Attention deficit hyperactivity disorder management

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Attention deficit hyperactivity disorder management are the treatment options available to people with attention-deficit/hyperactivity disorder (ADHD).

There are several effective and evidence-based options to treat people with ADHD. Multimodal treatment, that is, combined pharmacological and behavioral treatment, is the most effective ADHD management strategy, followed by medication alone, and then behavioral treatment.[1] However, these results have been questioned because the study from the multimodal treatment group phased out the behavioral procedure 3 months prior to the last evaluation point but continued the medication group.[2] Indeed, after 14 months the medication group lost its advantage to the long discontinued behavior modification group. By year eight socioeconomic status and family structure were the only predictive variables for ADHD treatment[3] A separate study highlighted the influence that nonclinical factors such as family size may have in mediating the use of pharmacologic therapies for children with ADHD.[4]

The most common stimulant medications are amphetamine mixed (Adderall) or dextroamphetamine (Dexedrine), and methylphenidate (Ritalin). Less common and less stimulant, also approved for the treatment of ADHD, are Atomoxetine (Strattera), guanfacine (Intuniv), and clonidine (Kapvay). Other medications which may be prescribed off-label include certain antidepressants such as tricyclic antidepressants, SNRIs or MAOIs.[5][6][7] The presence of comorbid (co-occurring) disorders make finding the right treatment and diagnosis much more costly and time-consuming. Having a comorbid disorder makes the treatment and diagnosis of ADHD more complicated, so it is recommended to assess and treat any comorbid disorders simultaneously.[8]

A variety of psychotherapeutic and behavior modification approaches to managing ADHD including psychotherapy and working memory training may be used. Improving the surrounding home and school environment with parent management training and classroom management can improve the behavior of children with ADHD.[9] Specialized ADHD coaches provide services and strategies to improve functioning, like time management or organizational suggestions. Self-control training programs have been shown to have limited effectiveness. Behaviorally based self-control does better than cognitive self-control training. A meta-analysis found that the use of behavior modification for ADHD are effective.[10]

As of 2006 there was a shortage of data regarding ADHD drugs' potential adverse effects,[11] with very few studies assessing the safety or efficacy of treatments beyond four months,[12] and no randomized controlled trials assessing for periods of usage longer than two years.[13][14] Treatment of preschool children is not recommended. The U.S. Food and Drug Administration (FDA) found that a large number of the controlled trials required subjects who were known to respond to stimulants or who had no history of intolerance to stimulants, and this limits assumed generalizability of the trials' results.

Psychosocial[edit]

There are a variety of psychotherapeutic approaches employed by psychologists and psychiatrists; the one used depends on the patient and the patient's symptoms. The approaches include psychotherapy, cognitive-behavior therapy, support groups, parent training, meditation, and social skills training. If psychotherapy fails to bring improvement, medications can be considered as an add-on or alternative.[15][16][17]

Psychotherapy[edit]

Psychotherapy is another option, with or without medication, that has been shown to be effective.[18]

Parent education and classroom management[edit]

Improving the surrounding home and school environment can improve the behavior of children with ADHD.[9] 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.[19] Improving the parents' understanding of the child's behavior and teaching them strategies to improve functioning and communication and discourage unwanted behavior has measurable effect on the children with ADHD.[9] The different educational interventions for the parents are jointly called Parent Management Training. Techniques include operant conditioning: a consistent application of rewards for meeting goals and good behavior (positive reinforcement) and punishments such as time-outs or revocation of privileges for failing to meet goals or poor behavior.[9] Classroom management is similar to parent management training; educators learn about ADHD and techniques to improve behavior applied to a classroom setting. Strategies utilized include increased structuring of classroom activities, daily feedback, and token economy.[9]

Working memory training[edit]

Many of the problems shown by children with ADHD are linked with deficits in working memory (or short-term memory). Training this memory may diminish some of symptoms of ADHD. In a study by Klingberg et al., children with ADHD who completed a computerized training program for working memory reported a decrease in ADHD symptoms and performed better on working memory tests than the control group. Some researchers attribute this to an improvement in working memory generally, while others believe it is merely the natural effect of practice.

Timers[edit]

Timers have been found to be effective for allowing people with ADHD to concentrate more effectively on the task at hand.[20] When a target is set, one method is to only turn the timer on whilst working on the given task. A physical stopwatch or an online timer may be used.

Medications[edit]

Stimulants[edit]

Adderall 25 mg XR. Adderall XR is one of the medications used to treat ADHD.

Stimulants are the most commonly prescribed medications for ADHD. The most common stimulant medications are methylphenidate (Ritalin, Metadate, Concerta), dexmethylphenidate (Focalin), dextroamphetamine (Dexedrine), mixed amphetamine salts (Adderall),[21] dextromethamphetamine (Desoxyn)[22] and lisdexamfetamine (Vyvanse).[23] According to several studies, use of stimulants (e.g. methylphenidate) can lead to development of drug tolerance to therapeutic doses; tolerance also occurs among high dose abusers of methylphenidate.[24] Controlled-release pharmaceuticals may allow once or twice daily administration of medication in the morning. 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.

Stimulants used to treat ADHD raise the extracellular concentrations of the neurotransmitters dopamine and norepinephrine which causes an increase in neurotransmission. The therapeutic benefits are due to noradrenergic effects at the locus coeruleus and the prefrontal cortex and dopaminergic effects at the nucleus accumbens.[25]

About 70 percent of children improve after being treated with stimulants in the short term, but this conclusion may be biased due to the high number of low quality clinical trials in the literature.[citation needed] The long-term effectiveness of methylphenidate has not been scientifically demonstrated, however long-term increases in plasticity of key brain regions (such as the prefrontal cortex) has been shown.[26][27] Serious concerns of publication bias regarding the use of methylphenidate for ADHD has also been noted.[28]

Although "under medical supervision, stimulant medications are considered safe",[9] the use of stimulant medications for the treatment of ADHD has generated controversy because of undesirable side effects and uncertain long-term effects[14][29][30][31] and social and ethical issues regarding their use and dispensation. The U.S. FDA has added black-box warnings to some ADHD medications, while the American Heart Association and the American Academy of Pediatrics feel that it is prudent to carefully assess children for heart conditions before treating them with stimulant medications.[32]

Stimulants are the most effective medications available for the treatment of ADHD.[1] Five different formulations of stimulants have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of ADHD: three derived from amphetamine and two derived from methylphenidate. Atomoxetine, guanfacine and clonidine are the only non-controlled, less-stimulant FDA approved drugs for the treatment of ADHD.

Short-term clinical trials have shown medications to be effective for treating ADHD, but the trials usually use exclusion criteria, meaning knowledge of medications for ADHD is based on a small subset of the typical patients seen in clinical practice.[33] They have not been found to improve school performance and data is lacking on long-term effectiveness and the severity of side effects. This class of medicines is generally regarded as one unit; however, they affect the brain differently.[34] Some investigations are dedicated to finding the similarities of children who respond to a specific medicine.[34] The behavioural response to stimulants in children is similar regardless of whether they have ADHD or not.[35]

Stimulant medication is an effective treatment[36] for adult attention-deficit hyperactivity disorder[37][38] although the response rate may be lower for adults than children.[39] Some physicians may recommend antidepressant drugs as the first line treatment instead of stimulants[40] although antidepressants have lower treatment effect sizes than stimulant medication.[41]

Amphetamines[edit]

Summary of Evidence on Amphetamine and ADHD
Name Symptom control Safety
Amphetamine (Adderall, Adderall XR)
  • No evidence on long-term treatment outcomes, but evidence shows that children taking this short-term are better able to concentrate, more thoughtful before acting, and less restless
  • According to Millchap et al., "a multicenter, placebo-controlled trial of amphetamine treatment for ADHD in Sweden found significant improvements in attention, hyperactivity, and disruptive behaviors and a mean change in IQ of +4.5 after more than 9 months of amphetamine [use]."[42]
  • Some clinicians have warned of increased risk of sudden unexplained death, stroke, or heart attack but three large, high-quality studies by the U.S. FDA refute these claims.[43][44][45]
  • May cause growth suppression during first 1–2 years of use. Evidence suggests that growth normalizes with longer use.
  • Contraindicated for people with glaucoma, high blood pressure, heart problems, or using MAOIs
  • high potential for abuse

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).[46] The differences in these two amphetamine-based medications is the enantiomeric mixture ratio, which results in slightly different effects between the medications. Another medication containing a similar but distinct compound, Desoxyn (pure dextromethamphetamine), is also used, although infrequently.[46]

Levoamphetamine and dextroamphetamine[edit]

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 dextroamphetamine because of levoamphetamine.[47] Levoamphetamine also provides Adderall with a longer clinical effect than dextroamphetamine. Some children with ADHD and comorbid disorders respond well to levoamphetamine.[34]

Dextromethamphetamine[edit]

The body metabolizes dextromethamphetamine into dextroamphetamine (in addition to less active metabolites). A quarter of dextromethamphetamine will ultimately become dextroamphetamine.[48] After comparing only the common ground between dextroamphetamine and dextromethamphetamine, the latter is said to be the stronger stimulant.[49] In theory — and in practice — a larger dose of dextroamphetamine is needed to achieve dextromethamphetamine's clinical potency. In fact, when dextroamphetamine and methylphenidate are unhelpful, some doctors may prescribe dextromethamphetamine. Although more rarely prescribed, anecdotal reports suggest dextromethamphetamine is very helpful in cases where the other two are ineffective, or cause limiting side effects.[50]

Methylphenidate-based medications[edit]

There are two different medicines derived from methylphenidate: Ritalin, which is half dextrothreomethylphenidate and half levothreomethylphenidate, that is, a mixture of the "chemical mirror images" of methylphenidate, and Focalin, which is pure dextrothreomethylphenidate. Dextrothreomethylphenidate has a higher pharmacological activity than its mirror levo-form or enantiomer. Levothreomethylphenidate has much weaker activity than the dextro isomer, and so for instance if Daytrana (methylphenidate in transdermal patch form) is used, then the levothreomethylphenidate comprising half of the administered dose, accounts for only around one thirteenth of the total clinical effect.[51] Methylphenidate has high potential for abuse and addiction due to its pharmacological similarity to cocaine and amphetamines.[52][53]

Non-stimulants[edit]

Atomoxetine (Strattera), guanfacine (Intuniv) and clonidine (Kapvay) are less-stimulant drugs approved for the treatment of ADHD. Other medications which may be prescribed off-label include certain antidepressants such as tricyclic antidepressants, SNRIs, SSRIs or MAOIs.[54][55][56][57]

Atomoxetine (Strattera) is less effective than stimulants for ADHD, is associated with individual cases of liver damage, and carries a U.S. FDA black box warning regarding suicidal idealization. Controlled studies show increases in heart rate, decreases of body weight, decreased appetite and treatment-emergent nausea.[58]

Intuniv is an extended release form of guanfacine. Intuniv has been approved by the FDA for the treatment of attention-deficit hyperactivity disorder (ADHD) in children as an alternative to stimulant medications. Its beneficial actions are likely due to its ability to strengthen prefrontal cortical regulation of attention and behavior.[59]

Clonidine (Kapvay), an α2A adrenergic receptor agonist has also been approved in the US. Clonidine was 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.[60] It may be more useful for comorbid Tourette syndrome.

Certain antidepressants such as tricyclic antidepressants, SNRIs or MAOIs are sometimes prescribed and are also effective in the treatment of ADHD.[5][6][7][61]

Other[edit]

Some medications used to treat ADHD are prescribed off-label,[62] outside the scope of their FDA-approved indications for various reasons. The U.S. FDA requires two 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 drug and dopamine agonist. There have been reports of low-dose amantadine having been successfully used off-label to treat ADHD.[63]
  • 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,[64] and has little or no effect on serotonergic re-uptake.[65] Bupropion is not a controlled substance. It is commonly prescribed as a timed release formulation to decrease the risk of side effects.
  • Milnacipran, an anti-depressant drug, is currently being investigated for potential to alleviate the symptoms of ADHD in adults.[66]
  • Modafinil (Provigil/Alertec/Sparlon) — Double-blind randomized controlled trials have demonstrated the efficacy and tolerability of modafinil,[67][68] however there are risks of serious side effects such as skin reactions and modafinil is not recommended for use in children.[69] In the U.S., it is off-label pending decision by the FDA on August 22, 2006. It was originally pending marketing on-label as Alertec but denied for a reported incidence of Stevens-Johnson Syndrome.[70]
  • Reboxetine (Edronax) — is a selective norepinephrine reuptake inhibitor which is mainly used as an antidepressant. Studies outside the U.S. have found it to be an effective treatment for ADHD,[71] and it is prescribed off-label for this purpose in Israel and some European countries, however reboxetine has never been approved by the U.S. FDA.
Antipsychotic medication

The use of atypical antipsychotic medication as an off-label treatment has been rising.[72] Antipsychotics work by blocking dopamine, whereas stimulants trigger its release. Atypical antipsychotics have been approved for use in children and teenagers with schizophrenia spectrum disorders and autistic spectrum disorders by the U.S. FDA.[73]

Non-ADHD children do not respond differently from ADHD children when prescribed antipsychotic drugs, which are also increasingly prescribed off-label for children with aggression or defiant behavior.[74] Social pressure to control a child's difficult and disruptive behavior, both at home and at school, may inadvertently change focus from what is in the best interest of the child's wellbeing; to how to render the child more compliant and easier to manage.

