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Attention deficit hyperactivity disorder management options are evidence-based practices with established treatment efficacy for
ADHD Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...
. 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 Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...
and non-stimulant medications indicated for the treatment of ADHD. The most commonly used stimulant medications include
methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent ...
(Ritalin, Concerta),
mixed amphetamine salts Adderall and Mydayis are trade names for a combination drug called mixed amphetamine salts containing four salts of amphetamine. The mixture is composed of equal parts racemic amphetamine and dextroamphetamine, which produces a (3:1) ratio bet ...
(Adderall, Mydayis),
dextroamphetamine Dextroamphetamine is a central nervous system (CNS) stimulant and an amphetamine enantiomer that is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance an ...
(Dexedrine), dextro-
methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamp ...
(Desoxyn), and
lisdexamfetamine Lisdexamfetamine, sold under the brand name Vyvanse among others, is a stimulant medication that is mainly used to treat attention deficit hyperactivity disorder (ADHD) in people over the age of five as well as moderate-to-severe binge eatin ...
(Vyvanse). Non-stimulant medications with a specific indication for ADHD include
atomoxetine Atomoxetine, sold under the brand name Strattera, among others, is a medication used to treat attention deficit hyperactivity disorder (ADHD). It may be used alone or along with psychostimulants. It is also used as a cognitive enhancer to imp ...
(Strattera),
viloxazine Viloxazine, sold under the brand name Qelbree and formerly as Vivalan among others, is a noradrenergic medication which is used in the treatment of attention deficit hyperactivity disorder (ADHD) in children and adults. It was marketed for almos ...
(Qelbree), guanfacine (Intuniv), and
clonidine Clonidine, sold under the brand name Catapres among others, is an α2-adrenergic agonist medication used to treat high blood pressure, ADHD, drug withdrawal ( alcohol, opioids, or nicotine), menopausal flushing, diarrhea, spasticity, and c ...
(Kapvay). Other medicines which may be prescribed
off-label Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although ...
include
bupropion Bupropion, sold under the brand names Wellbutrin and Zyban among others, is an atypical antidepressant primarily used to treat major depressive disorder and to support smoking cessation. It is also popular as an add-on medication in the cas ...
(Wellbutrin),
tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...
, SNRIs, or MAOIs. The presence of
comorbid In medicine, comorbidity - from Latin morbus ("sickness"), co ("together"), -ity (as if - several sicknesses together) - is the presence of one or more additional conditions often co-occurring (that is, concomitant or concurrent) with a primary ...
(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 simultaneously treat any comorbid disorders. A variety of
psychotherapeutic Psychotherapy (also psychological therapy, talk therapy, or talking therapy) is the use of psychological methods, particularly when based on regular personal interaction, to help a person change behavior, increase happiness, and overcome prob ...
and
behavior modification Behavior modification is an early approach that used respondent and operant conditioning to change behavior. Based on methodological behaviorism, overt behavior was modified with consequences, including positive and negative reinforcement conti ...
approaches to managing ADHD including psychotherapy and
working memory training Working memory training is intended to improve a person's working memory. Working memory is a central intellectual faculty, linked to IQ, ageing, and mental health. It has been claimed that working memory training programs are effective means, bot ...
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 Time management is the process of planning and exercising conscious control of time spent on specific activities, especially to increase effectiveness, efficiency, and productivity. It involves of various demands upon a person relating to wo ...
or organizational suggestions. Self-control training programs have been shown to have limited effectiveness. The parents and teachers must work together to help with the child's education. This includes engaging activities and limiting screen time. 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 trial A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical t ...
s assessing for periods of usage longer than two years.


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. In a 2019 review the effectiveness of social skills training was evaluated in children aged 5 to 18 years. At the time there was little evidence to support or refute this type of training for the treatment of ADHD in this age group.


Parents and classroom

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 Operant conditioning, also called instrumental conditioning, is a learning process where behaviors are modified through the association of stimuli with reinforcement or punishment. In it, operants—behaviors that affect one's environment—are c ...
: a consistent application of rewards for meeting goals and good behavior (
positive reinforcement In behavioral psychology, reinforcement is a consequence applied that will strengthen an organism's future behavior whenever that behavior is preceded by a specific antecedent stimulus. This strengthening effect may be measured as a higher fr ...
) 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 token economy is a system of contingency management based on the systematic reinforcement of target behavior. The reinforcers are symbols or tokens that can be exchanged for other reinforcers. A token economy is based on the principles of op ...
. In order for Token Economy to benefit students with ADHD, all staff must be consistent in rewarding the same behaviors. Additionally, establishing classroom routines will help to ensure that students with ADHD remain focused throughout the day.


