CPNP 2021 Spotlight: Stimulant Treatment for ADHD in Complex Cases

Michael Shuman, PharmD, BCPP, Staff Pharmacist
Central State Hospital, Lousiville, KY

At CPNP 2021, longstanding member Dr. Julie Dopheide provided an informative discussion on utilization of stimulants for attention deficit/hyperactivity disorder (ADHD) treatment across the lifespan. She started the presentation by pointing out that 5-10% of children carry a diagnosis of ADHD, with as many as 75% display symptoms that persist into adolescence and 50% into adulthood.^1-2 Furthermore, a subset may meet criteria for what is known as complex ADHD (slide 10).

As a result, it is crucially important to understand unique variables that would influence the risk and benefit of pharmacotherapy in each stage of life. For example, as many as 50% of persons diagnosed with ADHD have a comorbid conduct disorder or oppositional defiant disorder.^3-4 In such cases, once optimizing a stimulant dose, there may be additional benefit from augmentation with alpha₂ agonist or risperidone.

The first case discussed by Dr. Dopheide was that of Max, a four-year-old boy who was recently asked to not come back to his preschool program due to his hyperactive and oppositional behavior (again recall the high co-occurrence of these two conditions). Given his current age, she explains that methylphenidate would be the best option for starting pharmacologic treatment (assuming behavioral interventions were trialed initially and insufficient), with lisdexamfetamine a second-line option.^5-6 While mixed amphetamine salts are also available, there is literature which indicates that children do not tolerate these products as well and experience more side effects (i.e, headaches, anorexia, insomnia, and weight loss) when compared to methylphenidate.⁷

The second case discussed Angel, a 14 year old girl with history of autism spectrum disorder (ASD) and a mild intellectual disability (ID) who was recently diagnosed with complex ADHD. Audience members were advised that up to 25% of individuals with ASD also meet criteria for an ADHD diagnosis and that some may also demonstrate intellectual disability (ID).³ But how do these factors affect treatment decisions? Dr. Dopheide states that methylphenidate remains a first-line option for individuals with ASD and ADHD; however, response rates are lower in those with ASD compared to ADHD on its own.^3,8-9 Furthermore, side effects are more commonly reported, which results in higher discontinuation rates. Similar to patients with ASD and ADHD, methylphenidate also has the best evidence supporting its use among those with ID.¹⁰ In both ID and comorbid ASD, Alpha 2 agonists and guanfacine are second line options, with less evidence to support use of other stimulants besides methylphenidate.^3,8-10

The third case discussed  Cassie, a 32 year old woman who was first diagnosed with ADHD at age 18. Past medical history also included cannabis use disorder and morbid obesity; after bariatric surgery at age 22, she was noted to have lost 200 pounds. Family history included a mother with depression and anxiety and an uncle with ADHD who died by suicide. Dr. Dopheide used the case to compare and contrast ADHD symptoms in children and adults. She reminded the audience that among adults, symptoms such as inattention, impulsivity, and emotional dysregulation are more common with lower prevalence of hyperactivity.¹¹ Cassie’s case was also used to discuss examples of specific medical and psychiatric conditions which may increase risk of complex ADHD (slide 37).

Unlike in children, amphetamine formulations are associated with greater efficacy among adults and as a result are considered first line rather over methylphenidate products.^12-13 Of these, lisdexamfetamine was mentioned as the lone agent with approval for both Binge Eating Disorder and ADHD. Dr. Dopheide concluded Cassie’s case by discussing interactions between substance use, stimulants, and cardiovascular side effects. She notes that early recognition and treatment of ADHD may actually lower future rates of substance abuse.^14-16 One study found higher rate of cardiac events among individuals prescribed stimulants.¹⁷ Cannabis use may further increase blood pressure and heart rate.¹⁸

Take-Home Points

• ADHD is not simply a childhood condition but may persist across an individual’s lifespan
• Certain symptoms are less common later in life; adults are less likely to present with symptoms of hyperactivity
• Stimulants are first-line pharmacologic interventions regardless of population. Among children methylphenidate is preferred due to a more favorable safety profile, while for adults amphetamine products are preferred due to greater efficacy
• Treating ADHD early may actually reduce rates of substance abuse

