- Attention-deficit hyperactivity disorder management
There are several effective and clinically proven options to treat people with
attention-deficit hyperactivity disorder(ADHD). The most effective and cost efficient way is with stimulantmedication. The most common stimulant medications are methylphenidate, dextroamphetamine, and mixed amphetamine salts. [Stephen V. Faraone, P. (2003, September 18). Retrieved from Medscape Today: http://www.medscape.com/viewarticle/461543] Management with medication is the least expensive, followed by behavioral treatment, and combined treatment. Management with medication was more effective, yet more costly than community care, and more cost effective than combination treatment alone and behavioral treatment alone.cite journal | author = Jensen, et al | title = Cost-Effectiveness of ADHD Treatments: Findings from the Multimodal Treatment Study of Children With ADHD | journal = American Journal of Psychiatry | volume = 162 | pages = 1628–1636 (Page:1633) | year = 2005 | pmid = 16135621 | doi = 10.1176/appi.ajp.162.9.1628 [http://ajp.psychiatryonline.org/cgi/content/full/162/9/1628 Free full text] ] A recently published study provides an in-depth review of the cost effectiveness of alternative evidence-based treatment strategies, [cite book |last=Schlander |first=Michael |title=Health Technology Assessments by the National Institute for Health and Clinical Excellence: A Qualitative Study |publisher=Springer |location= [New York |year=2007 |pages=p. 119-145 |isbn=978-0-387-71995-5 |oclc= |doi=] extending findings reported earlier, and concluding that long-acting medications generally seem to provide good value for money.cite journal | author = Schlander | title = Long-acting medications for the hyperkinetic disorders: a note on cost-effectiveness | journal = European Child and Adolescent Psychiatry | volume = 16 (7) | pages = 421–429 (Page:421) | year = 2007 | doi = 10.1007/s00787-007-0615-2 [http://www.michaelschlander.com/pnp/publications_en/Schlander-CEAs-ADHD-Long-Acting-Meds-ECAP-2007.pdf] ] Comorbid (relating to two diseases that occur together, i.e. depression and ADHD) disorders make finding the right treatment and diagnosis much more costly and time consuming than a non comorbid disorder. Having a comorbid disorder complicates the treatment and diagnosis of ADHD so it is better to treat a comorbid disorder as soon as possible. [Waxmonsky, J. (2003, October). Psychiatry . Retrieved from Current Opinion in Pediatrics: http://www.co-pediatrics.com/pt/re/copeds/abstract.00008480-200310000-00006.htm;jsessionid=Hgbcw5tXdZQp51mmm57Tm222zcnCNF3Chx3nvNvH1nDZPtvPYrNn!1219373867!181195629!8091!-1] Some cases of comorbidities, including depression or an anxiety disorder, are best treated with the combined treatment of psychosocial therapies and medication and are better then when only present is ADHD.
The long term safety and effectiveness of ADHD medication has none been determined. Treatment of pre-school children is not recommended.cite web |url=http://www.nice.org.uk/nicemedia/pdf/CG72FullGuideline.pdf |title=CG72 Attention deficit hyperactivity disorder (ADHD): full guideline|accessdate=2008-10-08 |work= |publisher=NHS |date=24 September 2008 ]
Attention-Deficit Hyperactivity Disorder
Attention-Deficit Hyperactivity Disorder (ADHD) is a neurobehavioural developmental disorder [ [http://www.ninds.nih.gov/disorders/adhd/adhd.htm NINDS Attention Deficit-Hyperactivity Disorder Information Page.] National Institute of Neurological Disorders and Stroke (NINDS/NIH)
February 9, 2007. Retrieved on 2007-08-13.] characterized by a persistent pattern of inattention and/or hyperactivity, as well as forgetfulness, poor impulse control or impulsivity, and distractibility.Diagnostic and Statistical Manual of [American Psychiatric Association, 2000.] [ [http://www.behavenet.com/capsules/disorders/adhd.n Psychiatric Association|the American Psychiatric Association] , Fourth Edition, htm Attention-Deficit/Hyperactivity Disorder (ADHD).] Behavenet.com. Retrieved on December 11, 2006.] The most common symptoms of ADHD include, but are not limited to, are distractibility, difficulty with concentration and focus, short term memory slippage, procrastination, problems organizing ideas and belongings, tardiness, impulsivity, and weak planning and execution. [Lemer, P. (2003). Attention Deficit Disorder. Attention Deficit Disorder (ADD) and Attention Deficit Hyperactivity Disorder (ADHD, AD/HD) A Developmental Approach, Retrieved on November 17, 2007 from http://www.add-adhd.org/attention_deficits_ADHD.html] ADHD has three subtypes: predominantly inattentive, predominantly hyperactive, and combined. [Attention Deficit Hyperactivity Disorder. (2007, October 02). Retrieved from Medline Plus: http://www.nlm.nih.gov/medlineplus/attentiondeficithyperactivitydisorder.html]
The ADD is most likely a
heterogeneousdisorder caused by a combination of both genetics and environmental conditions. Researchers believe that a large majority of ADHD arises from a combination of various genes, many of which affect dopaminetransporters.Roman T, Rohde LA, Hutz MH. (2004). "Polymorphisms of the dopamine transporter gene: influence on response to methylphenidate in attention deficit-hyperactivity disorder." "American Journal of Pharmacogenomics" 4(2):83–92 PMID 15059031 ] It appears to be highly heritable. The estimated contribution of non genetic factors in 20 percent, the majority of which are trauma or toxic exposure. [PDFlink|1= [http://www.schwablearning.org/pdfs/2200_7-barktran.pdf?date=4-12-05 Barkley presentaiton.] |2=779 KB SchwabLearning.org.]
ADHD has a high rate of comorbidity [comorbid. (n.d.). Webster's New Millennium Dictionary of English, Preview Edition (v 0.9.7). Retrieved December 12, 2007, from Dictionary.com website: http://dictionary.reference.com/browse/comorbid] (relating to two diseases that occur together, i.e. ADHD and depression). [Barkley, R. A. (2003). Child Psychopathology. New York: Guilford Press.]
Oppositional defiant disorder, conduct disorder, anxiety, depression, bipolar disorder, and substance abusecan be comorbid conditions. Treating ADHD is much more difficult when comorbidities are present. [Stephen V. Faraone, PhD; Arun R. Kunwar, MD. ADHD in Children With Comorbid Conditions: Diagnosis, Misdiagnosis, and Keeping Tabs on Both. Medscape Psychiatry & Mental Health. ©2007 Medscape http://www.medscape.com/viewarticle/555748]
The formal diagnosis of ADHD is made by a qualified professional in the field based on a set number of criteria. In the USA these critera are laid down by the
American Psychiatric Associationin their Diagnostic and Statistical Manual of Mental Disorders ( DSM-IV), 4th edition.