Cognitive training

A 2013 paper published by two researchers from the
University of Oslo The University of Oslo ( no, Universitetet i Oslo; la, Universitas Osloensis) is a public research university located in Oslo, Norway. It is the highest ranked and oldest university in Norway. It is consistently ranked among the top universit ...
concluded that
working memory Working memory is a cognitive system with a limited capacity that can hold information temporarily. It is important for reasoning and the guidance of decision-making and behavior. Working memory is often used synonymously with short-term 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 , mottoeng = The Heights Yield to Endeavour , type = Public research university , established = 1862 – Hartley Institution1902 – Hartley University College1913 – Southampton University Coll ...
presented the result of meta analysis study of 14 recently published
randomized controlled trial A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical t ...
s (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".


Medications


Stimulants

Stimulants Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...
are the most commonly prescribed medications for ADHD. The stimulant medications indicated to treat ADHD are
methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent ...
(Ritalin, Concerta),
dexmethylphenidate Dexmethylphenidate, sold under the brand name Focalin among others, is a strong central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) in those over the age of five years. If no benefit i ...
(Focalin),
mixed amphetamine salts Adderall and Mydayis are trade names for a combination drug called mixed amphetamine salts containing four salts of amphetamine. The mixture is composed of equal parts racemic amphetamine and dextroamphetamine, which produces a (3:1) ratio bet ...
(Adderall, Mydayis),
dextroamphetamine Dextroamphetamine is a central nervous system (CNS) stimulant and an amphetamine enantiomer that is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance an ...
(Dexedrine),
lisdexamfetamine Lisdexamfetamine, sold under the brand name Vyvanse among others, is a stimulant medication that is mainly used to treat attention deficit hyperactivity disorder (ADHD) in people over the age of five as well as moderate-to-severe binge eatin ...
(Vyvanse), and in rare cases
methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamp ...
(Desoxyn). Controlled-release pharmaceuticals may allow once 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
neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neu ...
s
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...
and
norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad ...
, which increases cellular communication between
neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa ...
s that utilize these compounds. Stimulants increase the availability of synaptic dopamine, reduce the overactivity, impulsivity, and inattention characteristics of patients with ADHD, and improve associated behaviors, including on-task behavior, academic performance, and social functioning. The therapeutic benefits are due to
noradrenergic Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...
effects at the
locus coeruleus The locus coeruleus () (LC), also spelled locus caeruleus or locus ceruleus, is a nucleus in the pons of the brainstem involved with physiological responses to stress and panic. It is a part of the reticular activating system. The locus coer ...
and the
prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA ...
and
dopaminergic Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain pathways facilitate do ...
effects at the
ventral tegmental area The ventral tegmental area (VTA) (tegmentum is Latin for ''covering''), also known as the ventral tegmental area of Tsai, or simply ventral tegmentum, is a group of neurons located close to the midline on the floor of the midbrain. The VTA is the ...
,
nucleus accumbens The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for "nucleus adjacent to the septum") is a region in the basal forebrain rostral to the preoptic area of the hyp ...
, 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 may be a little harder to be prescribed because they are controlled substances and can be abused easily, an example of this would be Adderall. Studies consistently show that most students report using stimulant medications, legally or illegally to improve academic performance, specifically to increase concentration, organization, and the ability to stay up longer and study. Adderall is the most popular stimulant in the academic setting due to its reputation among students: high school, and college educations. The abuse of this drug has made prescribing it much more meticulous.
Stimulant Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...
s are the most effective medications available for the treatment of ADHD. Seven different formulations of stimulants have been approved by the U.S.
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
(FDA) for the treatment of ADHD: four
amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...
-based formulations, two
methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent ...
-based formulations, and dextromethamphetamine hydrochloride.
Atomoxetine Atomoxetine, sold under the brand name Strattera, among others, is a medication used to treat attention deficit hyperactivity disorder (ADHD). It may be used alone or along with psychostimulants. It is also used as a cognitive enhancer to imp ...
,
viloxazine Viloxazine, sold under the brand name Qelbree and formerly as Vivalan among others, is a noradrenergic medication which is used in the treatment of attention deficit hyperactivity disorder (ADHD) in children and adults. It was marketed for almos ...
, guanfacine, and
clonidine Clonidine, sold under the brand name Catapres among others, is an α2-adrenergic agonist medication used to treat high blood pressure, ADHD, drug withdrawal ( alcohol, opioids, or nicotine), menopausal flushing, diarrhea, spasticity, and c ...
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. Stimulants, however, may reduce the risk of unintentional injuries in children with ADHD. 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 much lower treatment
effect size In statistics, an effect size is a value measuring the strength of the relationship between two variables in a population, or a sample-based estimate of that quantity. It can refer to the value of a statistic calculated from a sample of data, the ...
s than stimulant medication.


