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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. The American Academy of Pediatrics recommends different treatment paradigms depending on the age of the person being treated. For those aged 4-5, the Academy recommends evidence-based parent- and/or teacher-administered behavior therapy, with the addition of methylphenidate only if there is continuing moderate-to-severe functional disturbances. For those aged 6-11, the use of medication in combination with behavior therapy is recommended, with the evidence for stimulant medications being stronger than that for other classes. For those aged 12-18, medication should be prescribed with the consent of the treated adolescent, preferably in combination with behavioral therapy. The evidence for the utility of behavioral interventions in this aged group was rated only "C" quality, however.^[1]

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.^[2]^[3]^[4] 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.^[5]

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.^[6] 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.^[7]

As of 2006 there was a shortage of data regarding ADHD drugs' potential adverse effects,^[8] with very few studies assessing the safety or efficacy of treatments beyond four months,^[9] and no randomized controlled trials assessing for periods of usage longer than two years.^[10]^[11]

Psychosocial

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.

Parent education and classroom management

Improving the surrounding home and school environment can improve the behavior of children with ADHD.^[6] 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.^[12] 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.^[6] 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.^[6] 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.^[6]

Working memory training

A 2013 meta analysis concluded that working memory training provides short term improvements in working memory skills, but that there was limited evidence that these improvements were sustained or that they were generalized to improved verbal ability, mathematical skills, attention, or word decoding.^[13]

Timers

Timers have been found to be effective for allowing people with ADHD to concentrate more effectively on the task at hand.^[14] 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

Stimulants

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),^[15] dextromethamphetamine (Desoxyn)^[16] and lisdexamfetamine (Vyvanse).^[17] 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.^[18] 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.^[19] Serious concerns of publication bias regarding the use of methylphenidate for ADHD has also been noted.^[20]

Stimulant medications are considered safe when used under medical supervision.^[6] Nonetheless, there are concerns that the long term safety of these drugs has not been adequately documented.^[11]^[8]^[21]^[22] and social and ethical issues regarding their use and dispensation. The U.S. FDA has added black-box warnings to some ADHD medications, warning that abuse can lead to psychotic episodes, psychological dependence, and that severe depression may occur during withdrawal from abusive use.^[23]

Stimulants are the most effective medications available for the treatment of ADHD.^[24] 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.^[25] 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.^[26] Some investigations are dedicated to finding the similarities of children who respond to a specific medicine.^[26] The behavioural response to stimulants in children is similar regardless of whether they have ADHD or not.^[27]

Stimulant medication is an effective treatment^[28] for adult attention-deficit hyperactivity disorder^[29]^[30] although the response rate may be lower for adults than children.^[31] Some physicians may recommend antidepressant drugs as the first line treatment instead of stimulants^[32] although antidepressants have lower treatment effect sizes than stimulant medication.^[33]

Amphetamines

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]."^[34]	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.^[35]^[36]^[37] 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).^[16] 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.^[16]

Levoamphetamine and dextroamphetamine

Levoamphetamine and dextroamphetamine have the same chemical formula but are mirror images of each other, the same way that a person's hands are the same but are mirror images of each other. This mirror difference is enough to cause the two compounds to be metabolized differently. Adderall begins to work before dextroamphetamine because of levoamphetamine.^[38] Levoamphetamine also provides Adderall with a longer clinical effect than dextroamphetamine. Some children with ADHD and comorbid disorders respond well to levoamphetamine.^[26]

Dextromethamphetamine

The body metabolizes dextromethamphetamine into dextroamphetamine (in addition to less active metabolites). A quarter of dextromethamphetamine will ultimately become dextroamphetamine.^[39] After comparing only the common ground between dextroamphetamine and dextromethamphetamine, the latter is said to be the stronger stimulant.^[40] 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.^[41]

Methylphenidate-based medications

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.^[42] Methylphenidate has high potential for abuse and addiction due to its pharmacological similarity to cocaine and amphetamines.^[43]

Non-stimulants

Atomoxetine (Strattera),^[44] 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.^[45]^[3]^[4]

Atomoxetine (Strattera) is less effective than stimulants for ADHD, is associated with rare cases of liver damage,^[46] and carries a U.S. FDA black box warning regarding suicidal ideation.^[47] Controlled studies show increases in heart rate, decreases of body weight, decreased appetite and treatment-emergent nausea.^[48]

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.^[49]

Clonidine (Kapvay), an α_2A 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.^[50] 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.^[2]^[3]^[4]