Treatment choices for AD/HD
ADHD can be treated by any physician MD or DO (usually family practice or pediatrician),
psychiatrists, psychiatric/mental health nurse practitioners, and neurologists; some practitioners of this type specialize in treating children with ADHD and others specialize in the treatment of adults with ADHD. Children's hospitals that have psychiatric units with programs dedicated to treating ADHD are often a good place to receive treatment, but a psychiatrist's or neurologist's office will generally have staff who can understand and treat ADHD effectively.
The treatment provider can provide the child’s school with a written ADHD diagnosis that informs the school of accommodations that may aid the student in academic endeavors. In the United States, an educational institution must make accommodations for a child with ADHD which now requires a full
psychological evaluationincluding a battery of tests and observational studies repeated every three years. These tests often pick up added learning diabilities which help qualify for even more benefits. If these test concure with the diagnosis, the school will enact a 504 or Individualize Educational Plan (IEP) for the student
Accommodations may include:
*Extended time for taking exams
*Extended due dates for homework
*A distraction-free environment during examination
*Permission to record lectures
*Copies of lecture notes
There are a variety of psychotherapy approaches employed by psychiatrists, the one used depends on the patient and the patient's symptoms.
Psychotherapy is another option, with or without medication, that has been shown to be effective. [Barkley, R. (2005) Take Charge of ADHD: The Complete Authoritative Guide for Parents NY: Guilford Publications]
Parents of children with ADHD often show similar deficits themselves, and thus may not be able to sufficiently help the child with his or her difficulties. Educating parents in the management of the disorder can be helpful. [Kazdin, Alan E. Parent management training : treatment for oppositional, aggressive, and antisocial behavior in children and adolescents. Oxford University Press, 2005 ] The different educational interventions for the parents are jointly called
Parent Management Training.
Working Memory Training
Many of the problems shown by children with ADHD can be traced back to deficits in
working memory(or short-term memory). By training and improving this memory some of the other symptoms may diminish as well. In a study by Klingberg et al, a computerized such training program has shown good results in working memory, even if the generalized effect to behavioural symptoms was not as clear. [Klingberg, T., Fernell, E., Olesen, P.J., Johnson, M., Gustafsson, P., Dahlstrom, K. Computerized training of working memory in children with ADHD--A randomized, controlled trial. Journal of the American Academy of Child & Adolescent Psychiatry, 2005, 44(2), 177–186.]
ADHD Coachingis a specialized type of life coaching that uses specific techniques geared toward working with the unique brain wiring of individuals with Attention-deficit hyperactivity disorder. Professional coaching is not a substitute for traditional, multimodal treatment for ADHD such as medication, diet, exercise, and therapy.
Only recently, studies on the cost-effectiveness of ADHD treatment have begun to appear. To date valid information is limited, although a review presented identified 11 health technology assessments and cost-effectiveness analyses, all of which compared the economic merits of at least two treatment alternatives. [cite web | author = Schlander, M. | url = http://www.michaelschlander.com/pnp/presentations_en/Schlander-Melbourne-ADHD-What-Have-We-Learnt-2006-Pres.pdf | format = PDF | publisher = michaelschlander.com | title = ADHD Treatment Cost-Effectiveness: What Have We Learnt? | accessdate = 2006-10-13]
Medications endorsed by American Psychiatric Association
Stimulants are the most effective medications available for the treatment of ADHD. This class of medicines is generally regarded as one unit; [Department of Health and Human Services PDFlink| [http://www.surgeongeneral.gov/library/mentalhealth/pdfs/c3.pdf "Mental Health: A Report of the Surgeon General"] |1.01 MB Page 142. Accessed 04/14/07] however, they affect the brain differently .cite journal | author = Arnold | title = Methylphenidate vs Amphetamine: Comparative Review | journal = Journal of Attention Disorders | volume = 3 | issue = 4 | pages = 200–211| year = 2000 | doi = 10.1177/108705470000300403] Some investigations are dedicated to finding the similarities of children who respond to a specific medicine .
Five different formulations of stimulants have been approved by the FDA for the treatment of ADHD: three derived from
amphetamineand two derived from methylphenidate. Atomoxetineis the only non-controlled Food and Drug Administration(FDA) approved drug for the treatment of ADHD, but is less effective than stimulants for ADHD, is associated with individual cases of liver damage, carries an FDA black box warningregarding suicidal ideation, and controlled studies show increases in heart rate, decreases of body weight, decreased appetite and treatment-emergent nausea. [Allen AJ, Kurlan RM, Gilbert DL, "et al." Atomoxetine treatment in children and adolescents with ADHD and comorbid tic disorders. "Neurology". 2005 Dec 27;65(12):1941-9. PMID 16380617]
Amphetamine based medications
Three different medicines derived from amphetamine are used in ADHD treatment. Their trade names are
Adderall(a mixture of 72% dextroamphetamine and 28% levoamphetamine), Dexedrine(pure dextroamphetamine), and Desoxyn(pure dextromethamphetamine). The differences in these three Amphetamine based medications' active compounds and mixture ratios results in each medications' slightly different activities.
Levoamphetamine and dextroamphetamine
Levoamphetamine and dextroamphetamine have the same chemical formula but are mirror images of each other, the same way that a person's hands are the same but are mirror images of each other. This mirror difference is enough to cause the two compounds to be metabolized differently. Adderall begins to work before Dexedrine because of levoamphetamine.cite journal | author = Glaser, et al | title = Differential Effects of Amphetamine Isomers on Dopamine in the Rat Striatum and Nucleus Accumbens Core | journal = Psychopharmacology | volume = 178 | pages = 250–258 (Page: 255) | year = 2005 | pmid = 15719230 | doi = 10.1007/s00213-004-2012-6] Levoamphetamine also provides Adderall with a longer clinical effect than Dexedrine. However, the brain’s preference for dextroamphetamine over levoamphetamine shows that the clinical value of Adderall is, for the most part, due to dextroamphetamine. A few children with ADHD and comorbid disorders have helpful responses to levoamphetamine.
