Attention-deficit hyperactivity disorder treatments
Encyclopedia
Attention-deficit/hyperactivity disorder management is the treatment options available to people with attention-deficit/hyperactivity disorder (ADHD).
There are several effective and clinically proven options to treat people with ADHD. Combined medical management and behavioral treatment is the most effective ADHD management strategy, followed by medication alone, and then behavioral treatment. However, these results have been questioned because the study from the multimodal treatment group faded the behavioral procedure 3 months prior to the last evaluation point but continued the medication group. Indeed, after 14 months the medication group lost its advantage to the long discontinued behavior modification group. By year eight socioeconomic status and family structure were the only predictive variable for ADHD treatment A separate study highlighted the influence that nonclinical factors such as family size may have in mediating the use of pharmacologic therapies for children with ADHD.
The most common stimulant medications are methylphenidate
(Ritalin), dextroamphetamine
(Dexedrine), and mixed amphetamine salts
(Adderall
). Atomoxetine (Strattera) and Guanfacine
(Intuniv) are non-stimulant drugs approved for the treatment of ADHD. Other medications which may be prescribed off-label include certain antidepressants such as tricyclic antidepressants, SNRIs or MAOIs. The presence of comorbid
(relating to two diseases that occur together, e.g. depression
and ADHD) disorders make finding the right treatment and diagnosis much more costly and time consuming.
A variety of psychotherapeutic and behavior modification
approaches to managing ADHD including psychotherapy
and working memory therapy may be used. Improving the surrounding home and school environment with parent management training
and classroom management can improve the behavior of children with ADHD. Specialized ADHD coaches provide services and strategies to improve functioning, like time management
or organizational suggestions. Self control training programs have shown to have limited effectiveness. Behaviorally based self control does better than cognitive self control training A meta-analysis
found that the use of behavior modification
for ADHD are effective.
As of 2006 there was a shortage of data regarding ADHD drugs' potential adverse effects, with very few studies assessing the safety or efficacy of treatments beyond four months, and no randomized controlled trial
s assessing for periods of usage longer than two years. Treatment of preschool children is not recommended. The U.S. Food and Drug Administration
(FDA) found that a large number of the controlled trials required subjects who were known to respond to stimulants or who had no history of intolerance to stimulants, and this limits assumed generalizability of the trials' results.
. Techniques include operant conditioning
: a consistent application of rewards for meeting goals and good behavior (positive reinforcement) and punishments such as time-outs or revocation or privileges for failing to meet goals or poor behavior. Classroom management is similar to parent management training; educators learn about ADHD and techniques to improve behavior applied to a classroom setting. Strategies utilized include increased structuring of classroom activities, daily feedback, and token economy
.
(or short-term memory). By training and improving this memory some of the other symptoms may diminish as well. In a study by Klingberg et al., a computerized training program has shown good results in working memory, even if the generalized effect to behavioural symptoms was not as clear.
(Ritalin, Metadate, Concerta), dexmethylphenidate
(Focalin), dextroamphetamine
(Dexedrine), mixed amphetamine salts
(Adderall
), dextromethamphetamine(Desoxyn) and lisdexamfetamine (Vyvanse). However, caution needs to be used when prescribing medications that increase levels of "feel-good" neurotransmitter
s like dopamine
, because they can be addictive (see article: amphetamine dependence
). According to several studies, use of stimulants (e.g. methylphenidate) can lead to development of drug tolerance to therapeutic doses; tolerance also occurs among high dose abusers of methylphenidate.
Stimulants used to treat ADHD raise the extracellular concentrations of the neurotransmitter
s dopamine
and norepinephrine
which causes an increase in neurotransmission
. The therapeutic benefits are due to noradrenergic effects at the locus coeruleus and the prefrontal cortex
and dopaminergic
effects at the nucleus accumbens
.
A meta analysis of clinical trials found that about 70 percent of children improve after being treated with stimulants in the short term but found that this conclusion may be biased due to the high number of low quality clinical trials in the literature. There have been no randomized placebo controlled clinical trials investigating the long term effectiveness of methylphenidate
(Ritalin) beyond 4 weeks. Thus the long term effectiveness of methylphenidate has not been scientifically demonstrated. Serious concerns of publication bias
regarding the use of methylphenidate for ADHD has also been noted.
