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 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.
There are a number of stimulant and non-stimulant medications indicated for the treatment of ADHD. The most commonly used stimulant medications include methylphenidate (Ritalin/Concerta), mixed amphetamine salts (Adderall), dextroamphetamine (Dexedrine), and lisdexamfetamine (Vyvanse). Non-stimulant medications with a specific indication for ADHD include atomoxetine (Strattera), guanfacine (Intuniv), and clonidine (Kapvay). Other medications which may be prescribed off-label include bupropion (Wellbutrin), tricyclic antidepressants, SNRIs, or MAOIs. The presence of comorbid (co-occurring) disorders can make finding the right treatment and diagnosis much more complicated, costly, and time-consuming, so it is recommended 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 been shown to have limited effectiveness.
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.
- 1 Psychosocial
- 2 Medications
- 3 Comparative efficacy, tolerability and regulatory status of ADHD medications
- 4 Concerns regarding stimulants
- 5 Cost-effectiveness
- 6 History
- 7 Alternative medicine
- 8 Comorbid disorders
- 9 References
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. 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 of 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.
A 2013 paper published by two researchers from the University of Oslo concluded that working memory training provides short term improvements, 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. A 2014 paper published by a group of researchers from the University of Southampton presented the result of meta analysis study of 14 recently published randomized controlled trials (RCTs). The authors concluded that "more evidence from well-blinded studies is required before cognitive training can be supported as a frontline treatment of core ADHD symptoms".
Timers have been found to be effective for allowing people with ADHD to concentrate more effectively on the task at hand.[better source needed] 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.
Stimulants are the most commonly prescribed medications for ADHD. The stimulant medications indicated to treat ADHD are methylphenidate (Ritalin, Concerta), dexmethylphenidate (Focalin), mixed amphetamine salts (Adderall), dextroamphetamine (Dexedrine) lisdexamfetamine (Vyvanse), and in rare cases methamphetamine (Desoxyn). 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. 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 increases cellular communication between neurons that utilize these compounds. The therapeutic benefits are due to noradrenergic effects at the locus coeruleus and the prefrontal cortex and dopaminergic effects at the ventral tegmental area, nucleus accumbens, and prefrontal cortex.
Stimulant medications are considered safe when used under medical supervision. Nonetheless, there are concerns that the long term safety of these drugs has not been adequately documented, as well as 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.
Stimulants are the most effective medications available for the treatment of ADHD. Six different formulations of stimulants have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of ADHD: four 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.
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. 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 behavioral 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.
Amphetamine is a chiral compound which is composed of two isomers: 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. Three different amphetamine-based pharmaceuticals are currently used in ADHD treatment: Adderall, dextroamphetamine, and lisdexamfetamine. Lisfexamfetamine is an inactive prodrug of dextroamphetamine (i.e., lisdexamfetamine itself doesn't do anything in the body, but it metabolizes into dextroamphetamine). Adderall is a proprietary mixture of (75%) dextroamphetamine and (25%) levoamphetamine salts, which results in very mild differences between their effects. Adderall begins to work before dextroamphetamine because of levoamphetamine. Levoamphetamine also provides Adderall with a longer clinical effect than dextroamphetamine. Some children with ADHD and comorbid disorders respond well to levoamphetamine.
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.
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.[better source needed]
Atomoxetine (Strattera), guanfacine (Intuniv) and clonidine (Kapvay) are less-stimulant drugs approved for the treatment of ADHD. Other medications which may be prescribed off-label include certain antidepressants such as tricyclic antidepressants (TCAs), SNRIs, SSRIs or MAOIs.
Atomoxetine (Strattera) is less effective than stimulants for ADHD, is associated with rare cases of liver damage,:5 and carries a U.S. FDA black box warning regarding suicidal ideation. 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 α2A adrenergic receptor agonist has also been approved in the US. Clonidine was initially developed as a treatment for high blood pressure. Low doses in evenings and/or afternoons are sometimes used in conjunction with stimulants to help with sleep and because clonidine sometimes helps moderate impulsive and oppositional behavior and may reduce tics. It may be more useful for comorbid Tourette syndrome.
Certain antidepressants such as tricyclic antidepressants, SNRIs or MAOIs are sometimes prescribed and appear effective in the treatment some of the symptoms ADHD. With concerns of side effects TCAs overall usefulness is not clear.
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.
- A 2012 systematic review found evidence for the utility of amantadine inconclusive.
- 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.
- Milnacipran, an anti-depressant drug, is currently being investigated for potential to alleviate the symptoms of ADHD in adults.
- Modafinil (Provigil/Alertec/Sparlon) — Double-blind randomized controlled trials 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.:7 In the U.S., it is off-label pending decision by the FDA on 22 August 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 U.S. 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 U.S. FDA.
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 from 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.
Comparative efficacy, tolerability and regulatory status of ADHD medications
|Generic name (INN)||Brand name(s)||TGA-labelled for ADHD?||MHRA-labelled for ADHD?||FDA-labelled for ADHD?||Pharmacologic class||Level of support||Notes on adverse effects[note 1]||Efficacy and miscellany[note 2]|
|Adderall[note 3]||Adderall||No||No||Yes (children ≥3 years; adults)||Monoamine reuptake inhibitor and releasing agent||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.|
|Yes (children ≥6 years & adults)||Yes (children ≥6 years & adults)||Yes (children ≥3 years; adults)||Monoamine reuptake inhibitor and releasing agent||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 1–1.5 hours of oral administration|
|Yes (children ≥12 years and adults)||Yes (children ≥6 years and adults)||Yes (children ≥6 years and adults)||Monoamine reuptake inhibitor and releasing agent||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.|
|Metamfetamine||Desoxyn||No||No||Yes (children ≥6 years & adults)||Monoamine reuptake inhibitor and releasing agent||Approved||Transient growth stunting, hypertension or hypotension, dependence and tolerance, direct neurotoxicity to dopamine and serotonin neurons, 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)|
|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)|
|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||Provigil, Modavigil||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.|
|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.|
|Amitriptyline||Elavil, Endep||No||No||No||Tricyclic antidepressant||Low||Sedation, anticholinergic effects, hypotension, suicidal ideation, urinary retention, angle-closure glaucoma, headache, dizziness, etc. Highly dangerous in overdose.:248||Delayed onset of action|
|No||No||No||Norepinephrine-dopamine reuptake inhibitor & nAChR antagonist||High||Seizures,:247 memory problems, concentration difficulties. Fairly dangerous in overdose.:248||Delayed onset of action. Probably less efficacious than atomoxetine and classical stimulant medications in children. May be slightly more effective than atomoxetine in adults, however.|
|Buspirone||Buspar||No||No||No||5-HT1A partial agonist||Low||Memory problems, dizziness, diarrhoea, nausea||Delayed onset of action. Being a 5-HT1A receptor partial agonist may afford it the ability to increase dopamine release in the prefrontal cortex.|
|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||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||Drowsiness, cardiovascular side effects, sexual dysfunction, weight gain, hypotension, seizures and anticholinergic effects. Dangerous in overdose.||Delayed onset of action.|
|Milnacipran||Savella, Ixel||No||No||No||Serotonin-norepinephrine reuptake inhibitor||Negligible||Hypertension, sexual dysfunction||Delayed onset of action.|
|No||No||No||Tricyclic antidepressant||Low||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||May be comparatively poorly-tolerated compared to other second-generation antidepressants. Fairly safe in overdose.:588–589||Delayed onset of action.|
|No||No||No||Serotonin-norepinephrine reuptake inhibitor||Moderate||Gastrointestinal effects (nausea, vomiting,:247 diarrhoea), weight loss, sexual dysfunction, hypertension, abnormal bleeding, hyponatraemia, suicidal ideation and seizures. Higher risk of provoking mania/hypomania in bipolar individuals than bupropion. Can prolong the QT interval.:117 Less dangerous than bupropion and tricyclic antidepressants in overdose but more dangerous than reboxetine, duloxetine and milnacipran.||Delayed onset of action.|
|No||No||No||NMDA antagonist and dopamine agonist||Low||Anxiety, anorexia, confusion, ataxia, hallucinations, dream abnormality, GI effects||?|
|Carbamazepine||Equetro, Tegretol, Teril||No||No||No||Sodium channel blocker||High||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||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.
Concerns regarding stimulants
The National Institute of Mental Health states that, "a one-size-fits-all approach does not apply for all children with ADHD." Some parents and professionals have raised questions about the side effects of drugs and their long-term use. A 2008 review stated 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. 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.