metabolizes dextromethamphetamine into dextroamphetamine (in addition to less important chemicals). A quarter of dextromethamphetamine will ultimately become dextroamphetamine. [cite journal | author = Schepers RJ "et al". | title = Methamphetamine and Amphetamine Pharmacokinetics in Oral Fluid and Plasma after Controlled Oral Methamphetamine Administration to Human Volunteers | journal = Clin Chemistry | volume = 49 | issue = 1 | pages = 121–132 (Pages:121,130) | year = 2003 | pmid = 12507968 | doi = 10.1373/49.1.121 [http://www.clinchem.org/cgi/content/full/49/1/121 Free full text] ] After comparing only the common ground between dextroamphetamine and dextromethamphetamine, the latter is said to be the stronger stimulant . [cite journal | author = Shoblock, et al | title = Neurochemical and Behavioral Differences Between D-Methamphetamine and D-Amphetamine in Rats | journal = Psychopharmacology | volume = 165 | pages = 359–369 (Page:366) | year = 2003 | pmid = 12491026 | doi = 10.1007/s00213-002-1288-7] In theory—and in practice—a larger dose of dextroamphetamine is needed to achieve dextromethamphetamine’s clinical potency. In fact, when Dexedrine and Ritalin are unhelpful, some doctors may prescribe Desoxyn. Although more rarely prescribed, anecdotal reports suggest Desoxyn is very helpful in cases where the other two are ineffective, or cause limiting side effects. [cite web | url = http://www.dr-bob.org/tips/split/Methamphetamine-for-ADHD.html | last = Williams | first = C. Donald | title = Methamphetamine for ADHD | date = 1996-04-21 | accessdate = 2007-04-15 | publisher = Psychopharmacology Tips]
Methylphenidate based medications
There are two different medicines derived from
methylphenidate: Ritalin, which is half dextrothreomethylphenidate and half levothreomethylphenidate, and Focalin, which is pure dextrothreomethylphenidate. Dextrothreomethylphenidate has a higher pharmocological activity than its mirror handed levo-form. The levothreomethylphenidate in orally taken Ritalin has no useful activity and therefore does not improve child’s symptoms; however, if Daytrana(Ritalin in transdermal patchform) is used, then levothreomethylphenidate accounts for about a thirteenth of the total clinical value . [cite journal | author = Heal DJ, Pierce DM | title = Methylphenidate and its isomers: their role in the treatment of attention-deficit hyperactivity disorder using a transdermal delivery system | journal = CNS Drugs | volume = 20 | issue = 9 | pages = 713–738 (Page:730) | year = 2006 | pmid = 16953648] Since children with ADHD do not seem to be able to identify when they are on the drug or placebo, this suggests a low liability for the development of any "addiction" to stimulants. [cite journal | author = Dalby JT, Kapelus GJ, Swanson JM, Kinsbourne M, Roberts W. |title = An examination of the double-blind design in drug research with hyperactive children |journal = Progress in Neuropsychopharmacology |volume = 2 |pages = 123–127 |year = 1978 |pmid = 364511 |doi = 10.1016/0364-7722(78)90031-0 ]
Controlled release of drugs
Doctors may prescribe a controlled release pharmaceutical so that patients only have to take medication in the morning, or at a time more convenient for the patient. This is especially helpful for children who do not like taking their medication in the middle of the school day. Several controlled release methods are used in the FDA approved medications for ADHD. Each way provides makes the FDA drugs pharmaceutically different.
Adderall and Dexedrine Spansules are examples of pharmaceuticals that use a system of two beads to achieve a controlled release. The beads are contained in a gelatin capsule that quickly dissolves in water, thus releasing the beads. The two different types of
beadsdissolve at different rates, thus extending the effects of the amphetamines. The company that markets Adderall is developing a new version of Adderall with three different kinds of beads that would be effective for up to 16 hours.
The only ADHD medication that currently utilizes
osmotic pressureto achieve a controlled release of medicine is Concerta. A tablet of Concerta is actually a coated capsule. The coating is a mix of methylphenidate hydrochlorideand binders such as lactose, povidone, and carnauba wax. Under that coating is a hollow filled capsule made of a semipermeable rigid membrane. The actual capsule is insoluble in water, but some of the ingredients that fill the capsule are water-soluble and others react in special ways with water. At one end of the capsule there is a laser drilled small hole, big enough for methylphenidate particles to pass through. The capsule's volume is partitioned into three sections. At the end closest to the hole is the first partition, which is a mixture containing a small concentration of methylphenidate. In the middle is the second partition is a different mixture that contains a higher concentration of methylphenidate. Occupying the third of the capsules volume that is furthest away from the small hole is triacetin, cellulose acetate, hypromellose, polyethylene glycol and polyethylene oxides.
Once swallowed, the capsule's shell quickly disintegrates and the methylphenidate that was contained in the shell is released. When water sweeps through the semipermeable membrane, the third partition that is furthest away from the capsule's hole will grow because the hypromellose absorbs water and swells up and the polyethylene glycol will increase the
osmotic pressure. This partition will slowly push the contents of the other two partitions out the small hole, starting with the lower concentrations of methylphenidate, once the lower concentration of methylphenidate has mostly left the capsule the higher concentration of methylphenidate will begin to be pushed out of the capsule's hole. The capsule will be pharmacologically inactive once all the methylphenidate is expelled.
This is a patch applied to the skin that allows the drug to diffuse through the skin layers and enter the bloodstream. Unlike oral drugs, it may be removed and replaced conveniently, so it is flexible around the patient's schedule. Daytrana is the brand name of a
transdermalpatch which is essentially the same formulation as Ritalin. Daytranais applied to the skin in the morning and the drug is evenly absorbed throughout the day, the patient should expect to feel the effects of Daytrana until two hours after the patch was removed, so patients should expect to take the patch off a few hours before bedtime. The collaborators that developed Daytrana are developing a transdermal patch version of dextroamphetamine and have completed phase 1 FDA human studies. This medicinal patch is code named SPD483 (a.k.a., ATS; Amphetamine Transdermal System; Amphetamine patch).
prodrugis a compound which is itself inactive, but when metabolized becomes pharmacologically active. Prodrugs are usually designed to improve oral bioavailabilityas the chemical properties of the active compound may cause it to be poorly absorbed from the gastrointestinal tract. Lisdexamfetamine(Sold as Vyvanse) is a prodrug of dextroamphetamine. Vyvanse is a geltin capsule that quickly dissolves once swollowed releasing lisdexamfetamine dimesylate.
