©2019 by Martin Whitely. Proudly created with Wix.com

Contact Us

ADHD Medications/Drugs

Although the behavioural basis of the diagnosis is controversial, the use of pharmaceutical interventions to treat the disorder is the primary source of controversy. Psychostimulants (amphetamines, near amphetamines and in the USA methamphetamine) are the most common class of drugs used to treat ADHD. Other non-pharmaceutical approaches to managing ADHD are discussed further below.

Stimulants

 

The most commonly used drugs to treat ADHD are psychostimulants containing dexamphetamine (brand names Adderall, Dexedrine, Dexostrat and Vyvanse) and methylphenidate (Ritalin, Concerta and Attenta) which temporarily enhance the uptake of dopamine in the brain.[1][2]  It is a common misconception that if a low dose stimulant narrows focus or calms a child that they must have ADHD.  With a low oral dose of stimulants most people regardless of their ADHD status become more narrowly focussed and compliant.[3]  This misconception has extended to the use of stimulants as a diagnostic tool.  The erroneous logic being that if an ADHD diagnosed child’s behaviour is modified after taking stimulants this confirms the diagnosis.

Stimulant behavioural effects are short-lived, lasting a matter of hours.  When the medications wear off there are often withdrawal effects that can be “worse than the child’s original or baseline behaviour” even after a single dose.[4]  However, there are a number of slow or extended release formulations of stimulants that have a number of benefits including less fluctuation in effective dosage, reduced need for top up doses during the school-day, and reduced risk of school yard diversion for non-medical use.[5]

Potential Adverse Effects of Stimulants- The use of stimulant medications may cause the following short term adverse events:

  • Increased blood pressure and heart rate.  In very rare cases where there is pre-existing cardiac abnormalities or other serious heart problems heart attacks, strokes and sudden deaths have occurred from taking usual doses in children and adolescents with pre-existing structural problems. Other cardiac reactions include angina, arrhythmia, palpitations and tachycardia.

  • Psychiatric Adverse Events - stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder. They may also cause a transient depressed mood and/or aggressive behavior.

  • Seizures - There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures.

  • Gastrointestinal reactions - abdominal pain, nausea.

  • Immune reactions - hypersensitivity reactions including skin rash, hives, fever, joint pain, and dermatitis.

  • Metabolism/Nutrition - anorexia, weight loss.

  • Nervous System Reactions - dizziness, drowsiness, dyskinesia, headache, toxic psychosis, exacerbation of motor and phonic tics, and Tourette syndrome

  • Obsessive-compulsive behaviours

  • Loss interest in social interactions

  • Blood/Lymphatic - leukopenia and/or anaemia.

  • Abnormal Liver Function – including in extreme cases liver failure.

  • Suppression of Growth

  • Depression

  • Insomnia

  • Stomach-ache

  • Appetite suppression. 

Less common side effects include hallucinations and hyper-excitability.[6]

Addiction and Abuse - Stimulant medications are pharmacologically similar to illicitly produced stimulants including methamphetamine and cocaine.[7]  In the USA methamphetamine (brand name Desoxyn) is approved for the treatment of ADHD in patients aged 6 and older.[8]

All prescription stimulants carry similar warnings to that for Dexedrine (dexamphetamine):

Amphetamines have a high potential for abuse. Administration of amphetamines for prolonged periods of time may lead to dependence and must be avoided. Particular attention should be paid to the possibility of subjects obtaining amphetamines for non-therapeutic use or distribution to others and the drugs should be prescribed and dispensed sparingly.[9]

Despite the potential for dependence and misuse, proponents contend that in the absence of controlled doses of prescription stimulants, or other less common pharmacological treatments, adolescents and adults with undiagnosed ADHD frequently use illicit drugs in uncontrolled doses.[10][11]  Numerous studies have found that undiagnosed and untreated ADHD significantly increases the risk of substance use disorders.[12]  Critics counter that these studies involve the retrospective diagnosis of a disorder which has onset in childhood and that “often stimulants become gateway drugs to illicit drugs”.[13] 

Editor's Comments: Proponents of ADHD prescribing are arguing that the best way to prevent impulsive and hyperactive children from becoming problematic drug users, is to give them a daily amphetamine habit. Do you believe them? I don't.