Amphetamine

Amphetamine is a chiral compound which is composed of two
isomers In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of 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 produce a small difference in their pharmacological properties; levoamphetamine has a slightly longer
half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ...
than dextroamphetamine, but dextroamphetamine is a more potent
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
stimulant. Although it is effective in reducing primary ADHD symptoms such as hyperactivity and inattention, multiple adverse side effects presented. Included in these were headaches, anxiety, nausea and insomnia. Five different amphetamine-based pharmaceuticals are currently used in ADHD treatment:
racemic amphetamine Amphetamine (contracted from Alpha and beta carbon, alpha-methylphenethylamine, methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolep ...
,
dextroamphetamine Dextroamphetamine is a central nervous system (CNS) stimulant and an amphetamine enantiomer that is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance an ...
,
lisdexamfetamine Lisdexamfetamine, sold under the brand name Vyvanse among others, is a stimulant medication that is mainly used to treat attention deficit hyperactivity disorder (ADHD) in people over the age of five as well as moderate-to-severe binge eatin ...
, and two mixed enantiomer products (
Adderall Adderall and Mydayis are trade names for a combination drug called mixed amphetamine salts containing four salts of amphetamine. The mixture is composed of equal parts racemic amphetamine and dextroamphetamine, which produces a (3:1) ratio ...
and Dyanavel XR). Lisdexamfetamine is an inactive
prodrug A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the dru ...
of dextroamphetamine (i.e., lisdexamfetamine itself does not 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. Dyanavel XR contains a similar mixture. 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.


= Methamphetamine

= The body metabolizes methamphetamine into amphetamine (in addition to less active
metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, ...
s). A quarter of methamphetamine will ultimately become amphetamine. After comparing only the common ground between dextroamphetamine and dextromethamphetamine, the latter is said to be the stronger stimulant.


Methylphenidate

Like amphetamine,
methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent ...
(MPH) is a chiral compound which is composed of two
isomers In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. ...
: d-threo-methylphenidate (also known as
dexmethylphenidate Dexmethylphenidate, sold under the brand name Focalin among others, is a strong central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) in those over the age of five years. If no benefit i ...
, d-methylphenidate, or d-MPH) and l-threo-methylphenidate (also known as l-methylphenidate or l-MPH). Both isomers 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. Unlike amphetamine, the difference in pharmacological properties between d-MPH and l-MPH is significant, as l-MPH is markedly inferior to d-MPH in its effects, which is due to a number of major differences between the isomers. There are two major medications derived from methylphenidate's isomers: a
racemic mixture In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...
of half d-threo-methylphenidate and half l-threo-methylphenidate called
methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent ...
(Ritalin, Concerta), and an enantiopure formulation containing just d-threo-methylphenidate called
dexmethylphenidate Dexmethylphenidate, sold under the brand name Focalin among others, is a strong central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) in those over the age of five years. If no benefit i ...
(Focalin).


Non-stimulants

Atomoxetine Atomoxetine, sold under the brand name Strattera, among others, is a medication used to treat attention deficit hyperactivity disorder (ADHD). It may be used alone or along with psychostimulants. It is also used as a cognitive enhancer to imp ...
,
viloxazine Viloxazine, sold under the brand name Qelbree and formerly as Vivalan among others, is a noradrenergic medication which is used in the treatment of attention deficit hyperactivity disorder (ADHD) in children and adults. It was marketed for almos ...
, guanfacine, and
clonidine Clonidine, sold under the brand name Catapres among others, is an α2-adrenergic agonist medication used to treat high blood pressure, ADHD, drug withdrawal ( alcohol, opioids, or nicotine), menopausal flushing, diarrhea, spasticity, and c ...
are drugs approved for the treatment of ADHD that have been classified as "non-stimulant". ;
Atomoxetine Atomoxetine, sold under the brand name Strattera, among others, is a medication used to treat attention deficit hyperactivity disorder (ADHD). It may be used alone or along with psychostimulants. It is also used as a cognitive enhancer to imp ...
: Atomoxetine is less effective than stimulants for ADHD, is associated with rare cases of liver damage, and carries a U.S. FDA
black box warning In the United States, a boxed warning (sometimes "black box warning", colloquially) is a type of warning that appears on the package insert for certain prescription drugs, so called because the U.S. Food and Drug Administration specifies that i ...
regarding suicidal ideation. Controlled studies show increases in heart rate, decreases of body weight, decreased appetite and treatment-emergent nausea. ;
Viloxazine Viloxazine, sold under the brand name Qelbree and formerly as Vivalan among others, is a noradrenergic medication which is used in the treatment of attention deficit hyperactivity disorder (ADHD) in children and adults. It was marketed for almos ...
: Acts as a selective
norepinephrine reuptake inhibitor A norepinephrine reuptake inhibitor (NRI, NERI) or noradrenaline reuptake inhibitor or adrenergic reuptake inhibitor (ARI), is a type of drug that acts as a reuptake inhibitor for the neurotransmitters norepinephrine (noradrenaline) and ep ...
(NRI). However, it may also act as an
antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, ri ...
of the
serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and va ...
5-HT2B receptor and as an
agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ag ...
of the serotonin 5-HT2C receptors, actions which may be involved in its therapeutic effects. It was marketed for more than two decades as an
antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common Side effect, side-effects of antidepressants include Xerostomia, dry mouth, weig ...
in Europe before being repurposed as a treatment for ADHD and launched in the United States in April 2021. ; Guanfacine : The extended release form 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 Clonidine, sold under the brand name Catapres among others, is an α2-adrenergic agonist medication used to treat high blood pressure, ADHD, drug withdrawal ( alcohol, opioids, or nicotine), menopausal flushing, diarrhea, spasticity, and c ...
: 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.


