In the last few years many prescribers do not prescribe IR-MPH in their practice, although clinical guidelines do not support this practice, especially in the titration phase. A pharmaceutical industry is very strong towards newer forms and atomoxetine, which is lower in term of efficacy (effect sizes obtained from meta-analyses). How IR-MPH should be used that patients with ADHD are treated more appropriate? Easy question but hard to answer.
In my opinion, the IR formulation is far more useful for dose titration. I find too, that many patients prefer it to the extended release formulations, even though many more prefer the latter. Both have their place.
Dear William,
I agree with You, for determination of appropriate dose and interval IR-MPH is far more appropriate, therefore a lack of consumption in those countries is not appropriate and could be connected with pharmaceutical marketing, especially after marketing. This process is seen in many countries worldwide.
In some patients switching after dosage determination could be logical, especially in patients who need long term day treatment and don't have many peaks of symptoms.
The best method is to determinate and choose appropriate form of MPH after dosage determination with IR form, however if all patients are switched is not appropriate and could be one of the alarm of inappropriate prescribing in ADHD.
See our article about situation in Slovenia.
J Child Adolesc Psychopharmacol. 2015 Apr;25(3):254-9.
At the end of the day, despite what treatment guidelines say about what is first line treatment for ADHD, it comes down to cost and value. Industry-sponsored articles from thought leaders in association with industry will not be able to answer this without bias. For patients without the resources to buy more expensive, patented, long-acting medications, then this is an easy answer- MPH-IR is a cost-effective solution. For 3rd-party payers that pay for more expensive, patented, long-acting medications, they should do their own cost-analysis and not be swayed by the biased literature regarding ADHD treatment guidelines.
Dear Carlos,
Thanks for this wonderful paper! I also work on meta-analysis. Please see our paper, which has been published in the Journal of Affective entitled: (Comparative efficacy and acceptability of atomoxetine, lisdexamfetamine, bupropion and methylphenidate in treatment of attention deficit hyperactivity disorder in children and adolescents: A meta-analysis with focus on bupropion.)
It is interesting that there is big difference between trials conducted in U.S. and Turkey, those in U.S. have higher effect sizes (about 1,5 SMD, Turkey 0,6). We need these trials, because of long term treatment. Interesting would be if we will have more study about atomoxetine and conduct network meta-analysis, however we are in big lack of 'direct' and 'indirect' long term studies. At the moment we have only short term studies of more medicals. Thanks again for this nice paper. What is interesting (second thing) and very important in long term practice (treatment) the effect sizes for IR-MPH are still very high (about 1,1, which means NNT about 2,5 and the number or percentage of wasted treatment only 20-30 %). These numbers are even higher if we compare these results with short term treatment meta-analysis (Faraone 2009; Faraone 2006; My meta-analysis publish in JAD), which is maybe surprising, if we know that down regulation procces takes place inside the brain and long term efficacy is therefore under question.
If I sum up, many thanks for this nice paper. At the moment we are working on a network meta-analysis for children and adolescents and the same research as we publushed in JAD for adults. These transitions of effect sizes between adolescents and adults are usually under question and are very important for daily work and appropriate treatment strategy in adolescent with ADHD.
Regards to Brazil,
Matej
I would say big No. MPH IR dies vert hard! My practice is always to start with MPH IR to establish tolerability, effectiveness and optimal dosing. Once achieved, for convenience I give bioequivalent dose of MPH-ER OROS. At times, I find patients respond differentially reflecting different kinetics. I also find IR formulation a user friendly when there is a need to boost effect of ER eg in exam time, or extra homework assignments, so, I usually opt for combining both. Another clinical situation where I find IR is more flexible is Autistic population. Besides, very young population find IR easily to divide, crush, and swallow unlike ER OROS (4 years and so), and, for me as a clinician to start very low in these populations, IR gives me this opportunity. For atomoxetine, I do believe despite industry-sponsored tête -à -tête studies with stimulants, us a SECOND line drug. Only it would be my first choice when there is a relative contraindication to use stimulants for eg abuse potential, severe tic disorder, marked anxiety, trichotillomania, parents' request, need for single dosing regimen and so forth. So, to sum up: MPH-IR would be more convenient for : 1) autism population 2) preschool population 3) in combination with ER OROS to cover up dips/boost response in time of extra academic demands. Trust this might help!
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