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 U.S. recently.[when?] 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. A survey conducted by the Centers for 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. The CDC notes that community samples suggest the incidence of ADHD in American children is higher than the five percent stated by the American Psychiatric Association in DSM-5. Using data from the 2011–2012 survey, CDC estimates that diagnoses rates in the U.S. are 15% for boys and 7% for girls. Approximately two-thirds of children with current diagnoses are prescribed stimulants. Likewise, there is concern about the rising use of methylphenidate (Ritalin), mainly to treat ADHD and similar disorders, in the UK.
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. 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. 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. "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."
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.
Cardiovascular side effects
There is concern that stimulants and Atomoxetine, which increase the heart rate and blood pressure, might cause serious cardiovascular problems.[better source needed] 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.
Psychiatric side effects
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. Even this incidence rate may be low, however, since the clinical trials often excluded children with previous, adverse reactions to ADHD medication.
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.
The long-term effects on mental health disorders in later life of chronic use of methylphenidate is unknown.
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, but humans experience normal development and nerve growth. 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.
Reviews of clinical stimulant research have established the safety and effectiveness of long-term amphetamine use for ADHD. Controlled trials spanning two years have demonstrated continuous treatment effectiveness and safety. 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.
Stimulant withdrawal and rebound effects
Tolerance to the therapeutic effects of stimulants can occur, with rebound of symptoms occurring when the dose wears off. Due to the risk of discontinuation and rebound effects doses should be gradually decreased rather than the medication being stopped abruptly. 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.
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.
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."
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 makes finding the right treatment and diagnosis much more costly than when comorbid disorders are absent.
The first reported evidence of stimulant medication used to treat children with concentration and hyperactivity problems came in 1937. Charles Bradley in Providence, Rhode Island reported that a group of children with behavioral problems improved after being treated with the stimulant Benzedrine. 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. 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.
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).
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.
Most alternative therapies do not have enough supporting evidence to recommend them. Moreover, when only the best conducted studies are taken into account results tend to be similar to placebo. Some proponents of alternative medicine advocate that alternative therapies may be tried before ADHD medications.
Neurofeedback (NF) or EEG biofeedback is a treatment strategy used for children, adolescents and adults with ADHD. 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.
No serious adverse side effects from neurofeedback have been reported. Research into neurofeedback has been mostly limited and of low quality. 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. In general no effects have been found in the most blinded ADHD measures, which could be indicating that positive results are due to the placebo effect.
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. On the other hand, 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.
Dietary supplements and specialized diets are sometimes used by people with ADHD with the intent to mitigate some or all of the symptoms. However 2009 article in the Harvard Mental Health Letter states, "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.
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 – 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. A 2011 meta analysis found a modest benefit relative to stimulant medications, but concluded that supplementation should be considered based on its benign side effect profile.
- 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.
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.
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. 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." Nevertheless, existing evidence neither refutes nor supports the association between ADHD and food colouring.
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.
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).
- Wolraich M, Brown L, Brown RT et al. (November 2011). "ADHD: clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents". Pediatrics 128 (5): 1007–22. doi:10.1542/peds.2011-2654. PMID 22003063.
- Stein MA (July 2004). "Innovations in attention-deficit/hyperactivity disorder pharmacotherapy: long-acting stimulant and nonstimulant treatments". Am J Manag Care 10 (4 Suppl): S89–98. PMID 15352535.
- Christman AK, Fermo JD, Markowitz JS; Fermo; Markowitz (August 2004). "Atomoxetine, a novel treatment for attention-deficit-hyperactivity disorder". Pharmacotherapy 24 (8): 1020–36. doi:10.1592/phco.24.11.1020.36146. PMID 15338851.
- Hazell, P (October 2005). "Do adrenergically active drugs have a role in the first-line treatment of attention-deficit/hyperactivity disorder?". Expert Opinion on Pharmacotherapy 6 (12): 1989–98. doi:10.1517/14656522.214.171.1249. PMID 16197353.
- Waxmonsky, James (October 2003). "Assessment and treatment of attention deficit hyperactivity disorder in children with comorbid psychiatric illness". Current Opinion in Pediatrics 15 (5): 476–482. doi:10.1097/00008480-200310000-00006. PMID 14508296. Retrieved 14 April 2013.
- American Academy of Pediatrics. Subcommittee on Attention-Deficit/Hyperactivity Disorder and Committee on Quality Improvement. (October 2001). "Clinical practice guideline: treatment of the school-aged child with attention-deficit/hyperactivity disorder". Pediatrics 108 (4): 1033–44. doi:10.1542/peds.108.4.1033. PMID 11581465.
- King, S; Griffin, S; Hodges, Z (July 2006). "A systematic review and economic model of the effectiveness and cost-effectiveness of methylphenidate, dexamfetamine and atomoxetine for the treatment of attention deficit hyperactivity disorder in children and adolescents". Health Technology Assessment 10 (23): iii–iv, xiii–146. doi:10.3310/hta10230. PMID 16796929.
- Murphy, Kevin R; Barkley, Russell A (2005). Attention-Deficit Hyperactivity Disorder: A Clinical Workbook (Third ed.). New York: Guilford Press. ISBN 1-59385-227-4.
- Lerner M, Wigal T (January 2008). "Long-term safety of stimulant medications used to treat children with ADHD". Pediatric annals 37 (1): 37–45. doi:10.3928/00904481-20080101-11. PMID 18240852.
- Stern HP, Stern TP (September 2002). "When children with attention-deficit/hyperactivity disorder become adults". South. Med. J. 95 (9): 985–91. doi:10.1097/00007611-200209000-00011. PMID 12356139.
- Kazdin, Alan E. Parent management training : treatment for oppositional, aggressive, and antisocial behavior in children and adolescents. Oxford University Press, 2005
- Melby-Lervåg M, Hulme C (February 2013). "Is working memory training effective? A meta-analytic review". Dev Psychol 49 (2): 270–91. doi:10.1037/a0028228. PMID 22612437.
- Sonuga-Barke, E; Brandeis, D; Holtmann, M; Cortese, S (Oct 2014). "Computer-based Cognitive Training for ADHD: A Review of Current Evidence.". Child and adolescent psychiatric clinics of North America 23 (4): 807–824. doi:10.1016/j.chc.2014.05.009. PMID 25220088.
- Aupperlee, Jana; Swank, Marianne Greer; Lien, My; Ripinski, Andrea (2004). "Treatments for ADHD". Resources and Supports for Teachers. Michigan State University School Psychology Program. Retrieved 30 May 2014.
- Sulzer D, Sonders MS, Poulsen NW, Galli A (April 2005). "Mechanisms of neurotransmitter release by amphetamines: a review". Progress in Neurobiology 75 (6): 406–33. doi:10.1016/j.pneurobio.2005.04.003. PMID 15955613.
- Howland RH (August 2008). "Lisdexamfetamine: a prodrug stimulant for ADHD". Journal of Psychosocial Nursing and Mental Health Services 46 (8): 19–22. doi:10.3928/02793695-20080801-05. PMID 18777964.
- National Toxicology Program (July 2005). "NTP-CERHR monograph on the potential human reproductive and developmental effects of amphetamines". Ntp Cerhr Mon (16): vii–III1. PMID 16130031.
- Swanson, James; Gupta, Suneel; Guinta, Diane; Flynn, Daniel; Agler, Dave; Lerner, Marc; Williams, Lillie; Shoulson, Ira et al. (September 1999). "Acute tolerance to methylphenidate in the treatment of attention deficit hyperactivity disorder in children". Clinical Pharmacology & Therapeutics 66 (3): 295–305. doi:10.1016/S0009-9236(99)70038-X. PMID 10511066.(subscription required)
- Malenka RC, Nestler EJ, Hyman SE (2009). "Chapters 10 and 13". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 266, 318–323. ISBN 978-0-07-148127-4.
New, palatable foods cause dopamine release from VTA neurons of the midbrain that project to the nucleus accumbens, prefrontal cortex, and other limbic structures that regulate emotion. Dopamine acts in the nucleus accumbens to attach motivational significance to stimuli associated with reward. ... It acts in the orbital prefrontal cortex to set a value on rewards ...