Long-term outcomes from Stimulant use for ADHD

Most of the studies into the efficacy of ADHD medications are short-term research trials that last no longer than a few months and primarily focus on short term symptom management. The ADHD Drug Effectiveness Review Project was a 2005 systematic review of all 2,287 studies that were identified through a comprehensive literature search.[15]  It was commissioned by fifteen US states in order to determine which ADHD medications were the safest and most cost effective.  The review concluded that “evidence on the effectiveness of pharmacotherapy for ADHD in young children is seriously lacking” and that there was “no evidence on long-term safety of drugs used to treat ADHD in adolescents”.  The review also found that “good quality evidence on the use of drugs to affect outcomes relating to global academic performance, consequences of risky behaviours, social achievements, etc. is lacking” and that overall the quality of evidence was poor.[15]  Since the publication of this review project, data has emerged in regards to the long term safety and efficacy of ADHD medications. 

The Multimodal Treatment Study for ADHD (the MTA Study) commenced in the late 1990’s compared the “benefits of multimodal and pharmacological interventions”.[16] While there were several methodological limitations, notably a lack of a placebo and blind raters, the MTA Study followed a significant number of children over several years.[17] The study compared intensive behavioural intervention, medication, these two treatments combined, and routine community care.[18]

After conducting the first fourteen months of the study the authors concluded that “carefully crafted medication management was superior to the behavioural treatment and to routine clinical care that included medication”.[19] However, in 2007, after an analysis of the three-year follow-up to the MTA Study[20], Pelham, one of the scientists who ran the study concluded: "I think we exaggerated the beneficial impact of medication in the first study. We had thought that children medicated longer would have better outcomes. That didn’t happen to be the case…In the short run [medication] will help the child behave better, in the long run it won’t. And that information should be made very clear to parents."[21]

The three-year MTA data also showed that children using behavioral therapy alone had “a slightly lower rate of substance abuse” and that “the [medicated] children had a substantial decrease in their rate of growth, so they weren’t growing as much as other kids in terms of both their height and their weight”.[21]  An 8-year MTA follow-up found no differences in outcomes for the four treatment groups, “demonstrating that regardless of treatment, participants showed improved outcomes (delinquency rating, reading and overall academic performance, and social skills) compared with baseline (pre-treatment)”.[22][23] 

Another longitudinal study, the Preschool Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS) also reported no long-term differences in “symptom severity… after adjustment for other variables” between ADHD diagnosed children “on and off” medication.[24]  The decreasing relative efficacy over time demonstrated in these studies supports the proposition that children mature at different rates and “that brains of children with ADHD, rather than developing abnormally (as in autism), mature later”.[25]

There is also evidence of sustained harms from stimulants among ADHD diagnosed children from long-term studies into children’s health and wellbeing conducted in Quebec, Canada and Western Australia.  The Quebec study, published in the Journal of Health Economics in 2014, followed the long term educational outcomes of 8,643 children of whom 9% had ever used stimulants for ADHD by age 16.[26]  The academic performance of the children medicated with stimulants for ADHD relative to their peers declined significantly in the years after commencing medication.  The Quebec study also found ADHD medicated children experienced deteriorations in “relationships with [their] parents” and “increases in the probability that a child has ever suffered from depression".[26]

