Implementing a Wider View of ADHD Clinical Presentation for Treatment Planning​

This discussion focuses on how clinicians can apply a wider view of attention-deficit/hyperactivity disorder (ADHD) to address residual symptoms of emotional dysregulation and executive dysfunction. After watching the video, test your knowledge with the quiz in the sidebar. 

To learn more, view the full series: ADHD Beyond The Core – What We’re Missing and Why It Matters. 

Matthews: Welcome, everyone, to section 4. Today, we're going to be discussing with colleagues Implementing a Wider View of ADHD Clinical Presentation for Treatment Planning. Now, we have to understand—and we talked about it in the previous sections—that we really must optimize pharmacological treatment plans to include the broader symptom control such as residual symptoms and emotional dysregulation, executive dysfunction. And right now, our current treatments for ADHD include stimulants as well as nonstimulants. But we've talked before about the limitations of these treatments. We understand residual symptoms can be very persistent despite treatment, like emotional dysregulation, impairments in executive function, anxiety. And these are, unfortunately, not often resolved or completely resolved by our current treatment options. We also can understand and appreciate the adverse effects that can come with these medication options and can ultimately impact adherence. Currently, our ADHD treatments primarily target norepinephrine and dopamine pathways, which can be insufficient for addressing the full clinical phenotype that we see in clinical practice.  

As many as 40 to 60% of patients do not experience improvement in emotional dysregulation or executive dysfunction, and we can appreciate the impact that this has on a patient's quality of life and their functioning. Current ADHD medications can be less effective on these emotional dysregulation symptoms compared with their effects on the core symptoms of ADHD. And it's really important for us as healthcare providers to assess for these associated features, comorbidities, for a complete and full clinical picture. Because this will help us guide our treatment interventions. So, it's essential to align the pharmacological interventions with the complex reality of treating ADHD, including those residual symptoms, comorbidities for effective symptom control. And this often takes an integrative approach to ADHD, including therapy and nonpharmacological interventions as well. But I would say that, colleagues, I would say you would agree with me that there's absolutely an unmet need for ADHD pharmacological interventions that can help address a broad and wide range of not only core symptoms, but the comorbidities and things like emotional dysregulation and executive function deficits, as well as anxiety. So, now that we've talked about ADHD, the comorbidities, the residual symptoms, associated features, I would like to really focus on the emotional dysregulation and any thoughts that you guys wanted to add to that because this is so common and can be so impairing. And right now, where we're at with our treatment options, I think it leaves us wanting a little bit more, doesn't it?  

Jain: Well said. You said it very well. So, unmet needs in psychiatry when it focuses on ADHD makes me think of the opening line from Charles Dickens' novel, which is, “It was the best of times, it was worst of times.” And the best of times is we have increasing awareness of ADHD, and we are increasingly treating it. But the worst of times, Desiree, is emotional dysregulation, I have to say is probably the greatest unmet need. And when I talk to the spouses of my patients, they often say, “While I do want him or her to be more organized, it's him losing his cool. It's him getting down on himself” that's such an issue. And they ask me to adjust the medication, and I'm often not able to help them as much as I should. So, you are completely right. That's a significant unmet need.  

Mattingly: You know, I was thinking. And I think we've gotten stuck in kind of a dichotomy. And I think the dichotomy is we tend to think about stimulant versus nonstimulant. We tend to think about norepinephrine versus dopamine when we know that ADHD is much richer than that. So, as we think about a world beyond stimulants and nonstimulants, I want something else. I want something that brings things to the table that we haven't had until now. Something that's broader in its approach that's broader in its spectrum of response that treats the associated features, the other comorbid conditions that we may be dealing with. So, I want a world beyond stimulants and nonstimulants. I want a world beyond norepinephrine or dopamine. I want to think about the other pathways in the brain that we've researched that we know get involved with these associated features and symptoms.  

Matthews: It's beautifully said. I think it can be quite frustrating as us—but also the patients, the families—that we might not be able to get this full symptom relief. And we understand that the residual symptoms absolutely have a big impact on just day-to-day functioning, the social quality of life. Andy, Dr Cutler, any thoughts that you wanted to add so we can wrap up our discussion today?  