Therapeutic (relatively low) doses of psychostimulants, such as methylphenidate and amphetamine, improve performance on working memory tasks both in normal subjects and those with ADHD. Positron emission tomography (PET) demonstrates that methylphenidate decreases regional cerebral blood flow in the dorsolateral prefrontal cortex and posterior parietal cortex while improving performance of a spacial working memory task. This suggests that cortical networks that normally process spatial working memory become more efficient in response to the drug. ... [It] is now believed that dopamine and norepinephrine, but not serotonin, produce the beneficial effects of stimulants on working memory. At abused (relatively high) doses, stimulants can interfere with working memory and cognitive control ... stimulants act not only on working memory function, but also on general levels of arousal and, within the nucleus accumbens, improve the saliency of tasks. Thus, stimulants improve performance on effortful but tedious tasks ... through indirect stimulation of dopamine and norepinephrine receptors.
- Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 148, 154–157. ISBN 978-0-07-148127-4.
DA has multiple actions in the prefrontal cortex. It promotes the "cognitive control" of behavior: the selection and successful monitoring of behavior to facilitate attainment of chosen goals. Aspects of cognitive control in which DA plays a role include working memory, the ability to hold information "on line" in order to guide actions, suppression of prepotent behaviors that compete with goal-directed actions, and control of attention and thus the ability to overcome distractions. Cognitive control is impaired in several disorders, including attention deficit hyperactivity disorder. ... Noradrenergic projections from the LC thus interact with dopaminergic projections from the VTA to regulate cognitive control. ... it has not been shown that 5HT makes a therapeutic contribution to treatment of ADHD.
- Lerner M, Wigal T (January 2008). "Long-term safety of stimulant medications used to treat children with ADHD". Pediatric annals 37 (1): 37–45. doi:10.3928/00904481-20080101-11. PMID 18240852.
- "Full U.S. CONCERTA® Prescribing Information". Janssen Pharmaceuticals, Inc. 15 July 2014.
- Jensen; Garcia, JA; Glied, S; Crowe, M; Foster, M; Schlander, M; Hinshaw, S; Vitiello, B; Arnold, LE (2005). "Cost-Effectiveness of ADHD Treatments: Findings from the Multimodal Treatment Study of Children With ADHD". American Journal of Psychiatry 162 (9): 1628–1636. doi:10.1176/appi.ajp.162.9.1628. PMID 16135621.
- Weiss MD, Gadow K, Wasdell MB (2006). "Effectiveness outcomes in attention-deficit/hyperactivity disorder". J Clin Psychiatry. 67 Suppl 8: 38–45. PMID 16961429.
- Arnold (2000). "Methylphenidate vs Amphetamine: Comparative Review". Journal of Attention Disorders 3 (4): 200–211. doi:10.1177/108705470000300403.
- Rapoport JL, Inoff-Germain G (2002). "Responses to methylphenidate in Attention-Deficit/Hyperactivity Disorder and normal children: update 2002". J Atten Disord. 6 Suppl 1: S57–60. PMID 12685519.
- Dusan Kolar, Amanda Keller, Maria Golfinopoulos, Lucy Cumyn, Cassidy Syer, and Lily Hechtman (February 2008). "Treatment of adults with attention-deficit/hyperactivity disorder". Neuropsychiatr Dis Treat 4 (1): 107–121. PMC 2515906. PMID 18728812.
- Spencer TJ. (April 2007). "Pharmacology of adult ADHD with stimulants". CNS Spectr 12 (4(supplement 6)): 8–11. PMID 17715564.
- Rostain, Anthony L. (September 2008). "ADHD in Adults: Attention-Deficit/Hyperactivity Disorder in Adults: Evidence-Based Recommendations for Management". Postgraduate Medicine 120 (3): 27–38. doi:10.3810/pgm.2008.09.1905. PMID 18824823.
- Spencer, Thomas. Biederman, Joseph. Wilens, Timothy (June 2004). "Stimulant treatment of adult attention-deficit/hyperactivity disorder". Psychiatric Clinics of North America 27 (2).
- Higgins ES (January 1999). "A comparative analysis of antidepressants and stimulants for the treatment of adults with attention-deficit hyperactivity disorder". J Fam Pract 48 (1): 15–20. PMID 9934377.
- Verbeeck W, Tuinier S, Bekkering GE. (February 2009). "Antidepressants in the treatment of adult attention-deficit hyperactivity disorder: a systematic review" (PDF). Adv Ther 26 (2): 170–184. doi:10.1007/s12325-009-0008-7. PMID 19238340.
- Heal DJ, Smith SL, Gosden J, Nutt DJ (June 2013). "Amphetamine, past and present – a pharmacological and clinical perspective". J. Psychopharmacol. 27 (6): 479–496. doi:10.1177/0269881113482532. PMC 3666194. PMID 23539642.
- Glaser; Thomas, TC; Joyce, BM; Castellanos, FX; Gerhardt, GA et al. (2005). "Differential Effects of Amphetamine Isomers on Dopamine in the Rat Striatum and Nucleus Accumbens Core". Psychopharmacology 178 (2–3): 250–258 (Page: 255). doi:10.1007/s00213-004-2012-6. PMID 15719230.
- Heal DJ, Pierce DM (2006). "Methylphenidate and its isomers: their role in the treatment of attention-deficit hyperactivity disorder using a transdermal delivery system". CNS Drugs 20 (9): 713–738 (Page:730). doi:10.2165/00023210-200620090-00002. PMID 16953648.
- Schepers, RJ (2003). "Methamphetamine and Amphetamine Pharmacokinetics in Oral Fluid and Plasma after Controlled Oral Methamphetamine Administration to Human Volunteers". Clin Chemistry 49 (1): 121–132 (Pages:121,130). doi:10.1373/49.1.121. PMID 12507968. Free full text
- Shoblock; Sullivan, EB; Maisonneuve, IM; Glick, SD et al. (2003). "Neurochemical and Behavioral Differences Between D-Methamphetamine and D-Amphetamine in Rats". Psychopharmacology 165 (4): 359–369 (Page:366). doi:10.1007/s00213-002-1288-7. PMID 12491026.
- Talmadge, John M.; Williams, C. Donald (April 1996). Hsiung, Robert, ed. "Methamphetamine for ADHD". Dr. Bob's Psychopharmacology Tips. Retrieved 15 April 2007.
- "Atomoxetine (marketed as Strattera) Information". U.S. Food and Drug Administration. Archived from the original on 9 July 2009. Retrieved 12 July 2009.
- Stein MA (July 2004). "Innovations in attention-deficit/hyperactivity disorder pharmacotherapy: long-acting stimulant and nonstimulant treatments". The American Journal of Managed Care 10 (4 Suppl): S89–98. PMID 15352535.
- "Strattera Prescribing Information" (PDF). Eli Lilly and Company. February 2014. Retrieved 6 September 2014.
- "Atomoxetine (marketed as Strattera) Information". FDA Center for Drug Evaluation and Research. 22 February 2007. Archived from the original on 11 May 2009.
- Allen, AJ; Kurlan, RM; Gilbert, DL; Coffey, BJ; Linder, SL; Lewis, DW; Winner, PK; Dunn, DW et al. (December 2005). "Atomoxetine treatment in children and adolescents with ADHD and comorbid tic disorders". Neurology 65 (12): 1941–9. doi:10.1212/01.wnl.0000188869.58300.a7. PMID 16380617.
- Arnsten AF. The use of alpha-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder. Expert Rev Neurother. 10:1595-605, 2010
- Frazin, Natalie (2 April 2002). "Methylphenidate and Clonidine Help Children With ADHD and Tics". National Institute of Neurological Disorders and Stroke. Archived from the original on 27 April 2007. Retrieved 15 April 2007.
- Otasowie, J; Castells, X; Ehimare, UP; Smith, CH (19 September 2014). "Tricyclic antidepressants for attention deficit hyperactivity disorder (ADHD) in children and adolescents.". The Cochrane database of systematic reviews 9: CD006997. doi:10.1002/14651858.CD006997.pub2. PMID 25238582.
- Lakhan, SE; Hagger-Johnson, G. (2007). "The impact of prescribed psychotropics on youth". Clinical Practice and Epidemiology in Mental Health 3 (1): 21. doi:10.1186/1745-0179-3-21. PMC 2100041. PMID 17949504.
- Sani G, Serra G, Kotzalidis GD et al. (August 2012). "The role of memantine in the treatment of psychiatric disorders other than the dementias: a review of current preclinical and clinical evidence". CNS Drugs 26 (8): 663–90. doi:10.2165/11634390-000000000-00000. PMID 22784018.
- PDF (170 KB). GlaxoSmithKline (September 2006). Retrieved 15 April 2007.