Higher rates of schizophrenia and bipolar disorder as well as increased severity of these disorders occur in individuals with a past history of stimulant use for ADHD in childhood.
Emergency room visits by children ages 10–14 involving Ritalin intoxication have now reached the same level as those for cocaine which indicates escalating abuse of this highly addictive drug. US and Canada account for a startling 95 percent of worldwide Ritalin consumption.
Both children with and without ADHD abuse stimulants, with ADHD individuals being at the highest risk of abusing or diverting their stimulant prescriptions. Between 16 and 29 percent of students who are prescribed stimulants report diverting their prescriptions. Between 5 and 9 percent of grade/primary and high school children and between 5 and 35 percent of college students have used nonprescribed stimulants. Most often their motivation is to concentrate, improve alertness, "get high," or to experiment.
One review indicates that long-term use of methylphenidate has potential for abuse
and addiction
due to its similarity pharmacologically to cocaine
and amphetamines. However, other doctors argue that use of stimulant therapy for ADHD does not increase the risk of subsequent substance abuse and may be protective against it when treatment is started in childhood. However, when stimulant therapy is started during adolescence or adulthood, there is an increased risk of subsequent substance abuse.
One study found that children with ADHD actually need to move more to maintain the required level of alertness while performing tasks that challenge their working memory. Performing math problems mentally and remembering multi-step directions are examples of tasks that require working memory, which involves remembering and manipulating information for a short time. These findings may also explain why stimulant medications improve the behavior of most children with ADHD. Those medications improve the physiological arousal of children with ADHD, increasing their alertness. Previous studies have shown that stimulant medications temporarily improve working memory abilities.
Although "under medical supervision, stimulant medications are considered safe", the use of stimulant medications for the treatment of ADHD has generated controversy because of undesirable side effects, uncertain long term effects and social and ethical issues regarding their use and dispensation. The U.S. FDA has added black-box warnings to some ADHD medications, while the American Heart Association
and the American Academy of Pediatrics
feel that it is prudent to carefully assess children for heart conditions before treating them with stimulant medications.
A novel stimulant drug that has been used to treat ADHD is modafinil
. There have been double-blind randomized controlled trials that have demonstrated the efficacy and tolerability of modafinil, however there are risks of serious side effects such as skin reactions and modafinil is not recommended for use in children.
Stimulant
s are the most effective medications available for the treatment of ADHD. Five different formulations of stimulants have been approved by the U.S. Food and Drug Administration
(FDA) for the treatment of ADHD: three derived from amphetamine
and two derived from methylphenidate
. Atomoxetine is the only non-controlled, non-stimulant FDA-approved drug for the treatment of ADHD. There are no differences in effectiveness between medications used for ADHD.
Short term clinical trials have shown medications to be effective for treating ADHD, but the trials usually use exclusion criteria, meaning knowledge on medications for ADHD is based on a small subset of the typical patients seen in clinical practice. They have not been found to improve school performance and data is lacking on long term effectiveness and the severity of side effects. This class of medicines is generally regarded as one unit; however, they affect the brain differently. Some investigations are dedicated to finding the similarities of children who respond to a specific medicine. The behavioural response to stimulants in children is similar regardless of whether they have ADHD or not.
Stimulant medication is an effective treatment for Adult Attention-deficit hyperactivity disorder although the response rate may be lower for adults than children.
Some physicians may recommend antidepressant drugs as the first line treatment instead of stimulants although antidepressants have lower treatment effect size
s than stimulant medication.
A study shown that children taking stimulant medications tend to be lighter in weight and shorter than their peers.
(a mixture of 72% dextroamphetamine
and 28% levoamphetamine
), Dexedrine (pure dextroamphetamine), and Desoxyn (pure dextromethamphetamine). The differences in these three Amphetamine based medications' active compounds and mixture ratios results in each medications' slightly different activities.