The Western Australian study, the Raine ADHD Study: Long-term outcomes associated with stimulant medication in the treatment of ADHD in children, reviewed the ADHD related data from the Raine Study, a longitudinal health and well-being study of Western Australian children that began with a pre-birth cohort of 2,900 expectant mothers.[27]  By age fourteen, 131 of the remaining 1,785 children in the study had ever been diagnosed with ADHD.  Observations of these children at ages 5, 10 and 13, and found evidence of raised diastolic blood pressure persisting for a number of years after children received stimulants.[28]  In addition among the 131 ADHD diagnosed children twenty-nine never received medication. Among the ADHD diagnosed children “ever receiving stimulant medication was found to increase the odds of being identified as performing below age level by a classroom teacher by a factor of 10.5 times”.[29]  A significant part of the rationale for 'medicating' ADHD diagnosed children is the hypothesis that managing the symptoms of ADHD symptoms with stimulants “allows children to learn skills and concepts” and that this helps children to achieve improved long term education outcomes.[29] 

The long-term data from the natural experiments in Western Australia and Quebec provide disturbing evidence that the use of stimulants to treat ADHD may significantly impede long-term academic outcomes. There are also concerns about long term cardiovascular outcomes, there is research that indicates that the extended use of stimulants may permanently impair dopamine pathways[30] and may increase the risk of cancer.[31]

Non-Stimulant Medications

Apart from stimulants the most commonly used ADHD medications is Atomoxetine Hydrochloride (brand name Strattera). Other non-stimulant drugs occasionally used include Clonidine (brand name Kapvay)[32] and Guanfacine (brand name Intuniv)[33].  All carry significant warnings for potential adverse effects.

 

Atomoxetine (Strattera)

Atomoxetine is a noradrenaline reuptake inhibitor. It was first trialled in the 1980s as an antidepressant branded Tomoxetine but was found to be ineffective.[34] It was licensed in the USA in 2002 for the treatment of ADHD particularly in patients who don’t get a therapeutic response or who experience side effects from stimulant medication. Unlike stimulants, atomoxetine is not addictive and is not diverted for illicit use but does not have immediate effects and can take 4-8 weeks before it modifies ADHD behavioural symptoms.[35]

Since coming to market the US FDA has issued specific warnings on Strattera about the increased risk of:

  • “Severe liver injury [that] can progress to liver failure in a small percentage of patients” (2004).[36]

  • “Suicidal thinking in children and adolescents with ADHD.” This is a black box (the highest level) warning (2005).[37]

  • Elevated “heart rate and blood pressure” (2011).[38] 

There have been numerous reports of severe adverse events including completed suicides by children taking Strattera. However, because many adverse events are not reported to regulatory authorities the prevalence of these effects is not known.[39]

For more information on the history of Strattera in Australia click here.

 

References

[1]  Other less commonly used brand names for methylphenidate include Methylin, Daytrana, Rubifen, Equasym and Metadate.

[2]  The National Institute on Drug Abuse website. “(NIDA) is a United States federal-government research institute whose mission is to "lead the Nation in bringing the power of science to bear on drug abuse and addiction."  https://www.drugabuse.gov/publications/research-reports/prescription-drugs/stimulants/how-do-stimulants-affect-brain-body

[3]  Lydia Furman, ‘What is Attention-Deficit Hyperactivity Disorder (ADHD)?’, Journal of Child Neurology, Vol. 20 No. 12, 2005, p. 998. https://www.researchgate.net/profile/Lydia_Furman/publication/7354308_What_Is_Attention-Deficit_Hyperactivity_Disorder_ADHD/links/5555e9b508ae6fd2d8232e29.pdf 

[4]  J. L. Rapoport, M. S. Buchsbaum, et al., ‘Dextroamphetamine: cognitive and behavioural effects in normal prepubertal boys’, Science, Vol. 199, No. 4323, (3 February 1978), p. 561. The dose was 0.5mg/kg. https://www.researchgate.net/profile/Christy_Ludlow/publication/22798084_DextroamphetamineCognitive_and_behavioral_effects_in_normal_prepubertal_boys/links/5597e85708ae5d8f3933c33a/DextroamphetamineCognitive-and-behavioral-effects-in-normal-prepubertal-boys.pdf