Cutler: Well, I'm thinking about the complex nature of ADHD and the fact that it's a disorder really marked by comorbidities. And we've been talking about associated features. So, I agree that we've been shining a very bright spotlight on attention and hyperactivity, impulsivity, and we're missing all of that beyond the spotlight. And I also think about how many of my patients are on more than 1 medication, multiple medications, combinations of stimulant and nonstimulant—or, as I mentioned earlier, stimulant and an SSRI, SNRI, even stimulants plus mood stabilizers, atypical antipsychotics. So, I think that's reasonable, but as we all know, you can get into trouble when you start adding combinations of medicines if you're not being really careful and rational. And I feel like the key here is, as we're talking about, to individualize your assessment and your evaluation of the patient as far as maybe what type of ADHD, what cluster of symptoms, but also the associated comorbidities. And then, thinking about really individualizing your treatment plan. And one of the things that's exciting for those of us involved in research and helping get new medications approved is there's hope on the horizon that maybe we will have medications that may even more effectively treat the complexities, if you will, of ADHD.  

Matthews: Absolutely. It sounds like maybe we should consider being a bit more inclusive and bringing other views, like we mentioned about serotonin and the potential role, especially hearing emotional dysregulation. We all think of serotonin, so it really makes sense in the future to consider more broad spectrum approach when it comes to our pharmacological treatments.  

Cutler: But also, to individualize and, at the risk of sounding trite, to personalize. We hear a lot about personalized medicine. Don't you agree? To really think more rather than just, here's how we treat ADHD, everybody gets this medicine. Or to really think about, we've got a lot of tools that we can maybe employ more creatively.  

Matthews: Well, thank you all for this wonderful discussion, and thank you all for joining us on this discussion about ADHD, the associated features and how we can really think about broadening our options for treatment. 

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Andrew Cutler, MD 
Dr Andrew J. Cutler is a clinical associate professor of psychiatry at SUNY Upstate Medical University in New York, and he serves as the chief medical officer of the Neuroscience Education Institute. He received his MD from the University of Virginia School of Medicine, where he was also elected to the Alpha Omega Alpha honor medical society and received the Merck Award for outstanding medical scholarship. He completed his medical internship, internal medicine residency, and psychiatry residency at the University of Virginia Medical Center, where he served as chief resident of psychiatric medicine and did research on dopamine receptor pharmacology.  Dr Cutler then served as the first assistant professor and director of psychiatric medicine at the University of Chicago.  He is board certified in both internal medicine and psychiatry. Dr Cutler has also been the principal investigator on over 400 psychiatric and medical clinical trials.   

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Rakesh Jain, MD, MPH
Dr Rakesh Jain is a clinical professor at the Texas Tech University School of Medicine. He attended medical school at the University of Calcutta in India. He then attended graduate school at the University of Texas School of Public Health in Houston, where he was awarded a “National Institute/Center for Disease Control Competitive Traineeship.” His research thesis focused on the impact of substance abuse. He graduated from the School of Public Health in 1987 with a Master of Public Health degree. Dr Jain served a 3-year residency in Psychiatry at the Department of Psychiatry and Behavioral Sciences at the University of Texas Medical School at Houston. He then obtained further specialty training, undergoing a 2-year fellowship in child and adolescent psychiatry. In addition, Dr Jain completed a postdoctoral fellowship in research psychiatry at the University of Texas Mental Sciences Institute in Houston. He was awarded the “National Research Service Award” for the support of this postdoctoral fellowship. 

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Desiree Matthews, PMHNP-BC 
Desiree Matthews is a board-certified psychiatric nurse practitioner with expertise in treating patients living with severe mental illness. Beyond clinical practice, Desiree has provided leadership in advocating for optimal patient outcomes and elevating healthcare provider education. Desiree is the founder and owner of Different MHP, a telepsychiatry practice founded with the mission of providing affordable, accessible, precision-focused, integrative psychiatry to patients through a rich and comprehensive mentorship of the health care providers within the company. 

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Greg Mattingly, MD 
Dr Greg Mattingly is a physician and principal investigator in clinical trials for Midwest Research Group. He is also a founding partner of St Charles Psychiatric Associates and an associate clinical professor at Washington University. A St Louis native, he earned his medical degree and received a Fulbright scholarship while attending Washington University. Dr Mattingly is board certified in adult and adolescent psychiatry and is a diplomat of the National Board of Medical Examiners. Dr Mattingly has been a principal investigator in over 400 clinical trials focusing on ADHD, anxiety disorders, major depression, bipolar disorder and schizophrenia. Having served on numerous national and international advisory panels, Dr Mattingly has received awards and distinctions for clinical leadership and neuroscience research. Dr Mattingly is also the President for the American Professional Society of ADHD and Related Disorders and is on the Scientific Advisory Board for the World Federation of ADHD.  