, the same way that a person's hands are the same but are mirror images of each other. This mirror difference is enough to cause the two compounds to be metabolized differently. Adderall begins to work before dextroamphetamine because of levoamphetamine. Levoamphetamine also provides Adderall with a longer clinical effect than dextroamphetamine. However, the brain’s preference for dextroamphetamine over levoamphetamine shows that the clinical value of Adderall is, for the most part, due to dextroamphetamine. A few children with ADHD and comorbid disorders have helpful responses to levoamphetamine.
There are two different medicines derived from methylphenidate
: Ritalin, which is half dextrothreomethylphenidate and half levothreomethylphenidate, 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
(Ritalin in transdermal patch
form) is used, then the levothreomethylphenidate comprising half of the administered dose, accounts for only around one thirteenth of the total clinical effect. Methylphenidate
has high potential for abuse
and addiction
due to its pharmacological similarity to cocaine
and amphetamines.
(Intuniv) are the only non-stimulant drugs approved for the treatment of ADHD. Other medications which may be prescribed off-label include α2A adrenergic receptor agonists such as clonidine
, certain antidepressants such as tricyclic antidepressants, SNRIs, SSRIs or MAOIs.
Atomoxetine (Strattera) is less effective than stimulants for ADHD, is associated with individual cases of liver damage, carries a U.S. FDA black box warning
regarding suicidal idealization, and 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.
Certain antidepressants such as tricyclic antidepressants, SNRIs or MAOIs are sometimes prescribed and are also effective in the treatment of ADHD.
, 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.
Antipsychotic medication
The use of atypical antipsychotic
medication as an off-label treatment has been rising. Antipsychotics work by blocking dopamine
, whereas stimulants trigger its release. Atypical antipsychotics have been approved for use in children and teenagers with schizophrenia
spectrum disorders and autistic spectrum disorders by the U.S. FDA.
Non-ADHD children do not respond differently than ADHD children when prescribed antipsychotic drugs, which are also increasingly prescribed off-label for children with aggression or defiant behavior. Social pressure to control a child's difficult and disruptive behavior, both at home and at school, may inadvertently change focus from what is in the best interest of the child's wellbeing; to how to render the child more compliant and easier to manage.
Careful approach needs to be taken when blocking dopamine function, which is responsible for the psychological reward system
. Excessive blocking of this neurotransmitter
can causedysphoria
. This may in turn cause suicidal ideation
, or lead some teenagers to compensate for their dopamine deficiency with illicit drugs or alcohol. Atypical antipsychotics are preferred for this reason, because they are less likely to cause movement disorders, dysphoria, and increased drug cravings that have been associated with older typical antipsychotics.Weight gain
, diabetes, lactation
, gynecomastia
, drooling
, dysphoria
, anhedonia
(inability to experience pleasure), fatigue, sexual dysfunction
, heart rhythm
problems and the possibility of tardive dyskinesia
, an irreversible movement disorder, are among the adverse events associated with antipsychotic drugs.
states that, "stimulant drugs, when used with medical supervision, are usually considered quite safe." Still, some parents and professionals have raised questions about the side effects of drugs and their long term use. A recent review states that ADHD studies "have major methodological deficiencies which are compounded by their restriction to school-age children, relatively short follow-up, and few data on adverse effects."
The American Heart Association
feel that it is prudent to carefully assess children for heart conditions before treating them with stimulant medications.
Several studies have found growth and weight suppression for stimulants. Compared to the behavior modification group at 8 years of the government-funded MTA study, the stimulant group had higher level of reported substance abuse.
(Ritalin), mainly to treat ADHD and similar disorders, in the UK. The incidence of ADHD is estimated at three to five percent of the population, while the number of children in the United States taking Ritalin is estimated at one to two percent. In a small study of four American communities, the reported incidence of ADHD varied from 1.6% to 9.4%. The study also found that only 12.5% of the children reportedly meeting the DSM-III-R ADHD criteria for ADHD had been treated with stimulants during the past year.
In 2007 the FDA requires all ADHD drug manufacturers to notify patients about serious cardiovascular side effects. This was due to reports of sudden death
in children taking these medications who had underlying heart problems and of high risk adults who suffered heart attacks and strokes.