- Stahl S, Pradko J, Haight B, Modell J, Rockett C, Learned-Coughlin S (2004). "A Review of the Neuropharmacology of Bupropion, a Dual Norepinephrine and Dopamine Reuptake Inhibitor". Prim Care Companion J Clin Psychiatry 6 (4): 159–166. doi:10.4088/PCC.v06n0403. PMC 514842. PMID 15361919.
- Kako, Yuki; Niwa, Y; Toyomaki, A; Yamanaka, H; Kitagawa, N; Denda, K; Koyama, T (April 2007). "A case of adult attention-deficit/hyperactivity disorder alleviated by milnacipran". Progress in Neuro-Psychopharmacology & Biological Psychiatry 31 (3): 772–775. doi:10.1016/j.pnpbp.2006.12.017. PMID 17300859.
- Biederman J, Swanson JM, Wigal SB, Boellner SW, Earl CQ, Lopez FA (May 2006). "A comparison of once-daily and divided doses of modafinil in children with attention-deficit/hyperactivity disorder: a randomized, double-blind, and placebo-controlled study". The Journal of Clinical Psychiatry 67 (5): 727–35. doi:10.4088/JCP.v67n0506. PMID 16841622.
- Greenhill LL, Biederman J, Boellner SW (May 2006). "A randomized, double-blind, placebo-controlled study of modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder". Journal of the American Academy of Child and Adolescent Psychiatry 45 (5): 503–11. doi:10.1097/01.chi.0000205709.63571.c9. PMID 16601402.
- Cephalon, Inc. (21 December 2007). "Modavigil Product Information". healthlinks.net. healthlinks.net Pty. Ltd. Archived from the original (PDF) on 21 July 2008. Retrieved 2 July 2008.
- Kumar R (2008). "Approved and investigational uses of modafinil : an evidence-based review". Drugs 68 (13): 1803–39. doi:10.2165/00003495-200868130-00003. PMID 18729534.
- Toren P, Ratner S, Weizman A, Lask M, Ben-Amitay G, Laor N. Reboxetine maintenance treatment in children with attention-deficit/hyperactivity disorder: a long-term follow-up study. Journal of Child and Adolescent Psychopharmacology. 2007 Dec;17(6):803-12. PMID 18315452
- Silverman, Ed (28 January 2008). "Florida Medicaid To Review Antipsychotics & ADHD". Pharmalot. UBM Canon Pharmaceutical Media Group. Archived from the original on 28 January 2012.
- Cullen, Kathryn R; Kumra, Sanjiv; Westerman, Marcus; Schulz, S Charles (1 March 2008). "Atypical Antipsychotics for Treatment of Schizophrenia Spectrum Disorders". Psychiatric Times. UBM Medica, LLC.
- Findling, Robert L (2003). "Dosing of Atypical Antipsychotics in Children and Adolescents". Primary Care Companion J Clin Psychiatry 5 (suppl 6): 10–13.
- Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
- Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8.
- Brunton, L; Chabner, B; Knollman, B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (12th ed.). New York: McGraw-Hill Professional. ISBN 978-0-07-162442-8.
- Gozal, David; Molfese, Dennis L (2005). ATTENTION DEFICIT HYPERACTIVITY DISORDER. Contemporary Clinical Neuroscience. Humana Press. ISBN 978-1-58829-312-1.
- Childress, AC; Berry, SA (February 2012). "Pharmacotherapy of Attention-Deficit Hyperactivity Disorder in Adolescents" (PDF). Drugs 72 (3): 309–325. doi:10.2165/11599580-000000000-00000. PMID 22316347. (subscription required)
- Santosh, PJ; Sattar, S; Canagaratnam, M (September 2011). "Efficacy and Tolerability of Pharmacotherapies for Attention-Deficit Hyperactivity Disorder in Adults" (PDF). CNS Drugs 25 (9): 737–763. doi:10.2165/11593070-000000000-00000. PMID 21870887. (subscription required)
- Faraone, SV; Glatt, SJ (June 2010). "A comparison of the efficacy of medications for adult attention-deficit/hyperactivity disorder using meta-analysis of effect sizes". Journal of Clinical Psychiatry 71 (6): 754–763. doi:10.4088/JCP.08m04902pur. PMID 20051220. (subscription required)
- "amphetamine/dextroamphetamine (Rx) – Adderall XR, Adderall". Medscape Drugs & Diseases.
- Miller GM (January 2011). "The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity". J. Neurochem. 116 (2): 164–176. doi:10.1111/j.1471-4159.2010.07109.x. PMC 3005101. PMID 21073468.
- Faraone, SV (December 2009). "Using Meta-analysis to Compare the Efficacy of Medications for Attention-Deficit/Hyperactivity Disorder in Youths" (PDF). Pharmacy and Therapeutics 34 (12): 678–694. PMC 2810184. PMID 20140141.
- Faraone, SV; Biederman, J; Spencer, TJ; Aleardi, M (October 2006). "Comparing the Efficacy of Medications for ADHD Using Meta-analysis". MedGenMed 8 (4): 4. PMC 1868385. PMID 17415287.
- "dextroamphetamine (Rx) – Dexedrine, Liquadd". Medscape Drugs & Diseases.
- "lisdexamfetamine (Rx) – Vyvanse". Medscape Drugs & Diseases.
- "PRODUCT INFORMATION VYVANSE® (lisdexamphetamine dimesilate)" (PDF). TGA eBusiness Services. Shire Australia Pty. Limited. 22 July 2013. Retrieved 12 December 2013.
- "methamphetamine (Rx) – Desoxyn". Medscape Drugs & Diseases.
- Malenka RC, Nestler EJ, Hyman SE (2009). "15". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 370. ISBN 978-0-07-148127-4.
Unlike cocaine and amphetamine, methamphetamine is directly toxic to midbrain dopamine neurons.
- Krasnova, IN; Cadet, JL (May 2009). "Methamphetamine toxicity and messengers of death". Brain Research Reviews 60 (2): 379–407. doi:10.1016/j.brainresrev.2009.03.002. PMC 2731235. PMID 19328213.
- "dexmethylphenidate (Rx) – Focalin, Focalin XR". Medscape Drugs & Diseases.
- "methylphenidate (Rx) – Ritalin, Ritalin SR". Medscape Drugs & Diseases.
- "atomoxetine (Rx) – Strattera". Medscape Drugs & Diseases.
- "modafinil (Rx) – Provigil". Medscape Drugs & Diseases.
- "clonidine (Rx) – Catapres, Catapres-TTS". Medscape Drugs & Diseases.
- "guanfacine (Rx) – Intuniv, Tenex". Medscape Drugs & Diseases.
- "amitriptyline (Rx) – Elavil, Levate". Medscape Drugs & Diseases.
- Guardiola, A; Terra, AR; Ferreira, LT; Londero, RG (September 1999). "[Use of amitriptyline in attention deficit hyperactivity disorder]". Arq Neuropsiquiatr (in Portuguese) 57 (3A): 599–605. doi:10.1590/S0004-282X1999000400010. PMID 10667283.
- White, N; Litovitz, T; Clancy, C (December 2008). "Suicidal antidepressant overdoses: a comparative analysis by antidepressant type" (PDF). Journal of Medical Toxicology 4 (4): 238–250. doi:10.1007/BF03161207. PMC 3550116. PMID 19031375.
- "bupropion (Rx) – Wellbutrin, Zyban". Medscape Drugs & Diseases.
- Maneeton, N; Maneeton, B; Srisurapanont, M; Martin, SD (December 2011). "Bupropion for adults with attention-deﬁcit hyperactivity disorder: Meta-analysis of randomized, placebo-controlled trials". Psychiatry and Clinical Neurosciences 65 (7): 611–617. doi:10.1111/j.1440-1819.2011.02264.x. PMID 22176279.
- "buspirone (Rx) – BuSpar, Buspirex". Medscape Drugs & Diseases.
- Malhotra, S; Santosh, PJ (April 1998). "An open clinical trial of buspirone in children with attention-deficit/hyperactivity disorder". Journal of the American Academy of Child and Adolescent Psychiatry 37 (4): 364–371. doi:10.1097/00004583-199804000-00013. PMID 9549956.
- Mohammadi, MR; Hafezi, P; Galeiha, A; Hajiaghaee, R; Akhondzadeh, S (November 2012). "Buspirone versus Methylphenidate in the Treatment of Children with Attention- Deficit/ Hyperactivity Disorder: Randomized Double-Blind Study". Acta Medica Iranica 50 (11): 723–728. PMID 23292622.
