In this final installment of ADDitude magazine’s two-part series, “The Future of ADHD” (the first part appeared in the Winter 2023 issue), I’ll explain each of the developments poised to revolutionize ADHD understanding and treatment.
New Pharmacologic Interventions for ADHD
Development of pharmacologic interventions for ADHD has mushroomed over the last two decades. Though researchers have made progress in developing non-stimulant treatment options (i.e., long-acting forms of clonidine and guanfacine, as well as atomoxetine and viloxazine), most of the FDA-approved agents are simply tweaks of methylphenidate and amphetamine compounds.
There are now more choices available to prescribers and patients, offering stimulant preparations of varying durations, delivery formats (patch, liquid, tablet, capsule), and pharmacokinetic profiles. It should be noted that both older and newer preparations are exceptionally effective for most patients and, when comparing them to non-stimulants in head-to-head trials and in clinical practice, the psychostimulants generally win hands-down. However, the various forms of psychostimulants differ in their rate of onset, duration of coverage, convenience (once daily vs. multiple doses daily), and cost.
Psychostimulants, however, are not effective for everyone; about 30% of patients may not have a satisfactory response.1 As a result, researchers are increasingly exploring the benefits of combining psychostimulant treatment with other compounds (e.g., methylphenidate paired with atomoxetine, or a dextroamphetamine compound plus guanfacine).
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The robust effectiveness of psychostimulants in treating ADHD has somewhat slowed the development of alternatives. However, researchers are exploring newer agents that target different neurotransmitter systems, including:
- Solriamfetol (used to treat excessive daytime drowsiness)
- Tipepidine (used as a cough suppressant)
- Amantadine (used to treat Parkinson’s disease)
- Dasotraline (used to treat depression and other disorders)
Not yet FDA-approved for ADHD, these compounds face two main challenges: matching the effectiveness of psychostimulants and effectively targeting symptoms not currently treated by psychostimulants.
ADHD and the Gut-Brain Axis
Emerging research suggests a significant, but underappreciated, relationship between the gut biome — a diverse community of microorganisms living in the digestive tract — and behavior and emotions. The gut and the brain communicate through the gut-brain axis, allowing gut microbiota to influence brain function and vice versa.
Multiple studies have now shown that abnormalities in the gut microbiome can affect mood, anxiety, and stress levels.2 Certain gut bacteria can even produce neurotransmitters like serotonin and gamma-aminobutyric acid (GABA), which play a crucial role in regulating emotions.3 Other gut bacteria can produce toxins, inflammatory molecules, and other metabolites that can cross the blood-brain barrier to adversely impact brain health and cognitive function.4
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Imbalances in the gut microbiome can be caused by diet, stress, and even antibiotic use during the prenatal period or during infancy.5 6 Longitudinal studies have shown that these gut factors can be linked to mental health disorders, including ADHD, in later childhood.7 Multiple studies also suggest that restoring a healthy gut balance through probiotics, prebiotics, or dietary changes might improve emotional wellbeing.8 Research involving the microbiome’s impact on human behavior and emotions is still emerging.
ADHD and Gene-Environment Interactions
ADHD is highly heritable; however, environmental influences are exceptionally important in determining whether, when, and how a set of genes will manifest in ADHD symptoms. Environments determine whether a particular illness or disease manifests. This area of research — how certain genes are differentially expressed due to differences in environments — is in its infancy.
A major challenge: Because there are so many genes and possible environmental factors unfolding over time, there are literally trillions of possible gene-environment interactions that could affect the timing, severity, and persistence of ADHD. Due to the likely number and complexity of these interactions, multiple replications across independent studies will be essential.
Several studies have already shown that the severity and persistence of ADHD can be a function of parent-child interactions and supervision across different settings.9 This is not a “blame the parents” finding, but, instead, suggests that certain interventions from caregivers (and possibly teachers, coaches, and other adults) may mitigate a child’s symptom severity and persistence. For example, teaching parents how to remain neutral, or even express warmth in the face of difficult behaviors, is likely an important area of intervention. Related findings indicate that parental rejection10 can affect a child’s outcomes, as can the level of household disorganization11, overall life stress12, and other factors. Attention to such challenges offers an opportunity for targeted interventions.
Many different factors contribute to ADHD’s etiology, timing of onset, and severity, as well as possibilities for prevention and person-specific treatment. Our research to date, and our research programs unfolding over the next decades, will continue to lead to advances in the way we diagnose and treat ADHD in childhood and in adults.