Studies indicated that, "the rate of sudden death of children taking ADHD medications do not appear to exceed the base rate of sudden death in the general population". Matthew Smith is purported to have died at age 14 after long-term use of Ritalin. The medical examiner determined that Smith died from Ritalin usage, but medical experts dispute this. The examiner also argued that it was likely that diabeticchildren were at higher risk for cardiac problems.
and or mania
with all drug treatments examined, including: Concerta, Ritalin LA, d-MPH, Atomoxetine, Adderall
XR, Modafinil
, MTS, and Metadate.
Sleep problems may occur.
Many of these drugs are associated with physical and psychological dependence.
While ADHD is associated with an increased risk of substance abuse
, stimulant medications have been shown to reduce the risk of subsequent development of substance abuse
.
reactions, psychosis
, depression
, and pregnancy
has received very little research and thus the long term effects of using stimulants for ADHD are largely unknown. There are no well defined withdrawal schedules for discontinuing long term use of stimulants. Short term clinical trials have shown an incidence of psychosis of 0.1%.Psychosis occurs more commonly as a result of chronic use effecting about 6% of children on long term methylphenidate. The long term effects on mental health disorders in later life of chronic use of methylphenidate is unknown.Concerns have been raised that long-term therapy might cause drug dependence, paranoia
, schizophrenia
and behavioral sensitisation, similar to other stimulants.Psychotic symptoms from methylphenidate can include, hearing voices
, visual hallucinations, urges to harm oneself, severeanxiety
, euphoria
, grandiosity
, paranoid delusions, confusion
, increased aggression
and irritability
.Methylphenidate psychosis is unpredictable in who it will occur. Family history of mental illness does not predict the incidence of stimulant toxicosis in ADHD children. High rates of childhood stimulant use are found in ADHD patients who will eventually be diagnosed with comorbid schizophrenia
and bipolar
disorder. Individuals with a diagnosis of bipolar or schizophrenia who were prescribed stimulants during childhood typically have a significantly earlier onset of the psychotic disorder and suffer a more severe clinical course of psychotic disorder.
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.
(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."
medication. Additionally, long-acting medications for ADHD, in comparison to short-acting varieties, generally seem to be cost effective.Comorbid
(relating to two diseases that occur together, e.g. depression
and ADHD) disorders make finding the right treatment and diagnosis much more costly than when comorbid disorders are absent.
reported that a group of children with behavioral problems improved after being treated with the stimulantBenzedrine
. In 1957, the stimulant methylphenidate
(Ritalin, which was first produced in 1950) became available under various names (including Focalin, Concerta, Metadate, and Methylin); 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.
In 1999 the largest study of treatment for ADHD was published in the American Journal of Psychiatry
. Known as the Multimodal Treatment Study of ADHD (MTA Study), it involved more than 570 children with ADHD at 6 sites in the United States and Canada randomly assigned to 4 treatment groups
. All 4 treatment groups showed marked improvement from the time of baseline measurements to completion of the study 14 months later. Behavioral treatment was as effective as medication alone on 16 of 19 outcome measures. This was especially good for the behavior modification group, since the behavioral protocols were faded 3 months prior to the last evaluation and the stimulant group continued to receive medication right up to the last evaluation point.
Some proponents of alternative medicine advocate that alternative therapies may be tried before ADHD medications, although not all ADHD children will have any effective response.
Some people report short-term positive results using medical cannabis
for treating ADHD and doctor David Bearman supported this treatment. However, long-term effects of cannabis
use can include substance dependence
, drug tolerance, increase risk for schizophrenia
, bipolar disorders, and major depression.
, impulsivity
and hyperactivity. There are no known side effects from biofeedback therapy although research into biofeedback has been limited and further research has been recommended.
