Pediatric Annals

Special Issue Article 

Diagnosis and Management of Comorbid Anxiety and ADHD in Pediatric Primary Care

Daniel Janiczak, MD; Marisa Perez-Reisler, MD; Rachel Ballard, MD

Abstract

Attention-deficit/hyperactivity disorder (ADHD) and anxiety disorders, which are the most common pediatric mental health problems, frequently co-occur. The overlap of symptoms and the varied presentations of both disorders can make diagnosis and treatment planning challenging. Picking an initial treatment target with reassessment of the diagnoses based on response may help clinicians successfully treat children with comorbid ADHD/anxiety. Treating ADHD with stimulants can lead to improvement in ADHD-related anxiety symptoms. Treating anxiety can reduce anxiety-related attentional problems and executive functioning. Atomoxetine and alpha agonists treat ADHD and may have some benefit for anxiety symptoms. Behavioral treatment should be part of the plan for ADHD co-occurring with anxiety disorders. [Pediatr Ann. 2020;49(10):e436–e439.]

Abstract

Attention-deficit/hyperactivity disorder (ADHD) and anxiety disorders, which are the most common pediatric mental health problems, frequently co-occur. The overlap of symptoms and the varied presentations of both disorders can make diagnosis and treatment planning challenging. Picking an initial treatment target with reassessment of the diagnoses based on response may help clinicians successfully treat children with comorbid ADHD/anxiety. Treating ADHD with stimulants can lead to improvement in ADHD-related anxiety symptoms. Treating anxiety can reduce anxiety-related attentional problems and executive functioning. Atomoxetine and alpha agonists treat ADHD and may have some benefit for anxiety symptoms. Behavioral treatment should be part of the plan for ADHD co-occurring with anxiety disorders. [Pediatr Ann. 2020;49(10):e436–e439.]

At first glance, attention-deficit/hyperactivity disorder (ADHD) and anxiety disorders seem unrelated. The child presenting with ADHD in the pediatric office seems active and boisterous, and teacher reports may indicate frequent classroom disruptions. A child presenting with anxiety may present as the polar opposite, timidly hiding behind a parent, avoiding eye contact, and speaking in a whisper.

Nonetheless, ADHD and anxiety are among the most common mental health diagnoses in youth. ADHD has a worldwide prevalence of 5.3%, and a lifetime prevalence of 11%.1,2 The lifetime prevalence of anxiety disorders is 15% to 32%.3 As two common conditions, comorbidity is expected. Close to one-third of children in the Multimodal Treatment of ADHD Study had co-occurring anxiety disorders,4 and estimates of comorbidity of anxiety and ADHD have ranged as high as 45%.5

ADHD subtypes are distinguished by the relative prominence of inattentive versus hyperactive/impulsive symptoms and include combined, predominantly inattentive, and predominantly hyperactive/impulsive presentation types.6 The anxiety disorders include separation anxiety, generalized anxiety disorder, social phobia, specific phobias, and panic disorder. Although both the pharmacologic treatment of ADHD7,8 and anxiety disorders9 are well established, how to proceed in evaluating and treating a child or adolescent presenting with both disorders is less clear.

Diagnostic Considerations

Relation Between ADHD and Anxiety Symptoms

Symptoms seen in both ADHD and anxiety include motor restlessness, fidgeting, and inattention10 (Figure 1). Poor concentration is common to both conditions, but the child with ADHD tends to be distracted by stimuli, whereas the child with anxiety is distracted by worries and fears. Anxiety is associated with poorer attention and executive11,12 and social functioning,13 which are best addressed by treating the anxiety. Similarly, patients with ADHD will develop anxiety that is normal, predictable, and proportional to their ADHD impairment. When ADHD is severe, children can experience significant anxiety that is best addressed by the effective treatment of ADHD.