- Sutherland, SM; Adler, LA; Chen, C; Smith, MD; Feltner, DE (2012). "An 8-Week, Randomized Controlled Trial of Atomoxetine, Atomoxetine Plus Buspirone, or Placebo in Adults With ADHD". The Journal of Clinical Psychiatry 73 (4): 445–450. doi:10.4088/JCP.10m06788. PMID 22313788.
- Davari-Ashtiani, R; Shahrbabaki, ME; Razjouyan, K; Amini, H; Mazhabdar, H (2010). "Buspirone Versus Methylphenidate in the Treatment of Attention Deﬁcit Hyperactivity Disorder: A Double-Blind and Randomized Trial" (PDF). Child Psychiatry and Human Development 41 (6): 641–648. doi:10.1007/s10578-010-0193-2. PMID 20517641.
- Bortolozzi, A; Masana, M; Díaz-Mataix, L; Cortés, R; Scorza, MC; Gingrich, JA; Toth, M; Artigas, F (November 2010). "Dopamine release induced by atypical antipsychotics in prefrontal cortex requires 5-HT1A receptors but not 5-HT2A receptors". The International Journal of Neuropsychopharmacology 13 (10): 1299–1314. doi:10.1017/S146114571000009X. PMID 20158933.
- Díaz-Mataix, L; Scorza, MC; Bortolozzi, A; Toth, M; Celada, P; Artigas, F (November 2005). "Involvement of 5-HT1A receptors in prefrontal cortex in the modulation of dopaminergic activity: role in atypical antipsychotic action" (PDF). The Journal of Neuroscience 25 (47): 10831–10843. doi:10.1523/JNEUROSCI.2999-05.2005. PMID 16306396.
- "desipramine (Rx) – Norpramin". Medscape Drugs & Diseases.
- "duloxetine (Rx) – Cymbalta". Medscape Drugs & Diseases.
- Bilodeau, M; Simon, T; Beauchamp, MH; Lespérance, P; Dubreucq, S; Dorée, JP; Tourjman, SV (May 2012). "Duloxetine in Adults With ADHD: A Randomized, Placebo-Controlled Pilot Study". Journal of Attention Disorders 18 (2): 169–75. doi:10.1177/1087054712443157. PMID 22582349.
- "imipramine (Rx) – Tofranil, Tofranil-PM". Medscape Drugs & Diseases.
- Biederman, J; Spencer, T (November 1999). "Attention-Deficit/Hyperactivity Disorder (ADHD) as a Noradrenergic Disorder". Biological Psychiatry 46 (9): 1234–1242. doi:10.1016/S0006-3223(99)00192-4. PMID 10560028.
- "milnacipran (Rx) – Savella". Medscape Drugs & Diseases.
- Kako, Y; Niwa, Y; Toyomaki, A; Yamanaka, H; Kitagawa, N; Denda, K; Koyama, T (April 2007). "A case of adult attention-deficit/hyperactivity disorder alleviated by milnacipran". Progress in Neuro-Psychopharmacology and Biological Psychiatry 31 (3): 772–775. doi:10.1016/j.pnpbp.2006.12.017. PMID 17300859.
- "nortriptyline (Rx) – Pamelor, Aventyl". Medscape Drugs & Diseases.
- Wilens, TE; Biederman, J; Geist, DE; Steingard, R; Spencer, T (March 1993). "Nortriptyline in the treatment of ADHD: a chart review of 58 cases". Journal of the American Academy of Child and Adolescent Psychiatry 32 (2): 343–349. doi:10.1097/00004583-199303000-00015. PMID 8444763.
- Spencer, T; Biederman, J; Wilens, T; Steingard, R; Geist, D (January 1993). "Nortriptyline treatment of children with attention-deficit hyperactivity disorder and tic disorder or Tourette's syndrome". Journal of the American Academy of Child and Adolescent Psychiatry 32 (1): 205–210. doi:10.1097/00004583-199301000-00029. PMID 8428873.
- Riahi, F; Tehrani-Doost, M; Shahrivar, Z; Alaghband-Rad, J (November 2010). "Efficacy of reboxetine in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled clinical trial". Human Psychopharmacology 25 (7–8): 570–576. doi:10.1002/hup.1158. PMID 21312292.
- Cipriani, A; Furukawa, TA; Salanti, G; Geddes, JR; Higgins, JP; Churchill, R; Watanabe, N; Nakagawa, A; Omori, IM; McGuire, H; Tansella, M; Barbui, C (February 2009). "Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis" (PDF). Lancet 373 (9665): 746–758. doi:10.1016/S0140-6736(09)60046-5. PMID 19185342.
- Taylor, D; Paton, C; Shitij, K (2012). The Maudsley prescribing guidelines in psychiatry. West Sussex: Wiley-Blackwell. ISBN 978-0-470-97948-8.
- "venlafaxine (Rx) – Effexor, Effexor XR". Medscape Drugs & Diseases.
- Ahmad Ghanizadeh, Roger D. Freeman, Michael Berk (March 2013). "Efficacy and adverse effects of venlafaxine in children and adolescents with ADHD: a systematic review of non-controlled and controlled trials". Reviews on recent clinical trials 8 (1): 2–8. doi:10.2174/1574887111308010002. PMID 23157376.
- Pacchiarotti, I; Bond, DJ; Baldessarini, RJ; Nolen, WA; Grunze, H; Licht, RW; Post, RM; Berk, M; Goodwin, GM; Sachs, GS; Tondo, L; Findling, RL; Youngstrom, EA; Tohen, M; Undurraga, J; González-Pinto, A; Goldberg, JF; Yildiz, A; Altshuler, LL; Calabrese, JR; Mitchell, PB; Thase, ME; Koukopoulos, A; Colom, F; Frye, MA; Malhi, GS; Fountoulakis, KN; Vázquez, G; Perlis, RH; Ketter, TA; Cassidy, F; Akiskal, H; Azorin, JM; Valentí, M; Mazzei, DH; Lafer, B; Kato, T; Mazzarini, L; Martínez-Aran, A; Parker, G; Souery, D; Ozerdem, A; McElroy, SL; Girardi, P; Bauer, M; Yatham, LN; Zarate, CA; Nierenberg, AA; Birmaher, B; Kanba, S; El-Mallakh, RS; Serretti, A; Rihmer, Z; Young, AH; Kotzalidis, GD; Macqueen, GM; Bowden, CL; Ghaemi, SN; Lopez-Jaramillo, C; Rybakowski, J; Ha, K; Perugi, G; Kasper, S; Amsterdam, JD; Hirschfeld, RM; Kapczinski, F; Vieta, E (November 2013). "The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders". The American Journal of Psychiatry 170 (11): 1249–1262. doi:10.1176/appi.ajp.2013.13020185. PMID 24030475.
- "amantadine (Rx) – Endantadine, Symmetrel". Medscape Drugs & Diseases.
- Mohammadi, MR; Kazemi, MR; Zia, E; Rezazadeh, SA; Tabrizi, M; Akhondzadeh, S (2010). "Amantadine versus methylphenidate in children and adolescents with attention deficit/hyperactivity disorder: a randomized, double-blind trial". Human Psychopharmacology 25 (7–8): 560–565. doi:10.1002/hup.1154. PMID 21312290.
- "carbamazepine (Rx) – Tegretol, Equetro". Medscape Drugs & Diseases.
- Silva, RR; Munoz, DM; Alpert, M (March 1996). "Carbamazepine Use in Children and Adolescents with Features of Attention-Deficit Hyperactivity Disorder: A Meta-Analysis". Journal of the American Academy of Child and Adolescent Psychiatry 35 (3): 352–358. doi:10.1097/00004583-199603000-00017. PMID 8714324.
- "memantine (Rx) – Namenda XR". Medscape Drugs & Diseases.
- Surman, CB; Hammerness, PG; Petty, C; Spencer, T; Doyle, R; Napolean, S; Chu, N; Yorks, D; Biederman, J (May 2013). "A pilot open label prospective study of memantine monotherapy in adults with ADHD". The World Journal of Biological Psychiatry 14 (4): 291–298. doi:10.3109/15622975.2011.623716. PMID 22436083.
- "Attention Deficit Hyperactivity Disorder (ADHD)". National Institute of Mental Health. National Institutes of Health (NIH). Retrieved 26 October 2013. Sub-section "Medications".