Other

Some medications used to treat ADHD are prescribed
off-label Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although ...
, outside the scope of their US government 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) and proper dosage and usage instructions are not as well characterized. ;
Bupropion Bupropion, sold under the brand names Wellbutrin and Zyban among others, is an atypical antidepressant primarily used to treat major depressive disorder and to support smoking cessation. It is also popular as an add-on medication in the cas ...
: Bupropion is classified as an atypical
antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common Side effect, side-effects of antidepressants include Xerostomia, dry mouth, weig ...
. It is the most common 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 reuptake. Bupropion is not a controlled substance. It is commonly prescribed as a timed release formulation to decrease the risk of side effects. ;
Modafinil Modafinil, sold under the brand name Provigil among others, is a central nervous system (CNS) stimulant medication used to treat sleepiness due to narcolepsy, shift work sleep disorder, and obstructive sleep apnea. While it has seen off-la ...
: A wakefulness-promoting agent that operates primarily as a selective, relatively weak, and atypical
dopamine reuptake inhibitor A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular ...
. Double-blind randomized controlled trials have demonstrated the efficacy and tolerability of modafinil in pediatric ADHD, There are risks of serious side effects such as
skin reactions Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different de ...
, however these are rare and modafinil is not recommended for use in children. In the United States, it was originally pending marketing on-label as Sparlon, but approval was denied by the FDA due to major concerns over the occurrence of
Stevens–Johnson syndrome Stevens–Johnson syndrome (SJS) is a type of severe skin reaction. Together with toxic epidermal necrolysis (TEN) and Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN), it forms a spectrum of disease, with SJS being less severe. Erythema ...
in clinical trials. ;
Selegiline Selegiline, also known as L-deprenyl and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. It is provided in the form of a capsule or ...
: Selegiline acts as a
monoamine oxidase inhibitor Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, esp ...
, and increases levels of
monoamine neurotransmitter Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin. All monoamines ar ...
s in the
brain A brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as Visual perception, vision. I ...
. At doses under 20 mg/day, selegiline is a selective and
irreversible inhibitor An enzyme inhibitor is a molecule that binds to an enzyme and blocks its activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which substrate molecules are converted into products. An enzyme facilitates a s ...
of monoamine oxidase B (MAO-B), increasing levels of
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...
in the brain. In clinical trials, Selegiline has been used in the treatment of
attention deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...
(ADHD). Selegiline may target specific symptoms of ADHD including: sustained attention, the learning of novel information, hyperactivity, and peer interactions. Selegiline has shown to be relatively effective in treating the inattention subtype of ADHD. Other medications which may be prescribed
off-label Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although ...
include certain antidepressants such as
tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...
(TCAs), SNRIs,
SSRIs Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracellu ...
, or MAOIs.