Core symptoms of attention-deficit/hyperactivity disorder (ADHD) and of generalized anxiety disorder, with areas of overlap. *Although irritability and sleep disturbance are not core ADHD symptoms, they are common among children and adolescents with ADHD.

Figure 1.

Core symptoms of attention-deficit/hyperactivity disorder (ADHD) and of generalized anxiety disorder, with areas of overlap. *Although irritability and sleep disturbance are not core ADHD symptoms, they are common among children and adolescents with ADHD.

Information Needed to Diagnose Comorbid ADHD and Anxiety

Interviews with the patient and family are critical for making both diagnoses, as are collateral sources of information. For a diagnosis of ADHD, a child must have a persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning present in two settings with onset before age 12 years. Rating scales such as the Vanderbilt ADHD Diagnostic rating scale14 and the Swanson, Nolan, and Pelham questionnaire-IV are useful in establishing the presence of ADHD symptoms.

In diagnosing anxiety disorders, both the parent's and the child's reports about the child's anxiety symptoms are critical. The clinician should consider separate patient and parents interviews as well as a combined interview. It may also be helpful to use the Screen for Child Anxiety-Related Emotional Disorders15 scale; this free tool helps differentiate between major subtypes of anxiety.

Treatment Considerations

Effects of Commonly Used ADHD Medications on Comorbid Anxiety

Stimulants are first-line treatment for ADHD and reduce both hyperactivity and inattentive symptoms.7 Expectations regarding the effect of stimulants treatment on both ADHD and anxiety depends in part on whether anxiety is an independent condition or secondary to ADHD impairment. Most short-term studies do not make this differentiation and should be interpreted with caution. In the 1990s, short-term studies indicated that stimulants administered to children with comorbid ADHD and anxiety led to more side effects and a poorer response to psychostimulants.16 Later, longer-term stimulant studies17 show that improvements in ADHD were comparable for children exhibiting ADHD with and without comorbid anxiety. Children administered psychostimulants also showed some improvement in anxiety.16 When ADHD-related anxiety impairment continues, additional pharmacotherapy targeting anxiety specifically may be indicated.

Atomoxetine is a norepinephrine reuptake inhibitor that is US Food and Drug Administration-approved for the treatment of ADHD in children age 8 to 17 years.18 Atomoxetine, which has moderate anti-anxiety effects,19 may be used as monotherapy for ADHD or in combination with a stimulant.7 An open comparison study showed that after 8 weeks, atomoxetine is as effective as methylphenidate for ADHD with additional improvement on anxiety symptoms as compared to methylphenidate.20 The challenge with interpreting this study (and any study targeting co-occurring conditions) is determining whether atomoxetine reduced ADHD and secondary anxiety, reduced anxiety and secondary attentional issues, or treated both. As atomoxetine has not been studied in children with anxiety disorders only, it cannot be claimed that atomoxetine treats anxiety. Advantages of atomoxetine for ADHD include: (1) it is not a controlled substance; (2) minimal appetite suppression, and (3) 24-hour efficacy. The main disadvantages include (1) needing to wait 3 to 6 weeks for treatment response and (2) lower effect size for treating ADHD7 and/or anxiety symptoms compared to stimulants or selective serotonin reuptake inhibitors (SSRIs).

The alpha agonists, clonidine and guanfacine in extended-release forms, are used to treat ADHD as monotherapy with moderate effect size or adjunctively with stimulants.7 Guanfacine extended-release was well tolerated in children and adolescents with anxiety disorders, but was not statistically better compared to placebo.21 Advantages of alpha agonists include (1) not being controlled substances, (2) minimal appetite suppression, and (3) 24-hour efficacy. Sedation, a common side effect, is mitigated to some extent by extended-release forms. The main disadvantage is needing to wait a few weeks to note treatment response and needing to taper when discontinuing treatment to avoid rebound hypertension.

Effects of Medications Used for Anxiety on Comorbid ADHD

SSRIs are first-line pharmacotherapy for anxiety disorders in children and adolescents. SSRIs have no known positive or negative effects on the core symptoms of ADHD.

