Attention deficit hyperactivity disorder management

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

There are several effective and clinically proven options to treat people with ADHD. Multimodal treatment, that is combined pharmacological and behavioral therapy, is the most effective ADHD management strategy, followed by medication alone, and then behavioral treatment. 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. 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 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.

The most common stimulant medications are methylphenidate (Ritalin), dextroamphetamine (Dexedrine), and mixed amphetamine salts (Adderall). Atomoxetine (Strattera), guanfacine (Intuniv) and clonidine (Kapvay) are non-stimulant drugs approved for the treatment of ADHD. Other medications which may be prescribed off-label include certain antidepressants such as tricyclic antidepressants, SNRIs or MAOIs. The presence of comorbid (relating to two diseases that occur together, e.g. depression and ADHD) disorders make finding the right treatment and diagnosis much more costly and time consuming. A child having a comorbid disorder makes the treatment and diagnosis of ADHD more complicated, so it is important to assess and treat any comorbid disorders simultaneously.

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. Specialized ADHD coaches provide services and strategies to improve functioning, like time management or organizational suggestions. Self-control training programs have 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.

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

On Wednesday, November 21, 2012, the online edition of the Peoria, Illinois-based Peoria Journal Star newspaper featured an Associated Press (AP) article by Marilynn Marchione, with AP Medical Writer Maria Cheng contributing from London. It cited a study, published in the New England Journal of Medicine, with Paul Lichtenstein, from the Karolinska Institute in Stockholm, Sweden, as lead author, which revealed that medications to treat ADHD (Ritalin, Adderall, and others) in adults (and older teens- over age 15) drastically lowered their likelihood of committing a crime (mainly burglary and theft, as opposed to truly violent crimes, like murder).

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. If psychotherapy fails to bring improvement, medications can be considered as an add-on or alternative.

Psychotherapy

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

Parent education and classroom management

Improving the surrounding home and school environment can improve the behavior of children with ADHD. 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. 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. 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 or privileges for failing to meet goals or poor behavior. 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.

Working memory training

Main article: Working memory training

Main article: Treatment of ADHD through working memory training

Many of the problems shown by children with ADHD can be traced back to deficits in working memory (or short-term memory). By training and improving this memory some of the other symptoms may diminish as well. In a study by Klingberg et al., a computerized training program has shown good results in working memory, even if the generalized effect to behavioural symptoms was not as clear.

Coaching

ADHD coaching is a specialized type of life coaching that uses specific techniques geared toward working with the unique brain wiring of individuals with attention-deficit/hyperactivity disorder. Professional coaching is not considered a substitute for traditional treatment such as medication and therapy.

Timers

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

Summary of Evidence on ADHD Drugs
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	Some clinicians have warned of increased risk of sudden unexplained death, stroke, or heart attack, but good quality studies do not exist to support these claims. 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

Stimulants

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 the chain subsitituted amphetamine methylphenidate (Ritalin, Metadate, Concerta), dexmethylphenidate (Focalin), dextroamphetamine (Dexedrine), mixed amphetamine salts (Adderall), dextromethamphetamine(Desoxyn) and lisdexamfetamine (Vyvanse). 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.

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.

A meta analysis of clinical trials found that about 70 percent of children improve after being treated with stimulants in the short term but found that this conclusion may be biased due to the high number of low quality clinical trials in the literature. There have been no randomized placebo controlled clinical trials investigating the long term effectiveness of methylphenidate (Ritalin) beyond 4 weeks. Thus the long term effectiveness of methylphenidate has not been scientifically demonstrated. Serious concerns of publication bias regarding the use of methylphenidate for ADHD has also been noted.

On occasion, treatment emergent psychosis can emerge during long-term therapy with methylphenidate. Stimulants such methylphenidate should be avoided in people who have a vulnerability to schizophrenia or addiction; however, psychotic symptoms may emerge during therapy with methylphenidate 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. 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.

Both children with and without ADHD abuse stimulants, with ADHD individuals being at the highest risk of abusing or diverting their stimulant prescriptions. Between 16 and 29 percent of students who are prescribed stimulants report diverting their prescriptions. 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.

