ADHD

A Look at Effects of Stimulant Treatment on ADHD

Researchers are working to gain a better understanding of long-term impacts.

Posted Jan 15, 2015

by Leslie Matuszewich, Ph.D., and Mercedes McWaters, guest contributors

Medication is an effective approach to helping children diagnosed with Attention Deficit Hyperactivity Disorder (ADHD), but more research is needed to explore the long-term effects on the brain.

Most of us are aware of the fact that ADHD is often treated with stimulant medications. While there are well-documented, short-term benefits of this type of treatment, the long-term effects are still being studied. This post discusses how the medications act in the brain immediately, helping symptoms of ADHD, and then touches on some of the issues surrounding long-term effects on behavior and brain functioning.

ADHD can make it difficult for children to succeed in school and disrupt functioning in other areas of their everyday lives. About 6.4 million U.S. children have been diagnosed with ADHD (Centers for Disease Control and Prevention [CDC], 2011) and the most common treatment approach is stimulant medication (Barbaresi et al., 2006). Stimulant treatments for ADHD include Ritalin, Concerta, Focalin, Metadate and Adderall.

Stimulant treatment has been used to help reduce the two major symptoms of ADHD: 1) inattention and 2) hyperactivity and impulsivity (American Psychiatric Association, 2013). Some children display both symptoms, while others exhibit primarily only one symptom. Frequently recognized behaviors associated with ADHD include:

1. Inattention – behaviors such as forgetting to complete homework, having difficulty organizing or planning a task, or trouble following instructions.

2. Hyperactivity and impulsivity – behaviors such as difficulty remaining in a seat, speaking out of turn, or engaging in too many tasks at once (see http://www.cdc.gov/ncbddd/adhd/research.html).

These ADHD symptoms are thought to stem from improper levels of chemical messengers, or neurotransmitters, in the brain. Two critical neurotransmitters are dopamine and norepinephrine. Their action and signaling mechanisms within many brain regions are essential for the regulation of attention and behavior (http://www.adhdandyou.com/hcp/neurobehavioral-disorder.aspx).

For individuals with ADHD, stimulant treatment helps to maintain optimal levels of dopamine and norepinephrine in the frontal cortex and other critical brain regions. The proper levels of these neurotransmitters help to reduce hyperactivity, inattention, and impulsivity (Arnsten 2009 for review).

While a particular medication may not clinically benefit all individuals for all symptoms, there are substantial benefits for many individuals (Fredriksen et al., 2012; Parker et al., 2013). As each type of medication differs slightly, different children might respond better to one type of medication compared to another. Unfortunately, there is no perfect method of determining the ‘best’ medication; often this process consists of trial and error.

Americans have reported concerns about pharmacological approaches to treatment, including their effectiveness and side effects, such as sleep abnormalities, loss of appetite, and nervousness. (For more discussion, see http://www.cdc.gov/ncbddd/adhd/research.html). These effects are important to consider.

Another concern with treating children with stimulants for ADHD is the long-term effects on the developing brain. During the ages that many children and adolescents receive stimulant medication for ADHD, the brain is still changing and maturing (Andersen, 2005). It is important to understand the effects of these medications on the brain after months or years of treatment.

A recent research paper reviewed much of the available information on brain structures of children with ADHD. Overall, the authors found that some areas of the brain in children with ADHD were reduced in volume compared to children of similar ages without ADHD. Stimulant treatment “normalized” particular brain regions, such that they were similar to children not diagnosed with ADHD (Schweren et al, 2013).

However, it is very difficult to study long-term effects of stimulant treatment in human children. Every child enters a study with a different treatment background (e.g. Ritalin v. Adderall, 2 years v. 6 years of treatment) and it makes it difficult to determine the cause of changes to the brain.

Our laboratory and others have recently studied stimulant treatment in young rats during their “childhood” ages. The lifespan of rats (~2 years) is shorter than humans and all developmental stages are faster, although similar to humans (Andersen, 2005), which makes rats very useful for studying ADHD medication and the brain. Rats can be given Ritalin orally, similar to a child, either on a cookie or in drinking water each day during their childhood years, and then tested in adulthood.