Medications not endorsed by American Psychiatric Association
Some medications used to treat ADHD are prescribed off-label, [Lakhan SE; Hagger-Johnson G. [http://www.cpementalhealth.com/content/3/1/21 The impact of prescribed psychotropics on youth] . "Clinical Practice and Epidemiology in Mental Health" 2007;3(21).] outside the scope of their FDA-approved indications for various reasons. The Food and Drug Administration (FDA) requires numerous clinical trials to prove a potential drug's safety and efficacy in treating ADHD. The drugs below have not been through these tests, so the efficacy is unproven (however these drugs have been licensed for other indications, so have been proven to be safe in those populations), however proper dosage and usage instructions are not as well characterized.
Amantadine(Symmetrel) — an antiviral drugand dopamine agonist. There have been reports of low-dose amantadine having been successfully used off-label to treat ADHD. [cite book |last=Hallowell |first=Edward M. |coauthors=John J. Ratey |title=Delivered from Distraction : Getting the Most out of Life with Attention Deficit Disorder |publisher=Ballantine Books |location= [New York |year=2005 |pages=p. 253–5 |isbn=0-345-44231-8 |oclc= |doi=]
Amineptine(Survector/Maneon) — a tricyclic antidepressantnow illegal in many countries for being thought to have a small potential for abuse. It is still legal in some parts of the EU, such as Spain and Italy; it is no longer available in the U.S., Canada, France or the UK.
Benzphetamine(Didrex) — a less powerful stimulant. It has little psychoactive effects until the liver metabolizes it into amphetamine and methamphetamine. Since this acts as a sustained release mechanism, it has lower abuse potential and is schedule 3.
Bupropion(Wellbutrin) is classified as an antidepressant. It is the most common of off-label prescription for ADHD. It inhibits the reuptake of norepinephrine, and to a lesser extent, dopamine, in neuronal synapses, [PDFlink| [http://us.gsk.com/products/assets/us_wellbutrin_tablets.pdf Wellbutrin: Prescribing Information] |170 KB. GlaxoSmithKline(September 2006). Retrieved on 2007-04-15.] and has little or no effect on serotonergic re-uptake. [cite journal | author = Stahl S, Pradko J, Haight B, Modell J, Rockett C, Learned-Coughlin S | title = A Review of the Neuropharmacology of Bupropion, a Dual Norepinephrine and Dopamine Reuptake Inhibitor | journal = Prim Care Companion J Clin Psychiatry | volume = 6 | issue = 4 | pages = 159–166 | year = 2004 | pmid = 15361919 PMC|514842] Bupropion is not a controlled substance. It is commonly prescribed as a timed release formulation to decrease the risk of side effects. Bupropionis not particularly known for its stimulant properties because at high doses it tends to cause seizures in a large portion of the population.
Clonidine— Initially developed as a treatment for high blood pressure, low doses in evenings and/or afternoons are sometimes used in conjunction with stimulants to help with sleep and because Clonidine sometimes helps moderate impulsive and oppositional behavior and may reduce tics. [cite web | last = Frazin | first = Natalie | url = http://www.ninds.nih.gov/news_and_events/news_articles/news_article_adhd.htm | title = Methylphenidate and Clonidine Help Children With ADHD and Tics | date = 2002-04-02 | publisher = National Institute of Neurological Disorders and Stroke| accessdate = 2007-04-15] It may be more useful for comorbid Tourette syndrome.
Modafinil(Provigil/Alertec/Sparlon) — In the U.S., it is currently off-label pending decision by the FDA on August 22, 2006. Was originally pending marketing on-label as Alertec but denied for a reported incidence of Stevens-Johnson Syndrome.
Pemoline(Cylert) — a stimulant used with great success until the late 1980s when it was discovered that this medication could cause liver damage. In March 2005, the makers of Cylert announced that it would discontinue the medication's production. It is no longer available in the United States.
Reboxetine(Edronax) — is a selective norepinephrine reuptake inhibitorwhich is mainly used as an antidepressant. Studies outside the USA have found it to be an effective treatment for ADHD, [Toren P, Ratner S, Weizman A, Lask M, Ben-Amitay G, Laor N. Reboxetine maintenance treatment in children with attention-deficit/hyperactivity disorder: a long-term follow-up study. "Journal of Child and Adolescent Psychopharmacology". 2007 Dec;17(6):803-12. PMID 18315452] and it is prescribed off-label for this purpose in Israel and some European countries, however reboxetine has never been approved by the FDA in the United States.
Selegiline— an MAOIcurrently being investigated for ADHD.
Emsamis a version of Selegiline delivered via transdermal patch.
Tricyclic anti-depressants are also occasionally prescribed, but they seem to only treat the hyperactive part of the condition. There is research on the
selective serotonin reuptake enhancerclass of medications (SSREs); currently, the only one available is tianeptine(trade name Stablon); this is an atypical tricyclic anti-depressant which is inconclusive in its efficacy and hence not approved. Tianeptineis not available in North America.
Experimental and alternative medicine treatments
Alternative medicine treatments
Many alternative treatments have been proposed for ADHD. However, none of the treatments has widespread acceptance in the mainstream medical community, and none of the alternative treatments has proven to cause significant reduction of ADHD symptoms.
Evening Primrose Oil, St.John's Wort, and Ginkgo bilobaare used as herbal remedies. Fact|date=September 2007
There are indications that children with ADHD are metabolically different from others. [Ward NI "et al." (1990). [http://www.diet-studies.com/ward90.html "The influence of the chemical additive tartrazine on the zinc status of hyperactive children: A double-blind placebo-controlled study".] "J Nutr Med"; 1 (1). 51-58.] [Ward NI (1997) [http://www.diet-studies.com/ward.html "Assessment of chemical factors in relation to child hyperactivity".] "Journal of Nutritional & Environmental Medicine (Abingdon)"; 7 (4). 333-342.] [Oades RD, Daniels R, Rascher W. "Plasma neuropeptide-Y levels, monoamine metabolism, electrolyte excretion and drinking behavior in children with attention-deficit hyperactivity disorder." "Psychiatry Res". 1998; August 17;80(2):177–86. PMID 9754697.]