One review indicates that long-term use of methylphenidate has potential for abuse and addiction due to its similarity pharmacologically to cocaine and amphetamines. However, other doctors argue that use of stimulant therapy for ADHD does not increase the risk of subsequent substance abuse and may be protective against it when treatment is started in childhood. However, when stimulant therapy is started during adolescence or adulthood, there is an increased risk of subsequent substance abuse.

Although "under medical supervision, stimulant medications are considered safe", the use of stimulant medications for the treatment of ADHD has generated controversy because of undesirable side effects, uncertain long term effects 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.

A novel stimulant drug that has been used to treat ADHD is modafinil. There have been double-blind randomized controlled trials that have demonstrated the efficacy and tolerability of modafinil, however there are risks of serious side effects such as skin reactions and modafinil is not recommended for use in children.

Stimulants are the most effective medications available for the treatment of ADHD. 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, non-stimulant FDA-approved drugs for the treatment of ADHD. There are no differences in effectiveness between medications used for ADHD.

Short term clinical trials have shown medications to be effective for treating ADHD, but the trials usually use exclusion criteria, meaning knowledge on medications for ADHD is based on a small subset of the typical patients seen in clinical practice. 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. Some investigations are dedicated to finding the similarities of children who respond to a specific medicine. The behavioural response to stimulants in children is similar regardless of whether they have ADHD or not.

Stimulant medication is an effective treatment for Adult Attention-deficit hyperactivity disorder although the response rate may be lower for adults than children. Some physicians may recommend antidepressant drugs as the first line treatment instead of stimulants although antidepressants have lower treatment effect sizes than stimulant medication.

A study showed that children taking stimulant medications tend to be lighter in weight and shorter than their peers. A 2012 study found that among patients (adults and in teenagers over age 15) with a diagnosis of ADHD, their criminality rate during periods of receiving ADHD medication was significantly reduced, compared with nonmedication periods. Criminality consisted of mainly burglary and theft, as opposed to truly violent crimes, like murder.

Amphetamines

Three different medicines derived from amphetamine are used in ADHD treatment. Their trade names are Adderall (a mixture of 72% dextroamphetamine and 28% levoamphetamine), Dexedrine (pure dextroamphetamine), and Desoxyn (pure dextromethamphetamine). The differences in these three amphetamine-based medications' active compounds and mixture ratios results in each medications' slightly different activities.

Levoamphetamine and dextroamphetamine

Levoamphetamine and dextroamphetamine have the same chemical formula but are mirror images of each other, the same way that a person's hands are the same but are mirror images of each other. This mirror difference is enough to cause the two compounds to be metabolized differently. Adderall begins to work before dextroamphetamine because of levoamphetamine. Levoamphetamine also provides Adderall with a longer clinical effect than dextroamphetamine. However, the brain’s preference for dextroamphetamine over levoamphetamine shows that the clinical value of Adderall is, for the most part, due to dextroamphetamine. A few children with ADHD and comorbid disorders have helpful responses to levoamphetamine.

Dextromethamphetamine

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

Methylphenidate-based medications

Methylphenidate

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. Methylphenidate has high potential for abuse and addiction due to its pharmacological similarity to cocaine and amphetamines.

Formulations

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.

Non stimulants

Atomoxetine (Strattera), guanfacine (Intuniv) and clonidine (Kapvay) are non-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.

Atomoxetine (Strattera) is less effective than stimulants for ADHD, is associated with individual cases of liver damage, 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.

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.

Clonidine (Kapvay), an α_2A adrenergic receptor agonist has also been approved in the US. Clonidine, initially developed as a treatment for high blood pressure, low doses in evenings and/or afternoons are sometimes used in conjunction with stimulants to help with sleep and because clonidine sometimes helps moderate impulsive and oppositional behavior and may reduce tics. 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.

Other

Some medications used to treat ADHD are prescribed off-label, 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.
• 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, and has little or no effect on serotonergic re-uptake. Bupropion is not a controlled substance. It is commonly prescribed as a timed release formulation to decrease the risk of side effects. Bupropion is not particularly known for its stimulant properties because at high doses it tends to cause seizures in a large portion of the population.
• Milnacipran, an anti-depressant drug, is currently being investigated for potential to alleviate the symptoms of ADHD in adults.