Other

Some medications used to treat ADHD are prescribed off-label,^[51] 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.^[52]
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,^[53] and has little or no effect on serotonergic re-uptake.^[54] 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.^[55]
Modafinil (Provigil/Alertec/Sparlon) — Double-blind randomized controlled trials have demonstrated the efficacy and tolerability of modafinil,^[56]^[57] however there are risks of serious side effects such as skin reactions and modafinil is not recommended for use in children.^[58] 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.^[59]
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,^[60] 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.^[61] 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.^[62]

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.^[63] 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

Generic name (INN)	Brand name(s)	TGA-labelled for ADHD?^[64]	MHRA-labelled for ADHD?^[65]	FDA-labelled for ADHD?^[66]	Pharmacologic class^[67]	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^[75]	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^[75]	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)^[76]	Yes (children ≥6 years and adults)	Yes (children ≥6 years and adults)	Monoamine reuptake inhibitor and releasing agent^[75]	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^[75]	Approved	Transient growth stunting, hypertension or hypotension, dependence and tolerance, direct neurotoxicity to dopamine and serotonin neurons,^[77]^[78] 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.^[64]
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^[79]	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^[80]	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-HT_1A partial agonist	Low^[81]^[82]^[83]^[84]	Memory problems, dizziness, diarrhoea, nausea	Delayed onset of action. Being a 5-HT_1A receptor partial agonist may afford it the ability to increase dopamine release in the prefrontal cortex.^[85]^[86]
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^[87]	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^[88]	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^[89]	Hypertension, sexual dysfunction	Delayed onset of action.
Nortriptyline	Allegron, Pamelor	No	No	No	Tricyclic antidepressant	Low^[90]^[91]	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^[92]	May be comparatively poorly-tolerated compared to other second-generation antidepressants.^[93] Fairly safe in overdose.^[94]	Delayed onset of action.
Venlafaxine	Efexor, Effexor	No	No	No	Serotonin-norepinephrine reuptake inhibitor	Moderate^[95]	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.^[96] Can prolong the QT interval.^[97] 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^[98]	Anxiety, anorexia, confusion, ataxia, hallucinations, dream abnormality, GI effects	?
Carbamazepine	Equetrol, Tegretol, Teril	No	No	No	Sodium channel blocker	High^[99]	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^[100]	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.

Notes

^ References:^[64]^[65]^[66]^[67]^[68]
^ References:^[69]^[70]^[71]^[72]^[73]^[74]
^ Unlike most drugs, Adderall has no generic (USAN, INN, or BAN) name. Also known as mixed amfetamine salts

Concerns regarding stimulants

The National Institute of Mental Health states that, "one-size-fits-all approach does not apply for all children with ADHD."^[101] Some parents and professionals have raised questions about the side effects of drugs and their long-term use.^[102] 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."^[10]

The American Heart Association feel that it is prudent to carefully assess children for heart conditions before treating them with stimulant medications.^[103]^[104] 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.^[105]^[106]^[107]^[108]

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.^[109]

Increase in use

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.^[110] 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.^[111] There is concern about the rising use of methylphenidate (Ritalin), mainly to treat ADHD and similar disorders, in the UK.^[112] The American Psychiatric Association estimates the incidence of ADHD at three to seven percent of the population,^[113] but current diagnoses rates in the U.S. are 15% for boys and 7% for girls.^[114] Approximately two-thirds of children with current diagnoses are prescribed stimulants.^[114]

Stimulant misuse

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.^[115] 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.^[116]

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.^[117]

Stimulant medications have the potential for abuse and dependence;^[118] however, several studies indicate that untreated ADHD is associated with greater risk of substance abuse and conduct disorders.^[119] The use of stimulants appears to reduce this risk.^[119]

Medication in preschoolers

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.^[120] The use of stimulant medication has not been approved by the FDA for children under the age of six.^[121] 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.^[122]^[123] 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.^[121] Evidence suggests that careful assessment and highly individualized behavioural interventions significantly improve both social and academic skills,^[124]^[125] 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."^[126]

Side effects

Growth delay and weight loss

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.^[127] 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.^[128] 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.^[129] 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

There is concern that stimulants and Atomoxetine, which increase the heart rate and blood pressure, might cause serious cardiovascular problems.^[130] 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.^[105]^[106]^[107]^[108]

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.^[105]^[106]^[107]^[108]

Psychiatric side effects

Many of these drugs are associated with physical and psychological dependence.^[131]

Sleep problems may occur,^[132] 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.^[133]^[134] This incidence of psychosis is higher than the 0.1% reported by previous short-term clinical trials.^[135] Even this new incidence rate may be low, however, since the clinical trials often excluded children with previous, adverse reactions to ADHD medication.^[133]

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.^[136]

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.^[137] The long-term effects on mental health disorders in later life of chronic use of methylphenidate is unknown.^[138]