One 2009 study concluded "that NF may be considered as a clinically effective module in the treatment of children with ADHD" The human brain emits electrical energy which is measured with electrodes on the brain. Biofeedback alerts the patient when beta waves are present. This theory believes that those with ADHD can train themselves to decrease ADHD symptoms. There is a distinct split in the scientific community about the effectiveness of the treatment. A number of studies indicate the scientific evidence has been increasing in recent years for the effectiveness of EEG biofeedback for the treatment of ADHD. According to a 2007 review, the effectiveness of the treatment was demonstrated to be equivalent to that of stimulant medication. The review noted that improvements are seen at the behavioral and neuropsychological level with the symptoms of inattention, hyperactivity and impulsivity, showing significant decreases after treatment. There are no known side effects from EEG biofeedback therapy. There are methodological limitations and weaknesses in study designs however. In a 2005 review, Loo and Barkley stated that problems including lack of blinding such as placebo control and randomization are significant limitations to the studies into EEG biofeedback and make definitive conclusions impossible to make. As a result more robust clinical studies have been strongly recommended. A German review in 2004 found that EEG biofeedback, also sometimes referred to as neurofeedback, is more effective than previously thought in treating attention
deficiency, impulsivity
and hyperactivity; short-term effects match those of stimulant treatment, and a persistent normalization of EEG parameters is found even after treatment--this is not found after treatment with stimulants. There are no known side effects from biofeedback therapy although research into biofeedback has been limited and further research has been recommended. An American review the following year also emphasized the benefits of this method. Similar findings were reported in a study by another German team in 2004.
s and specialized diets are sometimes used by people with ADHD with the intent to mitigate some or all of the symptoms. For example, Omega-3
supplementation (seal, fish or krill oil) may reduce ADHD symptoms for a subgroup of children and adolescents with ADHD "characterized by inattention and associated neurodevelopmental disorders." Although vitamin or mineral supplements (micronutrients) may help children diagnosed with particular deficiencies, there is no evidence that they are helpful for all children with ADHD. Furthermore, megadoses of vitamins, which can be toxic, must be avoided. In the United States, no dietary supplement has been approved for the treatment for ADHD by the FDA. There is however a pilot study done which shows that phosphatidyl serine (PS)
can help against ADHD.
Some popular supplements used to manage ADHD symptoms:
which involves removing salicylates, artificial colors and flavors, and certain synthetic preservatives from children's diets. However, studies have shown little if any effect of the Feingold diet
on the behavior of children with ADHD.
A meta-analysis has found that dietary elimination of artificial food coloring and preservatives provides a statistically significant benefit in children with ADHD. Other more recent studies agree with these conclusions. The UK Food Standards Agency (FSA) has called for a ban on the use of six artificial food colorings and the European Union (EU) has ruled that some food dyes must be labeled with the relevant E number as well as this warning: "may have an adverse effect on activity and attention in children."
who are referred to specialty clinics have a high rate of comorbid ADHD. Patients who have ADHD along with tic
s or tic disorder
s 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 antidepressant
s (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).
There are several effective and clinically proven options to treat people with ADHD. Combined medical management and behavioral treatment is the most effective ADHD management strategy, followed by medication alone, and then behavioral treatment. However, these results have been questioned because the study from the multimodal treatment group faded the behavioral procedure 3 months prior to the last evaluation point but continued the medication group. Indeed, after 14 months the medication group lost its advantage to the long discontinued behavior modification group. By year eight socioeconomic status and family structure were the only predictive variable for ADHD treatment A separate study highlighted the influence that nonclinical factors such as family size may have in mediating the use of pharmacologic therapies for children with ADHD.
The most common stimulant medications are methylphenidate
Methylphenidate
Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
(Ritalin), dextroamphetamine
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....
(Dexedrine), and mixed amphetamine salts
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
(Adderall
Adderall
Adderall is a brand name of amphetamine salts–based medication used for attention-deficit hyperactivity disorder and narcolepsy. It is a brand-name psychostimulant medication composed of racemic amphetamine aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine saccharide, and...
). Atomoxetine (Strattera) and Guanfacine
Guanfacine
Guanfacine is a sympatholytic. It is an agonist of the α2A subtype of norepinephrine receptors. These receptors are concentrated heavily in the prefrontal cortex and the locus coeruleus, with the potential to improve attention abilities via modulating post-synaptic α2A receptors in the prefrontal...
(Intuniv) are non-stimulant drugs approved for the treatment of ADHD. Other medications which may be prescribed off-label include certain antidepressants such as tricyclic antidepressants, SNRIs or MAOIs. The presence of comorbid
Comorbidity
In medicine, comorbidity is either the presence of one or more disorders in addition to a primary disease or disorder, or the effect of such additional disorders or diseases.- In medicine :...