Comparative efficacy, tolerability and regulatory status of ADHD medications[edit]

Generic name (INN) Brand name(s) TGA-labelled for ADHD?[75] MHRA-labelled for ADHD?[76] FDA-labelled for ADHD?[77] Pharmacologic class[78] Level of support Notes on adverse effects[note 1] Efficacy and miscellany[note 2]
CNS Stimulants
Classical
Adderall[note 3] Adderall No No Yes (children ≥3 years; adults) Monoamine reuptake inhibitor and releasing agent[86] Approved Transient growth stunting, hypertension or hypotension, dependence and tolerance, rare stimulant psychosis, and insomnia. Elimination is urinary pH-dependent Highly efficacious, therapeutic effects are usually seen within an hour of oral administration.
Dexamphetamine Dexamphetamine,
Dexedrine,
Dexrostat,
Liquadd
Yes (children ≥6 years & adults) Yes (children ≥6 years & adults) Yes (children ≥3 years; adults) Monoamine reuptake inhibitor and releasing agent[86] Approved Transient growth stunting, hypertension or hypotension, dependence and tolerance, rare stimulant psychosis, and insomnia. Elimination is urinary pH-dependent Highly efficacious, therapeutic effects are usually seen within an hour of oral administration
Lisdexamphetamine Elvanse,
Vyvanse
Yes (children ≥12 years and adults)[87] Yes (children ≥6 years and adults) Yes (children ≥6 years and adults) Monoamine reuptake inhibitor and releasing agent[86] Approved Transient growth stunting, hypertension or hypotension, dependence and tolerance, rare stimulant psychosis, and insomnia. Elimination of active metabolite, dexamfetamine, is pH-dependent Highly efficacious with rapid onset of action.
Methamphetamine Desoxyn No No Yes (children ≥6 years & adults) Monoamine reuptake inhibitor and releasing agent[86] Approved Transient growth stunting, hypertension or hypotension, dependence and tolerance, direct neurotoxicity to dopamine and serotonin neurons,[88][89] rare stimulant psychosis, and insomnia. Elimination is urinary pH-dependent Highly efficacious, therapeutic effects are usually seen within an hour of oral administration
Dexmethylphenidate Focalin No No Yes (children ≥6 years and adults) Norepinephrine-dopamine reuptake inhibitor Approved Transient growth stunting, dependence and tolerance, rare stimulant psychosis, hypertension, and insomnia. Highly efficacious, therapeutic effects are usually seen within 12 hours of oral administration (sustained release formulation)
Methylphenidate Concerta,
Ritalin
Yes (children ≥6 years and adults) Yes (children ≥6 years and adults) Yes (children ≥6 years and adults) Norepinephrine-dopamine reuptake inhibitor Approved Transient growth stunting, dependence and tolerance, rare stimulant psychosis, and insomnia. Highly efficacious, therapeutic effects are usually seen within 2–7 hours of oral administration (depending on formulation)
Non-classical
Atomoxetine Strattera Yes (children ≥6 years & adults) Yes (children ≥6 years & adults) Yes (children ≥6 years & adults) Norepinephrine reuptake inhibitor Approved Suicidal ideation, insomnia, anorexia, hypertension Less efficacious than classical stimulants and slower onset of action (usually takes at least a couple weeks)
Modafinil Modavigil, Provigil No No No Eugeroic Very high Stevens-Johnson syndrome, toxic epidermal necrolysis, suicidal ideation Rapid onset of action (matter of a few hours). May be less efficacious than atomoxetine and classical stimulants in paediatric ADHD, although in adult ADHD it seems as efficacious as classical stimulant medications.
α2 adrenoceptor agonists
Clonidine Catapres, Dixarit, Kapvay No No Yes (children ≥6 years) Alpha-2 adrenoceptor agonism Approved Sedation, hypotension, depression. Sedation tends to be more prominent with immediate-release formulations than with extended-release formulations. Delayed onset of action (1 week). Insufficient data to judge its relative efficacy. Only the more sedating, immediate-release formulations are available in some countries, including Australia.[75]
Guanfacine Intuniv, Tenex No No Yes (children ≥6 years) Alpha-2 adrenoceptor agonism Approved Sedation, hypotension, depression Delayed onset of action (1 week). May be slightly less efficacious than stimulant medications. Not available in many countries including Australia and the UK.
Antidepressants/Anxiolytics
Amitriptyline Elavil, Endep No No No Tricyclic antidepressant Low[90] Sedation, anticholinergic effects, hypotension, suicidal ideation, urinary retention, angle-closure glaucoma, headache, dizziness, etc. Highly dangerous in overdose. Delayed onset of action
Bupropion Prexaton,
Wellbutrin
No No No Norepinephrine-dopamine reuptake inhibitor & nAChR antagonist High[91] Seizures, memory problems, concentration difficulties. Fairly dangerous in overdose. Delayed onset of action. Probably less efficacious than atomoxetine and classical stimulant medications in children. May be slightly more effective than atomoxetine in adults, however.
Buspirone Buspar No No No 5-HT1A partial agonist Low[92][93][94][95] Memory problems, dizziness, diarrhoea, nausea Delayed onset of action. Being a 5-HT1A receptor partial agonist may afford it the ability to increase dopamine release in the prefrontal cortex.[96][97]
Desipramine Norpramin No No No Tricyclic antidepressant High Seizures, hypotension, anticholinergic effects, sedation, weight gain, cardiovascular effects and sexual dysfunction Delayed onset of action.
Duloxetine Cymbalta No No No Serotonin-norepinephrine reuptake inhibitor Moderate[98] Hypertensive crises, liver failure, myocardial infarction (heart attack), suicidal thoughts, Stevens-Johnson syndrome, sexual dysfunction Delayed onset of action.
Imipramine Tofranil No No No Tricyclic antidepressant Low[99] Drowsiness, cardiovascular side effects, sexual dysfunction, weight gain, hypotension, seizures and anticholinergic effects. Dangerous in overdose. Delayed onset of action.
Milnacipran Ixel, Savella No No No Serotonin-norepinephrine reuptake inhibitor Negligible[100] Hypertension, sexual dysfunction Delayed onset of action.
Nortriptyline Allegron,
Pamelor
No No No Tricyclic antidepressant Low[101][102] Drowsiness, cardiovascular side effects, sexual dysfunction, weight gain, hypotension, seizures and anticholinergic effects. Dangerous in overdose. Delayed onset of action.
Reboxetine Edronax No No No Norepinephrine reuptake inhibitor Moderate[103] May be comparatively poorly-tolerated compared to other second-generation antidepressants.[104] Fairly safe in overdose.[105] Delayed onset of action.
Venlafaxine Efexor,
Effexor
No No No Serotonin-norepinephrine reuptake inhibitor Moderate[106] Gastrointestinal effects (nausea, vomiting, diarrhoea), weight loss, sexual dysfunction, hypertension, abnormal bleeding, hyponatraemia, suicidal ideation and seizures. Higher risk of provoking mania/hypomania in bipolar individuals than bupropion.[107] Can prolong the QT interval.[108] Less dangerous than bupropion and tricyclic antidepressants in overdose but more dangerous than reboxetine, duloxetine and milnacipran. Delayed onset of action.
Miscellaneous others
Amantadine Endantadine,
Symmetrel
No No No NMDA antagonist and dopamine agonist Low[109] Anxiety, anorexia, confusion, ataxia, hallucinations, dream abnormality, GI effects  ?
Carbamazepine Equetrol, Tegretol, Teril No No No Sodium channel blocker High[110] Ataxia, myocardial infarction, Stevens-Johnson syndrome, hepatic failure, syndrome of inappropriate antidiuretic hormone secretion (SIADH), toxic epidermal necrolysis, pancreatitis, hyponatraemia, renal failure, congestive heart failure, eosinophilic myocarditis, blood dyscrasias (agranulocytosis, aplastic anaemia, leucopaenia, thrombocytopaenia, etc.)  ?
Memantine Namenda No No No NMDA antagonist Low[111] Anxiety, anorexia, confusion, ataxia, hallucinations, dream abnormality, GI effects  ?

Levels of support
- Approved indicates that the level of evidence to support the use of the drug in the treatment of ADHD is sufficient for at least one regulatory agency to have already approved it.
- Very high indicates at least ten randomised double-blind placebo-controlled trial support the use of the drug in the treatment of ADHD.
- High indicates that at least three positive randomised double blind placebo-controlled trials have been performed evaluating the efficacy of the drug.
- Moderate indicates that at least one moderately/large-sized (≥30 people) positive randomised double-blind placebo-controlled clinical trial has been performed to evaluate the efficacy of the drug.
- Low indicates that at least one positive open-label or double-blind non-placebo-controlled clinical trial has been performed to evaluate the efficacy of the drug, or a controlled trial that was inadequately sized (<30 participants) or poorly designed.
- Very low. At least two case reports have documented the successful use of the drug in the treatment of ADHD.
- Negligible. One positive case report and additional theoretical (e.g. based on the mechanism of action of the drug in question) support.

Concerns regarding stimulants[edit]

The National Institute of Mental Health states that, "one-size-fits-all approach does not apply for all children with ADHD."[112] Some parents and professionals have raised questions about the side effects of drugs and their long-term use.[113] A recent review states that ADHD studies "have major methodological deficiencies which are compounded by their restriction to school-age children, relatively short follow-up, and few data on adverse effects."[13]

The American Heart Association feel that it is prudent to carefully assess children for heart conditions before treating them with stimulant medications.[114][115] Recent extremely large-scale studies by the FDA indicate that, in children, young adults, and adults, there is no association between serious adverse cardiovascular events (sudden death, myocardial infarction, and stroke) and the medical use of amphetamine, methylphenidate, or other ADHD stimulants.[116][117][118][119]

Several studies have found growth and weight suppression for stimulants. Compared to the behavior modification group at 8 years of the government-funded MTA study, the stimulant group had higher level of reported substance abuse.[120]

Increase in use[edit]

Outpatient treatment rates have held steady in the U.S. recently. Prior to this, outpatient treatment for ADHD in the U.S. grew from 0.9 children per 100 in 1987 to 3.4 per 100 in 1997.[121] A survey conducted by the Centers of Disease Control and Prevention in 2011-2012 found 6.4 million children between the ages of 4 and 17 have been diagnosed with ADHD at some point, a 16% increase since 2007 and a 41% increase over the last decade.[122] There is concern about the rising use of methylphenidate (Ritalin), mainly to treat ADHD and similar disorders, in the UK.[123] The American Psychiatric Association estimates the incidence of ADHD at three to seven percent of the population,[124] but current diagnoses rates in the U.S. are 15% for boys and 7% for girls.[125] Approximately two-thirds of children with current diagnoses are prescribed stimulants.[125]

Stimulant misuse[edit]

There is non-medical prescription stimulant use. A 2003 study found that non prescription use by college students in the U.S. was 6.9%, with 4.1% using them within the last year.[126] A 2006 study with teens in Grades 7 to Grade 12 found that 2% reported non-medical use of prescription stimulant medication in the past 12 months, with 2% also reporting non-medical use of prescribed sedatives and/or anxiety medications, 3% using sleeping medications, and 12% reporting non-medical use of prescribed pain medications.[127]

The National Survey on Drug Use and Health reported that 15% of college students admitted to having used a psychotherapeutic drug for a purpose other than that for which it was prescribed. It also reported that 7% of the 15% said they used Adderall to party or to improve their attention span or grades.[128]

Stimulant medications have the potential for abuse and dependence;[129] however, several studies indicate that untreated ADHD is associated with greater risk of substance abuse and conduct disorders.[130] The use of stimulants appears to reduce this risk.[130]

Medication in preschoolers[edit]

Parents of children with ADHD note that they usually display their symptoms at an early age. There have been few longitudinal studies on the long-term effects psychostimulants have on children.[131] The use of stimulant medication has not been approved by the FDA for children under the age of six.[132] 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.[133][134] 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.[132] Evidence suggests that careful assessment and highly individualized behavioural interventions significantly improve both social and academic skills,[135][136] while medication only treats the symptoms of the disorder. "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."[137]

Side effects[edit]

Growth delay and weight loss[edit]

The stunting of growth in children has been a concern. Past studies suggested that long-term use of the drugs could stunt children's growth.[138] A considerable amount of growth hormones (20-40%) are released during the 60-90 minute period after falling asleep. This part of the sleep cycle is suppressed by stimulants, causing a deficit of growth hormones in the body.[139] 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.[140] One notion is that psychostimulant medication can decrease appetite which may result in loss of weight and may be a factor in stunted growth.