- Lakhan, SE; Hagger-Johnson, G (20 October 2007). "The impact of prescribed psychotropics on youth". Clinical Practice and Epidemiology in Mental Health 3 (1): 21. doi:10.1186/1745-0179-3-21. PMC 2100041. PMID 17949504.
- American Academy of Pediatrics; American Heart Association. (August 2008). "American Academy of Pediatrics/American Heart Association clarification of statement on cardiovascular evaluation and monitoring of children and adolescents with heart disease receiving medications for ADHD: May 16, 2008". J Dev Behav Pediatr 29 (4): 335. doi:10.1097/DBP.0b013e31318185dc14. PMID 18698199.
- Vetter, V. L.; Elia, J.; Erickson, C.; Berger, S.; Blum, N.; Uzark, K.; Webb, C. L.; American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee et al. (2008). "Cardiovascular Monitoring of Children and Adolescents With Heart Disease Receiving Medications for Attention Deficit/Hyperactivity Disorder: A Scientific Statement From the American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing". Circulation 117 (18): 2407–2423. doi:10.1161/CIRCULATIONAHA.107.189473. PMID 18427125.
- Cooper WO, Habel LA, Sox CM, Chan KA, Arbogast PG, Cheetham TC, Murray KT, Quinn VP, Stein CM, Callahan ST, Fireman BH, Fish FA, Kirshner HS, O'Duffy A, Connell FA, Ray WA (November 2011). "ADHD drugs and serious cardiovascular events in children and young adults". N. Engl. J. Med. 365 (20): 1896–1904. doi:10.1056/NEJMoa1110212. PMID 22043968.
- "FDA Drug Safety Communication: Safety Review Update of Medications used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in adults". United States Food and Drug Administration. 15 December 2011. Retrieved 4 November 2013.
- Habel LA, Cooper WO, Sox CM, Chan KA, Fireman BH, Arbogast PG, Cheetham TC, Quinn VP, Dublin S, Boudreau DM, Andrade SE, Pawloski PA, Raebel MA, Smith DH, Achacoso N, Uratsu C, Go AS, Sidney S, Nguyen-Huynh MN, Ray WA, Selby JV (December 2011). "ADHD medications and risk of serious cardiovascular events in young and middle-aged adults". JAMA 306 (24): 2673–2683. doi:10.1001/jama.2011.1830. PMC 3350308. PMID 22161946.
- "FDA Drug Safety Communication: Safety Review Update of Medications used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in children and young adults". United States Food and Drug Administration. 20 December 2011. Retrieved 4 November 2013.
- Molina, Brooke S.G.; Flory, Kate; Hinshaw, Stephen P.; Greiner, Andrew R.; Arnold, L. Eugene; Swanson, James M.; Hechtman, Lily; Jensen, al.; Vitiello, Benedetto; Hoza, Betsy; Pelham, William E.; Elliott, Glen R.; Wells, Karen C.; Abikoff, Howard B.; Gibbons, Robert D.; Marcus, SUE; Conners, C. Keith; Epstein, Jeffery N.; Greenhill, Laurence L.; March, John S.; Newcorn, Jeffrey H.; Severe, Joanne B.; Wigal, Timothy (2007). "Delinquent Behavior and Emerging Substance Use in the MTA at 36 Months: Prevalence, Course, and Treatment Effects". Journal of the American Academy of Child & Adolescent Psychiatry 46 (8): 1028–1040. doi:10.1097/chi.0b013e3180686d96.
- Name, LM; Gameroff, M; Marcus, MJ; Jensen, SC; Jensen, PS. (2003). "National trends in the treatment of attention deficit hyperactivity disorder". American Journal of Psychiatry 160 (6): 1071–1077. doi:10.1176/appi.ajp.160.6.1071. PMID 12777264.
- Schwarz, Alan; Cohen, Sarah (31 March 2013). "A.D.H.D. Seen in 11% of U.S. Children as Diagnoses Rise". New York Times. Retrieved 29 April 2013.
- "Attention-Deficit / Hyperactivity Disorder: Data & Statistics". Centers for Disease Control and Prevention. 13 November 2013. Retrieved 6 September 2014.
- "Rates of A.D.H.D. Diagnosis in Children". New York Times. 31 March 2013. Retrieved 26 October 2013.
- "Sharp rise in children's Ritalin use". BBC News. 19 July 2003. Retrieved 22 November 2013.
- Singh, Ilina (2008). "Beyond polemics: science and ethics of ADHD" (PDF). Nature Reviews Neuroscience 9 (12): 957–964. doi:10.1038/nrn2514. PMID 19020513.
- Greenhill, L.; Kollins, S.; Abikoff, H.; McCracken, J.; Riddle, M.; Swanson, J.; McGough, J.; Wigal, S. et al. (Nov 2006). "Efficacy and safety of immediate-release methylphenidate treatment for preschoolers with ADHD". J Am Acad Child Adolesc Psychiatry 45 (11): 1284–93. doi:10.1097/01.chi.0000235077.32661.61. PMID 17023867.
- Freudenheim, Milt (17 May 2004). "Behavior Drugs Lead in Sales For Children". The New York Times. Retrieved 25 April 2010.
- "Medco Settles Fraud, Kickback Charges for $155 Million". ConsumerAffairs. Consumers Unified LLC. 24 October 2006. Retrieved 26 October 2013.
- Wolraich, M.; Brown, L.; Wolraich, RT.; Brown, G.; Brown, M.; Dupaul, HM.; Earls, TG.; Feldman, B. et al. (November 2011). "ADHD: clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents". Pediatrics 128 (5): 1007–22. doi:10.1542/peds.2011-2654. PMID 22003063. Retrieved 22 November 2013.
- Chung, Jaeah (2013). "Medication Management of Preschool ADHD by Pediatric Sub-Specialists: Non-Compliance with AAP Clinical Guidelines". Retrieved 26 October 2013.[dead link]
- Manos, Michael J (2006). "Treating Severe ADHD in Very Young Children". Medscape Psychiatry 11 (1).
- "Questions over drugs for ADHD". BBC News. 12 November 2007. Retrieved 25 April 2010.
- Breggin (1999). "Psychostimulants in the Treatment of Children Diagnosed with ADHD: Risks and Mechanism of Action". International Journal of Risk & Safety in Medicine 12: 3–35.
- Wilens, T.E. (2004) Straight Talk About Medications For Kids. NY: The Guilford Press.
- Gelperin, Kate (9 February 2006). "Studying Cardiovascular Risk with Drug Treatments of ADHD: Feasibility of Available Study Methods in Children and Adults" (PDF). Food and Drug Administration (US).
- "ADHD Drug Labels" (PDF). Food and Drug Administration (US). 2006.
- Silver, Larry (February 2006). "ADHD Medications: Say No to Side Effects". ADDitude magazine. New Hope Media LLC.
- Boyles, Salynn (26 January 2009). "ADHD Drugs: Hallucinations Not Uncommon". WebMD. Retrieved 23 October 2013.
- Mosholder, Andrew D.; Gelperin, Kate (1 February 2009). "Hallucinations and Other Psychotic Symptoms Associated With the Use of Attention-Deficit/Hyperactivity Disorder Drugs in Children". Pediatrics (American Academy of Pediatrics) 123 (2): 611–616. doi:10.1542/peds.2008-0185. PMID 19171629. Retrieved 23 October 2013.
- Kraemer M, Uekermann J, Wiltfang J, Kis B (July 2010). "Methylphenidate-induced psychosis in adult attention-deficit/hyperactivity disorder: report of 3 new cases and review of the literature". Clin Neuropharmacol 33 (4): 204–6. doi:10.1097/WNF.0b013e3181e29174. PMID 20571380.
- Kimko HC, Cross JT, Abernethy DR (December 1999). "Pharmacokinetics and clinical effectiveness of methylphenidate". Clin Pharmacokinet 37 (6): 457–70. doi:10.2165/00003088-199937060-00002. PMID 10628897.
- Carvalho M, Carmo H, Costa VM, Capela JP, Pontes H, Remião F, Carvalho F, Bastos Mde L (August 2012). "Toxicity of amphetamines: an update". Arch. Toxicol. 86 (8): 1167–1231. doi:10.1007/s00204-012-0815-5. PMID 22392347.
- Berman S, O'Neill J, Fears S, Bartzokis G, London ED (2008). "Abuse of amphetamines and structural abnormalities in the brain". Ann. N. Y. Acad. Sci. 1141: 195–220. doi:10.1196/annals.1441.031. PMC 2769923. PMID 18991959.
- Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K (February 2013). "Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects". JAMA Psychiatry 70 (2): 185–198. doi:10.1001/jamapsychiatry.2013.277. PMID 23247506.
- Spencer TJ, Brown A, Seidman LJ, Valera EM, Makris N, Lomedico A, Faraone SV, Biederman J (September 2013). "Effect of psychostimulants on brain structure and function in ADHD: a qualitative literature review of magnetic resonance imaging-based neuroimaging studies". J. Clin. Psychiatry 74 (9): 902–917. doi:10.4088/JCP.12r08287. PMC 3801446. PMID 24107764.
- Frodl T, Skokauskas N (February 2012). "Meta-analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects.". Acta psychiatrica Scand. 125 (2): 114–126. doi:10.1111/j.1600-0447.2011.01786.x. PMID 22118249.
Basal ganglia regions like the right globus pallidus, the right putamen, and the nucleus caudatus are structurally affected in children with ADHD. These changes and alterations in limbic regions like ACC and amygdala are more pronounced in non-treated populations and seem to diminish over time from child to adulthood. Treatment seems to have positive effects on brain structure.
- Millichap JG (2010). "Chapter 3: Medications for ADHD". In Millichap JG. Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD (2nd ed.). New York: Springer. pp. 111–113. ISBN 978-1-4419-1396-8.
- Huang YS, Tsai MH (July 2011). "Long-term outcomes with medications for attention-deficit hyperactivity disorder: current status of knowledge". CNS Drugs 25 (7): 539–554. doi:10.2165/11589380-000000000-00000. PMID 21699268.
- Millichap JG (2010). "Chapter 3: Medications for ADHD". In Millichap JG. Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD (2nd ed.). New York: Springer. pp. 121–123. ISBN 978-1-4419-1396-8.
- Fusar-Poli P, Rubia K, Rossi G, Sartori G, Balottin U (March 2012). "Striatal dopamine transporter alterations in ADHD: pathophysiology or adaptation to psychostimulants? A meta-analysis". Am J Psychiatry 169 (3): 264–72. doi:10.1176/appi.ajp.2011.11060940. PMID 22294258.
- Kooij, SJ.; Bejerot, S.; Blackwell, A.; Caci, H.; Casas-Brugué, M.; Carpentier, PJ.; Edvinsson, D.; Fayyad, J. et al. (2010). "European consensus statement on diagnosis and treatment of adult ADHD: The European Network Adult ADHD". BMC Psychiatry 10: 67. doi:10.1186/1471-244X-10-67. PMC 2942810. PMID 20815868.
- British, Medical Association (September 2007). "4 Central Nervous System". British National Formulary (54 ed.). UK: Royal Pharmaceutical Society of Great Britain. p. 212. ISBN 978-0-85369-736-7. OCLC 852015259.
- Brown, TE. (Oct 2008). "ADD/ADHD and Impaired Executive Function in Clinical Practice". Curr Psychiatry Rep 10 (5): 407–11. doi:10.1007/s11920-008-0065-7. PMID 18803914.
- Cohen D, Leo J, Stanton T et al. (2002). "A boy who stops taking stimulants for "ADHD": commentaries on a Pediatrics case study". Ethical Hum Sci Serv 4 (3): 189–209. PMID 15278983.
- Schwartz RH, Rushton HG (May 2004). "Stuttering priapism associated with withdrawal from sustained-release methylphenidate". J. Pediatr. 144 (5): 675–6. doi:10.1016/j.jpeds.2003.12.039. PMID 15127013.
- Garland EJ (1998). "Pharmacotherapy of adolescent attention deficit hyperactivity disorder: challenges, choices and caveats". J. Psychopharmacol. (Oxford) 12 (4): 385–95. doi:10.1177/026988119801200410. PMID 10065914.
- Nolan EE, Gadow KD, Sprafkin J (April 1999). "Stimulant medication withdrawal during long-term therapy in children with comorbid attention-deficit hyperactivity disorder and chronic multiple tic disorder". Pediatrics 103 (4 Pt 1): 730–7. doi:10.1542/peds.103.4.730. PMID 10103294.
- Kidd PM (2000). "Attention deficit/hyperactivity disorder (ADHD) in children: rationale for its integrative management" (PDF). Altern Med Rev 5 (5): 402–28. PMID 11056411.
- Rosenfeld AA (February 1979). "Depression and psychotic regression following prolonged methylphenidate use and withdrawal: case report". Am J Psychiatry 136 (2): 226–8. PMID 760559.
- Smucker WD, Hedayat M (September 2001). "Evaluation and treatment of ADHD". Am Fam Physician 64 (5): 817–29. PMID 11563573.
- Riccio CA, Waldrop JJ, Reynolds CR, Lowe P (2001). "Effects of stimulants on the continuous performance test (CPT): implications for CPT use and interpretation". J Neuropsychiatry Clin Neurosci 13 (3): 326–35. doi:10.1176/appi.neuropsych.13.3.326. PMID 11514638.
- Ackerman, Todd (1 July 2005). "Closer look for possible Ritalin, cancer link". Houston Chronicle. Retrieved 10 July 2011.
- Walitza, Susanne et al. (June 2007). "Does Methylphenidate Cause a Cytogenetic Effect in Children with Attention Deficit Hyperactivity Disorder?". Environmental Health Perspectives 115 (6): 936–940. doi:10.1289/ehp.9866. PMC 1892117. PMID 17589603.
- Schlander (2007). "Long-acting medications for the hyperkinetic disorders: a note on cost-effectiveness". European Child and Adolescent Psychiatry 16 (7): 421–429 (Page:421). doi:10.1007/s00787-007-0615-2. PMID 17401606.
- Lange, KW.; Reichl, S.; Lange, KM.; Tucha, L.; Tucha, O. (Dec 2010). "The history of attention deficit hyperactivity disorder". Atten Defic Hyperact Disord 2 (4): 241–55. doi:10.1007/s12402-010-0045-8. PMC 3000907. PMID 21258430.
- Brown, Walter A (July 1998). "Charles Bradley, M.D., 1902–1979". American Journal of Psychiatry 155 (7): 968. Retrieved 15 September 2008.
- Bader, A; Adesman, A (Dec 2012). "Complementary and alternative therapies for children and adolescents with ADHD.". Current Opinion in Pediatrics 24 (6): 760–9. doi:10.1097/mop.0b013e32835a1a5f. PMID 23111680.
- Sonuga-Barke, EJ; Brandeis, D; Cortese, S; Daley, D; Ferrin, M; Holtmann, M; Stevenson, J; Danckaerts, M; van der Oord, S; Döpfner, M; Dittmann, RW; Simonoff, E; Zuddas, A; Banaschewski, T; Buitelaar, J; Coghill, D; Hollis, C; Konofal, E; Lecendreux, M; Wong, IC; Sergeant, J; European ADHD Guidelines, Group (1 March 2013). "Nonpharmacological interventions for ADHD: systematic review and meta-analyses of randomized controlled trials of dietary and psychological treatments.". The American Journal of Psychiatry 170 (3): 275–89. doi:10.1176/appi.ajp.2012.12070991. PMID 23360949.
- Greydanus, DE; Pratt, HD; Patel, DR (February 2007). "Attention deficit hyperactivity disorder across the lifespan: the child, adolescent, and adult". Disease-a-month 53 (2): 70–131. doi:10.1016/j.disamonth.2007.01.001. PMID 17386306.
- Moriyama TS, Polanczyk G, Caye A, Banaschewski T, Brandeis D, Rohde LA (July 2012). "Evidence-based information on the clinical use of neurofeedback for ADHD". Neurotherapeutics 9 (3): 588–98. doi:10.1007/s13311-012-0136-7. PMC 3441929. PMID 22930416.
- Lofthouse N, Arnold LE, Hurt E (October 2012). "Current status of neurofeedback for attention-deficit/hyperactivity disorder". Curr Psychiatry Rep 14 (5): 536–42. doi:10.1007/s11920-012-0301-z. PMID 22890816.
- Holtmann, M; Sonuga-Barke, E; Cortese, S; Brandeis, D (Oct 2014). "Neurofeedback for ADHD: A Review of Current Evidence.". Child and adolescent psychiatric clinics of North America 23 (4): 789–806. doi:10.1016/j.chc.2014.05.006. PMID 25220087.
- Jenks, Susan (9 March 2006). "ADHD patients play video games as part of treatment". USA Today.
