By: Aiśa Mrkulic PharmD Candidate c/o 2022
Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common reasons children require referrals for mental health services.¹ In fact, the American Academy of Pediatrics (AAP) recommends the screening of every child with ADHD for neuropsychiatric comorbidities. With, “one in every 20 children affected,” it exists as one of many contributors to our nation’s mental health crisis, a fitting backdrop for the FDA’s most recent announcements.¹ Biotech company Akili Interactive ultimately set out to capitalize on this public health issue. It was not long before the Akilians’ digital therapeutic EndeavourRx™(AKL-T01) became the first prescription treatment delivered through a videogame to achieve FDA-approval.
Difficulty concentrating remains the archetypical sign with which ADHD is associated; however, it is certainly not the sole target for ADHD therapy. No less than 6 symptoms, observable in at least 2 different settings, meets the Diagnostic and Statistical Manual of Mental Health Disorders, 5th Edition’s(DSM-5)criteria for formal diagnosis.² It is for this reason that diagnostic evaluation consists of, “behavioral observation in the classroom and at home”.¹ ADHD can be further categorized based on the classification of symptoms as one of the following: predominantly inattentive, predominantly hyperactive or combined, that is, involving both inattentiveness as well as hyperactivity.² According to the DSM-5,t he nature of the disorder’s presentation, like its symptom, is subject to change.1
AKL-T01 is currently compatible with Apple products however, devices must meet the minimum requirements outlined for prospective users. Akili Interactive’s inclusion of ‘Indications for Use’ and ‘Side Effects’ in its videogame’s instruction manual makes clear that the therapy is not indicated for all ADHD diagnoses, nor is it devoid of adverse effects. Noteworthy are that specifications under which the unconventional treatment improves attention function in qualified patients. Firstly, the proprietary videogame experience is intended for children aged 8-12 years old.³ The clearly defined patient population for which it was developed excludes those diagnosed with the primarily hyperactive variety of ADHD, favoring the inattentive and combined varieties instead. Labeling explicitly states, “AKL-T01 may not display benefits in typical behavioral symptoms, such as hyperactivity”.³ This first-of-its kind ADHD treatment was approved as an add-on therapy. Indeed, as it turns out, digital medicine is not a substitute for standard, guideline-driven, pharmacotherapy.
Nonetheless, those who wish to be among the first to experience “the future of medicine” are encouraged to join a waitlist. ⁴ In other words, FDA – approved AKL – T01 is not yet on the market. Akili Interactive invites the parents of inattentive gamers to gift their children the chance to play their medicine soon. While adults may be inclined to assume digital therapy is side – effect free, frustration (6.1%), headache (1.3%) , and dizziness (0.6%) were a few of the most common, transient, adverse effects observed.³ Cited findings were announced across , “five clinical studies, including a prospective, randomized control trial,” by the name of STARS – ADHD , which included a total of 600 participants.⁵ In this study, the intervention demonstrated, “a statistically significant improvement [as] compared to an educational style videogame on a change in the Attention Performance Index (API) of the Test of Variables of Attention (TOVA®), a computerized test cleared by FDA to evaluate the effects of interventions in ADHD”. ⁵ Suddenly, entertainment and efficacy prove strong drivers of adherence despite the presence of a side effect profile.
AK-T01 has made history as the first-ever digital therapy to bear the FDA’s stamp of approval. It cleared via the federal agency’s de-novo pathway, receiving its present classification as a novel medical device.⁶ In as little as 4 weeks of treatment with the, “medicine that feels like entertainment”, nearly 50% of child-subjects exhibited a meaningful improvement in day-to-day functioning.⁶ Accompanying a second month of treatment was an 18% increase in prevalence of the desired outcome.⁶ For up to one month, improvements in symptomatology were maintained after just one month of use.⁷ So how exactly does this digital therapy work? What is it about THIS video game that helps children manage their ADHD? At this time, there are no long-term studies which show that the benefits of AK-T01 use are not in fact transient.