Cardiovascular side effects[edit]

There is concern that stimulants and Atomoxetine, which increase the heart rate and blood pressure, might cause serious cardiovascular problems.[141] The current US FDA position on ADHD stimulants is that they are not likely to induce serious adverse cardiovascular events, unless there is already a pre-existing cardiovascular condition.[116][117][118][119]

Children, young adults, and adults taking ADHD medications are no more likely to suffer sudden cardiac death, stroke, or heart attack than members of the general population.[116][117][118][119]

Psychiatric side effects[edit]

Many of these drugs are associated with physical and psychological dependence.[142]

Sleep problems may occur,[143] but can also be an extremely common side effect of ADHD itself.[citation needed]

Increased rates of psychosis and/or mania are associated with many stimulants used to treat ADHD, including Concerta, Ritalin LA, d-MPH, Atomoxetine, Adderall XR, Modafinil, MTS, and Metadate. A 2009 FDA review of 49 clinical trials found that one to two percent of children taking stimulants for ADHD experienced hallucinations or other psychotic episodes. Nearly half of these were under the age of eleven, and approximately 90% had no history of similar psychiatric events. Hallucinations involving snakes, worms or insects were the most commonly reported.[144][145] This incidence of psychosis is higher than the 0.1% reported by previous short-term clinical trials.[146] Even this new incidence rate may be low, however, since the clinical trials often excluded children with previous, adverse reactions to ADHD medication.[144]

On occasion, treatment-emergent psychosis can emerge during long-term therapy with methylphenidate. Stimulants such as methylphenidate should be avoided in people who have a vulnerability to schizophrenia or addiction, but psychotic symptoms may emerge even in individuals without these risk factors. Regular psychiatric monitoring of people who are taking methylphenidate for adverse effects such as psychotic symptomatology (with regard to the need for dose adjustment or discontinuation of medication) has been recommended.[147]

Higher rates of schizophrenia and bipolar disorder as well as increased severity of these disorders occur in individuals with a past history of stimulant use for ADHD in childhood.[148] The long-term effects on mental health disorders in later life of chronic use of methylphenidate is unknown.[149]

Issues with long-term use of stimulant medication[edit]

Long-term methylphenidate or amphetamine exposure in some species is known to produce abnormal dopamine system development or nerve damage,[150][151] but humans experience normal development and nerve growth.[152][153][154] Magnetic resonance imaging studies suggest that long-term treatment with amphetamine or methylphenidate decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function of the right caudate nucleus.[152][153][154]

Reviews of clinical stimulant research have established the safety and effectiveness of long-term amphetamine use for ADHD.[155][156] Controlled trials spanning two years have demonstrated continuous treatment effectiveness and safety.[156][157] One review highlighted a 9 month randomized controlled trial of amphetamine in children that found an average increase of 4.5 IQ points and continued improvements in attention, disruptive behaviors, and hyperactivity.[157]

Stimulant withdrawal and rebound effects[edit]

Tolerance to the therapeutic effects of stimulants can occur,[158] with rebound of symptoms occurring when the dose wears off.[159] Due to the risk of discontinuation and rebound effects doses should be gradually decreased rather than the medication being stopped abruptly.[160] Rebound effects are often the result of the stimulant dosage being too high or the individual not being able to tolerate stimulant medication. Signs that the stimulant dose is too high include irritability, feeling stimulated or blunting of affect and personality.[161]

Stimulant withdrawal or rebound reactions can occur and should be minimised in intensity, i.e. via a gradual tapering off of medication over a period of weeks or months.[162][163][164] A very small study of abrupt withdrawal of stimulants did suggest that withdrawal reactions are not typical. Nonetheless withdrawal reactions may still occur in susceptible individuals.[165] The withdrawal or rebound symptoms of methylphenidate can include psychosis, irritability and depression and a return of ADHD symptoms in an exaggerated form. Methylphenidate may be worse for causing rebound and withdrawal effects due to its very short half life. Amphetamine may cause less severe rebound or withdrawal effects due to its somewhat longer half life.[52][166][167] Up to a third of ADHD children experience a rebound effect in ADHD symptoms when the methylphenidate dose wears off.[168]

Cancer[edit]

Concerns about chromosomal aberrations and possible cancer later in life was raised by a small-scale study on the use of methylphenidate, though a review by the Food and Drug Administration (FDA) found significant methodological problems with the study.[169] A follow-up study performed with improved methodology 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."[170]

Cost-effectiveness[edit]

Combined medical management and behavioral treatment is the most effective ADHD management strategy, followed by medication alone, and then behavioral treatment.[1] In terms of cost-effectiveness, management with medication has been shown to be the most cost-effective, followed by behavioral treatment, and combined treatment.[1] The individually most effective and cost-efficient way is with stimulant medication. Additionally, long-acting medications for ADHD, in comparison to short-acting varieties, generally seem to be cost-effective.[171] Comorbid (relating to two diseases that occur together, e.g. depression and ADHD) disorders makes finding the right treatment and diagnosis much more costly than when comorbid disorders are absent.

History[edit]

The first reported evidence of stimulant medication used to treat children with concentration and hyperactivity problems came in 1937.[172] Charles Bradley in Providence, Rhode Island reported that a group of children with behavioral problems improved after being treated with the stimulant Benzedrine.[172][173] In 1954, the stimulant methylphenidate (Ritalin, which was first produced in 1944) became available; it remains one of the most widely prescribed medications for ADHD.[172] Initially the drug was used to treat narcolepsy, chronic fatigue, depression, and to counter the sedating effects of other medications.[172] The drug began to be used for ADHD in the 1960s and steadily rose in use.[citation needed]

In 1975, pemoline (Cylert) was approved by the U.S. FDA for use in the treatment of ADHD. While an effective agent for managing the symptoms, the development of liver failure in 14 cases over the next 27 years would result in the manufacturer withdrawing this medication from the market. New delivery systems for medications were invented in 1999 that eliminated the need for multiple doses across the day or taking medication at school. These new systems include pellets of medication coated with various time-release substances to permit medications to dissolve hourly across an 8–12 hour period (Metadate CD, Adderall XR, Focalin XR) and an osmotic pump that extrudes a liquid methylphenidate sludge across an 8–12 hour period after ingestion (Concerta).[citation needed]

In 2003, atomoxetine (Strattera) received the first FDA approval for a nonstimulant drug to be used specifically for ADHD. In 2007, lisdexamfetamine (Vyvanse) becomes the first prodrug to receive FDA approval for ADHD.

In 1999 the largest study of treatment for ADHD was published in the American Journal of Psychiatry. Known as the Multimodal Treatment Study of ADHD (MTA Study), it involved more than 570 children with ADHD at 6 sites in the United States and Canada randomly assigned to 4 treatment groups. All 4 treatment groups showed marked improvement from the time of baseline measurements to completion of the study 14 months later. Behavioral treatment was as effective as medication alone on 16 of 19 outcome measures.[14] This was especially good for the behavior modification group, since the behavioral protocols were faded 3 months prior to the last evaluation and the stimulant group continued to receive medication right up to the last evaluation point.[2]

Alternative medicine[edit]

Ginkgo is a natural supplement used by some with ADHD.

Some proponents of alternative medicine advocate that alternative therapies may be tried before ADHD medications, although not all ADHD children will have any effective response.[52]

Neurofeedback[edit]

Neurofeedback (NF) or EEG biofeedback is a treatment strategy used for children, adolescents and adults with ADHD.[174] The human brain emits electrical energy which is measured with electrodes. Neurofeedback alerts the patient when beta waves are present. This theory believes that those with ADHD can train themselves to decrease ADHD symptoms.[citation needed]

No serious adverse side effects from neurofeedback have been reported.[175] Research into neurofeedback has been limited and of low quality.[175] While there is some indication on the effectiveness of biofeedback it is not conclusive: several studies have yielded positive results, however the best designed ones have either shown reduced effects or non-existing ones.[175][176]

Aerobic fitness[edit]

Aerobic fitness may improve cognitive functioning and neural organization related to executive control during pre-adolescent development, though more studies are needed in this area.[177] One study suggests that athletic performance in boys with ADHD may increase peer acceptance when accompanied by fewer negative behaviors.[178]

Massage Therapy[edit]

For children and adolescents with ADHD, pediatric massage therapy has been found to improve mood and increase on-task behaviors, while reducing anxiety and hyperactivity.[179][180]

Art Therapy[edit]

Art is thought by some to be an effective therapy for some of the symptoms of ADHD.[citation needed]

Media[edit]

Preliminary studies have supported the idea that playing video games is a form of neurofeedback, which helps those with ADHD self-regulate and improve learning.[181][182] On the other hand ADHD may experience great difficulty disengaging from the game, which may in turn negate any benefits gained from these activities,[183] and time management skills may be negatively impacted as well.[184]

Nature[edit]

Children who spend time outdoors in natural settings, such as parks, seem to display fewer symptoms of ADHD, which has been dubbed "Green Therapy".[185]

Dietary supplements[edit]

Dietary supplements and specialized diets are sometimes used by people with ADHD with the intent to mitigate some or all of the symptoms. For example, Omega-3 supplementation (seal, fish or krill oil) may reduce ADHD symptoms for a subgroup of children and adolescents with ADHD "characterized by inattention and associated neurodevelopmental disorders."[186] Although vitamin or mineral supplements (micronutrients) may help children diagnosed with particular deficiencies, there is no evidence that they are helpful for all children with ADHD. Furthermore, megadoses of vitamins, which can be toxic, must be avoided.[187] In the United States, no dietary supplement has been approved for the treatment for ADHD by the FDA.[188] There is however a pilot study done which shows that phosphatidyl serine (PS) can help against ADHD.[189]

Some popular supplements used to manage ADHD symptoms:

  • Zinc - Although the role of zinc in ADHD has not been elucidated, "numerous controlled studies report cross-sectional evidence of lower zinc tissue levels."[190]
  • Omega-3 fatty acids - Some studies suggest that a lack of omega-3 fatty acids is associated with certain ADHD symptoms.[191] 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 fat was found to be 30% higher than in controls, while the intake of many other nutrients was not different.[192][193] 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.[194] Researchers from CSIRO, Australia's national science agency, showed polyunsaturated fatty acids to provide "medium to strong positive treatment effects" in ADHD.[193] 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."[195] A 2008 study[186] 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.
  • Magnesium and 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 cell magnesium levels than controls (n =30). Intervention with magnesium and vitamin B6 reduced hyperactivity, hyperemotivity/aggressiveness and improved school attention.[196]
  • 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 ferritin who 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.[197]
  • Potassium - In 2007, Harvard-associated researchers described a form of ADHD that was well treated with over-the-counter potassium supplements. 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.[citation needed]
  • 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.[198]
  • Mild stimulants - Caffeine intake in moderate amounts may have benefits in ADHD due to caffeine's positive effects on cognition. Anxiety is the main side effect of caffeine, especially at high dosage.[199][200] Nicotine may improve the symptoms of ADHD in some people.[201]
  • Melatonin as well as careful daily sleep practices and light therapy, are sometimes used to treat the sleep disorders such as delayed sleep often associated with ADHD. ADHD itself has genetic commonality with the genes responsible for the human body clock (or circadian rhythm) and poor sleep and ADHD each increase the severity of the other; melatonin itself is a natural neurohormone responsible partly and in tiny amounts for the human body clock.