Drug-drug interactions between ADHD medications and SSRIs. There are no major drug-drug interactions between stimulants and SSRIs or alpha agonists and SSRIs. Fluoxetine and atomoxetine are both metabolized by cytochrome P450 2D6, and when taken together can increase each other's serum levels. Other drugs that mutually increase serum level with atomoxetine include paroxetine, bupropion, quinidine, and cimetidine.

Effects of treating anxiety on ADHD symptoms. To the extent that anxiety interferes with attention and executive functioning,11 treating anxiety may improve overall capacity to focus and executive functioning. For children with ADHD whose impulsivity is tempered by their anxiety disorder, treating anxiety may result in more impulsive behavior.

Nonpharmacologic treatment strategies for children with comorbid ADHD and anxiety. Children with ADHD and anxiety benefit from structured home environments with regular schedules, clear expectations, routines, rules, and consequences, and calm, neutral approaches to discipline.

For younger children with ADHD or anxiety, parent education about the disorders and how to support their child's unique needs is essential. Formal parent management training may benefit parents of children with ADHD and disruptive behavior. For children with anxiety disorders, first-line psychotherapy is cognitive-behavioral therapy (CBT) with graded exposures in which the child learns to master the experience causing anxiety, gradually extinguishing the fear response.

Determining an initial treatment approach. It may not always be apparent that a child has both ADHD and an anxiety disorder. If anxiety disorder is present (eg, separation, generalized, or social anxiety disorders) these symptoms may dominate and anxiety symptoms may need to be well controlled before attention problems become apparent. Children who are chronically restless, inattentive, and with limited capacity to describe their emotions may not be identified with an anxiety disorder until treated for ADHD. Failure to respond to treatment as expected should prompt a reassessment of the diagnosis, and comorbid ADHD or anxiety should be in the differential diagnosis for each other on reassessment.

Which disorder has more impact on the child's functioning? Current practice parameters7 and practice guidelines22 indicate initiating pharmacologic treatment depending on which disorder most impairs the child's functioning. When both disorders are present, current practice parameters7 recommend assuming the two disorders are indeed present and developing treatment plans for both. If it is unclear whether comorbidity is present or which disorder is more impairing, the most conservative approach to treatment involves initiating a psychostimulant and carefully monitoring treatment progress. This approach addresses the ADHD symptoms and may also reduce symptoms that are potentially anxiety related. If anxiety symptoms are consistent with one of the anxiety syndromes and are impairing, specific treatment for anxiety is warranted.

Which can we treat faster? It is possible to get pharmacotherapy for ADHD and anxiety underway quickly. When starting ADHD treatment with a stimulant, treatment response can be established in a few days to a few weeks. Stimulants start working immediately, and doses can be adjusted every few days. Stimulant side effects can emerge quickly, allowing patients and families to readily make decisions about acceptability. Nonstimulant medications for ADHD (atomoxetine and the alpha-agonists) require slow upward adjustments to avoid side effects, and up to 3 weeks at the target dose to see the full therapeutic effect at that dose. SSRIs for anxiety also require 3 to 6 weeks to assess for therapeutic efficacy. Starting ADHD treatment with a stimulant, followed by an SSRI for anxiety, is the most time-efficient strategy for pharmacotherapy for both disorders.

If we only want to use one medication, which one? Sometimes, the clinician wishes to keep pharmacotherapy of comorbid ADHD and anxiety to a minimum. Parents or patients may be uncomfortable with psychotropic medications in general, wish to avoid a particular class of medications, or only want to take one medication per day. Children with ADHD and anxiety may also have medical comorbidities and other potential drug-drug interactions. In these cases, one might consider a stimulant for the most effective treatment of the ADHD, combined with CBT for the anxiety. Despite caveats noted above, atomoxetine may address symptoms of both ADHD and anxiety.