Zinc- Although the role of zinc in ADHD has not be elucidated, "numerous controlled studies report cross-sectional evidence of lower zinc tissue levels."cite journal |author=Arnold LE, DiSilvestro RA |title=Zinc in attention-deficit/hyperactivity disorder |journal=Journal of child and adolescent psychopharmacology |volume=15 |issue=4 |pages=619–27 |year=2005 |pmid=16190793 |doi=10.1089/cap.2005.15.619 |issn= |accessdate=2007-07-30]
Omega-3 fatty acids- Some studies suggest that a lack of omega-3 fatty acidsis associated with certain ADHD symptoms. [Kadziela-Olech H, Piotrowska-Jastrzebska J. "The duration of breastfeeding and attention deficit hyperactivity disorder". "Rocz Akad Med Bialymst". 2005;50:302-6. PMID 16358988] and it has therefore been suggested that diet modification may play a role in the management of ADHD. People with ADHD were found to have significantly lower plasma phospholipids and erythrocytes omega-3 fatty acids. Their intake of saturated fatwas found to be 30% higher than in controls, while the intake of many other nutrients was not different.cite journal
author = Antalis C, Stevens L, Campbell M, Pazdro R, Ericson K, Burgess J
title = Omega-3 fatty acid status in attention-deficit/hyperactivity disorder
journal = Prostaglandins Leukot Essent Fatty Acids
volume = 75
issue = 4-5
pages = 299–308
year = 2006
pmid = 16962757
doi = 10.1016/j.plefa.2006.07.004] cite journal |author=Sinn N, Bryan J |title=Effect of supplementation with polyunsaturated fatty acids and micronutrients on learning and behavior problems associated with child ADHD |journal=Journal of developmental and behavioral pediatrics : JDBP |volume=28 |issue=2 |pages=82–91 |year=2007 |pmid=17435458 |doi=10.1097/01.DBP.0000267558.88457.a5 |issn= |accessdate=2007-07-30] In support of the idea that it is not the intake of essential fatty acids that causes low tissue levels, a preliminary study showed that exhaled
ethane, a marker of omega-3 fatty acids peroxidation, was higher in children with ADHD relative to controls.cite journal |author=Ross BM, McKenzie I, Glen I, Bennett CP |title=Increased levels of ethane, a non-invasive marker of n-3 fatty acid oxidation, in breath of children with attention deficit hyperactivity disorder |journal=Nutritional neuroscience |volume=6 |issue=5 |pages=277–81 |year=2003 |pmid=14609313 |doi=] Researchers from Australia's national science agency showed polyunsaturated fatty acids to provide "medium to strong positive treatment effects" in ADHD. Another double blind study conducted by the University of Oxford, where children were given omega 3 fatty acids concluded that "significant improvements for active treatment versus placebo were found in reading, spelling, and behavior over 3 months of treatment in parallel groups." [Alexandra J. Richardson / Paul Montgomery (2005): The Oxford-Durham Study: A Randomized, Controlled Trial of Dietary Supplementation With Fatty Acids in Children With Developmental Coordination Disorder. In: PEDIATRICS Vol. 115 No. 5 May 2005, pp. 1360-1366 (doi:10.1542/peds.2004-2164)] A 2008 studycite journal
author=Johnson M, Ostlund S, Fransson G, Kadesjö B, Gillberg C.
title = Omega-3/Omega-6 Fatty Acids for Attention Deficit Hyperactivity Disorder: A Randomized Placebo-Controlled Trial in Children and Adolescents.
journal=J Atten Disord
year = 2008 Apr 30
pmid=18448859] also concludes that Omega-3/Omega-6 supplementation reduces ADHD-symptoms for some. Thus it increasingly is documented in clinical studies that omega 3 fatty acids provide a safe way to treat hyperactivity.
Magnesiumand vitamin B6(pyridoxine) - In 2006, a study demonstrated that children with autism had significantly lower magnesium than controls, and that the correction of this deficit was therapeutic: Mousain-Bosc "et al" showed that children with ADHD (n = 46) had significantly lower red blood cellmagnesium levels than controls (n = 30). Intervention with magnesium and vitamin B6 reduced hyperactivity, hyperemotivity/aggressiveness and improved school attention."Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B6. I. Attention deficit hyperactivity disorders." Magnes Res. 2006 Mar;19(1):46-52. PMID: 16846100]
Iron supplements - In 2005, the official journal of the American Academy of Pediatrics, Pediatrics, published the case report of a child with ADHD with low ferritinwho showed "considerable behavioral improvement" after his ferritin was normalized by iron supplementation. Based on earlier studies on iron deficiency and attentional function (notably the dopamine synthesis aspect), the screening of ferritin levels in children with ADHD was suggested.cite journal |author=Konofal E, Cortese S, Lecendreux M, Arnulf I, Mouren MC |title=Effectiveness of iron supplementation in a young child with attention-deficit/hyperactivity disorder |journal=Pediatrics |volume=116 |issue=5 |pages=e732–4 |year=2005 |pmid=16263988 |doi=10.1542/peds.2005-0715]
Potassium- In 2007, Harvard-associated researchers described a form of ADHD that was well treated with over-the-counter potassiumsupplements. The molecular mechanism suggested by the authors was one producing sensory overstimulation, often triggered by ingesting carbohydrates, suggesting that people with ADHD who have sensitivity to sugar may be particularly likely to have this variant.
Feingold diet- Perhaps the best known of the dietary alternatives is the Feingold diet which involves removing salicylates, artificial colors and flavors, and certain synthetic preservatives from children's diets.Schnoll R, Burshteyn D, Cea-Aravena (2003). "Nutrition in the treatment of attention-deficit hyperactivity disorder: a neglected but important aspect". "J. Appl Psychophysiol Biofeedback" Mar;28(1):63–75. PMID 12737097.] However, studies have shown little if any effect of the Feingold dieton the behavior of children with ADHD.cite journal
author = Krummel DA, Seligson FH, Guthrie HA
title = Hyperactivity: is candy causal?
journal = Critical Reviews in Food Science & Nutrition
volume = 36
issue = 1-2
pages = 31–47
year = 1996
pmid = 8747098]
Medical cannabis- Medical cannabis is used by many people with ADHD, most often self-medicated, or occasionally, supervised by a doctor. [http://bbsnews.net/article.php/20071001105829361] [http://22.214.171.124/KortExplores/articles/files/omma3.php] [http://www.cyc.uvic.ca/research/ma_history.php]
* In the 1980s vitamin B6 was promoted as a helpful remedy for children with learning difficulties including inattentiveness, however, a study of large doses of vitamins with ADHD children showed that they were ineffective in changing behavior. [ cite journal |author = Haslam, RHA, Dalby, JT, Rademaker, AW. |title = Effects of megavitamin therapy on children with attention deficit disorders |journal = Pediatrics |year = 1984 |volume = 74 |pages = 103–111. PMID: 6234505 ]
*Mild stimulants such as
caffeine, theobromine, and nicotinemay improve the function of some children suffering from ADHD. [ Dalby, JT. "Will population decreases in caffeine consumption unveil attention deficit disorders in adults?" "Medical Hypotheses" 1985;18: 163-167.] [Leon, MR. "Effects of caffeine on cognitive, psychomotor, and affective performance of children with Attention-Deficit/Hyperactivity Disorder"."J Atten Disord", April 1, 2000; 4(1): 27 - 47. doi|10.1177/108705470000400103] [Eileen O'Connor [http://apa.org/monitor/jun01/dangersip.html "A sip into dangerous territory".] "Monitor on Psychology", Volume 32, No. 5 June 2001. Retrieved on 2007-04-15.] However, since ADHD is thought to be related to deficiencies of dopamineand/or norepinephrine, such treatments are not medically recognized, as opposed to amphetamine-like drugs which have significant dopaminergic and norepinephrinergic action.