Antipsychotic medication

Atypical antipsychotic The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as major tranquilizers and ne ...
medications, which are approved for the treatment of certain
behavioral disorder Emotional and behavioral disorders (EBD; also known as behavioral and emotional disorders) refer to a disability classification used in educational settings that allows educational institutions to provide special education and related services to ...
s, are sometimes prescribed
off-label Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although ...
as a combination therapy with stimulants for the treatment of
comorbid In medicine, comorbidity - from Latin morbus ("sickness"), co ("together"), -ity (as if - several sicknesses together) - is the presence of one or more additional conditions often co-occurring (that is, concomitant or concurrent) with a primary ...
(i.e., co-occurring diseases) ADHD and disruptive
behavioral disorder Emotional and behavioral disorders (EBD; also known as behavioral and emotional disorders) refer to a disability classification used in educational settings that allows educational institutions to provide special education and related services to ...
s. Canadian clinical practice guidelines only support the use of dopaminergic antipsychotics with selectivity for D2-type
dopamine receptor Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through diffe ...
s, particularly
risperidone Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It is taken either by mouth or by injection (subcutaneous or intramuscular). The injectable versions ...
, as a third-line treatment for both disorders following the failure of stimulant monotherapy and psychosocial interventions. Combined use of D2-type receptor antagonists and ADHD stimulants for the treatment of ADHD with
comorbid In medicine, comorbidity - from Latin morbus ("sickness"), co ("together"), -ity (as if - several sicknesses together) - is the presence of one or more additional conditions often co-occurring (that is, concomitant or concurrent) with a primary ...
behavioral disorder Emotional and behavioral disorders (EBD; also known as behavioral and emotional disorders) refer to a disability classification used in educational settings that allows educational institutions to provide special education and related services to ...
s does not appear to have significantly worse adverse effects than ADHD stimulant or antipsychotic monotherapy. Research suggests, but has not yet confirmed, the treatment efficacy of antipsychotic and stimulant combination treatment for both disorders; it is unclear if the combination therapy for both disorders is superior to stimulant or antipsychotic monotherapy. There is no evidence to support the use of any subclass of antipsychotics for the treatment of the core symptoms of ADHD (i.e., inattention and hyperactivity) without comorbid behavioral disorders. Dopaminergic antipsychotics affect dopamine neurons by binding to postsynaptic
dopamine receptor Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through diffe ...
s, where they function as
receptor antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of rece ...
s. In contrast, ADHD stimulants are
indirect agonist In pharmacology, an indirect agonist or indirect-acting agonist is a substance that enhances the release or action of an endogenous neurotransmitter but has no specific agonist activity at the neurotransmitter receptor itself. Indirect agonists wor ...
s of postsynaptic dopamine receptors; in other words, these stimulants increase levels of synaptic dopamine, which then binds to postsynaptic receptors. Stimulants increase the concentration of synaptic dopamine by activating certain presynaptic receptors (i.e.,
TAAR1 Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the ''TAAR1'' gene. TAAR1 is an intracellular amine-activated and G protein-coupled receptor (GPCR) that is primarily ex ...
) or by blocking or altering the function of reuptake transporters (e.g., DAT,
VMAT2 The solute carrier family 18 member 2 (SLC18A2) also known as vesicular monoamine transporter 2 (VMAT2) is a protein that in humans is encoded by the ''SLC18A2'' gene. SLC18A2 is an integral membrane protein that transports monoamines—partic ...
) in the presynaptic neuron.


Comparison


Concerns regarding stimulants

Some parents and professionals have raised questions about the side effects of drugs and their long-term use.


Increasing use

Outpatient treatment rates held steady in the U.S. from the last 1990s to early 2000s. 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 The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georg ...
in 2011–2012 found 11% of children between the ages of 4 and 17 were reported to have ever received a health care provider diagnosis of ADHD at some point (15% of boys and 7% of girls), 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 The American Psychiatric Association (APA) is the main professional organization of psychiatrists and trainee psychiatrists in the United States, and the largest psychiatric organization in the world. It has more than 37,000 members are invo ...
in
DSM-5 The ''Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition'' (DSM-5), is the 2013 update to the '' Diagnostic and Statistical Manual of Mental Disorders'', the taxonomic and diagnostic tool published by the American Psychiatri ...
, with 8.8% of U.S. children having a current diagnosis in the 2011 survey. However, only 6.1% of children in the 2011 survey were taking ADHD medication, suggesting as many as 17.5% of children with current ADHD were not receiving treatment.


Use 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 of stimulant use in 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 than 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."


Side effects


= Growth delay and weight loss

= There is some evidence of mild reductions in growth rate with prolonged stimulant treatment in children, but no causal relationship has been established and reductions do not appear to persist long-term. Weight loss almost always corresponds with loss of appetite, which may result from the medication. Severe weight loss is very uncommon though. Loss of appetite is very temporary and typically comes back as daily effects of stimulates wear off. Nausea, dizziness, and headaches, other side effect, can also indirectly affect appetite and result in weight loss.


= Cardiovascular

= There is concern that
stimulants Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...
and
atomoxetine Atomoxetine, sold under the brand name Strattera, among others, is a medication used to treat attention deficit hyperactivity disorder (ADHD). It may be used alone or along with psychostimulants. It is also used as a cognitive enhancer to imp ...
, which increase the heart rate and blood pressure, might cause serious cardiovascular problems. 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 A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which ma ...
, and
stroke A stroke is a disease, medical condition in which poor cerebral circulation, blood flow to the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemorr ...
) and the medical use of amphetamine, methylphenidate, or other ADHD stimulants.