• Modafinil (Provigil/Alertec/Sparlon) — 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.
• Reboxetine (Edronax) — is a selective norepinephrine reuptake inhibitor which is mainly used as an antidepressant. Studies outside the USA have found it to be an effective treatment for ADHD, and it is prescribed off-label for this purpose in Israel and some European countries, however reboxetine has never been approved by the FDA in the United States.

Antipsychotic medication

Risperdal (risperidone) 4 mg tablets.

The use of atypical antipsychotic medication as an off-label treatment has been rising. 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.

Non-ADHD children do not respond differently than ADHD children when prescribed antipsychotic drugs, which are also increasingly prescribed off-label for children with aggression or defiant behavior. 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.

Careful approach needs to be taken when blocking dopamine function, which is responsible for the psychological reward system. Excessive blocking of this neurotransmitter can causedysphoria. This may in turn cause suicidal ideation, or lead some teenagers to compensate for their dopamine deficiency with illicit drugs or alcohol. Atypical antipsychotics are preferred for this reason, because they are less likely to cause movement disorders, dysphoria, and increased drug cravings that have been associated with older typical antipsychotics.Weight gain, diabetes, lactation, gynecomastia, drooling, dysphoria, anhedonia (inability to experience pleasure), fatigue, sexual dysfunction, heart rhythm problems and the possibility of tardive dyskinesia, an irreversible^{[citation needed]} movement disorder, are among the adverse events associated with antipsychotic drugs.

Concerns regarding stimulants

Main article: Attention-deficit hyperactivity disorder controversies#Concerns about medication

The National Institute of Mental Health states that, "stimulant drugs, when used with medical supervision, are usually considered quite safe." Still, some parents and professionals have raised questions about the side effects of drugs and their long term use. 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."

The American Heart Association feel that it is prudent to carefully assess children for heart conditions before treating them with stimulant medications. 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.

Increase in use

Outpatient treatment rates have held steady in the US recently. Prior to this, outpatient treatment for ADHD in the US grew from 0.9 children per 100 in 1987 to 3.4 per 100 in 1997. 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. There is concern about the rising use of methylphenidate (Ritalin), mainly to treat ADHD and similar disorders, in the UK. The incidence of ADHD is estimated at three to five percent of the population, while the number of children in the United States taking Ritalin is estimated at one to two percent. In a small study of four American communities, the reported incidence of ADHD varied from 1.6% to 9.4%. The study also found that only 12.5% of the children reportedly meeting the DSM-III-R ADHD criteria for ADHD had been treated with stimulants during the past year.

Stimulant misuse

There is non-medical prescription stimulant use. A 2003 study found that non prescription use by college students in the US was 6.9% with 4.1% using them within the last year. 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.

Medication in preschoolers

Parents of children with ADHD note that they usually display their symptoms at an early age. Dr. John Van Brakle has stated, "pediatricians have long questioned whether such children can accurately be identified, given the overlap with normal behaviors in young children." There have been few longitudinal studies on the long-term effects psychostimulants have on children. The use of stimulant medication has not been approved by the FDA for children under the age of six. 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. Research on this issue has indicated that stimulant medication can help younger children with "severe ADHD symptoms" but typically at a lower dose then older children. It was also found that children at this age are more sensitive to side effects and should be closely monitored. Manos states, "it is prudent for physicians to be cautious," with medications. Evidence suggests that careful assessment and highly individualized behavioural interventions significantly improve both social and academic skills while medication only treats the symptoms of the disorder. Manos suggests that, "one of the primary reasons cited for the growing use of psychotropic interventions was that many physicians realize that psychological interventions are costly and difficult to sustain."

Side effects

General Side Effects

The FDA’s Adverse Event Reporting System (MedWatch) has documented 14,158 Adverse Drug Reactions in relation to ADHD stimulants between 2004 and 2011.

