ADHD Treatment Strategies Are Based on Evidence

Pharmacy TimesApril 2019 Mental Health
Volume 85
Issue 4

It is critical to stress that Attention-Deficit/Hyperactivity Disorder is probably a lifelong condition for most individuals with the condition.

Pharmacists may envision children who act without thinking, have difficulty paying attention, and squirm in their seats when they think about attention-deficit/hyperactivity disorder (ADHD). But ADHD, which affects an estimated 3% to 5% of Americans,1 occurs in individuals of all ages. Characterized by hyperactivity that is impairing and pervasive, inattention, and impulsivity, ADHD creates problems that can interfere with school, social life, and work.2 These problems tend to change over time (online figure). A growing concern is that the use of social media is being linked to increased symptoms in children.3

Experts are concerned that health professionals are not identifying and treating individuals with ADHD as aggressively as they could.4-8 Several recent meta-analyses confirm pharmacological treatment’s short-term efficacy—and long-term efficacy to a lesser extent.4-8 Research into nonpharmacological interventions (table 12) is less robust. For this reason, experts recommend prescribing behavioral interventions, in combination with medication, as the benefits outweigh the risks.

Researchers think that most ADHD medications work at the catecholamine pathways.9 They appear to increase the availability of synaptic dopamine or norepinephrine (eg, by blocking reuptake). Some study results indicate that individuals with untreated ADHD have dopamine deficits associated with low dopamine transporter (DAT) density. In individuals treated with stimulants, position-emission tomography imaging studies indicate transporter density increases with chronic treatment.9-11

Each medication has a specific mechanism of action12-17:

  • Amoxetine inhibits the norepinephrine transporter 1 and increases norepinephrine neu- rotransmission in the brain and dopamine in the prefrontal cortex. This is important because this area has few DATs.13
  • Amphetamine and methyphenidate inhibit DAT and norepinephrine transporters, functioning as reuptake inhibitors increasing neurotransmission.
  • Clonidine and guanfacine stimulate alpha-2 nor-adrenaline receptors in the central nervous system.
  • Bupropion is converted into 2 potent norepinephrine enhancers: hydroxybupropion and threohydrobupropion.
  • Tricyclic antidepressants block serotonin and norepinephrine transporters to enhance neurotransmission with little effect on DATs.
  • Modafinil induces an atypical conformational change in the monoamine transporter DAT.

Most drugs in development for ADHD focus on enhancing dopamine and norepinephrine levels, the traditional approach; enhancing drug delivery; and prolonging drug half-life.2


Most guidelines recommend parent behavioral training and social skills training for nonpharmacologic treatment.4-6 These interven- tions are critical in 2 specific populations4-6:

  • Children younger than 6 years, because drugs have been poorly studied in this population.
  • Individuals with severe ADHD at any age (ie, add cognitive behavioral therapy to the patient’s medication)

Meta-analyses indicate that individuals with ADHD who received nonpharmaccologic treatment had better long-term outcomes than their nontreated counterparts. Combined pharmacologic and non- pharmacologic treatment led to better outcomes than either alone.18


Many patients or their parents are reluctant to start or consid- er drug therapy for ADHD.19 Clinicians also can be somewhat reluctant to diagnose ADHD.20,21 Therefore, pharmacists need to discuss the evidence behind ADHD medications and their potential adverse effects (AEs) in patient-friendly language. They also need to solicit questions. It is critical to stress that evidence now indicates that ADHD is probably a lifelong condition for most.

The main concerns about treatment include the controlled status of stimulants and potential abuse, as well as the need for multiple daily doses. In addition, stimulant abuse problems receive considerable media attention and can be a barrier.22,23 Parents also worry about their children being labeled or stigmatized.21

Parents often think that their children will “grow out of it” or be concerned about AEs, especially growth delays (table 22,24).19,20 Working with clinicians, parents, and teachers to establish a patient’s behavior and sleep baseline before starting medication helps avoid blaming medicine for preexisting problems. If AEs occur, changing the dose, formulation, or medication may provide relief.


Managing ADHD symptoms and encouraging adherence requires discussions among caregivers, clinicians, and patients. Abuse potential, AEs, duration of action, effectiveness, and parental or patient preferences will guide treatment. Routine follow up and monitoring must guide decisions to adjust treatment.