(relating to two diseases that occur together, e.g. depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
and ADHD) disorders make finding the right treatment and diagnosis much more costly and time consuming.
A variety of psychotherapeutic and behavior modification
Behavior modification
Behavior modification is the use of empirically demonstrated behavior change techniques to increase or decrease the frequency of behaviors, such as altering an individual's behaviors and reactions to stimuli through positive and negative reinforcement of adaptive behavior and/or the reduction of...
approaches to managing ADHD including psychotherapy
Psychotherapy
Psychotherapy is a general term referring to any form of therapeutic interaction or treatment contracted between a trained professional and a client or patient; family, couple or group...
and working memory therapy may be used. Improving the surrounding home and school environment with parent management training
Parent Management Training
Parent Management Training is a programme that trains parents to manage their children's behavioural problems at home and at school. PMT works to correct maladaptive parent-child interactions especially as they apply to discipline...
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
Time management is the act or process of exercising conscious control over the amount of time spent on specific activities, especially to increase efficiency or productivity. Time management may be aided by a range of skills, tools, and techniques used to manage time when accomplishing specific...
or organizational suggestions. Self control training programs have shown to have limited effectiveness. Behaviorally based self control does better than cognitive self control training A meta-analysis
Meta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...
found that the use of behavior modification
Behavior modification
Behavior modification is the use of empirically demonstrated behavior change techniques to increase or decrease the frequency of behaviors, such as altering an individual's behaviors and reactions to stimuli through positive and negative reinforcement of adaptive behavior and/or the reduction of...
for ADHD are effective.
As of 2006 there was a shortage of data regarding ADHD drugs' potential adverse effects, with very few studies assessing the safety or efficacy of treatments beyond four months, and no randomized controlled trial
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
s assessing for periods of usage longer than two years. Treatment of preschool children is not recommended. The U.S. Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) found that a large number of the controlled trials required subjects who were known to respond to stimulants or who had no history of intolerance to stimulants, and this limits assumed generalizability of the trials' results.
Psychosocial
There are a variety of psychotherapeutic approaches employed by psychologists and psychiatrists; the one used depends on the patient and the patient's symptoms. The approaches include psychotherapy, cognitive-behavior therapy, support groups, parent training, meditation, and social skills training. If psychotherapy fails to bring improvement, medications can be considered as an add-on or alternative.Psychotherapy
Psychotherapy is another option, with or without medication, that has been shown to be effective.Parent education and classroom management
Improving the surrounding home and school environment can improve the behavior of children with ADHD. Parents of children with ADHD often show similar deficits themselves, and thus may not be able to sufficiently help the child with his or her difficulties. Improving the parents' understanding of the child's behavior and teaching them strategies to improve functioning and communication and discourage unwanted behavior has measurable affect on the children with ADHD. The different educational interventions for the parents are jointly called Parent Management TrainingParent Management Training
Parent Management Training is a programme that trains parents to manage their children's behavioural problems at home and at school. PMT works to correct maladaptive parent-child interactions especially as they apply to discipline...
. Techniques include operant conditioning
Operant conditioning
Operant conditioning is a form of psychological learning during which an individual modifies the occurrence and form of its own behavior due to the association of the behavior with a stimulus...
: a consistent application of rewards for meeting goals and good behavior (positive reinforcement) and punishments such as time-outs or revocation or privileges for failing to meet goals or poor behavior. Classroom management is similar to parent management training; educators learn about ADHD and techniques to improve behavior applied to a classroom setting. Strategies utilized include increased structuring of classroom activities, daily feedback, and token economy
Token economy
A token economy is a system of behavior modification based on the systematic positive reinforcement of target behavior. The reinforcers are symbols or tokens that can be exchanged for other reinforcers. Token economy is based on the principles of operant conditioning and can be situated within...
.
Working memory training
Many of the problems shown by children with ADHD can be traced back to deficits in working memoryWorking memory
Working memory has been defined as the system which actively holds information in the mind to do verbal and nonverbal tasks such as reasoning and comprehension, and to make it available for further information processing...