- Butnik S.M. (2005). "Neurofeedback in adolescents and adults with attention deficit hyperactivity disorder". Journal of Clinical Psychology 61 (5): 621–625. doi:10.1002/jclp.20124. PMID 15723361.
- Shaw R., Grayson A., Lewis V. (2000). "Inhibition, ADHD, and computer games: The inhibitory performance of children and ADHD on computerized tasks and games". Journal of Attention Disorders 8 (4): 160–168. doi:10.1177/1087054705278771. PMID 16110046.
- Tolchinsky A., Jefferson, S.D. (2011). "Problematic video game play in a college sample and its relationship to time management skills and Attention-Deficit/Hyperactivity disorder symptomology". Cyberpsychology, Behavior, and Social Networking 14 (9): 489–496. doi:10.1089/cyber.2010.0315. PMID 21288135.
- Lawson, W. (1 March 2004). "ADHD's Outdoor Cure". Psychology Today. Archived from the original on 26 November 2009. Retrieved 11 November 2009.
- Rojas, NL; Chan, E (2005). "Old and new controversies in the alternative treatment of attention-deficit hyperactivity disorder.". Mental retardation and developmental disabilities research reviews 11 (2): 116–30. doi:10.1002/mrdd.20064. PMID 15977318.
- "Diet and attention deficit hyperactivity disorder". Harvard Mental Health Letter 25 (12): 4–5. June 2009. PMID 19582942.
- "FDA Asks Attention-Deficit Hyperactivity Disorder (ADHD) Drug Manufacturers to Develop Patient Medication Guides". Food and Drug Administration. 21 September 2007. Archived from the original on 21 February 2008. Retrieved 13 April 2009.
- Arnold LE, DiSilvestro RA; Disilvestro (2005). "Zinc in attention-deficit/hyperactivity disorder". Journal of child and adolescent psychopharmacology 15 (4): 619–27. doi:10.1089/cap.2005.15.619. PMID 16190793.
- Gillies D, Sinn JKh, Lad SS, Leach MJ, Ross MJ; Sinn; Lad; Leach; Ross (2012). "Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents". Cochrane Database Syst Rev 7: CD007986. doi:10.1002/14651858.CD007986.pub2. PMID 22786509.
- Bloch MH, Qawasmi A; Qawasmi (October 2011). "Omega-3 fatty acid supplementation for the treatment of children with attention-deficit/hyperactivity disorder symptomatology: systematic review and meta-analysis". J Am Acad Child Adolesc Psychiatry 50 (10): 991–1000. doi:10.1016/j.jaac.2011.06.008. PMC 3625948. PMID 21961774.
- Haslam, RHA, Dalby, JT, Rademaker, AW.; Dalby; Rademaker (1984). "Effects of megavitamin therapy on children with attention deficit disorders". Pediatrics 74 (1): 103–111. PMID 6234505.
- Lara DR (2010). "Caffeine, mental health, and psychiatric disorders". J. Alzheimers Dis. 20 Suppl 1: S239–48. doi:10.3233/JAD-2010-1378 (inactive 2015-02-02). PMID 20164571.
- Leon, M. R. (2000). "Effects of caffeine on cognitive, psychomotor, and affective performance of children with Attention-Deficit/Hyperactivity Disorder". Journal of Attention Disorders 4: 27–47. doi:10.1177/108705470000400103.
- Toledano A, Alvarez MI, Toledano-Díaz A; Alvarez; Toledano-Díaz (September 2010). "Diversity and variability of the effects of nicotine on different cortical regions of the brain – therapeutic and toxicological implications". Cent Nerv Syst Agents Med Chem 10 (3): 180–206. doi:10.2174/1871524911006030180. PMID 20528766.
- Schnoll, R; Burshteyn, D; Cea-Aravena, J (March 2003). "Nutrition in the treatment of attention-deficit hyperactivity disorder: a neglected but important aspect". Applied psychophysiology and biofeedback 28 (1): 63–75. doi:10.1023/A:1022321017467. PMID 12737097.
- Krummel DA, Seligson FH, Guthrie HA; Seligson; Guthrie (1996). "Hyperactivity: is candy causal?". Critical Reviews in Food Science & Nutrition 36 (1–2): 31–47. doi:10.1080/10408399609527717. PMID 8747098.
- Nigg JT, Lewis K, Edinger T, Falk M; Lewis; Edinger; Falk (January 2012). "Meta-analysis of attention-deficit/hyperactivity disorder or attention-deficit/hyperactivity disorder symptoms, restriction diet, and synthetic food color additives". J Am Acad Child Adolesc Psychiatry 51 (1): 86–97.e8. doi:10.1016/j.jaac.2011.10.015. PMID 22176942.
- "Food coloring ban in the UK but usage continues for USA". BioHealthBase BRC Team.
- "Modernising the Rules on Food Additives and Labelling of Azo Dyes". FLEXNEWS: Business News for the Food Industry. Global Data Systems. 9 July 2008.
- Kleinman RE, Brown RT, Cutter GR, Dupaul GJ, Clydesdale FM; Brown; Cutter; Dupaul; Clydesdale (June 2011). "A research model for investigating the effects of artificial food colorings on children with ADHD". Pediatrics 127 (6): e1575–84. doi:10.1542/peds.2009-2206. PMID 21576306.
- Sukhodolsky DG, Scahill L, Zhang H, et al. Disruptive behavior in children with Tourette's syndrome: association with ADHD comorbidity, tic severity, and functional impairment. J Am Acad Child Adolesc Psychiatry. 2003 Jan;42(1) 98-105. PMID 12500082
* Hoekstra PJ, Steenhuis MP, Troost PW, et al. Relative contribution of attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and tic severity to social and behavioral problems in tic disorders. J Dev Behav Pediatr. 2004 Aug;25(4) 272-9. PMID 15308928
* Carter AS, O'Donnell DA, Schultz RT, et al. Social and emotional adjustment in children affected with Gilles de la Tourette's syndrome: associations with ADHD and family functioning. Attention Deficit Hyperactivity Disorder. J Child Psychol Psychiatry. 2000 Feb;41(2) 215-23. PMID 10750547
* Spencer, T; Biederman, J; Harding, M; O'Donnell, D; Wilens, T; Faraone, S; Coffey, B; Geller, D (October 1998). "Disentangling the overlap between Tourette's disorder and ADHD". J Child Psychol Psychiatry 39 (7): 1037–44. doi:10.1111/1469-7610.00406. PMID 9804036.
- Freeman, RD. Tourette's Syndrome: minimizing confusion. Retrieved 8 February 2006. RD Freeman, MD, is Clinic Head of Neuropsychiatry Clinic at British Columbia Children's Hospital, Vancouver, professional advisory board member of Tourette Syndrome Foundation of Canada, and former member of the Tourette Syndrome Association Medical Advisory Board. Freeman has over 180 journal-published articles on PubMed.
- Palumbo D, Spencer T, Lynch J, et al. Emergence of tics in children with ADHD: impact of once-daily OROS methylphenidate therapy. J Child Adolesc Psychopharmacol. 2004 Summer;14(2):185-94. PMID 15319016
* Kurlan R. Tourette's syndrome: are stimulants safe? Curr Neurol Neurosci Rep. 2003 Jul;3(4):285-8. PMID 12930697
* Law SF, Schachar RJ. Do typical clinical doses of methylphenidate cause tics in children treated for attention-deficit hyperactivity disorder? J Am Acad Child Adolesc Psychiatry. 1999 Aug;38(8):944-51. PMID 10434485
- Tourette's Syndrome Study, Group (February 2002). "Treatment of ADHD in children with tics: a randomized controlled trial". Neurology 58 (4): 527–36. doi:10.1212/WNL.58.4.527. PMID 11865128.
- Zinner, SH (November 2000). "Tourette disorder". Pediatrics in review / American Academy of Pediatrics 21 (11): 372–83. PMID 11077021.
- Scahill, L; Erenberg, G; Berlin, CM; Budman, C; Coffey, BJ; Jankovic, J; Kiessling, L; King, RA; Kurlan, R; Lang, Anthony; Mink, Jonathan; Murphy, Tanya; Zinner, Samual; Walkup, John; Tourette Syndrome Association Medical Advisory Board: Practice Committee (April 2006). "Contemporary assessment and pharmacotherapy of Tourette syndrome". NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics 3 (2): 192–206. doi:10.1016/j.nurx.2006.01.009. PMC 3593444. PMID 16554257.