service as a consultant or speaker for Adlon Therapeutics, Aevi Genomic Medicine, Akili Interactive, Allergan, Arbor Pharmaceuticals, Cingulate Therapeutics, Emalex Biosciences, Ironshore Pharmaceuticals, Jazz Pharmaceuticals, KemPharm, Lundbeck, Neos Therapeutics, Neurovance, NLS Pharma, Otsuka, Pearson, Pfizer, Purdue Pharma, Rhodes Pharmaceuticals, Sunovion, Supernus Pharmaceuticals, Takeda, and Tris Pharma.
-Dr Wolraich is professor emeritus from the University of Oklahoma Health Sciences Center. He is on the steering committee and a faculty member of the REACH Institute, a non-profit organization providing CME training on mental health to primary care physicians. He has no affiliations or investments where he receives any compensation, and he is no longer in any clinical practice.
-Dr Wilens is Chief, Division of Child and Adolescent Psychiatry and Co-Director of the Center for Addiction Medicine at Massachusetts General Hospital. He receives or has received grant support from NIH(NIDA). He is or has been a consultant for Arbor, Otsuka, Ironshore, KemPharm and Vallon. He is the author of Straight Talk About Psychiatric Medications for Kids (Guilford Press). He is co-editor of ADHD in Adults and Children (Cambridge University Press), Massachusetts General Hospital Comprehensive Clinical Psychiatry (Elsevier); and Massachusetts General Hospital Psychopharmacology and Neurotherapeutics (Elsevier). He is co-owner of a copyrighted diagnostic questionnaire (Before School Functioning Questionnaire) and has a licensing agreement with Ironshore (BSFQ Questionnaire). He serves as a clinical consultant to the US National Football League (ERM Associates), U.S. Minor/Major League Baseball; Gavin Foundation and Bay Cove Human Services.