ADHD Society Highlights Advances in ADHD Medications

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Last month the American Professional Society of ADHD and Related Disorders (APSARD) held its annual meeting in Washington, D.C. Among many highlights, the meeting’s poster session showcased several emerging trends in the field relating to advances in medications to treat attention-deficit/hyperactivity disorder (ADHD).

Taking Novel Methylphenidate Medication at Night May Reduce Early Morning ADHD Symptoms

Administering a novel methylphenidate medication that incorporates extended-release and delayed-release properties to children with ADHD in the evening may help to reduce ADHD symptoms commonly experienced immediately upon waking, according to the results of a recent phase III trial.

While generally safe and effective, the most commonly prescribed long-acting stimulants for ADHD often take a couple hours to begin working, often leaving children with poor symptom control for much of the early morning. HLD200 was designed to delay the initial drug release for 8 hours, thus enabling it to be taken each night and begin working as soon as children wake up.

Mary Ann McDonnell, Ph.D., of South Shore Psychiatric Services and colleagues evaluated the effectiveness of HLD200 in 43 children aged 6 to 12 in a trial that included a six-week, open-label dose optimization phase followed by a one-week, randomized and placebo-controlled test phase. By the end of the open-label phase, the children showed significant improvements in their ADHD symptoms, according to a variety of measures, including the Daily Rating of Evening and Morning Behavior (DREMB-R) scale.

Treatment-related adverse events were also fairly mild (with headache being most common), and the investigators noted that no participants dropped out during the open-label phase. Despite the evening administration, only 17 total sleep-related events occurred over the course of the study, McDonnell and colleagues reported.

This study was funded by Ironshore Pharmaceuticals and Development Inc.

Alcohol Does Not Alter Pharmacokinetics of Extended-Release Amphetamine

Alcohol is known to compromise the integrity of some extended-release medications, resulting in the release of high concentrations of the medication into the bloodstream. Despite the wide use of extended-release formulas in ADHD, there has been very little research on the physiological effects of alcohol in this class of medications.

As part of efforts to secure FDA approval for an orally disintegrating amphetamine (AMP XR-ODT), researchers from Mount Sinai Hospital in New York City and Neos Therapeutics (who developed AMP XR-ODT) examined the effects of alcohol on the rate and extent of amphetamine absorption and on the ability of the medication to retain its extended-release properties in a phase 1 study of adults.

A total of 32 healthy adults were given one tablet of AMP XR-ODT (equivalent to 30 mg amphetamine salts) and then assigned to drink 240 mL of varying concentrations of ethanol (0, 4, 20, or 40 percent alcohol solution) after the tablet dissolved. Blood samples were taken periodically over the next 60 hours. (The study was a four-part crossover design; thus, each patient consumed each concentration of ethanol over the course of the trial.)

None of the alcohol concentrations meaningfully altered the rate or extent of drug absorption in the participants, suggesting dose-dumping was not a factor. The combination of alcohol and the medication did not lead to any serious adverse effects or side effects that led to study dropout.

This study was funded by Neos Therapeutics Inc.

Dopamine Receptor Inhibitor Shows Potential for Use in Children, Adolescents

While stimulants remain a preferred choice in ADHD therapy, people are still looking for drug options that could show similar effectiveness but have less risk of abuse. One possibility might be dasotraline, a slow-acting inhibitor of dopamine and norepinephrine transporters, which acts on a different mechanism than fast-acting stimulants that directly release dopamine and norepinephrine.

Studies suggest dasotraline may be effective at reducing symptoms of ADHD in adults. A recently completed phase 1 trial also found that adults who took a single dose of dasotraline (8 mg, 16 mg, or 36 mg) over a 72-hour period liked the medication less than they did 40 mg or 80 mg of methylphenidate, suggesting the medication may have a lower potential for abuse.

To determine whether this drug might also be effective in children, researchers from Sunovion Pharmaceuticals Inc. assigned 50 children (aged 6 to 12) and 55 adolescents (aged 13 to 17) in the current study to receive doses ranging from 1 mg to 16 mg of the medication and then collected blood samples over a two-week period to assess the pharmacokinetic properties.

According to the poster, the researchers found that dasotraline had a profile in these pediatric subjects similar to that reported in adults, displaying a slow absorption and a long elimination half-life (average 56 to 84 hours).

Clinical trial simulations indicated that treating children with 2 mg to 4 mg of dasotraline per day would yield exposures that were equivalent to adults treated with doses in the range of 4 mg to 8 mg per day.

This study was funded by Sunovion Pharmaceuticals Inc. ■