Milnacipran, an anti-depressant drug, is currently being investigated for potential to alleviate the symptoms of ADHD in adults. [Citation
last = Kako
first = Yuki
author-link = Yuki Kako
date = April 2007
title = A case of adult attention-deficit/hyperactivity disorder alleviated by milnacipran
journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry
volume = 31
issue = 3
pages = 772–775
ISSN = 0278-5846]
Treatment of ADHD with Comorbid disorders
Because ADHD comorbidities are diverse and the rate of comorbidity is high, special care must dedicated to certain comorbidities. The FDA is not set up to address this issue, and does not approve medications for comorbidities, nonetheless certain such topics have been extensively researched.
Tourette syndromewho are referred to specialty clinics have a high rate of comorbid ADHD. Patients who have ADHD along with tics or tic disorders may also have problems with disruptive behaviors, overall functioning, and cognitivefunction, accounted for by the comorbid ADHD. [Sukhodolsky DG, Scahill L, Zhang H, "et al." Disruptive behavior in children with Tourette's syndrome: association with ADHD comorbidity, tic severity, and functional impairment. "J Am Acad Child Adolesc Psychiatry". 2003 Jan;42(1):98-105. PMID 12500082
* Hoekstra PJ, Steenhuis MP, Troost PW, "et al." Relative contribution of attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and tic severity to social and behavioral problems in tic disorders. "J Dev Behav Pediatr". 2004 Aug;25(4):272-9. PMID 15308928
* Carter AS, O'Donnell DA, Schultz RT, "et al." Social and emotional adjustment in children affected with Gilles de la Tourette's syndrome: associations with ADHD and family functioning. Attention Deficit Hyperactivity Disorder. "J Child Psychol Psychiatry". 2000 Feb;41(2):215-23. PMID 10750547
* Spencer T, Biederman J, Harding M, "et al." Disentangling the overlap between Tourette's disorder and ADHD. "J Child Psychol Psychiatry". 1998 Oct;39(7):1037-44. PMID 9804036]
The treatment of ADHD in the presence of tic disorders has long been a controversial topic. Past medical practice held that
stimulants(such as Ritalin) could not be used in the presence of tics, due to concern that their use might worsen tics;Freeman, RD. [http://www.tourette-confusion.blogspot.com/ Tourette's Syndrome: minimizing confusion] . Retrieved on 8 February 2006. RD Freeman, MD, is Clinic Head of Neuropsychiatry Clinic at British Columbia Children's Hospital, Vancouver, professional advisory board member of Tourette Syndrome Foundation of Canada, and former member of the Tourette Syndrome AssociationMedical Advisory Board. Dr. Freeman has over 180 journal-published articles on [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi PubMed.] ] however, multiple lines of research have shown that stimulants can be cautiously used in the presence of tic disorders. [Palumbo D, Spencer T, Lynch J, "et al." Emergence of tics in children with ADHD: impact of once-daily OROS methylphenidate therapy. "J Child Adolesc Psychopharmacol". 2004 Summer;14(2):185-94. PMID 15319016
* Kurlan R. Tourette's syndrome: are stimulants safe? "Curr Neurol Neurosci Rep". 2003 Jul;3(4):285-8. PMID 12930697
* Law SF, Schachar RJ. Do typical clinical doses of methylphenidate cause tics in children treated for attention-deficit hyperactivity disorder? "J Am Acad Child Adolesc Psychiatry". 1999 Aug;38(8):944-51. PMID 10434485
* Nolan EE, Gadow KD, Sprafkin J. Stimulant medication withdrawal during long-term therapy in children with comorbid attention-deficit hyperactivity disorder and chronic multiple tic disorder. "Pediatrics". 1999 Apr;103 (4 Pt 1):730-7. PMID 10103294] Several studies have shown that stimulants do not exacerbate tics any more than placebo does, and suggest that stimulants may even reduce tic severity. [Tourette's Syndrome Study Group. Treatment of ADHD in children with tics: a randomized controlled trial. "Neurology". 2002 Feb 26;58(4):527-36. PMID 11865128] Controversy remains, and the
PDRcontinues to carry a warning that stimulants should not be used in the presence of tic disorders, so physicians may be reluctant to use them. Others are comfortable using them and even advocate for a stimulant trial when ADHD co-occurs with tics, because the symptoms of ADHD can be more impairing than tics.Zinner SH. Tourette disorder. "Pediatr Rev". 2000;21(11):372-383. PMID 11077021]
The stimulants are the first line of treatment for ADHD, with proven efficacy, but they do fail in up to 20% of cases, even in patients without tic disorders.Scahill L, Erenberg G, Berlin CM Jr, Budman C, Coffey BJ, Jankovic J, Kiessling L, King RA, Kurlan R, Lang A, Mink J, Murphy T, Zinner S, Walkup J; Tourette Syndrome Association Medical Advisory Board: Practice Committee. Contemporary assessment and pharmacotherapy of Tourette syndrome. "NeuroRx." 2006 Apr;3(2):192–206. PMID 16554257] Current prescribed stimulant medications include:
methylphenidate(brand names Ritalin, Metadate, Concerta), dextroamphetamine(Dexedrine), and mixed amphetamine salts ( Adderall). Other medications can be used when stimulants are not an option. These include the alpha-2 agonists ( clonidineand guanfacine), tricyclic antidepressants ( desipramineand nortriptyline), and newer antidepressants ( bupropion, venlafaxineand atomoxetine). There have been case reports of tics worsening with bupropion(brand name Wellbutrin). There is good empirical support for the use of desipramine, bupropionand atomoxetine(brand name Strattera).
Concerns about the use of stimulant medication
National Institute of Mental Healthstates that, "stimulant drugs, when used with medical supervision, are usually considered quite safe." [ [http://www.nimh.nih.gov/health/publications/adhd/treatment.shtml NIMH · ADHD · The Treatment of ADHD ] ] Still, some parents and professionals have raised questions about the side effects of drugs and their long term use. [Lakhan SE; Hagger-Johnson G. http://www.cpementalhealth.com/content/3/1/21 The impact of prescribed psychotropics on youth. "Clinical Practice and Epidemiology in Mental Health" 2007;3(21).]