[5]  Elisa CascadeAmir H. Kalali, MD, and Richard H. Weisler, MD Short-acting versus Long-acting Medications for the Treatment of ADHD Psychiatry (Edgmont). 2008 Aug; 5(8): 24–27. Published online 2008 August https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695738/

[6]  These potential adverse effects are an amalgamation of  those listed on the Prescribing Information  Leaflets for Ritalin https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021284s020lbl.pdf  and Dexedrine https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/017078s042lbl.pdf

[7]  American Psychiatric Association, Treatments of Psychiatric Disorders: a task force report of the American Psychiatric Association, 1st ed., 1989, quoted in Breggin, Talking Back to Ritalin,, p. 71.

[8]  Desoxyn Prescribing Information https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/005378s026lbl.pdf

[9]  GlaxoSmithKline, Prescribing Information – Dexedrine (dextroamphetamine sulphate). Available at http://www.gskus.com/products/assets/us_dexedrine.pdf (accessed 28 July 2009).

[10]  Department of Health, Government of Western Australia, Inquiry into Attention Deficit Disorder and Attention Deficit Hyperactivity Disorder in Western Australia, Legislative Assembly, Transcript of evidence taken on 27 October 2003, p. 2 (Michelle Toner). http://www.parliament.wa.gov.au/parliament/commit.nsf/(Evidence+Lookup+by+Com+ID)/25EA67352611D66D48257831003B0260/$file/edu1126.2f.pdf

[11]  David Hay, ‘Why is ADHD so under-diagnosed and treated?’, ABC News: The Drum, 4 September 2008.  Available at http://www.abc.net.au/news/2008-08-29/why-is-adhd-so-under-diagnosed-and-treated/491866 (accessed 8 January 2013)

[12]  Young, J.T., Carruthers, S.J., Kaye, S., Allsop, S., Gilsenan, J., Degenhardt, L., van de Glind, G., van den Brink, W. and Preen, D. (2015). Comorbid attention deficit hyperactivity disorder and substance use disorder complexity and chronicity in treatment-seeking adults. Drug and Alcohol Review. https://onlinelibrary.wiley.com/doi/abs/10.1111/dar.12249

[13] Peter R. Breggin M.D. Testimony September 29, 2000 Before the Subcommittee on Oversight and Investigations Committee on Education and the Workforce U.S. House of Representatives available at http://breggin.com/breggin-testifies-before-congress-re-ritalin-and-adhd/

[14]  “…virtually every investigation ever done on ADHD drugs anywhere in the world” Alexander Otto (2005), ‘Are ADHD drugs safe? Report finds little proof’, The News Tribune, 13 September 2005. 

[15]  Marian S. McDonagh, Kim Petersen, et al (2007), Drug Class Review on Pharmacologic Treatments for ADHD: Final Report Update 4, Portland, Oregon Health & Science University.  Available at https://www.ncbi.nlm.nih.gov/pubmed/22420008 (accessed 13 February 2009).

[16]  Merle G. Paule, Andrew S. Rowland, Sherry A. Ferguson, et al., ‘Attention deficit/hyperactivity disorder: characteristics, interventions, and models’ in Neurotoxicology and Teratology, Vol. 22, No. 5, 2000, p. 631. Available at http://cat.inist.fr/?aModele=afficheN&cpsidt=1030283 (accessed 13 February 2009).

[17]  The MTA Study was ‘the first multisite, cooperative agreement treatment study of children, and the largest psychiatric/psychological treatment trial ever conducted by the (U.S.) National Institute of Mental Health. It examines the effectiveness of Medication vs. Psychosocial treatment vs. their combination for treatment of ADHD and compares these experimental arms to each other and to routine community care.’ K. C. Wells, W. E. Pelham, et al., ‘Psychosocial treatment strategies in the MTA study: rationale, methods, and critical issues in design and implementation’, (abstract), Journal of Abnormal Child Psychology, Vol. 28, No. 6, 2000. Available at http://www.ncbi.nlm.nih.gov/pubmed/11104313 (accessed 7 February 2008).