1. Wakelin C, Willemse M, Munnik E. A review of recent treatments for adults living with attention-deficit/hyperactivity disorder. S Afr J Psychiatr. 2023;29:2152. doi:10.4102/sajpsychiatry.v29i0.2152 
2. Barkley RA. ADHD in children: diagnosis, assessment, and management. ContinuingEdCourses.Net. Updated February 18, 2025. Accessed June 24, 2025. https://www.continuingedcourses.net/active/courses/course147.php 
3. Katzman MA, Bilkey TS, Chokka PR, Fallu A, Klassen LJ. Adult ADHD and comorbid disorders: clinical implications of a dimensional approach. BMC Psychiatry. 2017;17(1):302. doi:10.1186/s12888-017-1463-3  
4. National Academies of Sciences, Engineering, and Medicine. Adult Attention-Deficit/Hyperactivity Disorder: Diagnosis, Treatment, and Implications for Drug Development: Proceedings of a Workshop. National Academies Press (US); 2024.  
5. Schein J, Childress A, Gagnon-Sanschagrin P, et al. Treatment patterns among patients with attention-deficit/hyperactivity disorder and comorbid anxiety and/or depression in the United States: a retrospective claims analysis. Adv Ther. 2023;40(5):2265-2281. doi:10.1007/s12325-023-02458-5 
6. Schein J, Cloutier M, Gauthier-Loiselle M, et al. Symptoms associated with ADHD/treatment-related adverse side effects and their impact on quality of life and work productivity in adults with ADHD. Curr Med Res Opin. 2023;39(1):149-159. doi:10.1080/03007995.2022.2122228 
7. Brown TE, Brams M, Gao J, Gasior M, Childress A. Open-label administration of lisdexamfetamine dimesylate improves executive function impairments and symptoms of attention-deficit/hyperactivity disorder in adults. Postgrad Med. 2010;122(5):7-17. doi:10.3810/pgm.2010.09.2196 
8. Liman C, Schein J, Wu A, et al. Real world analysis of treatment change and response in adults with attention-deficit/hyperactivity disorder (ADHD) alone and with concomitant psychiatric comorbidities: results from an electronic health record database study in the United States. BMC Psychiatry. 2024;24(1):618. doi:10.1186/s12888-024-05994-8  
9. da Silva BS, Grevet EH, Silva L, et al. An overview on neurobiology and therapeutics of attention-deficit/hyperactivity disorder. Discov Ment Health. 2023;3:2. doi:10.1007/s44192-022-00030-1 
10. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Text rev. American Psychiatric Association; 2022. 
11. Isaac V, Lopez V, Escobar MJ. Arousal dysregulation and executive dysfunction in attention deficit hyperactivity disorder (ADHD). Front Psychiatry. 2024;14:1336040. doi:10.3389/fpsyt.2023.1336040 
12. Groves NB, Wells EL, Soto EF, et al. Executive functioning and emotion regulation in children with and without ADHD. Res Child Adolesc Psychopathol. 2022;50(6):721-735. doi:10.1007/s10802-021-00883-0 
13. Shaw P, Stringaris A, Nigg J, Leibenluft E. Emotion dysregulation in attention deficit hyperactivity disorder. Am J Psychiatry. 2014;171(3):276-293. doi:10.1176/appi.ajp.2013.13070966 
14. Soler-Gutiérrez AM, Pérez-González JC, Mayas J. Evidence of emotion dysregulation as a core symptom of adult ADHD: a systematic review. PLoS One. 2023;18(1):e0280131. doi:10.1371/journal.pone.0280131
15. Kofler MJ, Irwin LN, Soto EF, et al. Executive functioning heterogeneity in pediatric ADHD. J Abnorm Child Psychol. 2019;47(2):273-286. doi:10.1007/s10802-018-0438-2
16. Kosheleff AR, Mason O, Jain R, Koch J, Rubin J. Functional impairments associated with ADHD in adulthood and the impact of pharmacological treatment. J Atten Disord. 2023;27(7):669-697. doi:10.1177/10870547231158572 
17. Biederman J, DiSalvo ML, Hutt Vater CR, Woodworth KY, Faraone SV. Toward operationalizing executive function deficits in adults with ADHD using the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). J Clin Psychiatry. 2022;84(1):22m14530. doi:10.4088/JCP.22m14530 
18. Danielson ML, Claussen AH, Bitsko RH, et al. ADHD prevalence among US children and adolescents in 2022: diagnosis, severity, co-occurring disorders, and treatment. J Clin Child Adolesc Psychol. 2024;53(3):343-360. doi:10.1080/15374416.2024.2335625 
19. Faraone SV. The pharmacology of amphetamine and methylphenidate: relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities. Neurosci Biobehav Rev. 2018;87:255-270. doi:10.1016/j.neubiorev.2018.02.001 