Diets[edit]

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.[202] However, studies have shown little if any effect of the Feingold diet on the behavior of children with ADHD.[203]

Results of studies regarding the effect of eliminating artificial food coloring from the diet of children with ADHD have been very varied. It has been found that it might be effective in some children but as the published studies have been of low quality results can be more related to research problems such as publication bias.[204] The UK Food Standards Agency (FSA) has called for a ban on the use of six artificial food colorings[205] and the European Union (EU) has ruled that some food dyes must be labeled with the relevant E number as well as this warning: "may have an adverse effect on activity and attention in children."[206] Nevertheless existing evidence neither refutes nor supports the association between ADHD and food colouring.[207]

Comorbid disorders[edit]

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.

Tic disorders[edit]

Patients with Tourette syndrome who 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 cognitive function, accounted for by the comorbid ADHD.[208]

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;[209] however, multiple lines of research have shown that stimulants can be cautiously used in the presence of tic disorders.[210] Several studies have shown that stimulants do not exacerbate tics any more than placebo does, and suggest that stimulants may even reduce tic severity.[211] Controversy remains, and the PDR continues 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.[209][212]

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.[213] 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 (clonidine and guanfacine), tricyclic antidepressants (desipramine and nortriptyline), and newer antidepressants (bupropion and venlafaxine. There have been case reports of tics worsening with bupropion (brand name Wellbutrin). There is good empirical evidence for short-term safety and efficacy for the use of desipramine, bupropion and atomoxetine (Strattera).[213]

Legal status of medications[edit]

Stimulants legal status was recently reviewed by several international organizations:

  • Internationally, methylphenidate is a Schedule II drug under the Convention on Psychotropic Substances.[214]
  • In the United States, methylphenidate and amphetamines are classified as Schedule II controlled substances, the designation used for substances that have a recognized medical value but present a high likelihood for abuse because of their addictive potential.[215]
  • In the United Kingdom, methylphenidate is a controlled 'Class B' substance, and possession without prescription is illegal, with a sentence up to 14 years and/or an unlimited fine.[216]
  • In Australia, stimulants such as methylphenidate and dexamphetamine are Schedule 8 controlled poisons, and as a result have strict prescribing rules due to their potential for abuse.[217]

Notes[edit]

  1. ^ References:[75][76][77][78][79]
  2. ^ References:[80][81][82][83][84][85]
  3. ^ Unlike most drugs, Adderall has no generic (USAN, INN, or BAN) name. Also known as mixed amfetamine salts

References[edit]

  1. ^ a b c d Jensen, et al.; Garcia, JA; Glied, S; Crowe, M; Foster, M; Schlander, M; Hinshaw, S; Vitiello, B; Arnold, LE (2005). "Cost-Effectiveness of ADHD Treatments: Findings from the Multimodal Treatment Study of Children With ADHD". American Journal of Psychiatry 162 (9): 1628–1636 (Page:1633). doi:10.1176/appi.ajp.162.9.1628. PMID 16135621.  Free full text
  2. ^ a b Arnold, L.E.; Chuang, S.; Davies, M.; Abikoff, H.B; Conners, C.K.; Elliott, G.R.; Greenhill, L.L.; Hechtman, L.; Hinshaw, J.H. et al.; Hoza, Betsy; Jensen, Peter S.; Kraemer, Helena C.; Langworthy-Lam, Kristen S.; March, John S.; Newcorn, Jeffrey H.; Pelham, William E.; Severe, Joanne B.; Swanson, James M.; Vitiello, Benedetto; Wells, Karen C.; Wigal, Timothy (2004). "Nine Months of Multicomponent Behavioral Treatment for ADHD and Effectiveness of MTA Fading Procedures". Journal of Abnormal Child Psychology 32 (1): 39–51. doi:10.1023/B:JACP.0000007579.61289.31. PMID 14998110. 
  3. ^ Molina, BS; Hinshaw, SP; Swanson, JM; Arnold, LE; Vitiello, B; Jensen, PS; Epstein, JN; Hoza, B; Hechtman, L; Abikoff, Howard B.; Elliott, Glen R.; Greenhill, Laurence L.; Newcorn, Jeffrey H.; Wells, Karen C.; Wigal, Timothy; Gibbons, Robert D.; Hur, Kwan; Houck, Patricia R.; Mta Cooperative, Group (2009). "The MTA at 8 years: Prospective follow-up of children treated for combined type ADHD in the multisite study". Journal of the American Academy of Child and Adolescent Psychiatry 48 (5): 484–500. doi:10.1097/CHI.0b013e31819c23d0. PMC 3063150. PMID 19318991. 
  4. ^ Rabbani, A; Alexander GC (December 2009). "Impact of family structure on stimulant use among children with attention-deficit/hyperactivity disorder". Health Services Research 44 (6): 2060–2078. doi:10.1111/j.1475-6773.2009.01019.x. PMC 2796314. PMID 19732168. 
  5. ^ a b Stein MA (July 2004). "Innovations in attention-deficit/hyperactivity disorder pharmacotherapy: long-acting stimulant and nonstimulant treatments". Am J Manag Care 10 (4 Suppl): S89–98. PMID 15352535. 
  6. ^ a b Christman AK, Fermo JD, Markowitz JS (August 2004). "Atomoxetine, a novel treatment for attention-deficit-hyperactivity disorder". Pharmacotherapy 24 (8): 1020–36. doi:10.1592/phco.24.11.1020.36146. PMID 15338851. 
  7. ^ a b Hazell P (October 2005). "Do adrenergically active drugs have a role in the first-line treatment of attention-deficit/hyperactivity disorder?". Expert Opin Pharmacother 6 (12): 1989–98. doi:10.1517/14656566.6.12.1989. PMID 16197353. 
  8. ^ Waxmonsky, James (October 2003). "Assessment and treatment of attention deficit hyperactivity disorder in children with comorbid psychiatric illness". Current Opinion in Pediatrics 15 (5): 476–482. doi:10.1097/00008480-200310000-00006. PMID 14508296. Retrieved 14 April 2013. 
  9. ^ a b c d e f American Academy of Pediatrics. Subcommittee on Attention-Deficit/Hyperactivity Disorder and Committee on Quality Improvement. (October 2001). "Clinical practice guideline: treatment of the school-aged child with attention-deficit/hyperactivity disorder". Pediatrics 108 (4): 1033–44. doi:10.1542/peds.108.4.1033. PMID 11581465. 
  10. ^ Fabianoa, G.A.; Pelham Jr, W.E. Jr.; Coles, E.K.; Gnagy, E.M.; Chronis-Tuscano, A.; O'Connor, B.C. (2008). "A meta-analysis of behavioral treatments for attention-deficit/hyperactivity disorder". Clinical Psychology Review 29 (2): 129–140. doi:10.1016/j.cpr.2008.11.001. PMID 19131150. 
  11. ^ King S, Griffin S, Hodges Z, et al. (July 2006). "A systematic review and economic model of the effectiveness and cost-effectiveness of methylphenidate, dexamfetamine and atomoxetine for the treatment of attention deficit hyperactivity disorder in children and adolescents". Health Technol Assess 10 (23): iii–iv, xiii–146. PMID 16796929. 
  12. ^ Murphy, Kevin R.; Barkley, Russell A. (2005). Attention-Deficit Hyperactivity Disorder, Third Edition : A Clinical Workbook. New York: The Guilford Press. ISBN 1-59385-227-4. 
  13. ^ a b Lerner M, Wigal T (January 2008). "Long-term safety of stimulant medications used to treat children with ADHD". Pediatric annals 37 (1): 37–45. doi:10.3928/00904481-20080101-11. PMID 18240852. 
  14. ^ a b c Stern HP, Stern TP (September 2002). "When children with attention-deficit/hyperactivity disorder become adults". South. Med. J. 95 (9): 985–91. doi:10.1097/00007611-200209000-00011. PMID 12356139. 
  15. ^ Greydanus DE, Pratt HD, Patel DR (February 2007). "Attention deficit hyperactivity disorder across the lifespan: the child, adolescent, and adult". Dis Mon 53 (2): 70–131. doi:10.1016/j.disamonth.2007.01.001. PMID 17386306. 
  16. ^ Schlamp D (March 2007). "[My child is so restless]". MMW Fortschr Med (in German) 149 (10): 39–40. PMID 17408047. 
  17. ^ "Update on drugs for hyperactivity in childhood". Drug Ther Bull 45 (5): 37–40. May 2007. doi:10.1136/dtb.2007.45537. PMID 17536494. 
  18. ^ Barkley, R. (2005) Take Charge of ADHD: The Complete Authoritative Guide for Parents NY: Guilford Publications
  19. ^ Kazdin, Alan E. Parent management training : treatment for oppositional, aggressive, and antisocial behavior in children and adolescents. Oxford University Press, 2005
  20. ^ Treatments for ADHD , Michigan State University. Retrieved 30 May 2014.
  21. ^ Sulzer D, Sonders MS, Poulsen NW, Galli A (April 2005). "Mechanisms of neurotransmitter release by amphetamines: a review". Progress in Neurobiology 75 (6): 406–33. doi:10.1016/j.pneurobio.2005.04.003. PMID 15955613. 
  22. ^ National Toxicology, Program (July 2005). "NTP-CERHR monograph on the potential human reproductive and developmental effects of amphetamines". Ntp Cerhr Mon (16): vii–III1. PMID 16130031. 
  23. ^ Howland RH (August 2008). "Lisdexamfetamine: a prodrug stimulant for ADHD". Journal of Psychosocial Nursing and Mental Health Services 46 (8): 19–22. doi:10.3928/02793695-20080801-05. PMID 18777964. 
  24. ^ "Acute tolerance to methylphenidate in the treatment of attention deficit hyperactivity disorder in children". 
  25. ^ Solanto MV (July 1998). "Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration". Behavioural Brain Research 94 (1): 127–52. doi:10.1016/S0166-4328(97)00175-7. PMID 9708845. 
  26. ^ Kolb, Bryan; Mychasiuk, Richelle; Muhammad, Arif; Li, Yilin; Frost, Douglas; Gibb, Robbin (Oct 8, 2012). "Experience and the Developing Prefrontal Cortex". Proc National Academy of Science USA (109): 17186–17193. doi:10.1073/pnas.1121251109. PMC 3477383. 
  27. ^ Robinson, TE; Kolb, B (2004). "Structural Plasticity Associated with Exposure to Drugs of Abuse". Comparitive Neuroscience and Neurobiology (47): Suppl 1:33–46. PMID 15464124. Retrieved 26 June 2014. 
  28. ^ Schachter HM, Pham B, King J, Langford S, Moher D (November 2001). "How efficacious and safe is short-acting methylphenidate for the treatment of attention-deficit disorder in children and adolescents? A meta-analysis". CMAJ 165 (11): 1475–88. PMC 81663. PMID 11762571. 
  29. ^ King S, Griffin S, Hodges Z (July 2006). "A systematic review and economic model of the effectiveness and cost-effectiveness of methylphenidate, dexamfetamine and atomoxetine for the treatment of attention deficit hyperactivity disorder in children and adolescents". Health Technology Assessment 10 (23): iii–iv, xiii–146. PMID 16796929. 
  30. ^ Murphy, Kevin R.; Barkley, Russell A. (2005). Attention-Deficit Hyperactivity Disorder, Third Edition : A Clinical Workbook. New York: The Guilford Press. ISBN 1-59385-227-4. 
  31. ^ Lerner M, Wigal T (January 2008). "Long-term safety of stimulant medications used to treat children with ADHD". Pediatric annals 37 (1): 37–45. doi:10.3928/00904481-20080101-11. PMID 18240852. 
  32. ^ American Academy of Pediatrics/American Heart Association (August 2008). "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 of Developmental and Behavioral Pediatrics 29 (4): 335. doi:10.1097/DBP.0b013e31318185dc14. PMID 18698199. 
  33. ^ Weiss MD, Gadow K, Wasdell MB (2006). "Effectiveness outcomes in attention-deficit/hyperactivity disorder". J Clin Psychiatry. 67 Suppl 8: 38–45. PMID 16961429. 
  34. ^ a b c Arnold (2000). "Methylphenidate vs Amphetamine: Comparative Review". Journal of Attention Disorders 3 (4): 200–211. doi:10.1177/108705470000300403. 
  35. ^ Rapoport JL, Inoff-Germain G (2002). "Responses to methylphenidate in Attention-Deficit/Hyperactivity Disorder and normal children: update 2002". J Atten Disord. 6 Suppl 1: S57–60. PMID 12685519. 
  36. ^ Dusan Kolar, Amanda Keller, Maria Golfinopoulos, Lucy Cumyn, Cassidy Syer, and Lily Hechtman (February 2008). "Treatment of adults with attention-deficit/hyperactivity disorder". Neuropsychiatr Dis Treat 4 (1): 107–121. PMC 2515906. PMID 18728812. 
  37. ^ Spencer TJ. (April 2007). "Pharmacology of adult ADHD with stimulants". CNS Spectr 12 (4(supplement 6)): 8–11. PMID 17715564. 
  38. ^ Rostain, Anthony L. (September 2008). "ADHD in Adults: Attention-Deficit/Hyperactivity Disorder in Adults: Evidence-Based Recommendations for Management". Postgraduate Medicine 120 (3): 27–38. doi:10.3810/pgm.2008.09.1905. PMID 18824823. 
  39. ^ Spencer, Thomas. Biederman, Joseph. Wilens, Timothy (June 2004). "Stimulant treatment of adult attention-deficit/hyperactivity disorder". Psychiatric Clinics of North America 27 (2). 
  40. ^ Higgins ES (January 1999). "A comparative analysis of antidepressants and stimulants for the treatment of adults with attention-deficit hyperactivity disorder". J Fam Pract 48 (1): 15–20. PMID 9934377. 
  41. ^ Verbeeck W, Tuinier S, Bekkering GE. (February 2009). "Antidepressants in the treatment of adult attention-deficit hyperactivity disorder: a systematic review". Adv Ther 26 (2): 170–184. doi:10.1007/s12325-009-0008-7. PMID 19238340. 
  42. ^ Millichap, J. Gordon (2010). Attention deficit hyperactivity disorder handbook : a physician's guide to ADHD (2nd ed.). New York: Springer. p. 122. ISBN 978-1-4419-1396-8. "Long-Term Usage of Stimulants and Outcome of ADHD
    Studies of long-term, uninterrupted stimulant therapy for ADHD are infrequent. One recent report of a 15-month controlled trial of amphetamine in 62 children, aged 6–11 years, showed continued improvements in behavior and learning ability, with no serious side effects. A multicenter, placebo-controlled trial of amphetamine treatment for ADHD in Sweden found significant improvements in attention, hyperactivity, and disruptive behaviors and a mean change in IQ of +4.5 after more than 9 months of amphetamine sulfate. Side effects included decreased appetite in 56%,abdominal pain in 32%, tics in 29%, and visual hallucinations requiring dose reduction or withdrawal in 5%. Abdominal pain and tics occurred with equal frequency in the placebo group, and only one of 4 children with tics at baseline had an increase in symptoms during amphetamine (15 mg/day) treatment (Gillberg et al., 1997). The children in the Swedish study had a high incidence of comorbid diagnoses (42%), including pervasive developmental disorders, mild retardation, and oppositional defiant disorder. Long-term trials of stimulants in ADHD with less comorbidity would be expected to show greater beneficial effects and a lower incidence of side effects. The unusually high incidence of tic disorders in both treated and untreated children was remarkable."
     