ADHD Research: Next Steps
- Read: The Evolution of ADHD — Examining the Last 25 Years and the Future
- Read: Prenatal and Early Life Risk Factors of ADHD
- Watch: Epigenetics — Understanding Its Role in ADHD and Future Applications
- Hub: ADHD News & Research
Peter S. Jensen, M.D., is the founder of The REACH Institute, which trains providers in interventions for children’s mental health care.
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1 Spencer, T., Biederman, J., & Wilens, T. (2004). Nonstimulant treatment of adult attention-deficit/hyperactivity disorder. The Psychiatric clinics of North America, 27(2), 373–383. https://doi.org/10.1016/j.psc.2003.12.001
2 Xiong, R. G., Li, J., Cheng, J., Zhou, D. D., Wu, S. X., Huang, S. Y., Saimaiti, A., Yang, Z. J., Gan, R. Y., & Li, H. B. (2023). The Role of Gut Microbiota in Anxiety, Depression, and Other Mental Disorders as Well as the Protective Effects of Dietary Components. Nutrients, 15(14), 3258. https://doi.org/10.3390/nu15143258
3 Chen, Y., Xu, J., & Chen, Y. (2021). Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders. Nutrients, 13(6), 2099. https://doi.org/10.3390/nu13062099
4 Parker, A., Fonseca, S., & Carding, S. R. (2020). Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health. Gut microbes, 11(2), 135–157. https://doi.org/10.1080/19490976.2019.1638722
5 Madison, A., & Kiecolt-Glaser, J. K. (2019). Stress, depression, diet, and the gut microbiota: human-bacteria interactions at the core of psychoneuroimmunology and nutrition. Current opinion in behavioral sciences, 28, 105–110. https://doi.org/10.1016/j.cobeha.2019.01.011
6 Fish-Williamson, A., Hahn-Holbrook, J., Hobbs, M., Wallander, J., & Morton, S. M. B. (2022). Prenatal antibiotic exposure in pregnancy and early childhood socioemotional development. JCPP advances, 2(2), e12066. https://doi.org/10.1002/jcv2.12066
7 Cassidy-Bushrow, A. E., Sitarik, A. R., Johnson, C. C., Johnson-Hooper, T. M., Kassem, Z., Levin, A. M., Lynch, S. V., Ownby, D. R., Phillips, J. M., Yong, G. J. M., Wegienka, G., & Straughen, J. K. (2023). Early-life gut microbiota and attention deficit hyperactivity disorder in preadolescents. Pediatric research, 93(7), 2051–2060. https://doi.org/10.1038/s41390-022-02051-6
8 Bistas, K. G., & Tabet, J. P. (2023). The Benefits of Prebiotics and Probiotics on Mental Health. Cureus, 15(8), e43217. https://doi.org/10.7759/cureus.43217
9Haack, L. M., Villodas, M. T., McBurnett, K., Hinshaw, S., & Pfiffner, L. J. (2016). Parenting Mediates Symptoms and Impairment in Children With ADHD-Inattentive Type. Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53, 45(2), 155–166. https://doi.org/10.1080/15374416.2014.958840
10 Brinksma, D. M., Hoekstra, P. J., de Bildt, A., Buitelaar, J. K., van den Hoofdakker, B. J., Hartman, C. A., & Dietrich, A. (2023). Parental rejection in early adolescence predicts a persistent ADHD symptom trajectory across adolescence. European child & adolescent psychiatry, 32(1), 139–153. https://doi.org/10.1007/s00787-021-01844-0
11 Agnew-Blais, J. C., Wertz, J., Arseneault, L., Belsky, D. W., Danese, A., Pingault, J. B., Polanczyk, G. V., Sugden, K., Williams, B., & Moffitt, T. E. (2022). Mother’s and children’s ADHD genetic risk, household chaos and children’s ADHD symptoms: A gene-environment correlation study. Journal of child psychology and psychiatry, and allied disciplines, 63(10), 1153–1163. https://doi.org/10.1111/jcpp.13659
12 Hartman, C. A., Rommelse, N., van der Klugt, C. L., Wanders, R. B. K., & Timmerman, M. E. (2019). Stress Exposure and the Course of ADHD from Childhood to Young Adulthood: Comorbid Severe Emotion Dysregulation or Mood and Anxiety Problems. Journal of clinical medicine, 8(11), 1824. https://doi.org/10.3390/jcm8111824
Updated on January 14, 2025