American Heart Associationfeel that it is prudent to carefully assess children for heart conditions before treating them with stimulent medications. [cite journal |author= |title=American Academy of Pediatrics/American Heart Association clarification of statement on cardiovascular evaluation and monitoring of children and adolescents with heart disease receiving medications for ADHD: May 16, 2008 |journal=J Dev Behav Pediatr |volume=29 |issue=4 |pages=335 |year=2008 |month=August |pmid=18698199 |doi=10.1097/DBP.0b013e31318185dc14 |url=http://circ.ahajournals.org/cgi/content/full/117/18/2407]
Increase in use of stimulant medication in children
Outpatient treatment rates have held steady in the US recently. [http://www.nimh.nih.gov/press/adhdmedsuse.cfm "ADHD Medication Use Held Steady in Recent Years" April 2006] Prior to this, outpatient treatment for ADHD in the US grew from 0.9 children per 100 in 1987 to 3.4 per 100 in 1997. [name="olson" Olfson M, Gameroff MJ, Marcus SC, Jensen PS. (2003). "National trends in the treatment of attention deficit hyperactivity disorder". "American Journal of Psychiatry", 160 (6): 1071–1077 PMID 10326176] There is concern about the rising use of
methylphenidate(Ritalin), mainly to treat ADHD and similar disorders, in the UK. [ [http://news.bbc.co.uk/1/hi/health/3072445.stm BBC NEWS | Health | Sharp rise in children's Ritalin use ] ] The incidence of ADHD is estimated at three to five percent of the population, while the number of children in the United States taking Ritalin is estimated at one to two percent. [http://www.gladwell.com/1999/1999_02_02_a_ritalin.htm Running from Ritalin".] In a small study of four American communities, the reported incidence of ADHD varied from 1.6% to 9.4%. The study also found that only 12.5% of the children reportedly meeting the DSM-III-RADHD criteria for ADHD had been treated with stimulants during the past year. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10405496&query_hl=6&itool=pubmed_docsum Are stimulants overprescribed? Treatment of ADHD in four U.S. communities. "Journal of the American Academy of Child and Adolescent Psychiatry" 38 (7):797-804.]
Non-medical prescription stimulant use is high. A 2003 study found that non prescription use by college students in the US was 6.9% with 4.1% using them within the last year. [cite journal |author=McCabe SE, Knight JR, Teter CJ, Wechsler H |title=Non-medical use of prescription stimulants among US college students: prevalence and correlates from a national survey |journal=Addiction (Abingdon, England) |volume=100 |issue=1 |pages=96–106 |year=2005 |month=January |pmid=15598197 |doi=10.1111/j.1360-0443.2005.00944.x |url=]
Use of medication in preschoolers
It is believed that ADHD affects seven percent of the preschool-aged population.Fact|date=October 2008 Michael J. Manos of the Cleveland hospital for Children states, "Severe ADHD in children 2–4 years of age is especially problematic. Young children do not have the ability to use or respond to language to moderate behavior that older children have."Fact|date=October 2008 Evidence indicates that forty percent of children who show signs of ADHD are suspended from preschool, while approximately sixteen percent are eventually expelled. [The disorder, which makes it difficult for children to control their behavior and pay attention, affects about 7 percent of the school-aged population. The disorder has become a public health concern, however, because 40 percent of children who show signs of ADHD are suspended from preschool, while approximately 16 percent are eventually expelled.] Parents of children with ADHD note that they usually display their symptoms at an early age. Dr. John Van Brakle has stated, "pediatricians have long questioned whether such children can accurately be identified, given the overlap with normal behaviors in young children." [http://www.sciencedaily.com/releases/2007/08/070821143557.htm Nonmedicinal Treatment Touted For Preschoolers With ADHD ] ] The use of stimulant medication has not been approved by the FDA for children under the age of six. [http://www.sciencedaily.com/releases/2006/10/061016150730.htm Preschoolers With ADHD Improve With Low Doses Of Medication ] ] A growing trend is the diagnosis of younger children with ADHD. Prescriptions for children under the age of 5 rose nearly 50 percent from 2000 to 2003. [ [http://query.nytimes.com/gst/fullpage.html?res=9C0DEEDF143FF934A25756C0A9629C8B63 Behavior Drugs Lead in Sales For Children - New York Times ] ] Research on this issue has indicated that stimulant medication can help younger children with "severe ADHD symptoms" but typically at a lower dose then older children. It was also found that children at this age are more sensitive to side effects and should be closely monitored. Manos states, "it is prudent for physicians to be cautious," with medications. Evidence suggests that careful assessment and highly individualized behavioural interventions significantly improve both social and academic skills while medication only treats the symptoms of the disorder. Manos suggests that, "one of the primary reasons cited for the growing use of psychotropic interventions was that many physicians realize that psychological interventions are costly and difficult to sustain." [http://www.medscape.com/viewarticle/523542]
A study published in the November 2006 "Journal of the American Academy of Child and Adolescent Psychiatry" followed 300 three- to five-year-olds with severe ADHD (hyperactive/impulsive, inattentive, or combined type). One-third of those children experienced reduced ADHD symptoms after engaging in 10 weeks of behavior modification techniques wherein parents offered consistent praise, ignored negative behavior, and used time-outs. The remaining two-thirds showed improvement with a combination of behavior therapy and low doses of Ritalin. 11% of the children stopped treatment due to side effects including appetite reduction, insomnia, and anxiety. [Schusteff, Arlene. [http://www.additudemag.com/adhd/article/2488.html An ADHD Diagnosis for Preschool Children] "ADDitude" magazine, August 2007]
Harmful side effects
Two possible side effects of concern are the emergence of tics and stunting of growth in children. Despite belief to the contrary, no significant effects have been observed on the emergence of
tics. [ [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16175106&query_hl=11 ADHD treatment with once-daily OROS methylphenidat... [J Am Acad Child Adolesc Psychiatry. 2005 - PubMed Result ] ] Past studies suggested that "long-term use of the drugs could stunt children's growth." [ [http://news.bbc.co.uk/2/hi/uk_news/7090011.stm BBC NEWS | UK | Drugs for ADHD 'not the answer' ] ] However, more recent studies suggest that children eventually do reach normal height and weight. According to Wilens (2004), treated children with ADHD tend to grow at a slower rate but catch up during adolescence and adulthood. [Wilens, T.E. (2004) Straight Talk About Medications For Kids. NY: The Guilford Press.] One notion is that psychostimulant medication can decrease appetite which may result in loss of weight and may be a factor in stunted growth.