= Psychiatric

= Many of these drugs are associated with physical and psychological dependence. Sleep problems may occur. Methylphenidate can worsen
psychosis Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavi ...
in psychotic patients, and in very rare cases it has been associated with the emergence of new psychotic symptoms. It should be used with extreme caution in patients with
bipolar disorder Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of Depression (mood), depression and periods of abnormally elevated Mood (psychology), mood that last from days to weeks each. If the elevat ...
due to the potential induction of
mania Mania, also known as manic syndrome, is a mental and behavioral disorder defined as a state of abnormally elevated arousal, affect, and energy level, or "a state of heightened overall activation with enhanced affective expression together wi ...
or
hypomania Hypomania (literally "under mania" or "less than mania") is a mental and behavioural disorder, characterised essentially by an apparently non-contextual elevation of mood (euphoria) that contributes to persistently disinhibited behaviour. Th ...
. There have been very rare reports of
suicidal ideation Suicidal ideation, or suicidal thoughts, means having thoughts, ideas, or ruminations about the possibility of ending one's own life.World Health Organization, ''ICD-11 for Mortality and Morbidity Statistics'', ver. 09/2020MB26.A Suicidal ideatio ...
, but evidence does not support a link. The long-term effects on mental health disorders in later life of chronic use of methylphenidate is unknown. A 2009 FDA review of 49 clinical trials found that approximately 1.5% of children in clinical trials of medications for ADHD had experienced signs or symptoms of psychosis or mania. Postmarketing reports were also analyzed, with nearly half of them involving children under the age of eleven. Approximately 90% of cases had no reported previous history of similar psychiatric events. Hallucinations involving snakes, worms or insects were the most commonly reported symptoms.


Long-term use

Long-term methylphenidate or amphetamine exposure in some species is known to produce abnormal
dopamine system A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neurot ...
development or nerve damage, but humans experience normal development and nerve growth.
Magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...
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 The caudate nucleus is one of the structures that make up the corpus striatum, which is a component of the basal ganglia in the human brain. While the caudate nucleus has long been associated with motor processes due to its role in Parkinson's d ...
. 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 nine-month
randomized controlled trial A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical t ...
of amphetamine in children that found an average increase of 4.5 IQ points and continued improvements in attention, disruptive behaviors, and hyperactivity.


Withdrawal and rebound

Tolerance to the therapeutic effects of stimulants can occur, and rebound of symptoms may occur when the dose wears off. 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 can be minimised in intensity via a gradual tapering off of medication over a period of weeks or months. A small study of abrupt withdrawal of stimulants did suggest that withdrawal reactions are not typical, and may only occur in susceptible individuals.


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 The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
(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."


History

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 Providence is the capital and most populous city of the U.S. state of Rhode Island. One of the oldest cities in New England, it was founded in 1636 by Roger Williams, a Reformed Baptist theologian and religious exile from the Massachusetts ...
, reported that a group of children with behavioral problems improved after being treated with the stimulant
Benzedrine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...
. In 1954, the stimulant
methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent ...
(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 Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affect ...
, 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 Pemoline, sold under the brand name Cylert among others, is a stimulant medication which has been used in the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy. It has been discontinued in most countries to due to rare ...
(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 Atomoxetine, sold under the brand name Strattera, among others, is a medication used to treat attention deficit hyperactivity disorder (ADHD). It may be used alone or along with psychostimulants. It is also used as a cognitive enhancer to imp ...
(Strattera) received the first FDA approval for a nonstimulant drug to be used specifically for ADHD. In 2007,
lisdexamfetamine Lisdexamfetamine, sold under the brand name Vyvanse among others, is a stimulant medication that is mainly used to treat attention deficit hyperactivity disorder (ADHD) in people over the age of five as well as moderate-to-severe binge eatin ...
(Vyvanse) became the first
prodrug A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the dru ...
for ADHD to receive FDA approval. In March 2019, a
Purdue Pharma Purdue Pharma L.P., formerly the Purdue Frederick Company, is an American privately held pharmaceutical company founded by John Purdue Gray. It was owned principally by members of the Sackler family as descendants of Mortimer and Raymond Sackl ...
subsidiary received approval from the FDA for Adhansia XR, a methylphenidate medication to treat ADHD.


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 Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...
medication. Additionally, long-acting medications for ADHD, in comparison to short-acting varieties, generally seem to be cost-effective.
Comorbid In medicine, comorbidity - from Latin morbus ("sickness"), co ("together"), -ity (as if - several sicknesses together) - is the presence of one or more additional conditions often co-occurring (that is, concomitant or concurrent) with a primary ...
(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.