  43. ^ "ADHD Medications and Risk of Stroke In Young and Middle-Aged Adults". Retrieved 11 June 2013. 
  44. ^ "ADHD Medications and Risk of Serious Coronary Heart Disease in Young and Middle-Aged Adults". Retrieved 11 June 2013. 
  45. ^ "Attention Deficit Hyperactivity Disorder Medications and Risk of Serious Cardiovascular Disease in Children and Youth". Retrieved 11 June 2013. 
  46. ^ a b National Toxicology, Program (July 2005). "NTP-CERHR monograph on the potential human reproductive and developmental effects of amphetamines". Ntp Cerhr Mon (16): vii–III1. PMID 16130031. 
  47. ^ Glaser, et al.; Thomas, TC; Joyce, BM; Castellanos, FX; Gerhardt, GA (2005). "Differential Effects of Amphetamine Isomers on Dopamine in the Rat Striatum and Nucleus Accumbens Core". Psychopharmacology 178 (2–3): 250–258 (Page: 255). doi:10.1007/s00213-004-2012-6. PMID 15719230. 
  48. ^ Schepers RJ et al. (2003). "Methamphetamine and Amphetamine Pharmacokinetics in Oral Fluid and Plasma after Controlled Oral Methamphetamine Administration to Human Volunteers". Clin Chemistry 49 (1): 121–132 (Pages:121,130). doi:10.1373/49.1.121. PMID 12507968.  Free full text
  49. ^ Shoblock, et al.; Sullivan, EB; Maisonneuve, IM; Glick, SD (2003). "Neurochemical and Behavioral Differences Between D-Methamphetamine and D-Amphetamine in Rats". Psychopharmacology 165 (4): 359–369 (Page:366). doi:10.1007/s00213-002-1288-7. PMID 12491026. 
  50. ^ Williams, C. Donald (21 April 1996). "Methamphetamine for ADHD". Psychopharmacology Tips. Retrieved 15 April 2007. 
  51. ^ Heal DJ, Pierce DM (2006). "Methylphenidate and its isomers: their role in the treatment of attention-deficit hyperactivity disorder using a transdermal delivery system". CNS Drugs 20 (9): 713–738 (Page:730). doi:10.2165/00023210-200620090-00002. PMID 16953648. 
  52. ^ a b c Kidd PM (2000). "Attention deficit/hyperactivity disorder (ADHD) in children: rationale for its integrative management" (PDF). Altern Med Rev 5 (5): 402–28. PMID 11056411. 
  53. ^ Zhu J, Reith ME (2008). "Role of the dopamine transporter in the action of psychostimulants, nicotine, and other drugs of abuse". CNS & Neurological Disorders Drug Targets 7 (5): 393–409. doi:10.2174/187152708786927877. PMC 3133725. PMID 19128199. 
  54. ^ Stein MA (July 2004). "Innovations in attention-deficit/hyperactivity disorder pharmacotherapy: long-acting stimulant and nonstimulant treatments". The American Journal of Managed Care 10 (4 Suppl): S89–98. PMID 15352535. 
  55. ^ Christman AK, Fermo JD, Markowitz JS (August 2004). "Atomoxetine, a novel treatment for attention-deficit-hyperactivity disorder". Pharmacotherapy 24 (8): 1020–36. doi:10.1592/phco.24.11.1020.36146. PMID 15338851. 
  56. ^ Hazell P (October 2005). "Do adrenergically active drugs have a role in the first-line treatment of attention-deficit/hyperactivity disorder?". Expert Opinion on Pharmacotherapy 6 (12): 1989–98. doi:10.1517/14656566.6.12.1989. PMID 16197353. 
  57. ^ "Atomoxetine (marketed as Strattera) Information". Archived from the original on 9 July 2009. Retrieved 12 July 2009. 
  58. ^ Allen, AJ, Kurlan, RM, Gilbert, DL, Coffey, BJ, Linder, SL, Lewis, DW, Winner, PK, Dunn, DW, Dure, LS, Sallee, F. R., Milton, D. R., Mintz, M. I., Ricardi, R. K., Erenberg, G., Layton, L. L., Feldman, P. D., Kelsey, D. K., Spencer, T. J. (December 2005). "Atomoxetine treatment in children and adolescents with ADHD and comorbid tic disorders". Neurology 65 (12): 1941–9. doi:10.1212/01.wnl.0000188869.58300.a7. PMID 16380617. 
  59. ^ Arnsten AF. The use of alpha-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder. Expert Rev Neurother. 10:1595-605, 2010
  60. ^ Frazin, Natalie (2 April 2002). "Methylphenidate and Clonidine Help Children With ADHD and Tics". National Institute of Neurological Disorders and Stroke. Archived from the original on 27 April 2007. Retrieved 15 April 2007. 
  61. ^ "Atomoxetine (marketed as Strattera) Information". 
  62. ^ Lakhan, SE; Hagger-Johnson, G. (2007). "The impact of prescribed psychotropics on youth". Clinical Practice and Epidemiology in Mental Health 3 (1): 21. doi:10.1186/1745-0179-3-21. PMC 2100041. PMID 17949504. 
  63. ^ Hallowell, Edward M.; John J. Ratey (2005). Delivered from Distraction : Getting the Most out of Life with Attention Deficit Disorder. New York: Ballantine Books. pp. 253–5. ISBN 0-345-44231-8. 
  64. ^ Wellbutrin: Prescribing Information PDF (170 KB). GlaxoSmithKline (September 2006). Retrieved 15 April 2007.
  65. ^ Stahl S, Pradko J, Haight B, Modell J, Rockett C, Learned-Coughlin S (2004). "A Review of the Neuropharmacology of Bupropion, a Dual Norepinephrine and Dopamine Reuptake Inhibitor". Prim Care Companion J Clin Psychiatry 6 (4): 159–166. doi:10.4088/PCC.v06n0403. PMC 514842. PMID 15361919. 
  66. ^ Kako, Yuki; Niwa, Y; Toyomaki, A; Yamanaka, H; Kitagawa, N; Denda, K; Koyama, T (April 2007). "A case of adult attention-deficit/hyperactivity disorder alleviated by milnacipran". Progress in Neuro-Psychopharmacology & Biological Psychiatry 31 (3): 772–775. doi:10.1016/j.pnpbp.2006.12.017. PMID 17300859. 
  67. ^ Biederman J, Swanson JM, Wigal SB, Boellner SW, Earl CQ, Lopez FA (May 2006). "A comparison of once-daily and divided doses of modafinil in children with attention-deficit/hyperactivity disorder: a randomized, double-blind, and placebo-controlled study". The Journal of Clinical Psychiatry 67 (5): 727–35. doi:10.4088/JCP.v67n0506. PMID 16841622. 
  68. ^ Greenhill LL, Biederman J, Boellner SW (May 2006). "A randomized, double-blind, placebo-controlled study of modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder". Journal of the American Academy of Child and Adolescent Psychiatry 45 (5): 503–11. doi:10.1097/01.chi.0000205709.63571.c9. PMID 16601402. 
  69. ^ "Modavigil Product Information". Archived from the original on 21 July 2008. Retrieved 2 July 2008. 
  70. ^ Kumar R (2008). "Approved and investigational uses of modafinil : an evidence-based review". Drugs 68 (13): 1803–39. doi:10.2165/00003495-200868130-00003. PMID 18729534. 
  71. ^ 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
  72. ^ - Florida Medicaid To Review Antipsychotics & ADHD
  73. ^ "Atypical Antipsychotics for Treatment of Schizophrenia Spectrum Disorders". 
  74. ^ Physicians Postgraduate Press, Inc., Dosing of Atypical Antipsychotics in Children and Adolescents
  75. ^ a b c Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.  edit
  76. ^ a b Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8.  edit
  77. ^ a b "Varies with drug". Medscape Reference. WebMD. Retrieved 14 November 2013. 
  78. ^ a b Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (in English) (12th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-162442-8.  edit
  79. ^ White, N; Litovitz, T; Clancy, C (December 2008). "Suicidal antidepressant overdoses: a comparative analysis by antidepressant type". Journal of Medical Toxicology 4 (4): 238–250. doi:10.1007/BF03161207. PMC 3550116. PMID 19031375.  edit
  80. ^ Gozal, David; Molfese, Dennis L (2005). ATTENTION DEFICIT HYPERACTIVITY DISORDER. Contemporary Clinical Neuroscience. Humana Press. ISBN 9781588293121. 
  81. ^ Childress, AC; Berry, SA (February 2012). "Pharmacotherapy of Attention-Deficit Hyperactivity Disorder in Adolescents". Drugs 72 (3): 309–325. doi:10.2165/11599580-000000000-00000. PMID 22316347. 
  82. ^ Santosh, PJ; Sattar, S; Canagaratnam, M (September 2011). "Efficacy and Tolerability of Pharmacotherapies for Attention-Deficit Hyperactivity Disorder in Adults" (PDF). CNS Drugs 25 (9): 737–763. doi:10.2165/11593070-000000000-00000. PMID 21870887. 
  83. ^ Faraone, SV (December 2009). "Using Meta-analysis to Compare the Efficacy of Medications for Attention-Deficit/Hyperactivity Disorder in Youths" (PDF). P&T 34 (12): 678–694. PMC 2810184. PMID 20140141. 
  84. ^ Faraone, SV; Biederman, J; Spencer, TJ; Aleardi, M (October 2006). "Comparing the Efficacy of Medications for ADHD Using Meta-analysis". MedGenMed 8 (4): 4. PMC 1868385. PMID 17415287. 
  85. ^ Faraone, SV; Glatt, SJ (June 2010). "A comparison of the efficacy of medications for adult attention-deficit/hyperactivity disorder using meta-analysis of effect sizes". Journal of Clinical Psychiatry 71 (6): 754–763. doi:10.4088/JCP.08m04902pur. PMID 20051220. 
  86. ^ a b c d Miller GM (January 2011). "The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity". J. Neurochem. 116 (2): 164–176. doi:10.1111/j.1471-4159.2010.07109.x. PMC 3005101. PMID 21073468. 
  87. ^ "PRODUCT INFORMATION VYVANSE® (lisdexamphetamine dimesilate)" (PDF). TGA eBusiness Services. Shire Australia Pty. Limited. 22 July 2013. Retrieved 12 December 2013. 
  88. ^ Malenka RC, Nestler EJ, Hyman SE (2009). "15". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 370. ISBN 9780071481274. "Unlike cocaine and amphetamine, methamphetamine is directly toxic to midbrain dopamine neurons." 
  89. ^ Krasnova, IN; Cadet, JL (May 2009). "Methamphetamine toxicity and messengers of death". Brain Research Reviews 60 (2): 379–407. doi:10.1016/j.brainresrev.2009.03.002. PMC 2731235. PMID 19328213. 
  90. ^ Guardiola, A; Terra, AR; Ferreira, LT; Londero, RG (September 1999). "[Use of amitriptyline in attention deficit hyperactivity disorder]". Arq Neuropsiquiatr (in Portuguese) 57 (3A): 599–605. doi:10.1590/S0004-282X1999000400010. PMID 10667283. 
  91. ^ Maneeton, N; Maneeton, B; Srisurapanont, M; Martin, SD (December 2011). "Bupropion for adults with attention-deficit hyperactivity disorder: Meta-analysis of randomized, placebo-controlled trials". Psychiatry and Clinical Neurosciences 65 (7): 611–617. doi:10.1111/j.1440-1819.2011.02264.x. PMID 22176279. 
  92. ^ Malhotra, S; Santosh, PJ (April 1998). "An open clinical trial of buspirone in children with attention-deficit/hyperactivity disorder". Journal of the American Academy of Child and Adolescent Psychiatry 37 (4): 364–371. doi:10.1097/00004583-199804000-00013. PMID 9549956. 
