Long-term Benefits and Safety of ADHD Drug Treatment

ADHD Drug Treatment in the Long-Term


Long-term Safety and Benefits of ADHD Drug Treatment 


Two thirds of patients prescribed ADHD medication stop taking it within a year. Patients stop their medications for all sorts of reasons including side effects, a mistrust of pharmaceutical manufacturers or of the health care system, costs, etc.  Patients with Inattentive ADD (ADHD-PI, Inattentive ADHD) may find stimulant medication difficult to stay on because of side effects such as sluggishness, depression or anxiety but other patients and parents stop because of concerns regarding the the long term safety and benefits of ADHD drug treatments.

Those of us with children on stimulant medication have nagging concerns about the long-term brain changes brought about by ADHD drug treatment, the brain changes that will persist into adulthood, and about whether these permanent brain changes will be beneficial or not.  There is little disagreement, in the medical community, about the long term effects of not treating ADHD. Researchers and medical providers or all specialties agree that ADHD should be diagnosed early and treated immediately. The reason for this unanimous conclusion is related to the findings from research studies that have followed people with ADHD over long periods of time. These studies, called longitudinal studies, are expensive and difficult to perform but the findings from these studies also carry a great deal of weight.

There have been several longitudinal studies looking at what happens to untreated kids with ADHD when they reach adulthood. The results of these longitudinal studies have consistently shown that untreated ADHD results in increased risks of:
  • · Poor academic outcomes 
  • · Poor job related outcomes 
  • · Mood disorders 
  • · Addictive disorders 
  • · Adolescent and Young Adult delinquency 
Despite an understanding of the negative risks associated with non-treatment, many patients and parents have concerns regarding the long term benefits of drug therapy as well as the long term risks. The most loudly voiced concerns regarding risks involve questions about stimulant treatment and:
The majority of longitudinal studies performed looking at these three specific risks have found that there are no long term cardiac risks from the use of ADHD stimulants, that stimulant use may, in fact, lower not increase the risk of illegal drug use, and that stimulants do cause small reductions in weight and bone growth.

The question of ADHD drug treatment and academic success is less certain. While it is clear that not treating ADHD results in more academic failure. There is little persuasive evidence that patients that are treated with drug therapy fare much better. A longitudinal review study looking at almost 9000 patients with ADHD found that long-term medication use was associated with small improvements in standardized test scores but the evidence for long-term improvements in school grades and grade retention was less compelling.

Other questions such as whether the stimulants permanently change the size or connectivity of the brain, whether the stimulants enable brain plasticity changes that are beneficial in the long term and whether stimulants cause permanent genetic or epigenetic changes that are beneficial or detrimental are more difficult to answer. Some animal and human longitudinal studies have suggested that there are no permanent neurological or genetic changes that result from ADHD drug treatment but other studies have suggested just the opposite.

While these research questions are important and have, as of yet, not been answered, most patients, parents and providers are more concerned with more practical matters such as whether continued stimulant medication use results in any permanent brain improvement or deterioration.

I will discuss these questions in my next post. I have included references for those of you that would like to read more about these important issues.



Clin Child Fam Psychol Rev. 2012 Sep;15(3):215-33. doi: 10.1007/s10567-012-0117-8.
Does long-term medication use improve the academic outcomes of youth with attention-deficit/hyperactivity disorder?
Langberg JM, Becker SP.

J Child Adolesc Psychopharmacol. 2010 Oct;20(5):387-93. doi: 10.1089/cap.2009.0107.
Childhood stimulant treatment and teen depression: is there a relationship?
Staikova E, Marks DJ, Miller CJ, Newcorn JH, Halperin JM.
Source
Queens College, City University of New York, Flushing, New York 11367, USA.

Psychopharmacology (Berl). 2011 Jun;215(3):467-81. doi: 10.1007/s00213-011-2166-y. Epub 2011 Feb 8.
Reward processing in male adults with childhood ADHD--a comparison between drug-naïve and methylphenidate-treated subjects.
Stoy M, Schlagenhauf F, Schlochtermeier L, Wrase J, Knutson B, Lehmkuhl U, Huss M, Heinz A, Ströhle A.

J Neurosci. 2012 Jan 18;32(3):841-9. doi: 10.1523/JNEUROSCI.4461-11.2012.
Methylphenidate-elicited dopamine increases in ventral striatum are associated with long-term symptom improvement in adults with attention deficit hyperactivity disorder.
Volkow ND, Wang GJ, Tomasi D, Kollins SH, Wigal TL, Newcorn JH, Telang FW, Fowler JS, Logan J, Wong CT, Swanson JM.

J Clin Psychiatry. 2012 Jul;73(7):941-50. doi: 10.4088/JCP.11m07529.
Adult outcome of attention-deficit/hyperactivity disorder: a controlled 16-year follow-up study.
Biederman J, Petty CR, Woodworth KY, Lomedico A, Hyder LL, Faraone SV.

Am J Prev Med. 2012 Aug;43(2 Suppl 1):S57-66. doi: 10.1016/j.amepre.2012.04.023.
Risk and direct protective factors for youth violence: results from the National Longitudinal Study of Adolescent Health.
Bernat DH, Oakes JM, Pettingell SL, Resnick M.




Biol Psychiatry. 2003 Dec 15;54(12):1330-7.
Enduring behavioral effects of early exposure to methylphenidate in rats.
Carlezon WA Jr, Mague SD, Andersen SL.

Fischer, M., Barkley, R.A., Smallish, L., Fletcher, K. (2005). Executive function in hyperactive children as young adults: attention, inhibition, response perseveration, and the impact of comorbidity. Developmental Neuropsychology. 27 (1), 107-133.

Improving Long-term Efficacy and Effectiveness Outcomes in ADHD: A Treatment Development Workshop
National Institute of Mental Health (NIMH)
Division of Pediatric Translational Research and Treatment Development (DPTR)
Division of Services and Intervention Research (DSIR)
March 12, 2007 – March 13, 2007

Brain Struct Funct. 2012 Nov 27. [Epub ahead of print]
Stimulant drugs trigger transient volumetric changes in the human ventral striatum.
Hoekzema E, Carmona S, Ramos-Quiroga JA, Canals C, Moreno A, Fernández VR, Picado M, Bosch R, Duñó L, Soliva JC, Rovira M, Bulbena A, Tobeña A, Casas M, Vilarroya O.

Eur Neuropsychopharmacol. 2012 Nov 16. pii: S0924-977X(12)00305-7. doi: 10.1016/j.euroneuro.2012.10.014. [Epub ahead of print]
MR imaging of the effects of methylphenidate on brain structure and function in Attention-Deficit/Hyperactivity Disorder.
Schweren LJ, de Zeeuw P, Durston S.

Behav Sci Law. 2012 Mar-Apr;30(2):121-39. doi: 10.1002/bsl.2005. Epub 2012 Feb 28.
ADHD and delinquency--a developmental perspective.
von Polier GG, Vloet TD, Herpertz-Dahlmann B.

Eur Neuropsychopharmacol. 2012 Aug 20. [Epub ahead of print]
Long-term efficacy and safety of treatment with stimulants and atomoxetine in adult ADHD: A review of controlled and naturalistic studies.
Fredriksen M, Halmøy A, Faraone SV, Haavik J.

Int J Pediatr Endocrinol. 2012 Dec 5;2012(1):30. [Epub ahead of print]
Weight loss on stimulant medication: how does it affect body composition and bone metabolism? -- A prospective longitudinal study.
Poulton A, Briody J, McCorquodale T, Melzer E, Herrmann M, Baur LA, Duque G.

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