20. Fu X, Wu W, Wu Y, et al. Adult ADHD and comorbid anxiety and depressive disorders: a review of etiology and treatment. Front Psychiatry. 2025;16:1597559. doi:10.3389/fpsyt.2025.1597559 
21. Lalonde MA, Briese R, Paris A, Kozy BJ. Approaches to treating children with ADHD and common comorbidities. J Pediatr Health Care. 2025;39(2):318-325. doi: 10.1016/j.pedhc.2024.08.001 
22. Balazs J, Kereszteny A. Attention-deficit/hyperactivity disorder and suicide: a systematic review. World J Psychiatry. 2017;7(1):44-59. doi:10.5498/wjp.v7.i1.44 
23. Holst Y, Thorell LB. Functional impairments among adults with ADHD: a comparison with adults with other psychiatric disorders and links to executive deficits. Appl Neuropsychol Adult. 2020;27(3):243-255. doi:10.1080/23279095.2018.1532429 
24. Quenneville AF, Kalogeropoulou E, Nicastro R, et al. Anxiety disorders in adult ADHD: a frequent comorbidity and a risk factor for externalizing problems. Psychiatry Res. 2022;310:114423. doi:10.1016/j.psychres.2022.114423 
25. Parsley I, Zhang Z, Hausmann M, et al. Effectiveness of stimulant medications on disruptive behavior and mood problems in young children. Clin Psychopharmacol Neurosci. 2020;18(3):402-411. doi:10.9758/cpn.2020.18.3.402  
26. Oluwabusi OO, Parke S, Ambrosini PJ. Tourette syndrome associated with attention deficit hyperactivity disorder: the impact of tics and psychopharmacological treatment options. World J Clin Pediatr. 2016;5(1):128-135. doi:10.5409/wjcp.v5.i1.128 
27. Li L, Chang Z, Sun J, et al. Attention-deficit/hyperactivity disorder as a risk factor for cardiovascular diseases: a nationwide population-based cohort study. World Psychiatry. 2022;21(3):452-459. doi:10.1002/wps.21020 
28. Sun S, Kuja-Halkola R, Faraone SV, et al. Association of psychiatric comorbidity with the risk of premature death among children and adults with attention-deficit/hyperactivity disorder. JAMA Psychiatry. 2019;76(11):1141-1149. doi:10.1001/jamapsychiatry.2019.1944 
29. Mehta TR, Monegro A, Nene Y, et al. Neurobiology of ADHD: a review. Curr Dev Disord Rep. 2019;6:235-240. doi:10.1007/s40474-019-00182-w 
30. Pourhamzeh M, Moravej FG, Arabi M, et al. The roles of serotonin in neuropsychiatric disorders. Cell Mol Neurobiol. 2022;42(6):1671-1692. doi:10.1007/s10571-021-01064-9 
31. de Lima RMS, Barth B, Arcego DM, et al. Amygdala 5-HTT gene network moderates the effects of postnatal adversity on attention problems: anatomo-functional correlation and epigenetic changes. Front Neurosci. 2020;14:198. doi:10.3389/fnins.2020.00198 
32. Solomon MB, Yegla B, Newcorn JH, et al. Revisiting the role of serotonin in attention-deficit hyperactivity disorder: new insights from preclinical and clinical studies. Clin Drug Investig. 2025. doi:10.1007/s40261-025-01473-4 
33. Conio B, Martino M, Magioncalda P, et al. Opposite effects of dopamine and serotonin on resting-state networks: review and implications for psychiatric disorders. Mol Psychiatry. 2020;25(1):82-93. doi:10.1038/s41380-019-0406-4 
34. Jackson EF, Riley TB, Overton PG. Serotonin dysfunction in ADHD. J Neurodev Disord. 2025;17(1):20. doi:10.1186/s11689-025-09610-y 
35. Matuskey D, Gallezot JD, Nabulsi N, et al. Neurotransmitter transporter occupancy following administration of centanafadine sustained-release tablets: A phase 1 study in healthy male adults. J Psychopharmacol. 2023;37(2):164-171. doi:10.1177/02698811221140008 
36. Brown TE, Romero B, Sarocco P, et al. The patient perspective: unmet treatment needs in adults with attention-deficit/hyperactivity disorder. Prim Care Companion CNS Disord. 2019;21(3):18m02397. doi:10.4088/PCC.18m02397 
37. Lenzi F, Cortese S, Harris J, Masi G. Pharmacotherapy of emotional dysregulation in adults with ADHD: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2018;84:359-367. doi:10.1016/j.neubiorev.2017.08.010 
38. Stamatis CA, Heusser AC, Simon TJ, Ala'ilima T, Kollins SH. Real-time cognitive performance metrics derived from a digital therapeutic for inattention predict ADHD-related clinical outcomes: Replication across three independent trials of AKL-T01. Transl Psychiatry. 2024;14(1):328. doi:10.1038/s41398-024-03045-0