Evening Dose of Long-Acting ADHD Med Closer to Release

Although long-acting psychostimulants, including methylphenidate (MPH), provide helpful pharmacotherapy for youth with attention-deficit hyperactivity disorder (ADHD), the medications often have a two-hour time delay before they become effective.

The practice of taking meds the first thing in the morning commonly means a user is vulnerable to inadequate symptom control and impaired functioning during the early morning routine. Mornings can become a particularly challenging time of day for school-age children with ADHD and their families.

Now, in a new study, a formulation that allows the delivery of an evening dosage led to significant improvement in ADHD symptoms and functional impairment the first thing the next morning, when compared to a placebo.

Early morning effectiveness is important as prior studies have shown mornings are often problematic.

In one study using electronic diaries, mothers reported that their own and their family’s activities were significantly restricted when their child received mediation in the morning. The mothers also expressed that they experienced a lower quality of life and believed their parenting effectiveness was less than adequate.

A recent survey of 201 primary caregivers of youth with ADHD revealed that, despite routine morning administration of stimulant medication, ∼75.6 percent of caregivers regarded the early morning as a time associated with moderate-to-severe ADHD-related functional impairment in their children.

These findings were corroborated by a subsequent survey of 350 primary caregivers of youth with and without ADHD, which also found that early morning functional (EMF) impairment in stimulant-treated youth with ADHD significantly diminished the emotional well-being of caregivers and exerted a pervasive functional burden on the entire family unit.

These findings suggest that inadequately controlled early morning ADHD symptoms and EMF impairment remain significant burdens on stimulant-treated youth with ADHD and their families.

Despite the documented importance of EMF impairment clinical trials of stimulant-treated children with ADHD have primarily focused on improving symptoms during the school day and after-school homework time.

To date, only one randomized, placebo-controlled trial has assessed the efficacy of a long-acting stimulant monotherapy on at-home EMF impairment. In that four week crossover study of 30 children with ADHD, very early morning administration of an MPH transdermal patch significantly reduced EMF impairment compared with placebo, as measured by the investigator-rated Before-School Functioning Questionnaire (BSFQ).

However, very early administration is inconvenient if done before normal awakening time, and is only possible with a patch formulation in which the patient does not have to be awake. In addition, early morning administration may potentially compromise ADHD coverage in the late afternoon/early evening.

Now, a new phase three study of children ages six to 12 years with ADHD has shown benefits from a delayed-release, long-acting formulation of the stimulant methylphenidate, when taken in the evening.

Children taking the delayed-release stimulant did not have to wait for a morning dose to take effect and also benefited from improved symptoms later in the afternoon and evening.

An article describing the study appears in the  Journal of Child and Adolescent Psychopharmacology.

The drug formulation delays release of the active ingredient for eight to 10 hours and then provides controlled extended release designed to cover the early morning into the evening.

Researchers discovered the medication was well tolerated, with the main adverse effects of appetite suppression and insomnia being similar to those commonly reported for other formulations of methylphenidate.

The study was coauthored by Steven Pliszka, M.D., from the University of Texas Health Science Center at San Antonio and colleagues from Massachusetts General Hospital, Westside Medical Family Practice, University of Tennessee Health Science Center (Memphis, TN), as well as other pharmaceutical researchers on behalf of the HLD200-108 Study Group.

Source: Mary Ann Liebert