There is also concern that the use of stimulants, which increase the pulse rate, in those with heart or
hypertensionproblems might cause serious health issues. [ [http://www.nytimes.com/2006/02/21/health/21psyc.html Heart Risks With Stimulant Use? Maybe. Worry? For Some. - New York Times ] ] The Pediatric Advisory Committee of the Food and Drug Administration(FDA) released a statement in 2005, identifying two possible safety concerns regarding Concerta and other brands of methylphenidate: psychiatric adverse events and cardiovascular adverse events. [ [http://www.fda.gov/ohrms/dockets/ac/05/slides/2005-4152s2_07_Murphy_files/frame.htm Statement on Concerta and Methylphenidate for the June 30 PA ] ] Citation broken|date=April 2008 After looking into the deaths of 25 people, including 19 children, the FDA advisory panel voted, on February 9, 2006, in favor of requiring Ritalin and other stimulant drugs to carry a strong "black box" warning. [ [http://news.yahoo.com/s/ap/20060209/ap_on_he_me/attention_deficit] Dead link|date=March 2008] Citation broken|date=April 2008 The next year, an FDA advisory panel eschewed the "black box" warning label - instead recommending that pharmaceutical companies rewrite their prescription labels to make risks and side effects easier to understand. [ [http://www.additudemag.com/addnews/29/1166.html, FDA Rejects "Black Box" Warning for Stimulant Meds] , "ADDitude" magazine, June 2006] Deaths attributed to methylphenidate are extremely rare, and are believed to be caused by undetected heart abnormalities and/or interactions with other drugs. Further study also indicated that, "the rate of sudden death of children taking ADHD medications do not appear to exceed the base rate of sudden death in the general population". Matthew Smith is purported to have died at age 14 after long-term use of Ritalin. The medical examiner determined that Smith died from Ritalin usage, but medical experts dispute this. The examiner also argued that it was likely that diabetic children were at higher risk for cardiac problems. [ [http://www.cbsnews.com/stories/2000/04/18/national/main185425.shtml Questions Raised Over Ritalin, Michigan Teen Matthew Smith Dies From Psychotropic Drug - CBS News ] ]
In addition, headaches, sleep problems, and loss of appetite are common side effects cited by users of ADD stimulant medications like Methylphenidate (Ritalin), dextro-amphetamine (Dexedrine), and dextro-amphetamine/levo-amphetamine (Adderall). [Silver, Larry M.D. [http://www.additudemag.com/adhd/article/957.html ADHD Medications: Say No to Side Effects] , "ADDitude" magazine, February 2006. ]
Questions about the long term effectiveness of stimulant medication
The short term use of stimulant medication has been shown to be effective yet its long term effects are yet to be determined. The Multimodal Treatment Study of Children with ADHD study concluded that while drugs such as Ritalin and Concerta (a delayed release form of Ritalin) worked in the short term, there was no demonstrable improvement in children's behavior after three years of medication." [ [http://www.foxnews.com/story/0,2933,310596,00.html FOXNews.com - Report: ADHD Drugs May Stunt Growth, Long-Term Effectiveness Unknown - Health News | Current Health News | Medical News ] ]
A meta analysis done in 2008 found no randomized controlled trials assessing the harms or benefits of treatment beyond two years.cite web |url=http://ti.ubc.ca/en/letter69 |title=What is the evidence for using CNS stimulants to treat ADHD in children? |accessdate=2008-09-10 |work= |publisher= |date=March - May 2008 ]
Wilens and other professionals have shown that the controlled use of medication can reduce the likelihood of substance abuse later on.Fact|date=October 2008 A 2007 study from the Mayo clinic found that, "treatment with stimulant medication during childhood was associated with more favorable long-term school outcomes." [cite journal |author=Barbaresi WJ, Katusic SK, Colligan RC, Weaver AL, Jacobsen SJ |title=Modifiers of long-term school outcomes for children with attention-deficit/hyperactivity disorder: does treatment with stimulant medication make a difference? Results from a population-based study |journal=Journal of developmental and behavioral pediatrics : JDBP |volume=28 |issue=4 |pages=274–87 |year=2007 |month=August |pmid=17700079 |doi=10.1097/DBP.0b013e3180cabc28 |url=]
Questions about the possibility of stimulant medication causing cancer
A small-scale 2005 Texas study indicated that methylphenidate might cause
chromosomeaberrations. [ [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16297714&query_hl=9 Cytogenetic effects in children treated with methy... [Cancer Lett. 2005 - PubMed Result ] ] At the time this study caused concern because of the link between chromosome aberrations and cancer. The authors of the study stated that all the children in this study showed suspicious DNA changes within a very short time and suggested that further research was warranted. A team from the Food and Drug Administration(FDA), the National Institutes of Health(NIH) and the Environmental Protection Agency (EPA) went to Texas in 2005 to evaluate the methodology of the study. Dr. David Jacobson-Kram of the FDA said that the study had flaws in its methods but that its results could not be dismissed. Flaws cited are (1) that the study did not include a control group on placebo, and (2) that it is too small. A follow up study led by a team of six scientists from the Department of Child and Adolescent Psychiatry and Psychotherapy and the Department of Toxicology, University of Würzburg, Würzburg, Germany looked at this issue with an in-depth study. They sought to respond to the challenge noted above to attempt to replicate the results of El-Zein et al. in a larger study. Their paper was completed in 2006 and published in 2007 in Environmental Health Perspectives(EHP), the peer-reviewed journal of the United States' National Institute of Environmental Health Sciences. This study used a larger cohort and a longer period of follow-up and included a small group of long-term users, but otherwise used what researchers believed to be an identical methodology to that used by El-Zein et al. (They note that El-Zein et al. published a short study report and did not publish detailed descriptions of methodology.) After follow-ups at six months, the researchers found no evidence that methylphenidate might cause cancer, stating "the concern regarding a potential increase in the risk of developing cancer later in life after long-term MPH treatment is not supported." [cite journal| title=Does Methylphenidate Cause a Cytogenetic Effect in Children with Attention Deficit Hyperactivity Disorder?| journal=Environmental Health Perspectives| date=June 2007 | volume=115| issue=6|pages=936–940| url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1892117| author=Walitza, Susanne, et al| pmid=17589603| doi=10.1289/ehp.9866]
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