• 9 cases of sexual dysfunction
• 11 cases of homicide
• 12 cases of psychosis
• 13 cases of violence-related symptoms
• 21 cases of birth defects
• 23 cases of physical Assault
• 25 cases of coma
• 30 cases of hostility
• 44 cases of diabetes
• 52 cases of homicidal ideation
• 147 cases of mania
• 220 cases of death/sudden death
• 464 cases of depression
• 495 cases of abnormal behavior
• 499 cases of anxiety
• 593 cases of hallucinations
• 636 cases of aggression
• 871 cases of suicidal ideation/behavior (completed suicides and suicide attempts)

By their own admission, only 1-10% of side effects are ever reported to the FDA so the true number of side effects that occur is far higher.

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." 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. 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. One notion is that psychostimulant medication can decrease appetite which may result in loss of weight and may be a factor in stunted growth.

Side effects on the brain

Psychostimulants have negative effects on both the gross and biochemical functions of the brain, including the frontal lobes and basal ganglia, which are involved in motor control, learning routine behaviors, motivation, and cognitive and emotional functions. Psychostimulants have also been indicated to disrupt growth hormones, which could affect brain development. A study led by psychologist Stacy A. Castner of the Yale University School of Medicine revealed how amphetamines such Adderall can have long term effects on the mind. In the study, rhesus monkeys were given escalating injected doses of amphetamine over either six or twelve weeks. Compared to monkeys given inactive saline, the monkeys who received the drug displayed deficits in short term memory. This lasted for at least three years after they were given the drug. The researchers in this study connected this deficiency to a significantly lower level of dopamine activity in the frontal cortex. Another study by neurologist George A. Ricaurte and his team at the Johns Hopkins University School of Medicine supports this idea as well and is more compelling because the amphetamine was administered by mouth, like Adderall and other psychostimulants, and given twice a day to resemble the way the dose is taken by humans. A group of baboons and squirrel monkeys drank as orange cocktail containing the amphetamines twice a day for four weeks. Two to four weeks after they had begun taking the amphetamines, the researchers on the team detected evidence of brain damage. They found lower levels of dopamine and fewer dopamine transporters on the nerve endings in the striatum, which is involved in executive functions such as planning, memory, attention, and time perception, in the animals given the amphetamines compared to those who were not.

Cardiovascular side effects

There is concern that stimulants and Atomoxetine, which increase the heart rate and blood pressure, might cause serious cardiovascular problems.

In 2007 the FDA requires all ADHD drug manufacturers to notify patients about serious cardiovascular side effects. This was due to reports of sudden death in children taking these medications who had underlying heart problems and of high risk adults who suffered heart attacks and strokes.

Studies indicated that, "the rate of sudden death of children taking ADHD medications do not appear to exceed the base rate of sudden death in the general population". Matthew Smith is purported to have died at age 14 after long-term use of Ritalin. The medical examiner determined that Smith died from Ritalin usage, but medical experts dispute this. The examiner also argued that it was likely that diabetic children were at higher risk for cardiac problems.

Psychiatric side effects

In 2006 the FDA examined the occurrence of psychiatric side effects in ADHD medication. They found increased rates of psychosis and or mania with all drug treatments examined, including: Concerta, Ritalin LA, d-MPH, Atomoxetine, Adderall XR, Modafinil, MTS, and Metadate.

Sleep problems may occur, but can also be an extremely common side-effect of ADHD itself.

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

Issues with long-term use of stimulant medication

The short term use of stimulant medication has been shown to be effective yet its long term effects are yet to be determined. The Multimodal Treatment Study of Children with ADHD concluded that while drugs such as Ritalin and Concerta (a delayed release form of Ritalin) worked in the short term, there was no demonstrable improvement in children's behavior after three years of medication." A long-term study by Swanson et al. treated nearly 600 children in the 1990s for fourteen months to compare methylphenidate (the active ingredient in Ritalin) verses behavioral treatment. The study consisted of three groups: medication only, behavioral treatment only, and a combination of both. Although it was found that medication was more effective in reducing symptoms, 54% of the medication-alone group required a dose increase of on average 19% per unit of body weight. In a follow-up to the study, the children in the medication-only group reported having lost half of the benefit of medication by the end of two-years, and all of it by the end of three years. Similar results were found in a two-year study in 2005 of 200 children taking Concerta, a delay-release form of methylphenidate. Medication was effective through the second year, but only if the dosage was increased 15% on averaged per unit of body weight.