  93. ^ Mohammadi, MR; Hafezi, P; Galeiha, A; Hajiaghaee, R; Akhondzadeh, S (November 2012). "Buspirone versus Methylphenidate in the Treatment of Children with Attention- Deficit/ Hyperactivity Disorder: Randomized Double-Blind Study". Acta Medica Iranica 50 (11): 723–728. PMID 23292622. 
  94. ^ Sutherland, SM; Adler, LA; Chen, C; Smith, MD; Feltner, DE (2012). "An 8-Week, Randomized Controlled Trial of Atomoxetine, Atomoxetine Plus Buspirone, or Placebo in Adults With ADHD". The Journal of Clinical Psychiatry 73 (4): 445–450. doi:10.4088/JCP.10m06788. PMID 22313788. 
  95. ^ Davari-Ashtiani, R; Shahrbabaki, ME; Razjouyan, K; Amini, H; Mazhabdar, H (2010). "Buspirone Versus Methylphenidate in the Treatment of Attention Deficit Hyperactivity Disorder: A Double-Blind and Randomized Trial" (PDF). Child Psychiatry and Human Development 41 (6): 641–648. doi:10.1007/s10578-010-0193-2. PMID 20517641. 
  96. ^ Bortolozzi, A; Masana, M; Díaz-Mataix, L; Cortés, R; Scorza, MC; Gingrich, JA; Toth, M; Artigas, F (November 2010). "Dopamine release induced by atypical antipsychotics in prefrontal cortex requires 5-HT1A receptors but not 5-HT2A receptors". The International Journal of Neuropsychopharmacology 13 (10): 1299–1314. doi:10.1017/S146114571000009X. PMID 20158933. 
  97. ^ Díaz-Mataix, L; Scorza, MC; Bortolozzi, A; Toth, M; Celada, P; Artigas, F (November 2005). "Involvement of 5-HT1A receptors in prefrontal cortex in the modulation of dopaminergic activity: role in atypical antipsychotic action" (PDF). The Journal of Neuroscience 25 (47): 10831–10843. doi:10.1523/JNEUROSCI.2999-05.2005. PMID 16306396. 
  98. ^ Bilodeau, M; Simon, T; Beauchamp, MH; Lespérance, P; Dubreucq, S; Dorée, JP; Tourjman, SV (May 2012). "Duloxetine in Adults With ADHD: A Randomized, Placebo-Controlled Pilot Study". Journal of Attention Disorders 18 (2): 169–75. doi:10.1177/1087054712443157. PMID 22582349. 
  99. ^ Biederman, J; Spencer, T (November 1999). "Attention-Deficit/Hyperactivity Disorder (ADHD) as a Noradrenergic Disorder". Biological Psychiatry 46 (9): 1234–1242. doi:10.1016/S0006-3223(99)00192-4. PMID 10560028. 
  100. ^ Kako, Y; Niwa, Y; Toyomaki, A; Yamanaka, H; Kitagawa, N; Denda, K; Koyama, T (April 2007). "A case of adult attention-deficit/hyperactivity disorder alleviated by milnacipran". Progress in Neuro-Psychopharmacology and Biological Psychiatry 31 (3): 772–775. doi:10.1016/j.pnpbp.2006.12.017. PMID 17300859. 
  101. ^ Wilens, TE; Biederman, J; Geist, DE; Steingard, R; Spencer, T (March 1993). "Nortriptyline in the treatment of ADHD: a chart review of 58 cases". Journal of the American Academy of Child and Adolescent Psychiatry 32 (2): 343–349. doi:10.1097/00004583-199303000-00015. PMID 8444763. 
  102. ^ Spencer, T; Biederman, J; Wilens, T; Steingard, R; Geist, D (January 1993). "Nortriptyline treatment of children with attention-deficit hyperactivity disorder and tic disorder or Tourette's syndrome". Journal of the American Academy of Child and Adolescent Psychiatry 32 (1): 205–210. doi:10.1097/00004583-199301000-00029. PMID 8428873. 
  103. ^ Riahi, F; Tehrani-Doost, M; Shahrivar, Z; Alaghband-Rad, J (November 2010). "Efficacy of reboxetine in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled clinical trial". Human Psychopharmacology 25 (7–8): 570–576. doi:10.1002/hup.1158. PMID 21312292. 
  104. ^ Cipriani, A; Furukawa, TA; Salanti, G; Geddes, JR; Higgins, JP; Churchill, R; Watanabe, N; Nakagawa, A; Omori, IM; McGuire, H; Tansella, M; Barbui, C (February 2009). "Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis" (PDF). Lancet 373 (9665): 746–758. doi:10.1016/S0140-6736(09)60046-5. PMID 19185342.  edit
  105. ^ Taylor, D; Paton, C; Shitij, K (2012). The Maudsley prescribing guidelines in psychiatry (in English). West Sussex: Wiley-Blackwell. pp. 588–589. ISBN 978-0-470-97948-8.  edit
  106. ^ Ahmad Ghanizadeh, Roger D. Freeman, Michael Berk (March 2013). "Efficacy and adverse effects of venlafaxine in children and adolescents with ADHD: a systematic review of non-controlled and controlled trials". Reviews on recent clinical trials 8 (1): 2–8. doi:10.2174/1574887111308010002. PMID 23157376. 
  107. ^ Pacchiarotti, I; Bond, DJ; Baldessarini, RJ; Nolen, WA; Grunze, H; Licht, RW; Post, RM; Berk, M; Goodwin, GM; Sachs, GS; Tondo, L; Findling, RL; Youngstrom, EA; Tohen, M; Undurraga, J; González-Pinto, A; Goldberg, JF; Yildiz, A; Altshuler, LL; Calabrese, JR; Mitchell, PB; Thase, ME; Koukopoulos, A; Colom, F; Frye, MA; Malhi, GS; Fountoulakis, KN; Vázquez, G; Perlis, RH; Ketter, TA; Cassidy, F; Akiskal, H; Azorin, JM; Valentí, M; Mazzei, DH; Lafer, B; Kato, T; Mazzarini, L; Martínez-Aran, A; Parker, G; Souery, D; Ozerdem, A; McElroy, SL; Girardi, P; Bauer, M; Yatham, LN; Zarate, CA; Nierenberg, AA; Birmaher, B; Kanba, S; El-Mallakh, RS; Serretti, A; Rihmer, Z; Young, AH; Kotzalidis, GD; Macqueen, GM; Bowden, CL; Ghaemi, SN; Lopez-Jaramillo, C; Rybakowski, J; Ha, K; Perugi, G; Kasper, S; Amsterdam, JD; Hirschfeld, RM; Kapczinski, F; Vieta, E (November 2013). "The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders". The American Journal of Psychiatry 170 (11): 1249–1262. doi:10.1176/appi.ajp.2013.13020185. PMID 24030475.  edit
  108. ^ Taylor, D; Paton, C; Shitij, K (2012). The Maudsley prescribing guidelines in psychiatry (in English). West Sussex: Wiley-Blackwell. p. 117. ISBN 978-0-470-97948-8.  edit
  109. ^ Mohammadi, MR; Kazemi, MR; Zia, E; Rezazadeh, SA; Tabrizi, M; Akhondzadeh, S (2010). "Amantadine versus methylphenidate in children and adolescents with attention deficit/hyperactivity disorder: a randomized, double-blind trial". Human Psychopharmacology 25 (7–8): 560–565. doi:10.1002/hup.1154. PMID 21312290. 
  110. ^ Silva, RR; Munoz, DM; Alpert, M (March 1996). "Carbamazepine Use in Children and Adolescents with Features of Attention-Deficit Hyperactivity Disorder: A Meta-Analysis". Journal of the American Academy of Child and Adolescent Psychiatry 35 (3): 352–358. doi:10.1097/00004583-199603000-00017. PMID 8714324. 
  111. ^ Surman, CB; Hammerness, PG; Petty, C; Spencer, T; Doyle, R; Napolean, S; Chu, N; Yorks, D; Biederman, J (May 2013). "A pilot open label prospective study of memantine monotherapy in adults with ADHD". The World Journal of Biological Psychiatry 14 (4): 291–298. doi:10.3109/15622975.2011.623716. PMID 22436083. 
  112. ^ "NIMH - Attention Deficit Hyperactivity Disorder (ADHD)- Treatment". National Institutes of Health (NIH). Retrieved 26 October 2013. 
  113. ^ 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).
  114. ^ American Academy of Pediatrics/American Heart Association. (August 2008). "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". J Dev Behav Pediatr 29 (4): 335. doi:10.1097/DBP.0b013e31318185dc14. PMID 18698199. 
  115. ^ Vetter, V. L.; Elia, J.; Erickson, C.; Berger, S.; Blum, N.; Uzark, K.; Webb, C. L.; American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee; American Heart Association Council on Cardiovascular Nursing (2008). "Cardiovascular Monitoring of Children and Adolescents With Heart Disease Receiving Medications for Attention Deficit/Hyperactivity Disorder: A Scientific Statement From the American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing". Circulation 117 (18): 2407–2423. doi:10.1161/CIRCULATIONAHA.107.189473. PMID 18427125. 
  116. ^ a b c Cooper WO, Habel LA, Sox CM, Chan KA, Arbogast PG, Cheetham TC, Murray KT, Quinn VP, Stein CM, Callahan ST, Fireman BH, Fish FA, Kirshner HS, O'Duffy A, Connell FA, Ray WA (November 2011). "ADHD drugs and serious cardiovascular events in children and young adults". N. Engl. J. Med. 365 (20): 1896–1904. doi:10.1056/NEJMoa1110212. PMID 22043968. 
  117. ^ a b c "FDA Drug Safety Communication: Safety Review Update...adults". United States Food and Drug Administration. 15 December 2011. Retrieved 4 November 2013. 
  118. ^ a b c Habel LA, Cooper WO, Sox CM, Chan KA, Fireman BH, Arbogast PG, Cheetham TC, Quinn VP, Dublin S, Boudreau DM, Andrade SE, Pawloski PA, Raebel MA, Smith DH, Achacoso N, Uratsu C, Go AS, Sidney S, Nguyen-Huynh MN, Ray WA, Selby JV (December 2011). "ADHD medications and risk of serious cardiovascular events in young and middle-aged adults". JAMA 306 (24): 2673–2683. doi:10.1001/jama.2011.1830. PMC 3350308. PMID 22161946. 
  119. ^ a b c "FDA Drug Safety Communication: Safety Review Update...children and young adults". United States Food and Drug Administration. 20 December 2011. Retrieved 4 November 2013. 
  120. ^ Molina, Brooke S.G.; Flory, Kate; Hinshaw, Stephen P.; Greiner, Andrew R.; Arnold, L. Eugene; Swanson, James M.; Hechtman, Lily; Jensen, al.; Vitiello, Benedetto; Hoza, Betsy; Pelham, William E.; Elliott, Glen R.; Wells, Karen C.; Abikoff, Howard B.; Gibbons, Robert D.; Marcus, SUE; Conners, C. Keith; Epstein, Jeffery N.; Greenhill, Laurence L.; March, John S.; Newcorn, Jeffrey H.; Severe, Joanne B.; Wigal, Timothy (2007). "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 46 (8): 1028–1040. doi:10.1097/chi.0b013e3180686d96. 
  121. ^ Name, LM; Gameroff, M; Marcus, MJ; Jensen, SC; Jensen, PS. (2003). "National trends in the treatment of attention deficit hyperactivity disorder". American Journal of Psychiatry 160 (6): 1071–1077. doi:10.1176/appi.ajp.160.6.1071. PMID 12777264. 
  122. ^ Schwarz and Cohen (31 March 2013). "More Diagnoses of A.D.H.D. Causing Concern". The New York Times. Retrieved 29 April 2013. 
  123. ^ "Sharp rise in children's Ritalin use". BBC News. 19 July 2003. Retrieved 22 November 2013. 
  124. ^ "Attention-Deficit / Hyperactivity Disorder: Data & Statistics". Center for Disease Control. Retrieved 26 October 2013. 
  125. ^ a b "A.D.H.D. Seen in 11% of U.S. Children as Diagnoses Rise". New York Times. 31 March 2013. Retrieved 26 October 2013. 