Issues with long-term use of stimulant medication

Long-term methylphenidate or amphetamine exposure in some species is known to produce abnormal dopamine system development or nerve damage,^[139]^[140] but humans experience normal development and nerve growth.^[141]^[142]^[143] 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.^[141]^[142]^[143]

Reviews of clinical stimulant research have established the safety and effectiveness of long-term amphetamine use for ADHD.^[144]^[145] Controlled trials spanning two years have demonstrated continuous treatment effectiveness and safety.^[145]^[146] 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.^[146]

Stimulant withdrawal and rebound effects

Tolerance to the therapeutic effects of stimulants can occur,^[147] with rebound of symptoms occurring when the dose wears off.^[148] Due to the risk of discontinuation and rebound effects doses should be gradually decreased rather than the medication being stopped abruptly.^[149] 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.^[150]

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.^[151]^[152]^[153] 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.^[154] 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.^[155]^[156]^[157] Up to a third of ADHD children experience a rebound effect in ADHD symptoms when the methylphenidate dose wears off.^[158]

Cancer

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.^[159] 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."^[160]

Cost-effectiveness

Combined medical management and behavioral treatment is the most effective ADHD management strategy, followed by medication alone, and then behavioral treatment.^[24] In terms of cost-effectiveness, management with medication has been shown to be the most cost-effective, followed by behavioral treatment, and combined treatment.^[24] 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.^[161] 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

The first reported evidence of stimulant medication used to treat children with concentration and hyperactivity problems came in 1937.^[162] Charles Bradley in Providence, Rhode Island reported that a group of children with behavioral problems improved after being treated with the stimulant Benzedrine.^[162]^[163] 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.^[162] Initially the drug was used to treat narcolepsy, chronic fatigue, depression, and to counter the sedating effects of other medications.^[162] 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.

Alternative medicine

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.^[155]

Neurofeedback

Neurofeedback (NF) or EEG biofeedback is a treatment strategy used for children, adolescents and adults with ADHD.^[164] 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.^[165] Research into neurofeedback has been limited and of low quality.^[165] 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.^[165]^[166]

Art Therapy

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

Media

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.^[167]^[168] On the other hand ADHD may experience great difficulty disengaging from the game, which may in turn negate any benefits gained from these activities,^[169] and time management skills may be negatively impacted as well.^[170]

Nature

Children who spend time outdoors in natural settings, such as parks, seem to display fewer symptoms of ADHD, which has been dubbed "Green Therapy".^[171]

Dietary supplements

Dietary supplements and specialized diets are sometimes used by people with ADHD with the intent to mitigate some or all of the symptoms. 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.^[172] In the United States, no dietary supplement has been approved for the treatment for ADHD by the FDA.^[173]

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."^[174]
Omega-3 fatty acids - A 2012 Cochrane review found little evidence that supplementation with omega-3 or other polyunsaturated fatty acids provide any improvement in the symptoms of ADHD in children or adolescents.^[175]

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.^[176]
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.^[177]
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.^[178]
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.^[179]^[180] Nicotine may improve the symptoms of ADHD in some people.^[181]
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

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.^[182] However, studies have shown little if any effect of the Feingold diet on the behavior of children with ADHD.^[183]

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.^[184] The UK Food Standards Agency (FSA) has called for a ban on the use of six artificial food colorings^[185] 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."^[186] Nevertheless existing evidence neither refutes nor supports the association between ADHD and food colouring.^[187]

Comorbid disorders

Because ADHD comorbidities are diverse and the rate of comorbidity is high, special care must dedicated to certain comorbidities. The FDA is not set up to address this issue, and does not approve medications for comorbidities, nonetheless certain such topics have been extensively researched.

Tic disorders

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.^[188]

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;^[189] however, multiple lines of research have shown that stimulants can be cautiously used in the presence of tic disorders.^[190] Several studies have shown that stimulants do not exacerbate tics any more than placebo does, and suggest that stimulants may even reduce tic severity.^[191] 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.^[189]^[192]

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.^[193] 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).^[193]

Legal status of medications

Stimulants legal status was recently reviewed by several international organizations:

Internationally, methylphenidate is a Schedule II drug under the Convention on Psychotropic Substances.^[194]
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.^[195]
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.^[196]
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.^[197]

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[69] References:^[64]^[65]^[66]^[67]^[68]

[76] References:^[69]^[70]^[71]^[72]^[73]^[74]

[77] Unlike most drugs, Adderall has no generic (USAN, INN, or BAN) name. Also known as mixed amfetamine salts