While ADHD is associated with an increased risk of substance abuse, stimulant medications have been shown to reduce the risk of subsequent development of substance abuse.

Long term use and schizophrenia and drug induced psychosis

Although the safety profile of short-term methylphenidate therapy in clinical trials has been well established, repeated use of psychostimulants such as methylphenidate is less clear. The long term effects of methylphenidate in drug addiction, withdrawal reactions, psychosis, depression, and pregnancy has received very little research and thus the long term effects of using stimulants for ADHD are largely unknown. There are no well defined withdrawal schedules for discontinuing long term use of stimulants. Short term clinical trials have shown an incidence of psychosis of 0.1%. One small-sample study found that 6% of children on long-term stimulant medication experienced had experienced some kind of psychotic symptom. The long term effects on mental health disorders in later life of chronic use of methylphenidate is unknown. Concerns have been raised that long-term therapy might cause drug dependence, paranoia, schizophrenia and behavioral sensitisation, similar to other stimulants. Psychotic symptoms from methylphenidate can include, hearing voices, visual hallucinations, urges to harm oneself, severe anxiety, euphoria, grandiosity, paranoid delusions, confusion, increased aggression and irritability.Methylphenidate psychosis is unpredictable in who it will occur. Family history of mental illness does not predict the incidence of stimulant toxicosis in ADHD children. High rates of childhood stimulant use are found in ADHD patients who will eventually be diagnosed with comorbid schizophrenia and bipolar disorder. Individuals with a diagnosis of bipolar or schizophrenia who were prescribed stimulants during childhood typically have a significantly earlier onset of the psychotic disorder and suffer a more severe clinical course of psychotic disorder.

Stimulant withdrawal and rebound effects

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. 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. 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. Up to a third of ADHD children experience a rebound effect in ADHD symptoms when the methylphenidate dose wears off.

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. 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."

Cost effectiveness

Combined medical management and behavioral treatment is the most effective ADHD management strategy, followed by medication alone, and then behavioral treatment. In terms of cost-effectiveness, management with medication has been shown to be the most cost-effective, followed by behavioral treatment, and combined treatment. 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.Comorbid (relating to two diseases that occur together, e.g. depression and ADHD) disorders make 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. Dr. Charles Bradley in Providence, Rhode Island reported that a group of children with behavioral problems improved after being treated with the stimulant Benzedrine. In 1957, the stimulant methylphenidate (Ritalin, which was first produced in 1950) became available; it remains one of the most widely prescribed medications for ADHD. Initially the drug was used to treat narcolepsy, chronic fatigue, depression, and to counter the sedating effects of other medications. 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. 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.

Alternative medicine

Ginkgo is a natural supplement used by some with ADHD.

See also: Alternative therapies for developmental and learning disabilities

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.

Neurofeedback

Neurofeedback (NF) or EEG biofeedback is a treatment strategy used for children, adolescents and adults with ADHD. Neurofeedback, is effective in treating attention, impulsivity and hyperactivity.It is based on four principles: Recognizing how the mind (perceptions) and body (physical responses) interact, recognizing that the mind and body try to reach homeostasis, recognizing that cognitive control can help physiologic control, and being interested in learning skills to create homeostasis.

