An open study of adjunct OROS-methylphenidate in children who are atomoxetine partial responders: II. Tolerability and pharmacokinetics.
OBJECTIVE
The aim of this study was to evaluate the tolerability of adding OROS methylphenidate (MPH) to children who are partial responders to atomoxetine (ATMX) in the treatment of attention-deficit/hyperactivity disorder (ADHD).


METHODS
This was a two-phase, 7-week, open study in children aged 6-17 years. Phase 1 initiated ATMX for a minimum of 4 weeks. Phase 2 entered partial responders to ATMX and added OROS MPH to their regimen. Safety was assessed using blood pressure and heart rate measurements, electrocardiogram readings, AEs, laboratories, and ATMX levels.


RESULTS
Fifty subjects who were partial responders to ATMX received the combination therapy, with 41 subjects completing the entire protocol. As reported elsewhere (Wilens et al., 2009 ), OROS MPH added to partial responders of ATMX was accompanied by a 40% reduction in the ADHD rating scale score and improvements in executive functioning. However, the combination of ATMX plus OROS MPH was associated with greater rates of insomnia, irritability, and loss of appetite compared to ATMX alone. A small significant increase in diastolic blood pressure was observed during adjunctive OROS MPH, with no clinically meaningful changes in electrocardiogram (ECG) parameters during the study. ATMX levels and liver function tests did not significantly change during the combination treatment.


CONCLUSIONS
Adjunct OROS MPH in ATMX partial responders yielded an additive adverse effect burden in this short-term study. Further controlled research with larger samples of children is warranted.
Hammerness
Paul
P
Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Harvard Medical School , Boston Massachusetts, USA.
Georgiopoulos
Anna
A
Doyle
Robert L
RL
Utzinger
Linsey
L
Schillinger
Mary
M
Martelon
Marykate
M
Brodziak
Kerry
K
Biederman
Joseph
J
Wilens
Timothy E
TE
D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy; D001794:Blood Pressure / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D003692:Delayed-Action Preparations; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D008774:Methylphenidate / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011437:Propylamines / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use
D018759:Adrenergic Uptake Inhibitors; D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D011437:Propylamines; D008774:Methylphenidate; D000069445:Atomoxetine Hydrochloride