Conclusion

Overlap of symptoms and varied presentations of ADHD and anxiety disorders can make diagnosis and treatment-plan development challenging. Understanding the overlapping symptom patterns as well as the differences between these disorders helps inform initial and sequential treatment plans

Ultimately, recommendations must be acceptable to the patient and family. Some families will have learned about treatment options and will be ready to start treating both disorders. Other families will prefer a stepwise approach. Creating a brief roadmap with treatment options and contingency plans can help partner with patients and families.

References

  1. Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA. The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry. 2007;164(6):942–948. doi:10.1176/ajp.2007.164.6.942 [CrossRef] PMID:17541055
  2. Visser SN, Danielson ML, Bitsko RH, et al. Trends in the parent-report of health care provider-diagnosed and medicated attention-deficit/hyperactivity disorder: United States, 2003–2011. J Am Acad Child Adolesc Psychiatry. 2014;53(1):34–46.e2. doi:10.1016/j.jaac.2013.09.001 [CrossRef] PMID:24342384
  3. Essau CA, Gabbidon J. Epidemiology, comorbidity and mental health service utilization. In Essau CA, Gabbidon J, eds. Epidemiology, Comorbidity and Mental Health Service Utilization. Wiley-Blackwell; 2012:23–43.
  4. Jensen PS, Hinshaw SP, Kraemer HC, et al. ADHD comorbidity findings from the MTA study: comparing comorbid subgroups. J Am Acad Child Adolesc Psychiatry. 2001;40(2):147–158. doi:10.1097/00004583-200102000-00009 [CrossRef] PMID:11211363
  5. Biederman J, Newcorn J, Sprich S. Comorbidity of attention deficit hyperactivity disorder with conduct, depressive, anxiety, and other disorders. Am J Psychiatry. 1991;148(5):564–577. doi:10.1176/ajp.148.5.564 [CrossRef] PMID:2018156
  6. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.
  7. Wolraich ML, Hagan JF Jr, Allan C, et al. Erratum for: Clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics. 2020;145(3):e20193997. doi:10.1542/peds.2019-3997 [CrossRef] PMID: 32111626
  8. Wolraich ML, Hagan JF Jr, Allan C, et al. Erratum in: Clinical practice guidelines for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics. 2019;144(4):e20192528. doi:10.1542/peds.2019-2528 [CrossRef] PMID:31570648
  9. Walkup JT, Albano AM, Piacentini J, et al. Cognitive behavioral therapy, sertraline, or a combination in childhood anxiety. N Engl J Med. 2008;359(26):2753–2766. doi:10.1056/NEJMoa0804633 [CrossRef] PMID:18974308
  10. Connolly SD, Bernstein GAWork Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with anxiety disorders. J Am Acad Child Adolesc Psychiatry. 2007;46(2):267–283. doi:10.1097/01.chi.0000246070.23695.06 [CrossRef] PMID:17242630
  11. Newcorn JH, Halperin JM, Jensen PS, et al. Symptom profiles in children with ADHD: effects of comorbidity and gender. J Am Acad Child Adolesc Psychiatry. 2001;40(2):137–146. doi:10.1097/00004583-200102000-00008 [CrossRef] PMID:11214601
  12. Tannock R, Ickowicz A, Schachar R. Differential effects of methylphenidate on working memory in ADHD children with and without comorbid anxiety. J Am Acad Child Adolesc Psychiatry. 1995;34(7):886–896. doi:10.1097/00004583-199507000-00012 [CrossRef] PMID:7649959
  13. Bishop C, Mulraney M, Rinehart N, Sciberras E. An examination of the association between anxiety and social functioning in youth with ADHD: a systematic review. Psychiatry Res. 2019;273:402–421. doi:10.1016/j.psychres.2019.01.039 [CrossRef] PMID:30684786