References

1. Wolraich ML, Hagan JF Jr, Allan C, et al. Clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics. 2019; 144(4):e20192528.
2. Bijlenga D, Ulberstad F, Thorell LB, et al. Objective assessment of attention-deficit/hyperactivity disorder in older adults compared with controls using the QbTest. Int J Geriatr Psychiatry. 2019; 34(10): 1526-33.
3. Barbaresi WJ, Campbell L, Diekroger EA, et al. Clinical practice guideline for the assessment and treatment of children and adolescents with complex ADHD. J Developmental and Behavioral Pediatrics 2020; 41: S35-57.
4. Dopheide JA, Stutzman DL, Pliszka SR. ADHD. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, editors. Pharmacotherapy: A Pathophysiologic Approach. 11th ed. Columbus (OH): McGraw-Hill; 2019.
5. Wigal S, Chappell P, Palumbo D, et al. Diagnosis and treatment options for preschoolers with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2020; 30(2): 104-18.
6. Childress AC, Findling RL, Wu J, et al. Lisdexamfetamine dimesylate for preschool children with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2020; 30(3): 128-136.
7. Clavenna A, Bonati M. Safety of medicines used for ADHD in children: a review of published prospective clinical trials. Arch Dis Child. 2014; 99(9): 866-72.
8. Scahill L, Bearss K, Sarhangian R, et al. Using a patient-centered outcome measure to test methylphenidate versus placebo in children with autism spectrum disorder. J Child Adolesc Psychopharmacol. 2017; 27(2): 125-31.
9. Sturman N, Deckx L, van Driel ML. Methylphenidate for children and adolescents with autism spectrum disorder. Cochrane Database Syst Rev. 2017; 11(11): CD011144.
10. Miller J, Perera B, Shankar R. Clinical guidance on pharmacotherapy for the treatment of attention-deficit hyperactivity disorder (ADHD) for people with intellectual disability. Expert Opin Pharmacother. 2020; 21(15): 1897-1913.
11. Kooij JJS, Bijlenga D, Salerno L, et al. Updated European Consensus Statement on diagnosis and treatment of adult ADHD. Eur Psychiatry. 2019; 56: 14-34.
12. Cortese S, Adamo N, Del Giovane C, et al. Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: A systematic review and network meta-analysis. Lancet Psychiatry. 2018; 5(9): 727-38.
13. Steingard R, Taskiran S, Connor DF, Markowitz JS, Stein MA. New formulations of stimulants: An update for clinicians. J Child Adolesc Psychopharmacol. 2019; 29(5): 324-39.
14. Wimberley T, Agerbo E, Horsdal HT, et al. Genetic liability to ADHD and substance use disorders in individuals with ADHD. Addiction. 2020; 115(7): 1368-377.
15. Molina BSG, Howard AL, Swanson JM, et al. Substance use through adolescence into early adulthood after childhood-diagnosed ADHD: Findings from the MTA longitudinal study. J Child Psychol Psychiatry. 2018; 59(6): 692-702.
16. McCabe SE, Dickinson K, West BT, Wilens TE. Age of onset, duration, and type of medication therapy for attention-deficit/hyperactivity disorder and substance use during adolescence: A multi-cohort national study. J Am Acad Child Adolesc Psychiatry. 2016; 55(6): 479-86.
17. Dalsgaard S, Kvist AP, Leckman JF, Nielsen HS, Simonsen M. Cardiovascular safety of stimulants in children with attention-deficit/hyperactivity disorder: a nationwide prospective cohort study. J Child Adolesc Psychopharmacol. 2014; 24(6): 302-10.
18. Notzon DP, Pavlicova M, Glass A, et al. ADHD Is highly prevalent in patients seeking treatment for cannabis use disorders. J Atten Disord. 2020; 24(11): 1487-92.