[18]  Monica Shaw†, Paul Hodgkins, Hervé Caci, Susan Young, Jennifer Kahle, Alisa G Woods, L Eugene Arnold. A systematic review and analysis of long-term outcomes in attention deficit hyperactivity disorder: effects of treatment and non-treatment BMC Medicine201210:99 https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-10-99

[19]  The study was sponsored by the National Institute of Mental Health (NIMH) and conducted at six separate US sites. At each site, the study compared four treatment conditions: medication management alone, combined medication management and behavioural therapy, behavioural therapy, and community care. The average age of the children was eight and 80 per cent were boys. For more information, see The MTA Cooperative Group, ‘A 14-Month Randomized Clinical Trial of Treatment Strategies for Attention-Deficit/Hyperactivity Disorder’, Archives of General Psychiatry, 56, 1999, p. 1073.

[20]  Brooke Molina, Kate Flory, Stephen P. Hinshaw et al., ‘Delinquent Behavior and Emerging Substance Use in the MTA at 36 Months: Prevalence, Course, and Treatment Effects’, Journal of the American Academy of Child & Adolescent Psychiatry, Vol. 46 No. 8, August 2007: pp. 1028–1040

[21]  Allegra Stratton, ‘Questions raised Ritalin of no long-term benefit, study finds’, The Guardian, November 12th, 2007. Available at https://www.theguardian.com/news/2007/nov/12/uknews.health (accessed 15 May 2019).

[22]  Monica Shaw, Paul Hodgkins, Hervé Caci, Susan Young, Jennifer Kahle, Alisa G Woods, L Eugene, Arnold A systematic review and analysis of long-term outcomes in attention deficit hyperactivity disorder: effects of treatment and non-treatment BMC Medicine201210:99 https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-10-99

[23]  Molina, B. S. G., Hinshaw, S. P., Swanson, J. M., Arnold, L. E., Vitiello, B., Jensen, P. S., & Cooperative Grp, M. T. A. (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. doi:10.1097/CHI.0b013e31819c23d0 https://www.google.com.au/?gfe_rd=cr&dcr=0&ei=IbDgWYCGAsyBX5ufkMgI

[24]  “Medication status during follow-up, on versus off, did not predict symptom severity change from year 3 to year 6 after adjustment for other variables.” Riddle, M.A., Yershova, K., Lazzaretto, D., Paykina, N., Yenokyan, G., Greenhill, L., … Posner, K. (2013). The preschool attention-deficit/hyperactivity disorder treatment study (PATS) 6-year follow-up. Journal of the American Academy of Child & Adolescent Psychiatry, 52(3), 264–278.e2. doi:10.1016/j.jaac.2012.12.007 https://www.ncbi.nlm.nih.gov/pubmed/23452683

[25]  Joseph M. Rey, ‘In the long run, skills are as good as pills for attention deficit hyperactivity disorder’, The Medical Journal of Australia, 188:3, 2008, p. 134. https://www.mja.com.au/journal/2008/188/3/long-run-skills-are-good-pills-attention-deficit-hyperactivity-disorder

[26]  Janet CurrieMark Stabile, and Lauren Jones. Do Stimulant Medications Improve Educational and Behavioral Outcomes for Children with ADHD? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815037/

[27]  The Raine Study started in 1989, when 2900 pregnant women were recruited into a  comprehensive health and wellbeing research study at King Edward Memorial Hospital to examine ultrasound imaging. The mothers were assessed during pregnancy and after the children were born, and at one year, then two, three and five years of age. Information on their height, weight, eating, walking, talking, eating, behaviour, any medical conditions or illness etc. was collected. Further follow ups of the cohort have been conducted at eight, ten, fourteen, and seventeen years of age. At each follow-up information is collected from the parents and the child. see http://www.rainestudy.org.au (accessed 7 May 2010). 

