ADHD Treatment Strategies Are Based on Evidence

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 action^12-17:

• 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

NONPHARMACOLOGIC TREATMENT

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

• 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

PATIENT RELUCTANCE

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 2^2,24).^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.

CONCLUSION

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.

References

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• 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.
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• Arnsten AF, Li BM. Neurobiology of executive functions: catecholamine influences on prefrontal cortical functions. Biol Psychiatry. 2005;57:1377-1384.
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• 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.
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• 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.
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• 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.
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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.