No serious adverse side effects from nerofeedback have been reported. A few short-term effects have been reported including periods of negative feelings, and fatigue or dizziness when going through the treatment, but these are rare. Research into neurofeedback has been limited and further research has been recommended. One 2009 study concluded "that NF may be considered as a clinically effective module in the treatment of children with ADHD" The human brain emits electrical energy which is measured with electrodes on the brain. Neurofeedback alerts the patient when beta waves are present. This theory believes that those with ADHD can train themselves to decrease ADHD symptoms. There is a distinct split in the scientific community about the effectiveness of the treatment. A number of studies indicate the scientific evidence has been increasing in recent years for the effectiveness of EEG biofeedback for the treatment of ADHD. According to a 2007 review, the effectiveness of the treatment was demonstrated to be equivalent to that of stimulant medication. The review noted that improvements are seen at the behavioral and neuropsychological level with the symptoms of inattention, hyperactivity and impulsivity, showing significant decreases after treatment. There are no known side effects from EEG biofeedback therapy. There are methodological limitations and weaknesses in study designs however. In a 2005 review, Loo and Barkley stated that problems including lack of blinding such as placebo control and randomization are significant limitations to the studies into neurofeedback and make definitive conclusions impossible to make. As a result more robust clinical studies have been strongly recommended. A study by Fuchs and colleges evaluating the effectiveness of neurotherapy to stimulant medication gave evidence to the comparable effectiveness of neurofeedback to stimulant medication. Fuchs assigned 22 children from a Social-Pediatric Hospital whose ages were between 8 and 12 and who were diagnosed with ADHD to receive thirty 45-minute sessions of neurofeedback over ten weeks. A control group consisting of 11 children equitable sex and age was medicated with methylphenidate. Each group was given an IQ test, T.O.V.A, paper pencil (d2) and IOWA Conners Behavior test before and after the treatment. The children in both groups improved significantly on all tests. A German review in 2004 found that neurofeedback is more effective than previously thought in treating attention deficiency, impulsivity and hyperactivity; short-term effects match those of stimulant treatment, and a persistent normalization of EEG parameters is found even after treatment—this is not found after treatment with stimulants. An American review the following year also emphasized the benefits of this method. Similar findings were reported in a study by another German team in 2004.

Aerobic fitness

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. One study suggests that athletic performance in boys with ADHD may increase peer acceptance when accompanied by fewer negative behaviors.

Massage Therapy

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.

Art Therapy

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

Media

Other sources, including some psychologists who have written on the subject, feel that cutting down on time spent on television, video games, or violent media can help some children. For example, one study indicated a correlation between excessive TV time as a child with higher rates of ADHD symptoms. However, parents have long argued that their ADHD children have little to no attention problems while sitting in front of the television or playing video games for extended time periods. Indeed, studies support the idea that playing video games is a form of neurofeedback, which helps those with ADHD self-regulate and improve learning,at a neural level. ADHD children may feel more control while playing casual video games, thereby building their confidence. However, these findings are specific to very controlled conditions, from the types of video games studied to the administrator of the tests, who are trained to carefully measure brain waves. Therefore, it is not likely that these effects would generalize to every video game or context. It is also important to note that although symptoms may be controlled during game play, children with ADHD may experience great difficulty disengaging from the game, which may in turn negate any benefits gained from these activities, and time management skills may be negatively impacted as well. In addition, researchers caution parents against abandoning traditional treatment options for replacement with video gaming.

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".

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. 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." 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. In the United States, no dietary supplement has been approved for the treatment for ADHD by the FDA. There is however a pilot study done which shows that phosphatidyl serine (PS) can help against ADHD.

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."
• Omega-3 fatty acids - Some studies suggest that a lack of omega-3 fatty acids is associated with certain ADHD symptoms. 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. 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. Researchers from CSIRO, Australia's national science agency, showed polyunsaturated fatty acids to provide "medium to strong positive treatment effects" in ADHD. Another double blind study conducted by the University of Oxford, where children were given omega 3 fatty acids concluded that "significant improvements for active treatment versus placebo were found in reading, spelling, and behavior over 3 months of treatment in parallel groups." A 2008 study 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.
• 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.
• 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.
• 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. Nicotine may improve the symptoms of ADHD in some people.
• Melatonin and modafinil (Provigil), 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

Main article: Diet and attention deficit hyperactivity disorder

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

A meta-analysis has found that dietary elimination of artificial food coloring and preservatives provides a statistically significant benefit in children with ADHD. Other more recent studies agree with these conclusions. The UK Food Standards Agency (FSA) has called for a ban on the use of six artificial food colorings 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."

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.

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

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. 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).