Scott Kellog, Vice President of Medical Devices at Akili Interactive had this to say to skeptics, “The clearance of EndeavourRx ™ marks the culmination of nearly a decade of research and development”.⁶ It is through a “videogame interface” that AK-T01 successfully activates the brain’s prefrontal cortex (PFC), responsible for attentiveness among other things.⁸ “Sensory stimuli” are carefully integrated alongside “motor challenges”, with the ultimate goal of improved focus “through progressive obstacles”.⁸ “As a child progresses in gameplay, the technology is continuously measuring their performance and using adaptive algorithms to adjust the difficulty and personalize the treatment experience for each individual,” a spokesperson for Akili Interactive tells Observer.⁸
Tom Huddleston Jr, BS, MS, of CNBC best described the first-of-its-kind, digital therapy, “In the game, players steer a flying craft through obstacle courses where they have to avoid hazards, like fire pits or underwater mines, while collecting targets…children should, aim to complete five missions in the allotted time…once complete, the game will not allow them to play any further missions until the following day”.⁹
Dr. Natalie Weder, MD, child and adolescent psychiatrist at the Child Mind Institute, explains that video games are especially appealing to children with an ADHD diagnosis.¹⁰ Perhaps Akili Interactive pursued the development of a worthwhile therapy after all. At the same time, it is theorized that those with ADHD turn to gaming for self-medication. The million-dollar question is as follows; Just how well do bursts of pleasure-promoting dopamine translate to real-world scenarios?
In its announcement of the milestone, the FDA introduces AK-T01,t he unprecedented digital therapeutic, as the very first to be, “granted marketing authorization by the FDA for any type of condition”.⁸ FDA-approval is a guarantee of safety and efficacy, unless, of course, post-marketing surveillance reveals otherwise. Ultimately, it is AK-T01’s performance under real-word conditions that will determine its place in therapy.
- ADHD and ADD. Mental Health America Websitehttps://www.mhanational.org/conditions/adhd-and-add. Accessed June 16, 2020.
- Attention Deficit/Hyperactivity Disorder (ADHD): Symptoms and Diagnosis. Center for Disease Control and Prevention Website. https://www.cdc.gov/ncbddd/adhd/diagnosis.html. Updated April 8, 2020. Accessed June17, 2020.
- EndeavourRx™: Instructions for Use. Akili Interactive Labs Website. https://my.akili.care/endeavor/IFU/Endeavor_IFU_1_3_0.pdf. Updated June 2020.Accessed June 18, 2020.
- EndeavourRx™: The First-and-Only Prescription Treatment Delivered Through a Video Game. Akili Interactive Labs Website. https://www.akiliinteractive.com/. Accessed June16, 2020
- Akili Announces FDA Clearance of EndeavourRx™ for Children with ADHD, the First Prescription Treatment Delivered Through a Video Game. Akili Interactive Labs Website.https://www.akiliinteractive.com/news-collection/akili-announces-endeavortm-attention-treatment-is-now-available-for-children-with-attention-deficit-hyperactivity-disorder-adhd-al3pw. Published June 15, 2020. Accessed June 18, 2020
- De Novo Classification Request. US Food and Drug Administration Website.https://www.fda.gov/medical-devices/premarket-submissions/de-novo-classification-request. Updated November 20, 2019. Accessed June 18, 2020.
- Laurie Martin. The Videogame Will See You Now.https://www.psychiatrictimes.com/view/video-game-will-see-you-now. Psychiatric Times website. Published June 22, 2020. Accessed December 18, 2020.
- Andy Hirschfeld. Inside the World’s First Prescription Videogames and The Kids They’re Helping.https://observer.com/2020/07/endeavor-rx-first-prescription-video-game-therapy-revolution/. The Observer Website. Published July, 16, 2020. Accessed December 13, 2020
- Tom Huddleston Jr. See the first-ever video game approved by the FDA as a mental health treatment. CNBC Website. https://www.cnbc.com/2020/06/17/video-endeavorrx-is-first-video-game-approved-by-fda-to-treat-adhd.html. Published June 17, 2020.Accessed December 13, 2020
- Caroline Miller. Do Video Games Cause ADHD? Child Mind Institute Website. https://childmind.org/article/do-video-games-cause-adhd/. Accessed June 19, 2020
- FDA Permits Marketing of First Game-Based Digital Therapeutic to Improve Attention Function in Children with ADHD. US Food and Drug Administration Website.https://www.fda.gov/news-events/press-announcements/fda-permits-marketing-first-game-based-digital-therapeutic-improve-attention-function-children-adhd. Published June 15, 2020. Accessed June 16, 2020