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@@ Line 324: / Line 324: @@
 * [[Zinc]] - Although the role of zinc in ADHD has not been elucidated, "numerous controlled studies report cross-sectional evidence of lower zinc tissue levels."<ref name="pmid16190793">{{cite journal|author=Arnold LE, DiSilvestro RA|title=Zinc in attention-deficit/hyperactivity disorder|journal=Journal of child and adolescent psychopharmacology|volume=15|issue=4|pages=619&ndash;27|year=2005|pmid=16190793|doi=10.1089/cap.2005.15.619}}</ref>
+* [[Omega-3 fatty acids]] - A 2012 Cochrane review found little evidence that supplementation with omega-3 or other polyunsaturated fatty acids provide any improvement in the symptoms of ADHD in children or adolescents.<ref>{{cite journal |author=Gillies D, Sinn JKh, Lad SS, Leach MJ, Ross MJ |title=Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents |journal=Cochrane Database Syst Rev |volume=7 |issue= |pages=CD007986 |year=2012 |pmid=22786509 |doi=10.1002/14651858.CD007986.pub2 |url=}}</ref>
-* [[Omega-3 fatty acids]] - Some studies suggest that a lack of [[omega-3 fatty acids]] is associated with certain ADHD symptoms.<ref>{{cite journal | last1 = Kadziela-Olech | first1 = H | last2 = Piotrowska-Jastrzebska | first2 = J. | author-separator =, | author-name-separator= | year = 2005 | title = The duration of breastfeeding and attention deficit hyperactivity disorder | url = | journal = Rocz Akad Med Bialymst | volume = 50 | issue = | pages = 302–6 | pmid = 16358988 }}</ref> 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.<ref name="pmid16962757">{{cite journal
-| author=Antalis C, Stevens L, Campbell M, Pazdro R, Ericson K, Burgess J
-| title=Omega-3 fatty acid status in attention-deficit/hyperactivity disorder
-| journal=Prostaglandins Leukot Essent Fatty Acids
-| volume=75
-| issue=4–5
-| pages=299&ndash;308
-| year=2006
-| pmid=16962757
-| doi=10.1016/j.plefa.2006.07.004
-}}</ref><ref name="pmid17435458">{{cite journal|author=Sinn N, Bryan J|title=Effect of supplementation with polyunsaturated fatty acids and micronutrients on learning and behavior problems associated with child ADHD|journal=Journal of developmental and behavioral pediatrics : JDBP|volume=28|issue=2|pages=82&ndash;91|year=2007|pmid=17435458|doi=10.1097/01.DBP.0000267558.88457.a5}}</ref> 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.<ref name="pmid14609313">{{cite journal|author=Ross BM, McKenzie I, Glen I, Bennett CP|title=Increased levels of ethane, a non-invasive marker of n-3 fatty acid oxidation, in breath of children with attention deficit hyperactivity disorder|journal=Nutritional neuroscience|volume=6|issue=5|pages=277&ndash;81|year=2003|pmid=14609313|doi=10.1080/10284150310001612203}}</ref> Researchers from CSIRO, Australia's national science agency, showed polyunsaturated fatty acids to provide "medium to strong positive treatment effects" in ADHD.<ref name="pmid17435458" /> 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."<ref>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}}</ref> A 2008 study<ref name="Johnson08"/> 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|vitamin B<sub>6</sub>]] (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 B<sub>6</sub> reduced hyperactivity, hyperemotivity/aggressiveness and improved school attention.<ref name="MgB6">"Improvement of neurobehavioral disorders in children supplemented with magnesium-vitamin B<sub>6</sub>. I. Attention deficit hyperactivity disorders." Magnes Res. 2006 Mar;19(1):46-52. PMID 16846100</ref>

v t e Attention deficit hyperactivity disorder (ADHD)
Main articles	History of ADHD ADHD in adults ADHD controversies ADHD management ADHD coaching Epidemiology of ADHD Major characteristics: Attention Hyperactivity Impulsivity
Sub-types	ADHD predominantly inattentive (ADHD-I) ADHD predominantly hyperactive (ADHD-H) ADHD combined type (ADHD-C)
Medications	Stimulants: Methylphenidate (Ritalin, Concerta, and others) Dexmethylphenidate (Focalin, Focalin XR) Amphetamine (Evekeo, Adderall, Adzenys XR, Dyanavel XR) Dextroamphetamine (Dexedrine, Zenzedi, ProCentra, and others) Lisdexamfetamine (Vyvanse) Methamphetamine (Desoxyn) Non-stimulant: Atomoxetine (Strattera) Guanfacine (Tenex (off-label), Intuniv) Clonidine (Catapres (off-label), Kapvay) Bupropion (Wellbutrin (off-label), Zyban) Investigational: List of investigational attention deficit hyperactivity disorder drugs
Related or outdated topics	Delayed gratification Auditory processing disorder Deficits in attention, motor control and perception Developmental coordination disorder Low arousal theory Sluggish cognitive tempo Sensory processing disorder Hunter versus farmer hypothesis
Category