  126. ^ McCabe SE, Knight JR, Teter CJ, Wechsler H (January 2005). "Non-medical use of prescription stimulants among US college students: prevalence and correlates from a national survey". Addiction (Abingdon, England) 100 (1): 96–106. doi:10.1111/j.1360-0443.2005.00944.x. PMID 15598197. 
  127. ^ Boyd CJ, McCabe SE, Cranford JA, Young A (December 2006). "Adolescents' motivations to abuse prescription medications". Pediatrics 118 (6): 2472–2480. doi:10.1542/peds.2006-1644. PMC 1785364. PMID 17142533. 
  128. ^ Workman, T; Eells (2010). "Assessing the Risks and Issues: Prescription Drug Abuse on Campus". National Conference for Law and Higher Education. Retrieved 14 March 2013. 
  129. ^ Oregon Health & Science University, Portland, Oregon (2009). "Black box warnings of ADHD drugs approved by the US Food and Drug Administration". United States National Library of Medicine. Retrieved 17 January 2014. 
  130. ^ a b Malenka RC, Nestler EJ, Hyman SE (2009). "13". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 322–323. ISBN 9780071481274. 
  131. ^ Singh, Ilina (2008). "Beyond polemics: science and ethics of ADHD". Nature Reviews Neuroscience 9 (12): 957–964. doi:10.1038/nrn2514. PMID 19020513. 
  132. ^ a b Greenhill, L.; Kollins, S.; Abikoff, H.; McCracken, J.; Riddle, M.; Swanson, J.; McGough, J.; Wigal, S.; Wigal, T.; Vitiello, Benedetto; Skrobala, A; Posner, K; Ghuman, J; Cunningham, C; Davies, M; Chuang, S; Cooper, T (Nov 2006). "Efficacy and safety of immediate-release methylphenidate treatment for preschoolers with ADHD". J Am Acad Child Adolesc Psychiatry 45 (11): 1284–93. doi:10.1097/01.chi.0000235077.32661.61. PMID 17023867. 
  133. ^ Freudenheim, Milt (17 May 2004). "Behavior Drugs Lead in Sales For Children". The New York Times. Retrieved 25 April 2010. 
  134. ^ "Medco Settles Fraud, Kickback Charges for $155 Million". Consumers Unified LLC. 2006. Retrieved 26 October 2013. 
  135. ^ Wolraich, M.; Brown, L.; Wolraich, RT.; Brown, G.; Brown, M.; Dupaul, HM.; Earls, TG.; Feldman, B.; Ganiats, B.; Kaplanek, B; Meyer, B; Perrin, B; Pierce, J; Reiff, K; Stein, M; Visser, MT; Visser, S; Steering Committee on Quality Improvement Management; Steering Committee on Quality Improvement Management (November 2011). "ADHD: clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents". Pediatrics 128 (5): 1007–22. doi:10.1542/peds.2011-2654. PMID 22003063. Retrieved 22 November 2013. 
  136. ^ Chung, Jaeah (2013). "Medication Management of Preschool ADHD by Pediatric Sub-Specialists: Non-Compliance with AAP Clinical Guidelines". Retrieved 26 October 2013. 
  137. ^ http://www.medscape.com/viewarticle/523542
  138. ^ "Questions over drugs for ADHD". BBC News. 12 November 2007. Retrieved 25 April 2010. 
  139. ^ Breggin (1999). "Psychostimulants in the Treatment of Children Diagnosed with ADHD: Risks and Mechanism of Action". International Journal of Risk & Safety in Medicine 12: 3–35. 
  140. ^ Wilens, T.E. (2004) Straight Talk About Medications For Kids. NY: The Guilford Press.
  141. ^ "www.fda.gov" (PDF). 
  142. ^ "www.fda.gov" (PDF). 
  143. ^ Silver, Larry M.D. ADHD Medications: Say No to Side Effects,ADDitude magazine, February 2006.
  144. ^ a b Boyles, Salynn (26 January 2009). "ADHD Drugs: Hallucinations Not Uncommon". WebMD. Retrieved 23 October 2013. 
  145. ^ Mosholder, Andrew D.; Gelperin, Kate (1 February 2009). "Hallucinations and Other Psychotic Symptoms Associated With the Use of Attention-Deficit/Hyperactivity Disorder Drugs in Children". Pediatrics (American Academy of Pediatrics) 123 (2): 611–616. doi:10.1542/peds.2008-0185. PMID 19171629. Retrieved 23 October 2013. 
  146. ^ "Ritalin & Ritalin-SR Prescribing Information" (PDF). Novartis. April 2007. 
  147. ^ Kraemer M, Uekermann J, Wiltfang J, Kis B (July 2010). "Methylphenidate-induced psychosis in adult attention-deficit/hyperactivity disorder: report of 3 new cases and review of the literature". Clin Neuropharmacol 33 (4): 204–6. doi:10.1097/WNF.0b013e3181e29174. PMID 20571380. 
  148. ^ Ross RG (July 2006). "Psychotic and manic-like symptoms during stimulant treatment of attention deficit hyperactivity disorder". The American Journal of Psychiatry 163 (7): 1149–52. doi:10.1176/appi.ajp.163.7.1149. PMID 16816217. 
  149. ^ Kimko HC, Cross JT, Abernethy DR (December 1999). "Pharmacokinetics and clinical effectiveness of methylphenidate". Clin Pharmacokinet 37 (6): 457–70. doi:10.2165/00003088-199937060-00002. PMID 10628897. 
  150. ^ Carvalho M, Carmo H, Costa VM, Capela JP, Pontes H, Remião F, Carvalho F, Bastos Mde L (August 2012). "Toxicity of amphetamines: an update". Arch. Toxicol. 86 (8): 1167–1231. doi:10.1007/s00204-012-0815-5. PMID 22392347. 
  151. ^ Berman S, O'Neill J, Fears S, Bartzokis G, London ED (2008). "Abuse of amphetamines and structural abnormalities in the brain". Ann. N. Y. Acad. Sci. 1141: 195–220. doi:10.1196/annals.1441.031. PMC 2769923. PMID 18991959. 
  152. ^ a b Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K (February 2013). "Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects". JAMA Psychiatry 70 (2): 185–198. doi:10.1001/jamapsychiatry.2013.277. PMID 23247506. 
  153. ^ a b Spencer TJ, Brown A, Seidman LJ, Valera EM, Makris N, Lomedico A, Faraone SV, Biederman J (September 2013). "Effect of psychostimulants on brain structure and function in ADHD: a qualitative literature review of magnetic resonance imaging-based neuroimaging studies". J. Clin. Psychiatry 74 (9): 902–917. doi:10.4088/JCP.12r08287. PMC 3801446. PMID 24107764. 
  154. ^ a b Frodl T, Skokauskas N (February 2012). "Meta-analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects.". Acta psychiatrica Scand. 125 (2): 114–126. PMID 22118249. "Basal ganglia regions like the right globus pallidus, the right putamen, and the nucleus caudatus are structurally affected in children with ADHD. These changes and alterations in limbic regions like ACC and amygdala are more pronounced in non-treated populations and seem to diminish over time from child to adulthood. Treatment seems to have positive effects on brain structure." 
  155. ^ Millichap JG (2010). "Chapter 3: Medications for ADHD". In Millichap JG. Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD (2nd ed.). New York: Springer. pp. 111–113. ISBN 9781441913968. 
  156. ^ a b Huang YS, Tsai MH (July 2011). "Long-term outcomes with medications for attention-deficit hyperactivity disorder: current status of knowledge". CNS Drugs 25 (7): 539–554. doi:10.2165/11589380-000000000-00000. PMID 21699268. 
  157. ^ a b Millichap JG (2010). "Chapter 3: Medications for ADHD". In Millichap JG. Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD (2nd ed.). New York: Springer. pp. 121–123. ISBN 9781441913968. 
  158. ^ Fusar-Poli P, Rubia K, Rossi G, Sartori G, Balottin U (March 2012). "Striatal dopamine transporter alterations in ADHD: pathophysiology or adaptation to psychostimulants? A meta-analysis". Am J Psychiatry 169 (3): 264–72. doi:10.1176/appi.ajp.2011.11060940. PMID 22294258. 
  159. ^ Kooij, SJ.; Bejerot, S.; Blackwell, A.; Caci, H.; Casas-Brugué, M.; Carpentier, PJ.; Edvinsson, D.; Fayyad, J.; Foeken, K. et al. (2010). "European consensus statement on diagnosis and treatment of adult ADHD: The European Network Adult ADHD". BMC Psychiatry 10: 67. doi:10.1186/1471-244X-10-67. PMC 2942810. PMID 20815868. 
  160. ^ British, Medical Association (September 2007). "4 Central Nervous System". British National Formulary (54 ed.). UK: Royal Pharmaceutical Society of Great Britain. p. 212. ISBN 978-0-85369-736-7. OCLC 852015259. 
  161. ^ Brown, TE. (Oct 2008). "ADD/ADHD and Impaired Executive Function in Clinical Practice". Curr Psychiatry Rep 10 (5): 407–11. doi:10.1007/s11920-008-0065-7. PMID 18803914. 
  162. ^ Cohen D, Leo J, Stanton T, et al. (2002). "A boy who stops taking stimulants for "ADHD": commentaries on a Pediatrics case study". Ethical Hum Sci Serv 4 (3): 189–209. PMID 15278983. 
  163. ^ Schwartz RH, Rushton HG (May 2004). "Stuttering priapism associated with withdrawal from sustained-release methylphenidate". J. Pediatr. 144 (5): 675–6. doi:10.1016/j.jpeds.2003.12.039. PMID 15127013. 
  164. ^ Garland EJ (1998). "Pharmacotherapy of adolescent attention deficit hyperactivity disorder: challenges, choices and caveats". J. Psychopharmacol. (Oxford) 12 (4): 385–95. doi:10.1177/026988119801200410. PMID 10065914. 
  165. ^ Nolan EE, Gadow KD, Sprafkin J (April 1999). "Stimulant medication withdrawal during long-term therapy in children with comorbid attention-deficit hyperactivity disorder and chronic multiple tic disorder". Pediatrics 103 (4 Pt 1): 730–7. doi:10.1542/peds.103.4.730. PMID 10103294. 
  166. ^ Rosenfeld AA (February 1979). "Depression and psychotic regression following prolonged methylphenidate use and withdrawal: case report". Am J Psychiatry 136 (2): 226–8. PMID 760559. 
  167. ^ Smucker WD, Hedayat M (September 2001). "Evaluation and treatment of ADHD". Am Fam Physician 64 (5): 817–29. PMID 11563573. 
  168. ^ Riccio CA, Waldrop JJ, Reynolds CR, Lowe P (2001). "Effects of stimulants on the continuous performance test (CPT): implications for CPT use and interpretation". J Neuropsychiatry Clin Neurosci 13 (3): 326–35. doi:10.1176/appi.neuropsych.13.3.326. PMID 11514638. 
  169. ^ Ackerman, Todd (1 July 2005). "Closer look for possible Ritalin, cancer link". Houston Chronicle. Retrieved 10 July 2011. 
  170. ^ Walitza, Susanne, et al. (June 2007). "Does Methylphenidate Cause a Cytogenetic Effect in Children with Attention Deficit Hyperactivity Disorder?". Environmental Health Perspectives 115 (6): 936–940. doi:10.1289/ehp.9866. PMC 1892117. PMID 17589603. 
  171. ^ Schlander (2007). "Long-acting medications for the hyperkinetic disorders: a note on cost-effectiveness". European Child and Adolescent Psychiatry 16 (7): 421–429 (Page:421). doi:10.1007/s00787-007-0615-2. PMID 17401606. [1]