Dietary supplements

Individuals with hypokalemic sensory overstimulation are sometimes diagnosed as having attention deficit hyperactivity disorder (ADHD), raising the possibility that a subtype of ADHD has a cause that can be understood mechanistically and treated in a novel way. The sensory overload is treatable with oral
potassium gluconate Potassium gluconate is the potassium salt of the conjugate base of gluconic acid. It is also referred to as 2,3,4,5,6-pentahydroxycaproic acid potassium salt, D-gluconic acid potassium salt, or potassium D-gluconate. It contains 16.69% potassium ...
.


Alternative medicine

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.


Neurofeedback

Neurofeedback Neurofeedback (NFB), also called neurotherapy, is a type of biofeedback that presents real-time feedback from brain activity in order to reinforce healthy brain function through operant conditioning. Typically, electrical activity from the brain i ...
(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.


Media

Preliminary studies have supported the idea that playing video games is a form of neurofeedback, which helps those with ADHD self-regulate and improve learning. Memory, multitasking, fluid intelligence, and other cognitive talents may be improved by certain computer programmes and video games. 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.


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". But it may be due to reverse causation.


Diet

There is insufficient evidence to support dietary changes in ADHD and thus they are not recommended by the
American Academy of Pediatrics The American Academy of Pediatrics (AAP) is an American professional association of pediatricians, headquartered in Itasca, Illinois. It maintains its Department of Federal Affairs office in Washington, D.C. Background The Academy was found ...
as of 2019. Perhaps the best known of the dietary alternatives is the Feingold diet which involves removing
salicylates Salicylic acid is an organic compound with the formula HOC6H4CO2H. A colorless, bitter-tasting solid, it is a precursor to and a metabolite of aspirin (acetylsalicylic acid). It is a plant hormone, and has been listed by the EPA Toxic Substanc ...
, 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 In published academic research, publication bias occurs when the outcome of an experiment or research study biases the decision to publish or otherwise distribute it. Publishing only results that show a significant finding disturbs the balance o ...
. 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.
Dietary supplement A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...
s and specialized diets are sometimes used by people with ADHD with the intent to mitigate some or all of the symptoms. However a 2009 article in the ''Harvard Mental Health Letter'' states, "Although vitamin or mineral supplements icronutrientsmay 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: *
Caffeine Caffeine is a central nervous system (CNS) stimulant of the methylxanthine chemical classification, class. It is mainly recreational drug use, used recreationally as a Nootropic, cognitive enhancer, increasing alertness and attentional perfor ...
– ADHD is associated with increased caffeine consumption, and caffeine's
stimulant Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...
effects on
cognition Cognition refers to "the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, though ...
may have some benefits for ADHD. Limited evidence suggests a small therapeutic effect that is markedly inferior to standard treatments like methylphenidate and dextroamphetamine while still producing similar or greater side effects. *
Nicotine Nicotine is a naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and '' Duboisia hopwoodii'') and is widely used recreationally as a stimulant and anxiolytic. As a pharmaceutical drug, it is use ...
– The association between ADHD and nicotine intake is well known, and limited evidence suggests that nicotine may help improve some of the symptoms of ADHD, although the effect is generally small. *
Omega-3 fatty acids Omega−3 fatty acids, also called Omega-3 oils, ω−3 fatty acids or ''n''−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond, three atoms away from the terminal methyl group in their chem ...
– A 2012 Cochrane review found little evidence that supplementation with omega-3 or other polyunsaturated fatty acids provides any improvement in the symptoms of ADHD in children or adolescents. A 2011 meta analysis found a "small but significant benefit", with benefits being "modest compared to the efficacy of currently available pharmacological treatments for ADHD". The review concluded that supplementation may be worth consideration as an augmentative treatment in combination with medication due to its "relatively benign side-effect profile", but not as a primary treatment. Most research on omega-3 fatty acids is considered to be of very poor quality with widespread methodological weaknesses. *
Zinc Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...
– Although the role of zinc in ADHD has not been elucidated, there is a small amount of limited evidence that lower tissue zinc levels may be associated with ADHD. In the absence of a demonstrated zinc deficiency (which is rare outside of developing countries), zinc supplementation is not recommended as a treatment option for ADHD. * 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.


