Treatment Selection for Adult ADHD

Theresa R. Cerulli, MD: After being so thorough in how you approach diagnosis, what about treatments for ADHD [attention-deficit/hyperactivity disorder] in the adult population? What factors are guiding your psychopharmacologic selections, and your nonpsychopharmacologic treatments? Rakesh, do you want to lead us in this category?

Rakesh Jain, MD, MPH: I’d be happy to, Theresa. What a great question. Because we have so many choices, the responsibility of thinking this out clearly does rest on the shoulders of today’s very empowered clinicians. This is what I would use at the very minimum: when I’m thinking about factors, I’m thinking about the mechanism of action of my particular intervention. I’m thinking about its individual signature on efficacy and safety. I’m thinking about long-term data. I’m thinking about which particular comorbidity or comorbidities I’m dealing with. What am I looking for in terms of duration of response, quickness of onset, and by the way, what is the patient’s preference? Adult ADHD care, like anything else, really rests on the shoulders of shared decision-making with the patient. And with the adult patient, as Birgit said so eloquently, sometimes it’s a family affair. So pulling them all in to look at the factors that I’ve just articulated is a good way to start the conversation.

David W. Goodman, MD: I might add a few details for this. This is where it gets very complicated and very overwhelming. There are over 30 stimulant preparations on the market. It is a dizzying amount of choices even for us who are experts. You boil down the 30-plus stimulants into 2 categories. For methylphenidate, there are 3 preparations: racemic methylphenidate, dexmethylphenidate, and then you have the prodrug, serdexmethylphenidate. So that’s 3 under methylphenidate. You have 4 under amphetamine: racemic amphetamine, mixed amphetamine salts, d-amphetamine is the isomer, and then lisdexamfetamine is the prodrug. From those stimulant medications, you then have delivery systems, and the delivery systems determine how fast it starts, how long it lasts, what the drop-off is. So how do you shift back and forth between a methylphenidate and an amphetamine? Do you know that given all of the guidelines, the international guidelines, there is no algorithmic approach in child, adolescent, or adult psychiatry that gives you any indication of how you should go through this? Do you change compounds, or do you stay with a compound and go to a different delivery system?

Beyond the stimulants, you then have the nonstimulants. You have atomoxetine that’s been around for 2 decades, and viloxazine, which is recently approved for children and adolescents. Then you have alpha-2 agonists and you have off-label. So, the clinician in their mind has to become comfortable with a few of these compounds and then walk through them. If the patient doesn’t respond, then you refer off to a specialist if you’re a primary care doctor. Eighty-five percent of the patients will respond to either the first or second stimulant medication, but 15% will not respond to a stimulant medication. At least not the first 2, and that doesn’t mean they don’t have ADHD. This is like the patient who has a hard-to-treat medical disorder. They just need more expertise.

That’s how I think through the morass of pharmacologic choices. Then you have the psychotherapies on top of all that that get individualized based on emotion dysregulation, which is difficulty controlling your moods, or executive function, which has to do with organization and working memory. There has to be some development of an algorithmic thought process here that hopefully my colleagues and I are working on developing.

Theresa R. Cerulli, MD: Is there a scientific rationale for each category of therapeutic agent?

David W. Goodman, MD: Well, you can say mechanism of action, but if you look at methylphenidate and amphetamines in group data, they’re equally efficacious. Now the term effectiveness, that is, in a naturalistic study, are there elements of adherence that are problematic? If you look at the MTA study, which is the child study that divided patients up into medication and behavior, and behavior medication and community, adherence was tested by saliva. And it found that the adherence was not as great as they had thought; 50% of these children were missing a significant number of doses. Then when you asked the parents, “how is the adherence,” there was a disconnect between what the parents were reporting as adherence and what the saliva concentrations were. So, when the patient isn’t responding to a medication, you have to be sure that the patient is taking the medicine consistently. These are some of the elements that I’m thinking about. I know everybody here treats patients, and so it’s interesting to see how they sort through these multiple choices.

Greg Mattingly, MD: If I was going to take a bit of a developmental approach to treatment, preschoolers, the recommendations are if a kid’s having difficulties below the age of 5, behavioral therapy first, and only go to medicine if behavioral therapy hasn’t worked. School-aged children, the recommendations are medicines plus behavioral interventions. That can be coaching about how to organize your day, how to regulate your emotions, but it’s the combination together. For adults, the recommendations around the world are that medications are a foundation of treatment. So, you can do medications, then on top of that you can do lifestyle management, behavioral therapy, relationship therapy, self-esteem therapy. But medication is a foundation of treatment for adult ADHD, and those are the recommendations around the world. This includes the NICE [National Institute for Health and Care Excellence] guidelines in the United Kingdom, guidelines in Canada, and recommendations pretty much globally when it comes to adult ADHD.

Transcript Edited for Clarity