Initial findings from our laboratory suggest that adult female rats perform better on learning and memory tasks when given Ritalin as young rats, compared to female rats given no treatment. Unexpectedly, male rats given Ritalin performed the same as untreated rats in the same learning task, suggesting that the differences in stimulant treatment might depend upon gender. We hope to determine where in the brain Ritalin facilitates the behavioral improvements in female rats seen months after the last treatment.

In conclusion, scientific understanding of the fast actions of stimulant medication in the brain is quite clear, such that stimulants change the neurotransmitter levels. But the long-term effects of childhood stimulant treatment on the brain are still being measured (Molina et al., 2009).

More research is helping us to understand whether there are treatment approaches for childhood ADHD that could result in enhanced learning and memory throughout a lifetime. Indeed, that would be an exciting possibility for those who suffer from the disorder.

Leslie Matuszewich is an associate professor of psychology at Northern Illinois University. She is in the neuroscience and behavior program and teaches courses in biopsychology, research methods and psychopharmacology. Her research interests include the effects of chronic stress on brain function and behaviors, sex differences in motivated behaviors, and long-term effects of early stimulant exposure.

Mercedes McWaters is a graduate student in the Neuroscience and Behavior psychology program at Northern Illinois University. Her research interests include the long-term effects of early stimulant exposure, motivation, and the effects of stress on the brain and behavior.

References

American Psychiatric Association. (2013). Attention Deficit/Hyperactivity Disorder. In Diagnostic and statistical manual of mental disorder (5th ed.). http://www.psychiatry.org/file%20library/practice/dsm/dsm-5/dsm-5-adhd-f...

Anderson, S.L. (2005). Stimulants in the developing brain. Trends in Pharmacological Sciences, 26(5), 237-243.

Arnsten, A.F.T. (2009). The emerging neurobiology of attention deficit hyperactivity disorder: The key role of the prefrontal association cortex. Journal of Pediatric Psychology, 154(5).

Barbaresi, W.J., Katusic, S.K., Colligan, R.C., Weaver, A.L., Leibson, C.L., Jacobsen, S.J. (2006) Long-term stimulant medication treatment of attention-deficit/hyperactivity disorder: results from a population-based study. Journal of Development Behavior Pediatrics, 27(1), 1-10.

Bussing, R., Zima, B.T., Mason, D.M., Meyer, J.M., White, K., & Garvan, C.W. (2012). ADHD knowledge, perceptions and information sources: Perspectives from a community sample of adolescents and their parents. Journal of Adolescent Health, 51(6), 593-600.

Centers for Disease Control and Prevention (CDC). (2011). Attention-Deficit/Hyperactivity Disorder (ADHD). Retrieved from http://www.cdc.gov/ncbddd/adhd/data.html 30, 419-427.

Fredriksen, M., Halmoy, A., Faraone, S.V. & Haavik, J. (2013) Long-term efficacy and safety of treatment with stimulants and atomoxetine in adult ADHD: a review of controlled and naturalistic studies. European Neuropsychopharmacology, 23(6): 508-527.

Johnston, C., Hommersen, P., & Seipp, C. (2008). Acceptability of behavioral and pharmacological treatments for attention-deficit/hyperactivity disorder: relations to child and parent characteristics. Behavior Therapy, 39(1), 22-32.

Molina, B.S, Hinshaw S.P., Swanson J.M., Arnold L.E., Vitiello B., Jensen P.S., . . . MTA Cooperative Group. (2009). The MTA at 8 years: prospective follow-up of children treated for combined-type ADHD in a multisite study. Journal of the American Academy of Child and Adolescent Psychiatry, 48(5):484-500.

Parker, J., Wales, G., Chalhoub, N., Harpin, V. (2013) The long-term outcomes of interventions for the management of attention-deficit hyperactivity disorder in children and adolescents: a systematic review of randomized controlled trials. Psychology Research and Behavior Management, 6: 87-99.

Schweren LJ, de Zeeuw P, Durston S. (2013) MR imaging of the effects of methylphenidate on brain structure and function in attention-deficit/hyperactivity disorder. European Neuropsychopharmacology, 23(10):1151-64.