Exercise

Regular
physical exercise Exercise is a body activity that enhances or maintains physical fitness and overall health and wellness. It is performed for various reasons, to aid growth and improve strength, develop muscles and the cardiovascular system, hone athletic s ...
, particularly
aerobic exercise Aerobic exercise (also known as endurance activities, cardio or cardio-respiratory exercise) is physical exercise of low to high intensity that depends primarily on the aerobic energy-generating process. "Aerobic" is defined as "relating to, inv ...
, is an effective add-on treatment for ADHD in children and adults, particularly when combined with stimulant medication (although the best intensity and type of aerobic exercise for improving symptoms are not currently known). The long-term effects of regular aerobic exercise in ADHD individuals include better behavior and motor abilities, improved
executive functions In cognitive science and neuropsychology, executive functions (collectively referred to as executive function and cognitive control) are a set of cognitive processes that are necessary for the cognitive control of behavior: selecting and su ...
(including attention, inhibitory control, and
planning Planning is the process of thinking regarding the activities required to achieve a desired goal. Planning is based on foresight, the fundamental capacity for mental time travel. The evolution of forethought, the capacity to think ahead, is c ...
, among other cognitive domains), faster information processing speed, and better memory. Parent-teacher ratings of behavioral and socio-emotional outcomes in response to regular aerobic exercise include: better overall function, reduced ADHD symptoms, better self-esteem, reduced levels of anxiety and depression, fewer somatic complaints, better academic and classroom behavior, and improved social behavior. Exercising while on stimulant medication augments the effect of stimulant medication on executive function. It is believed that these short-term effects of exercise are mediated by an increased abundance of synaptic dopamine and norepinephrine in the brain.


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 Tourette syndrome or Tourette's syndrome (abbreviated as TS or Tourette's) is a common neurodevelopmental disorder that begins in childhood or adolescence. It is characterized by multiple movement (motor) tics and at least one vocal (phonic) ...
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 Cognition refers to "the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought ...
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 Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...
could not be used in the presence of tics, due to concern that their use might worsen tics; 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 Tourette Canada (formerly Tourette Syndrome Foundation of Canada) is a Canadian voluntary organization based in Mississauga, Ontario. It was formed in 1976, and is dedicated to improving the quality of life for those with or affected by Tourette sy ...
, and former member of the Tourette Syndrome Association Medical Advisory Board. Freeman has over 180 journal-published articles o
PubMed.
/ref> 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. A 2011
Cochrane Collaboration Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health profess ...
review concluded that most major ADHD medications were effective in children with tics, and that stimulants did not generally worsen tics outside of individual cases.
Methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent ...
, guanfacine,
clonidine Clonidine, sold under the brand name Catapres among others, is an α2-adrenergic agonist medication used to treat high blood pressure, ADHD, drug withdrawal ( alcohol, opioids, or nicotine), menopausal flushing, diarrhea, spasticity, and c ...
, and desipramine were associated with improvement of tic symptoms. 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,
dextroamphetamine Dextroamphetamine is a central nervous system (CNS) stimulant and an amphetamine enantiomer that is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance an ...
, and mixed amphetamine salts (
Adderall Adderall and Mydayis are trade names for a combination drug called mixed amphetamine salts containing four salts of amphetamine. The mixture is composed of equal parts racemic amphetamine and dextroamphetamine, which produces a (3:1) ratio ...
). Other medications can be used when stimulants are not an option. These include the alpha-2 agonists (clonidine and guanfacine),
tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...
s (desipramine and
nortriptyline Nortriptyline, sold under the brand name Pamelor, among others, is a medication used to treat depression. This medicine is used for: neuropathic pain, attention deficit hyperactivity disorder (ADHD), smoking cessation and anxiety. As with many ...
), and newer antidepressants (
bupropion Bupropion, sold under the brand names Wellbutrin and Zyban among others, is an atypical antidepressant primarily used to treat major depressive disorder and to support smoking cessation. It is also popular as an add-on medication in the cas ...
and
venlafaxine Venlafaxine, sold under the brand name Effexor among others, is an antidepressant medication of the serotonin-norepinephrine reuptake inhibitor (SNRI) class. It is used to treat major depressive disorder, generalized anxiety disorder, panic ...
). There have been case reports of tics worsening with bupropion. There is good empirical evidence for short-term safety and efficacy for the use of desipramine, bupropion and
atomoxetine Atomoxetine, sold under the brand name Strattera, among others, is a medication used to treat attention deficit hyperactivity disorder (ADHD). It may be used alone or along with psychostimulants. It is also used as a cognitive enhancer to imp ...
.


See also

* List of investigational attention deficit hyperactivity disorder drugs


Further reading

* Johnson M., Johnels J.Å., Östlund S., Cedergren K., Omanovic Z., Hjalmarsson K., Jakobsson K., Högstedt J., Billstedt E. (2021). Long-term medication for ADHD and development of cognitive functions in children and adolescents. ''Journal of Psychiatric Research'', ''142,'' 204-209. https://doi.org/10.1016/j.jpsychires.2021.07.055


References


External links

{{DEFAULTSORT:Attention-Deficit Hyperactivity Disorder Management Attention deficit hyperactivity disorder management, Amphetamine Methylphenidate de:Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung#Behandlung fr:Trouble déficitaire de l'attention avec hyperactivité#Traitement