By: Regina Bussing, M.D., M.S.H.S
Phil and so here is the table that they constructed for the for the new corn study so you basically have subjects assigned to either or off atomoxetine or placebo and then at the overall group level you basically see in effect size of point 8 for us and off point six for atomoxetine but then when they ended up breaking it down into those that were treatment-naive
And those who have previous treatment you actually get for the treatment naive ones oh point nine the previous treatment a point five and you know this is now one study we can’t like turn that into the gospel but it’s at least i think respectable enough to to consider what’s going on here the other interesting phenomenon was that they had they had forty four
Percent of their sample both responding to the orals anitha moxa 10 but 34 responded to one and not the other and then also of note nearly a quarter didn’t respond to either you know so even though we have a lot to offer for adhd treatment we still don’t have something to offer for everybody so for our later discussion keep in mind these numbers please and that
Would move us to the new kid on the block so to speak the maguann 15 xr g xr in the a lot of studies abbreviated or named in tunis they just received their fda approval for a 6 to 17 year olds and i found this really interesting because when i was in fellowship training we were certainly kind of instructed and it seemed like what would you expect you see you know
Clinically oh the alpha agonists they’re really helpful for impulsivity and aggression but they don’t do so much for for inattention but actually that’s not really the and and the work that has been done by artisan and her group looking at what the alpha agonists might be doing i think has definitely stimulated me to rethink this so i thought because it’s new we
Can go basic here basic prescribing information there are some things here that are worth considering if we’re switching somebody from regular guanfacine to the extended-release we’re not supposed to be going oh they’re on that much guanfacine now i’m just going to convert it to that much of the extended-release because the pharmacokinetics are really different
So you’re supposed to taper them off the guanfacine and then start them again so that’s not necessarily intuitive with in tunis so we’re thinking about the benefits are observed at the dosages of point 0520 point oh eight milligrams per kilogram daily and then based on the clinical trials is the admonition that doses up to point 1 2 milligram per kilogram may
Provide additional benefits but really beyond that no point to push it beyond that and then when we’re going to talk about those are just later i constructed a excel table that where we can look at okay so what does that actually mean this is a situation where we’re not supposed to take that with a happy meal or with the with x and bacon because this probably has
To do with the release mechanism you know that in the high-fat environment low acidity you get greater exposure and then the other important thing is of course to taper it this is a medication that a child who visits the parent a on the weekend and lives with parent be during the week you know that’s the kind of child where you have to say you can’t just stop this
On the weekend because this needs to be tapers down and we have these dose dosage strengths here round long round long white and green for 1 2 3 and 4 milligrams now the clinical trials that the fda approval is based on consisted of two randomized clinical trial trial phase three studies they included youth 6 to 17 years and in each case there was also a to label
Open extension study and it was interesting they kind of came on the heels of each other that they conducted the first one and if you note the first one is described by bieber lederman at all so they in that study there was a two three and four milligram treatment option and it was a forced escalation pattern so there was no one milligram option and when the data
Was analyzed it seemed clear like especially we’re talking there’s some young children here that don’t weigh that much two milligrams may not really be what you want to target so then promptly the next study had a one milligram option but you could only get randomized to that if the child was below 50 milligrams because it wasn’t expected that it would do anything
If they were heavier so otherwise quite similar and and then please also note in the indies open-label extensions they started out 240 children but then they were 198 dropouts along the way over a period of two years and because we were a site for both of them no i i had my little group of children that stayed on the in tunis and it actually you know at that point
It was open label so you knew what you were doing it really worked and that’s why some of them stayed in there and i guess it did not work well enough over the long haul for everybody but dropout is a problem in in any case so the in efficacy studies both of them we find superiority of confessing over placebo and the important insights were that you really need to
Look at this on a weight stratified basis the effect size is really varied from point for one in the in this low dose range 0 point 0 1 2 point 0 for up to an effect size of 1.3 for in the high dosage range here and note that that in the fda approval that dosage range isn’t really recommended but if you wanted to think about where do we have safety data we do have
Safety data for this dose range and you see also the clinical global impression response rate goes up with the with the milligram per kilogram dosing when we work with with the this medication keep in mind that because you have to work up to the right dosage benefits will not start immediately that’s different from the stimulants and now on the other hand the benefits
Can last longer than eight hours and they’re not going to interfere with sleep so that can be quite a benefit lasting eight to 14 hours and possibly longer pretty clearly children seem to have butter better responses than adolescents and likely that is a weight-based dosing phenomena to some degree because you are not going to be pushing adolescents up to these
Dosage levels that a child can get to you know this is just graphically showing the efficacy data so we see we see of course the placebo responses to medications but you see a separation and this is showing the effects by by pill strength and then this is copied right out of the paper by sally at all so this is showing you the effects here by pill strength here by
By a dosing weight-based dosing and this is the reason why the in the fda approval you basically have this admonition that doses no above point 08 can provide additional benefit but you don’t see this one appearing in the open-label studies we we get reports that that you have significant reductions from baseline to end point that these productions of were apparent
At 1 month and we’re sustained for two years we’re just keeping in mind that the rate of drop out was high and tolerability i think is a bigger story here you know because with this medication we we already know from the clinical experiences with clonidine and guanfacine per se that you’re now looking at a profile of potential sedation and somnolence and fatigue or they call it the ssf
Transcribed from video
Pediatric ADHD Treatment of Comorbid Aggression – Part 3 By medicaiddrug