  172. ^ a b c d Lange, KW.; Reichl, S.; Lange, KM.; Tucha, L.; Tucha, O. (Dec 2010). "The history of attention deficit hyperactivity disorder". Atten Defic Hyperact Disord 2 (4): 241–55. doi:10.1007/s12402-010-0045-8. PMC 3000907. PMID 21258430. 
  173. ^ Charles Bradley, M.D., 1902–1979, retrieved 15 September 2008" American Journal of Psychiatry 155:968
  174. ^ Greydanus DE, Pratt HD, Patel DR (February 2007). "Attention deficit hyperactivity disorder across the lifespan: the child, adolescent, and adult". Disease-a-month 53 (2): 70–131. doi:10.1016/j.disamonth.2007.01.001. PMID 17386306. 
  175. ^ a b c Moriyama TS, Polanczyk G, Caye A, Banaschewski T, Brandeis D, Rohde LA (July 2012). "Evidence-based information on the clinical use of neurofeedback for ADHD". Neurotherapeutics 9 (3): 588–98. doi:10.1007/s13311-012-0136-7. PMC 3441929. PMID 22930416. 
  176. ^ Lofthouse N, Arnold LE, Hurt E (October 2012). "Current status of neurofeedback for attention-deficit/hyperactivity disorder". Curr Psychiatry Rep 14 (5): 536–42. doi:10.1007/s11920-012-0301-z. PMID 22890816. 
  177. ^ Hillman, C.; Buck, S.M.; Themanson, J.R.; Pontifex, M.B; Castelli, D.M. (2009). "Aerobic fitness and cognitive development: Event-related brain potential and task performance indices of executive control in preadolescent children". Developmental Psychology 45 (1): 114–125. doi:10.1037/a0014437. PMID 19209995. 
  178. ^ Lopez-Williams, Andy, Chacko, Anil, Wymbs, Brian T, Fabiano, Gregory A, Seymour, K. E., Gnagy, E. M., Chronis, A. M., Burrows-Maclean, L., Pelham, W. E., Morris, T. L. (2005). "Athletic Performance and Social Behavior as Predictors of Peer Acceptance in Children Diagnosed With Attention-Deficit/Hyperactivity Disorder". Journal of Emotional and Behavioral Disorders 13 (3): 173–180. doi:10.1177/10634266050130030501. 
  179. ^ Field T., Quintino O., Hernandez-Reif M., Koslovsky G. (1998). "Adolescents with attention deficit hyperactivity disorder benefit from massage therapy". Adolescence 33 (129): 103–108. PMID 9583664. 
  180. ^ Khilnani S., Field T., Hernandez-Reif M., Schanberg S. (2003). "Massage therapy improves mood and behavior of students with attention-deficit/hyperactivity disorder". Adolescence 38 (152): 623–38. PMID 15053490. 
  181. ^ Jenks, Susan (9 March 2006). "ADHD patients play video games as part of treatment". USA Today. 
  182. ^ Butnik S.M. (2005). "Neurofeedback in adolescents and adults with attention deficit hyperactivity disorder". Journal of Clinical Psychology 61 (5): 621–625. doi:10.1002/jclp.20124. PMID 15723361. 
  183. ^ Shaw R., Grayson A., Lewis V. (2000). "Inhibition, ADHD, and computer games: The inhibitory performance of children and ADHD on computerized tasks and games". Journal of Attention Disorders 8 (4): 160–168. doi:10.1177/1087054705278771. PMID 16110046. 
  184. ^ Tolchinsky A., Jefferson, S.D. (2011). "Problematic video game play in a college sample and its relationship to time management skills and Attention-Deficit/Hyperactivity disorder symptomology". Cyberpsychology, Behavior, and Social Networking 14 (9): 489–496. doi:10.1089/cyber.2010.0315. PMID 21288135. 
  185. ^ Lawson, W. (1 March 2004). "ADHD's Outdoor Cure". Psychology Today. Archived from the original on 26 November 2009. Retrieved 11 November 2009. 
  186. ^ a b Johnson M, Ostlund S, Fransson G, Kadesjö B, Gillberg C (March 2009). "Omega-3/omega-6 fatty acids for attention deficit hyperactivity disorder: a randomized placebo-controlled trial in children and adolescents". Journal of Attention Disorders 12 (5): 394–401. doi:10.1177/1087054708316261. PMID 18448859. 
  187. ^ "Diet and attention deficit hyperactivity disorder." Harvard Mental Health Letter. June 2009
  188. ^ "FDA Asks Attention-Deficit Hyperactivity Disorder (ADHD) Drug Manufacturers to Develop Patient Medication Guides". Food and Drug Administration. 21 September 2007. Archived from the original on 21 February 2008. Retrieved 13 April 2009. 
  189. ^ S. HIRAYAMA,Y. MASUDA,R. RABELER. "Effect of phosphatidylserine administration on symptoms of Attention-deficit/hyperactivity disorder in children". Agro Food 17 (5): 32–36. 
  190. ^ Arnold LE, DiSilvestro RA (2005). "Zinc in attention-deficit/hyperactivity disorder". Journal of child and adolescent psychopharmacology 15 (4): 619–27. doi:10.1089/cap.2005.15.619. PMID 16190793. 
  191. ^ Kadziela-Olech, H, Piotrowska-Jastrzebska, J. (2005). "The duration of breastfeeding and attention deficit hyperactivity disorder". Rocz Akad Med Bialymst 50: 302–6. PMID 16358988. 
  192. ^ Antalis C, Stevens L, Campbell M, Pazdro R, Ericson K, Burgess J (2006). "Omega-3 fatty acid status in attention-deficit/hyperactivity disorder". Prostaglandins Leukot Essent Fatty Acids 75 (4–5): 299–308. doi:10.1016/j.plefa.2006.07.004. PMID 16962757. 
  193. ^ a b Sinn N, Bryan J (2007). "Effect of supplementation with polyunsaturated fatty acids and micronutrients on learning and behavior problems associated with child ADHD". Journal of developmental and behavioral pediatrics : JDBP 28 (2): 82–91. doi:10.1097/01.DBP.0000267558.88457.a5. PMID 17435458. 
  194. ^ Ross BM, McKenzie I, Glen I, Bennett CP (2003). "Increased levels of ethane, a non-invasive marker of n-3 fatty acid oxidation, in breath of children with attention deficit hyperactivity disorder". Nutritional neuroscience 6 (5): 277–81. doi:10.1080/10284150310001612203. PMID 14609313. 
  195. ^ 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
  196. ^ "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
  197. ^ Konofal E, Cortese S, Lecendreux M, Arnulf I, Mouren MC (2005). "Effectiveness of iron supplementation in a young child with attention-deficit/hyperactivity disorder". Pediatrics 116 (5): e732–4. doi:10.1542/peds.2005-0715. PMID 16263988. 
  198. ^ Haslam, RHA, Dalby, JT, Rademaker, AW. (1984). "Effects of megavitamin therapy on children with attention deficit disorders". Pediatrics 74 (1): 103–111. PMID 6234505. 
  199. ^ Lara DR (2010). "Caffeine, mental health, and psychiatric disorders". J. Alzheimers Dis. 20 Suppl 1: S239–48. doi:10.3233/JAD-2010-1378. PMID 20164571. 
  200. ^ Leon, MR. "Effects of caffeine on cognitive, psychomotor, and affective performance of children with Attention-Deficit/Hyperactivity Disorder".J Atten Disord, 1 April 2000; 4(1): 27 - 47. doi:10.1177/108705470000400103
  201. ^ Toledano A, Alvarez MI, Toledano-Díaz A (September 2010). "Diversity and variability of the effects of nicotine on different cortical regions of the brain - therapeutic and toxicological implications". Cent Nerv Syst Agents Med Chem 10 (3): 180–206. doi:10.2174/1871524911006030180. PMID 20528766. 
  202. ^ Schnoll, R, Burshteyn, D, Cea-Aravena, J (March 2003). "Nutrition in the treatment of attention-deficit hyperactivity disorder: a neglected but important aspect". Applied psychophysiology and biofeedback 28 (1): 63–75. doi:10.1023/A:1022321017467. PMID 12737097. 
  203. ^ Krummel DA, Seligson FH, Guthrie HA (1996). "Hyperactivity: is candy causal?". Critical Reviews in Food Science & Nutrition 36 (1–2): 31–47. doi:10.1080/10408399609527717. PMID 8747098. 
  204. ^ Nigg JT, Lewis K, Edinger T, Falk M (January 2012). "Meta-analysis of attention-deficit/hyperactivity disorder or attention-deficit/hyperactivity disorder symptoms, restriction diet, and synthetic food color additives". J Am Acad Child Adolesc Psychiatry 51 (1): 86–97.e8. doi:10.1016/j.jaac.2011.10.015. PMID 22176942. 
  205. ^ "Europe-wide call for food colour ban | Manufacturing | ICM Commercial & Business News". 
  206. ^ "Modernising the Rules on Food Additives and Labelling of Azo Dyes - Food Industry News". 
  207. ^ Kleinman RE, Brown RT, Cutter GR, Dupaul GJ, Clydesdale FM (June 2011). "A research model for investigating the effects of artificial food colorings on children with ADHD". Pediatrics 127 (6): e1575–84. doi:10.1542/peds.2009-2206. PMID 21576306. 
  208. ^ 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, O'Donnell, D, Wilens, T, Faraone, S, Coffey, B, Geller, D (October 1998). "Disentangling the overlap between Tourette's disorder and ADHD". J Child Psychol Psychiatry 39 (7): 1037–44. doi:10.1111/1469-7610.00406. PMID 9804036. 
  209. ^ a b Freeman, RD. Tourette's Syndrome: minimizing confusion. Retrieved 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 Association Medical Advisory Board. Freeman has over 180 journal-published articles on PubMed.
  210. ^ 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
  211. ^ Tourette's Syndrome Study, Group (February 2002). "Treatment of ADHD in children with tics: a randomized controlled trial". Neurology 58 (4): 527–36. doi:10.1212/WNL.58.4.527. PMID 11865128. 
  212. ^ Zinner, SH (November 2000). "Tourette disorder". Pediatrics in review / American Academy of Pediatrics 21 (11): 372–83. PMID 11077021. 
  213. ^ a b Scahill, L, Erenberg, G, Berlin, CM, Budman, C, Coffey, BJ, Jankovic, J, Kiessling, L, King, RA, Kurlan, R, Lang, Anthony, Mink, Jonathan, Murphy, Tanya, Zinner, Samual, Walkup, John, Tourette Syndrome Association Medical Advisory Board: Practice Committee (April 2006). "Contemporary assessment and pharmacotherapy of Tourette syndrome". NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics 3 (2): 192–206. doi:10.1016/j.nurx.2006.01.009. PMC 3593444. PMID 16554257. 
  214. ^ United Nations (May 2010). "List of Psychotropic Substances under International Control" (PDF). 24th edition. International Narcotics Control Board. p. 6. 
  215. ^ Kollins SH (May 2008). "A qualitative review of issues arising in the use of psycho-stimulant medications in patients with ADHD and co-morbid substance use disorders". Curr Med Res Opin 24 (5): 1345–57. doi:10.1185/030079908X280707. PMID 18384709. 
  216. ^ Home Office (2010). "Drugs and the law". The Misuse of Drugs Act. United Kingdom: HomeOffice.gov.uk. 
  217. ^ Department of Health (September 2010). "Information for medical practitioners" (DOC). Australia: Australian Government.