What is the Minimum Effective Dose of OROS Methylphenidate for Adolescents?
Dosing stimulants is never easy. There are various rules of thumb—for example, 0.5 mg/kg for amphetamine preparations and 1 mg/kg for methylphenidate preparations—but these have not been empirically validated. Ortho- McNeil Janssen funded a recent study designed to define the optimal dose of their medication OROS methylphenidate (Concerta, a controlled release MPH that lasts for 10 to 12 hours) for adolescents.
Two hundred and twenty adolescents ages 13 to 18 with ADHD were enrolled in a four-week, open label trial examining escalating dose-titration of OROS MPH to determine minimum dose required for response (defined as a 30% or greater reduction in baseline ADHD Rating Scale score and a rating of “good” or “excellent” on the Global Assessment of Effectiveness Scale).
All participants started with 18 mg of OROS for one week. Nonresponders had their doses raised in weekly increments (from 18 mg to 36 mg to 54 mg to 72 mg) until a minimal response was achieved, or they reached the maximum dose for this trial (72 mg).
About two thirds (65.4%) of patients required a dose of 54 mg or higher to meet criterion for improvement (27% responded to 54 mg dose; another 38% needed 72 mg to reach response). Eleven patients did not meet the requirements for improvement even at the 72 mg dose. Was there any way to predict which kids would need higher doses? Those with more severe ADHD symptoms at onset required higher doses, but neither age nor height nor weight were significant factors in predicting effective dose.
As expected, adolescents required a higher absolute dose of OROS than children to achieve results. However, when the dose is adjusted for weight, adolescents actually need a slightly lower dose than children (0.84 mg/kg, compared to 1.1 mg/kg for younger kids).
Fifty_seven percent of participants reported one or more drug related adverse events. The most common of these were anorexia (ranging from 6% to 10% dependent on dose) and headache (ranging from 9% to 11% depending dose) (Newcorn JH et al., J Child Adolesc Psychopharm 2010;20(3):187–196).
CCPR’s Take:While this study was clearly designed to showcase the manufacturer’s product, it is still a useful study clinically, because OROS MPH is used by so many psychiatrists and dosing guidance is always welcome. The authors conclude that a target dose of 1 mg/kg is reasonable for most adolescents.
Trends in Medication Use for Children with Insomnia
Children with psychiatric disorders often present with insomnia in addition to their primary symptoms. How should we treat insomnia in children? Every clinician seems to have his or her favorite goto hypnotic. In an effort to determine which hypnotics American child psychiatrists favor, a group of researchers surveyed members of the American Academy of Child and Adolescent Psychiatry.
A modified version of the Pediatric Drug Survey instrument (created by researchers to study prescribing practices among pediatricians) was mailed to 6,018 child psychiatrists; 1,273 responded. The questionnaire was designed to collect data on four areas: 1) prevalence of problem insomnia among patients; 2) medication strategies for managing insomnia in four different clinical groups: mental retardation/ developmental delay (MD/DD) or autism, ADHD, anxiety disorder (AD), or mood disorder (MD); 3) reasons for and against using medication to treat insomnia; and 4) demographic information about the respondents (ie, age, gender, academic affiliation). In this study, insomnia was defined as bedtime resistance, and/or significant difficulty falling and/or staying asleep.
The average psychiatrists said that over a typical one month period, they treat 28% of their pediatric patients with some type of insomnia medication. They were most likely to treat insomnia in older patients (32% of patients ages 13 to 18) and least likely to treat their youngest patients (3.5% of those under two years old).
Psychiatrists’ choice of medication varied based on the comorbid psychiatric condition. For patients with insomnia associated with ADHD, alpha agonists (such as clonidine) were the most popular medications, prescribed by 81% of psychiatrists surveyed. For insomnia in anxiety, mood, and developmental disorders, trazodone and sedating antidepressants were by far the most popular, prescribed by 65 to 85% of psychiatrists, depending on the disorder.
Here is the overall total percentage of psychiatrists who reported prescribing each medications group: Alpha agonists, 87%; trazodone, 85.8%; sedating antidepressants, 83.2%; atypical antipsychotics, 68.9%; SSRIs, 66.6%; benzodiazapines, 54.5%; short acting hypnotics, 50.2%; anticonvulsants, 49.1%; and tricyclics, 48.3%. Regarding over-the-counter medications, antihistamines such as Benadryl were commonly recommended for all disorders (used by nearly 70% of psychiatrists) followed by melatonin, which was a distant second (about 40%).
Interestingly, physicians who had the most years in practice were the least likely to report prescribing medication to treat insomnia in most cases, as were those with academic appointments at medical schools. Whether this reflects the wisdom to know when not to prescribe, or, alternatively, a refusal to keep up with new trends is not addressed by the study (Owens JA et al., Sleep Med 2010; online ahead of print).
CCPR’s Take: The study was funded by Sanofi Aventis, the makers of Ambien and Ambien CR, and some apparent commercial bias came through in the discussion section, in which the researchers expressed dismay that so much trazodone is being prescribed and that non-benzodiazepines are relatively underprescribed. Nonetheless, this data is useful, if only to show us what the current standard of pediatric insomnia treatment seems to be. When considering prescribing sleep aids to children and adolescents with insomnia, we should remember to ask about computer and television use and consumption of sugary soft drinks or energy drinks, all of which can affect sleep.