[28]  Long-term cardiovascular damage: "The most noteworthy finding in the study was the association between stimulant medication and diastolic blood pressure. Compared to not receiving medication, the consistent use of stimulant medication was associated with a significantly higher diastolic blood pressure (of over 10mmHg). This effect did not appear to be solely attributable to any short-term effects of stimulant medication, as when comparing groups who were currently receiving medication, it was found that those who had consistently received medication at all time points had a significantly higher mean diastolic blood pressure than those who had not consistently received medication in the past (difference of 7mmHg). These findings indicate there may be a lasting longer term effect of stimulant medication on diastolic blood pressure above and beyond the immediate short-term side effects.”

Government of Western Australia, Department of Health, Raine ADHD Study: Long-term outcomes associated with stimulant medication in the treatment of ADHD in children, Department of Health, Perth, 2010. https://www.health.wa.gov.au/publications/documents/MICADHD_Raine_ADHD_Study_report_022010.pdf

[29]  Government of Western Australia, Department of Health, Raine ADHD Study: Long-term outcomes associated with stimulant medication in the treatment of ADHD in children, Department of Health, Perth, 2010. p.6.  https://www.health.wa.gov.au/publications/documents/MICADHD_Raine_ADHD_Study_report_022010.pdf

[30]  Gene-Jack Wang,1,2,3,* Nora D. Volkow,4,5 Timothy Wigal,6 Scott H. Kollins,7 Jeffrey H. Newcorn,3 Frank Telang,5 Jean Logan,2 Millard Jayne,5 Christopher T. Wong,5 Hao Han,8 Joanna S. Fowler,2,3 Wei Zhu,8 and James M. Swanson6 Long-Term Stimulant Treatment Affects Brain Dopamine Transporter Level in Patients with Attention Deficit Hyperactive Disorder. Published online 2013 May 15. doi:  10.1371/journal.pone.0063023  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655054/  

[31]  El-Zein RA, Abdel-Rahman SZ, Hay MJ, et al. Cytogenetic effects in children treated with methylphenidate. Cancer Lett. 2005;230:284–291. https://www.ncbi.nlm.nih.gov/pubmed/16297714

[32]  KAPVAY HIGHLIGHTS OF PRESCRIBING INFORMATION available at  https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022331s001s002lbl.pdf

[33] INTUNIV HIGHLIGHTS OF PRESCRIBING INFORMATION available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022037s009lbl.pdf

[34]  G. Chouinard, L. Annable, and J. Bradwejn (1984), ‘An early phase II clinical trial of tomoxetine (LY139603) in the treatment of newly admitted depressed patients’, Psychopharmacology, 83, p.126.

[35]  National Alliance on Mental Illness Minresota - Fact Sheet http://www.namihelps.org/assets/PDFs/fact-sheets/Medications/Strattera.pdf

[36]  Food and Drug Administration (March 2005), Warning on Liver Injury from Strattera: FDA Patient Safety News: Show #37. Available at http://www.accessdata.fda.gov/psn/printer.cfm?id=302 (accessed 18 July 2007).

[37]  Food and Drug Administration (29 September 2005), Public Health Advisory: Suicidal Thinking in Children and Adolescents Being Treated with Strattera (Atomoxetine). Available http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/PublicHealthAdvisories/ucm051733.htm (accessed 13 September 2009)

[38]  Department of Health and Ageing (2011), Therapeutic Goods Administration, ‘Atomoxetine (Strattera)  - risk of increased blood pressure and/or heart rate’, 2 November 2011.  Available at http://www.tga.gov.au/safety/alerts-medicine-atomoxetine-111102.htm)  (accessed 5 June 2012).

[39]  A 2008 study by Curtin University pharmacologist Con Berbatis identified that only a tiny fraction (for general practitioners in Australia only 2 per cent) of adverse events are reported. - Con Berbatis, ‘Primary care and Pharmacy: 4. Large contributions to national adverse reaction reporting by pharmacists in Australia’, i2P E-Magazine, Issue 72, June 2008, p. 1.