  14. Wolraich ML, Bard DE, Neas B, Doffing M, Beck L. The psychometric properties of the Vanderbilt attention-deficit hyperactivity disorder diagnostic teacher rating scale in a community population. J Dev Behav Pediatr. 2013;34(2):83–93. doi:10.1097/DBP.0b013e31827d55c3 [CrossRef] PMID:23363973
  15. Birmaher B, Brent DA, Chiappetta L, Bridge J, Monga S, Baugher M. Psychometric properties of the Screen for Child Anxiety Related Emotional Disorders (SCARED): a replication study. J Am Acad Child Adolesc Psychiatry. 1999;38(10):1230–1236. doi:10.1097/00004583-199910000-00011 [CrossRef] PMID:10517055
  16. Abikoff H, McGough J, Vitiello B, et al. RUPP ADHD/Anxiety Study Group. Sequential pharmacotherapy for children with comorbid attention-deficit/hyperactivity and anxiety disorders. J Am Acad Child Adolesc Psychiatry. 2005;44(5):418–427. doi:10.1097/01.chi.0000155320.52322.37 [CrossRef] PMID:15843763
  17. The MTA Cooperative Group. A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. 1999;56(12):1073–1086. doi:10.1001/archpsyc.56.12.1073 [CrossRef] PMID:10591283
  18. Atomoxetine. Package insert. Eli Lilly and Company; 2003.
  19. Geller D, Donnelly C, Lopez F, et al. Atomoxetine treatment for pediatric patients with attention-deficit/hyperactivity disorder with comorbid anxiety disorder. J Am Acad Child Adolesc Psychiatry.2007;46(9):1119–1127. doi:10.1097/chi.0b013e3180ca8385 [CrossRef] PMID:17712235
  20. Snircova E, Marcincakova-Husarova V, Hrtanek I, Kulhan T, Ondrejka I, Nosalova G. Anxiety reduction on atomoxetine and methylphenidate medication in children with ADHD. Pediatr Int (Roma). 2016;58(6):476–481. doi:10.1111/ped.12847 [CrossRef] PMID:26579704
  21. Strawn JR, Compton SN, Robertson B, Albano AM, Hamdani M, Rynn MA. Extended release guanfacine in pediatric anxiety disorders: a pilot, randomized, placebo-controlled trial. J Child Adolesc Psychopharmacol. 2017;27(1):29–37. doi:10.1089/cap.2016.0132 [CrossRef] PMID:28165762
  22. Wolraich M, Brown L, Brown RT, et al. Steering Committee on Quality Improvement and Management. ADHD: clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics. 2011;128(5):1007–1022. doi:10.1542/peds.2011-2654 [CrossRef] PMID:22003063
Authors

Daniel Janiczak, MD, is a Fellow in Child and Adolescent Psychiatry, Northwestern University Feinberg School of Medicine. Marisa Perez-Reisler, MD, is a Staff Psychiatrist, Pritzker Department of Psychiatry and Behavioral Health, Ann & Robert H. Lurie Children's Hospital of Chicago; and an Assistant Professor, Northwestern University Feinberg School of Medicine. Rachel Ballard, MD, is an Attending Psychiatrist, Pritzker Department of Psychiatry and Behavioral Health, Ann & Robert H. Lurie Children's Hospital of Chicago; and a Professor of Child and Adolescent Psychiatry and of Pediatrics, Northwestern University Feinberg School of Medicine.

Address correspondence to Daniel Janiczak, MD, Ann & Robert H. Lurie Children's Hospital of Chicago, 225 E. Chicago Avenue, Box 10, Chicago, IL 60611; email: djaniczak@luriechildrens.org.

Disclosure: Marisa Perez-Reisler discloses that her spouse is a consultant for Otsuka Pharmaceuticals. The remaining authors have no relevant financial relationships to disclose.

The authors thank the Pritzker Foundation for their support of our efforts to improve mental health care access and treatment.

10.3928/19382359-20200922-01

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