One phase 3 trial, for example, reported the findings on a new extended-release methylphenidate drug intended to be taken before bed to alleviate morning symptoms of ADHD. The drug, HLD200, delays methylphenidate release for 8 to 10 hours and was tested in a trial of 163 children, age 6 to 12, with a prior response to methylphenidate. The study showed a significant improvement compared with placebo in overall ADHD symptoms and symptom management in early morning and evening. A separate phase 1 study also explored its use in adults.
“Right now, a lot of families are having a lot of difficulty in the morning, and it looks like [the new drug] lasts comparably to the sustained release doses,” Elliott said.
Another drug in development is dasotraline, a dopamine and norepinephrine reuptake inhibitor with an extended half-life of approximately 47 to 77 hours, according to Rob Goldman, PhD, head of clinical development and medical affairs, CNS, at Sunovion, the drug’s manufacturer. In Goldman’s study, presented at APSARD, results from 336 children were reported from an initial enrollment of 342 children between age 6 and 12. A significant improvement in ADHD symptoms, seen in both inattentive and hyperactivity/impulsivity subscale scores, occurred in children who took a 4-mg per day dose, while a the group receiving 2 mg per day showed no significant improvement over the placebo group.
The most common adverse effects were insomnia and decreased appetite, occurring in 1 in 5 of the children receiving 4 mg/d, and insomnia was the most common reason for discontinuation. As with stimulants, the other adverse effects, occurring between 5% and 9% of children, included weight loss, irritability, nasopharyngitis, and nausea. No serious adverse events occurred.
Results of a previous study last year suggested the drug has a low potential for abuse, but no head-to-head studies with other ADHD treatment agents have been conducted to compare abuse potential or effectiveness, Goldman said. The study also did not include participants who didn’t respond to other stimulants, but “there is a need for additional treatments to offer longer duration of effect and low abuse liability,” Goldman added. Sunovion intends to submit a New Drug Application for dasotraline to the FDA in 2017 for treatment of ADHD in adults and children.
Common Comorbidities Require Attention, Too
Several sessions at APSARD addressed the co-occurrence of ADHD in children with autism spectrum disorder (ASD), and a range of other conditions also commonly affect individuals with ADHD. Up to two-thirds of individuals with ADHD, research suggests, have another developmental, behavioral, or mental health condition, including anxiety, mood disorders, ASD, sleep disorders, Tourette syndrome, oppositional defiant disorder, conduct disorder, substance use disorders, and dyslexia or another learning disorder.
Even beyond these conditions and their established diagnostic criteria, additional challenges in treating individuals with ADHD are addressing symptoms that frequently coexist with the condition but do not explicitly fall under the diagnostic umbrella of ADHD or any other common comorbidities.
“A lot of kids with ADHD have executive functioning problems, and the stimulants often don’t help with executive functioning problems,” Elliott said. “Stimulants primarily address attention, impulsivity, and hyperactivity. These other areas aren’t part of the diagnosis of ADHD but are much more common in individuals with ADHD than individuals without ADHD.”
Just as scientists are learning that hyperactivity has different pathways in the brain, it appears that these executive functioning challenges have different pathways that researchers know little about. Ideally, as more basic science begins illuminating the mechanisms behind these difficulties and overall ADHD symptomology, new therapeutic opportunities will arise.
- Goldman R, Adler L, Spencer T, et al. S23. Dasotraline in children with attention deficit hyperactivity disorder: results of a phase 2/3 randomized, double-blind, placebo-controlled study. Presented January 14, 2017. APSARD 2017, January 13-15, 2027, Washington, DC.
- Kooij JJ, Huss M, Asherson P, et al. Distinguishing comorbidity and successful management of adult ADHD [Published online April 12, 2012]. J Atten Dis. doi:10.1177/1087054711435361
- Larson K, Russ SA, Kahn RS, Halfon N. Patterns of comorbidity, functioning, and service use for US children with ADHD [Published online February 7, 2011]. Pediatrics. doi:10.1542/peds.2010-0165
- 4. Pliszka S, Arnold V, Marraffino A, et al. F25. Efficacy and safety of HLD200 in children with attention-deficit/hyperactivity disorder: results from a pivotal phase 3 trial. Presented on January 13, 2017 at APSARD 2017, January 13-15, 2017, Washington, DC.