  • 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;164:942-948.
  • Caye A, Swanson JM, Coghill D, Rohde LA. Treatment strategies for ADHD: an evidence-based guide to select optimal treatment. Mol Psychiatry. 2018 Jun 28. doi: 10.1038/s41380-018-0116-3. [Epub ahead of print]
  • Ra CK, Cho J, Stone MD, et al. Association of digital media use with subsequent symptoms of attention-deficit/hyperactivity disorder among adolescents. JAMA. 2018;320(3):255-263.
  • Excellence NIfC. Attention deficit hyperactivity disorder: the NICE guideline on diagnosis and management of ADHD in children, young people and adults. London: The British Psychological Society and the Royal College of Psychiatrists; 2009.
  • Subcommittee on Attention-Deficit/Hyperactivity D, Steering Committee on Quality I, Management, Wolraich M, Brown L, Brown RT, et al. ADHD: clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics. 2011;128:1007—1022.
  • Pliszka S, Issues AWGoQ. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2007;46:894—921.
  • Canadian Attention Deficit Hyperactivity Disorder Resource Alliance (CADDRA). Canadian ADHD practice guidelines. Third Edition. Toronto, ON: CADDRA; 2011.
  • Bolea-Alamanac B, Nutt DJ, Adamou M, et al. Evidence-based guidelines for the pharmacological management of attention deficit hyperactivity disorder: update on recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2014;28:179—203.
  • Arnsten AF, Li BM. Neurobiology of executive functions: catecholamine influences on prefrontal cortical functions. Biol Psychiatry. 2005;57:1377-1384.
  • Dougherty DD, Bonab AA, Spencer TJ, Rauch SL, Madras BK, Fischman AJ. Dopamine transporter density in patients with attention deficit hyperactivity disorder. Lancet. 1999;354:2132-2133.
  • Krause KH, Dresel S, Krause J, Kung HF, Tatsch K, Lochmuller H. Elevated striatal dopamine transporter in a drug naive patient with Tourette syndrome and attention deficit/ hyperactivity disorder: positive effect of methylphenidate. J Neurol. 2002;249:1116—1118.
  • Wilens TE. Effects of methylphenidate on the catecholaminergic system in attention-deficit/hyperactivity disorder. J Clin Psychopharmacol. 2008;28:S46-S53.
  • Swanson CJ, Perry KW, Koch-Krueger S, et al. Effect of the attention deficit/hyperactivity disorder drug atomoxetine on extracellular concentrations of norepinephrine and dopamine in several brain regions of the rat. Neuropharmacology. 2006;50:755-760.
  • Arnsten AF. The use of α-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder. Expert Rev Neurother. 2010;10:1595-1605.
  • Learned-Coughlin SM, Bergstrom M, et al. In vivo activity of bupropion at the human dopamine transporter as measured by positron emission tomography. Biol Psychiatry. 2003;54:800-805.
  • Goodman R, Ford T, Richards H, Gatward R, Meltzer H. The Development and Well-Being Assessment: description and initial validation of an integrated assessment of child and adolescent psychopathology. J Child Psychol Psychiatry. 2000;41:645-655.
  • Schmitt KC, Reith ME. The atypical stimulant and nootropic modafinil interacts with the dopamine transporter in a different manner than classical cocaine-like inhibitors. PLoS ONE. 2011;6:e25790.
  • Arnold LE, Hodgkins P, Caci H, Kahle J, Young S. Effect of treatment modality on long-term outcomes in attention-deficit/hyperactivity disorder: a systematic review. PLoS ONE. 2015;10:e0116407.
  • Canela C, Buadze A, Dube A, Eich D, Liebrenz M. Attitudes toward stimulant treatment of offspring of adult patients with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2017;27(5):422-428.
  • Adler LA, Barkley RA, Newcorn JH. Performance improvement CME: adult ADHD. J Clin Psychiatry. 2011;72(4):e15.
  • Tatlow-Golden M, Prihodova L, Gavin B, Cullen W, McNicholas F. What do general practitioners know about ADHD? Attitudes and knowledge among first-contact gatekeepers: systematic narrative review. BMC Fam Pract. 2016;17(1):129.
  • Burtner J, Behling M, Cassidy T, Butler SF. Prevalence of nonmedical use and routes of administration for prescription stimulant medications among adults in a substance abuse treatment population. J Addict Dis. 2018:1-12.
  • Cassidy TA, Varughese S, Russo L, Budman SH, Eaton TA, Butler SF. Nonmedical use and diversion of ADHD stimulants among U.S. adults Ages 18-49: A national Internet survey. J Atten Disord. 2015;19(7):630-440.
  • Boorady R. Side Effects of ADHD Medication. Child Mind Institute. Accessed February 1, 2019.

Jeannette Y. Wick, MBA, RPh, FASCP, is an assistant director of the Office of Pharmacy Professional Development at the University of Connecticut School of Pharmacy in Storrs.

Related Videos
Practice Pearl #1 Active Surveillance vs Treatment in Patients with NETs
© 2024 MJH Life Sciences

All rights reserved.