Pediatric Psychopharmacology for Treatment of ADHD, Depression, and Anxiety

Dear Dr. Furman,

Many thanks for your thoughtful reader response to our article "Pediatric Psychopharmacology for Treatment of ADHD, Depression, and Anxiety." Your points are very well-received and underscore important principles of pediatric psychopharmacology, specifically: 1) while the objective of our paper was to review prescribing practice, we do reiterate the critical importance of considering the child as a whole and in context and therefore of including evidence-based behavioral therapy in treatment planning and 2) in considering the pediatric patient in the scope of ongoing development, it is essential to constantly re-evaluate the risk- benefit ratio of psychopharmacology- it is incumbent upon the prescribing clinician to monitor ongoing need for medication as some children may stabilize and no longer necessitate medication intervention.

We also briefly referenced the Multimodal Treatment Study of Children with ADHD (MTA) trial and refer readers to this landmark study that has greatly informed ADHD psychopharmacologic practice to date (see references in original review article, which include MTA follow-up findings at two, three, six and eight years); there are a wealth of interesting and valuable clinical correlates that are beyond the scope of our psychopharmacology primer. Indeed, the longitudinal data provided up to eight years later has been complex: the MTA trial did demonstrate that superiority of stimulant medication treatment deteriorated to match outcomes of children in the other treatment arms though all groups continued to demonstrate improvement relative to baseline (i.e., early group randomization did not predict long-term outcome). The MTA workgroup acknowledges the challenge of explaining this long-term follow-up data. Perhaps another take-away conclusion from these results is the potential chronicity of ADHD and the importance of any interventions at all. Additionally, medication non-compliance was confirmed in the MTA trial and is very much a treatment issue that also bears consideration in interpreting data and in practice.

Even in light of MTA longitudinal data, practice parameters of both the American Academy of Pediatrics and the American Academy of Child and Adolescent Psychiatry recommend stimulant medication consideration for children and adolescents with ADHD. However, this discussion is instrumental in conveying the understanding that the objective of psychopharmacology is to improve function and alleviate distress but not necessarily normalize or cure mental illness.

Ultimately, we agree with your points, Dr. Furman, of behavioral therapy (to include parent management training mentioned in the case vignette) and eventual discussion with Joey and his family about consideration of trial discontinuation of his stimulant after a period of stability.

We thank you again for your excellent discussion points; your response highlights the complex and sometimes polarizing aspects of psychopharmacology prescribing.

Sincerely,

Cathy Southammakosane and Kristine Schmitz

Conflict of Interest:

None declared

Dear Editor,

Drs. Southammakosame and Schmitz provide a well written, pragmatic and case based state of the art approach to pharmacology of ADHD and other disorders, but additional details about stimulant treatment may be of interest.1 The longest prospective randomized controlled trial of stimulants for ADHD is the Multimodal treatment of ADHD trial (MTA), whose results are widely publicized as supporting efficacy of stimulant treatment for ADHD ("Recommendations are robustly evidence based" 1). The MTA produced fascinating and contradictory results which were not widely disseminated, and remain essentially buried in the psychiatric literature.

Although the groups randomized to receive stimulants had a better outcome at 14 months as measured by SNAP-ADHD score, all results beyond that point (when the trial assumed a "naturalistic" or observational design) are quite different. At 24 months, SNAP ratings for all groups, whether receiving medication or not, were essentially the same, and at 36 months groups did not differ on any outcome measure. Further, children receiving any stimulant showed both significantly greater symptom deterioration in the period from 24 to 36 months, and higher delinquency at 24 and 36 months.2 This effect (the deterioration) was not due to self- selection, medication non-compliance or initial treatment assignment, as best the investigators could determine.3 And finally at 8 years, in almost every analysis, the original treatment groups were not significantly different on any of 24 measures, even after adjustment for the 62% decrease in medication use after the initial 14 month randomized controlled period.4 These authors further concluded, "To our knowledge, these findings are the first in the ADHD treatment literature to document, for a wide range of symptom and functioning outcomes, the sustained absence of long-term effects of an initial period of randomly assigned treatment." 4

Additionally, readers may not be aware that compliance with medication use was monitored closely during the initial 14 months of the MTA, and was surprising poor: "...only 136 (53.5%) of the subjects were adherent at every time point at which saliva assays were taken.." and "...24.8% of the 254 participants were nonadherent on 50% or more of their repeated saliva assays."5

So in summary, it is also reasonable to ask whether Joey's stimulants should be carefully discontinued at 14 months after the start of treatment, since he could show deterioration by 3 years and we cannot anticipate any change in outcome at 8 years after starting treatment. Or, based on the same evidence, should he and his family receive behavioral support and counselling without stimulants, since after 24 months his outcome will likely be the same? The tsunami wave of endorsement for stimulant treatment by psychiatrists, pediatricians, educators and Pharmaceutical manufacturers permits little discussion of such alternative approaches, which are equally evidence based.

Sincerely, Lydia Furman MD

1. Southammakosame C and Schmitz K. Pediatric Psychopharmacology for Treatment of ADHD, Depression, and Anxiety. Pediatr 2015; 136:351-359 2. Jensen PS, Arnold LE, Swanson JM, Vitiello B, Abikoff HB, Greenhill LL, et al. 3-year follow-up of the NIMH MTA study. J Am Acad Child Adolesc Psychiatry. 2007; 46: 989-1002. 3. Swanson JM, Hinshaw SP, Arnold LE, Gibbons RD, Marcus S, Hur K, et al. Secondary evaluations of MTA 36-month outcomes: propensity score and growth mixture model analyses. J Am Acad Child Adolesc Psychiatry. 2007; 46:1003-14. 4. Molina BS, Hinshaw SP, Swanson JM, Arnold LE, Vitiello B, Jensen PS, et al The MTA at 8 years: prospective follow-up of children treated for combined-type ADHD in a multisite study. J Am Acad Child Adolesc Psychiatry. 2009;48:484-500 (pages 494 and. 5. Pappadopulos E, Jensen PS, Chait AR, Arnold LE, Swanson JM, Greenhill LL, et al Medication adherence in the MTA: saliva methylphenidate samples versus parent report and mediating effect of concomitant behavioral treatment. J Am Acad Child Adolesc Psychiatry. 2009; 48: 501-10.

Conflict of Interest:

None declared