(or short-term memory). By training and improving this memory some of the other symptoms may diminish as well. In a study by Klingberg et al., a computerized training program has shown good results in working memory, even if the generalized effect to behavioural symptoms was not as clear.
Coaching
ADHD Coaching is a specialized type of life coaching that uses specific techniques geared toward working with the unique brain wiring of individuals with attention-deficit/hyperactivity disorder. Professional coaching is not considered a substitute for traditional treatment such as medication and therapy.Medications
Stimulants
Stimulants are the most commonly prescribed medications for ADHD. The most common stimulant medications are the chain subsitituted amphetamine methylphenidateMethylphenidate
Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
(Ritalin, Metadate, Concerta), dexmethylphenidate
Dexmethylphenidate
Dexmethylphenidate, otherwise known as d-threo-methylphenidate , is the dextrorotatory enantiomer of methylphenidate. It is a norepinephrine-dopamine reuptake inhibitor and releasing agent and thus a psychostimulant, which affects the CNS...
(Focalin), dextroamphetamine
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....
(Dexedrine), mixed amphetamine salts
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
(Adderall
Adderall
Adderall is a brand name of amphetamine salts–based medication used for attention-deficit hyperactivity disorder and narcolepsy. It is a brand-name psychostimulant medication composed of racemic amphetamine aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine saccharide, and...
), dextromethamphetamine(Desoxyn) and lisdexamfetamine (Vyvanse). However, caution needs to be used when prescribing medications that increase levels of "feel-good" neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
s like dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
, because they can be addictive (see article: amphetamine dependence
Amphetamine dependence
Amphetamine dependence refers to a state of dependence on a drug in the amphetamine class.Tolerance is developed rapidly in amphetamine abuse, thereby the amount of the drug that is needed to satisfy the addiction needs to be increased at regular intervals....
). According to several studies, use of stimulants (e.g. methylphenidate) can lead to development of drug tolerance to therapeutic doses; tolerance also occurs among high dose abusers of methylphenidate.
Stimulants used to treat ADHD raise the extracellular concentrations of the neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
s dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
and norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
which causes an increase in neurotransmission
Neurotransmission
Neurotransmission , also called synaptic transmission, is the process by which signaling molecules called neurotransmitters are released by a neuron , and bind to and activate the receptors of another neuron...
. The therapeutic benefits are due to noradrenergic effects at the locus coeruleus and the prefrontal cortex
Prefrontal cortex
The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas.This brain region has been implicated in planning complex cognitive behaviors, personality expression, decision making and moderating correct social behavior...
and dopaminergic
Dopaminergic
Dopaminergic means related to the neurotransmitter dopamine. For example, certain proteins such as the dopamine transporter , vesicular monoamine transporter 2 , and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine...
effects at the nucleus accumbens
Nucleus accumbens
The nucleus accumbens , also known as the accumbens nucleus or as the nucleus accumbens septi , is a collection of neurons and forms the main part of the ventral striatum...
.
A meta analysis of clinical trials found that about 70 percent of children improve after being treated with stimulants in the short term but found that this conclusion may be biased due to the high number of low quality clinical trials in the literature. There have been no randomized placebo controlled clinical trials investigating the long term effectiveness of methylphenidate
Methylphenidate
Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
(Ritalin) beyond 4 weeks. Thus the long term effectiveness of methylphenidate has not been scientifically demonstrated. Serious concerns of publication bias
Publication bias
Publication bias is the tendency of researchers, editors, and pharmaceutical companies to handle the reporting of experimental results that are positive differently from results that are negative or inconclusive, leading to bias in the overall published literature...
regarding the use of methylphenidate for ADHD has also been noted.
Higher rates of schizophrenia and bipolar disorder as well as increased severity of these disorders occur in individuals with a past history of stimulant use for ADHD in childhood.
Emergency room visits by children ages 10–14 involving Ritalin intoxication have now reached the same level as those for cocaine which indicates escalating abuse of this highly addictive drug. US and Canada account for a startling 95 percent of worldwide Ritalin consumption.
Both children with and without ADHD abuse stimulants, with ADHD individuals being at the highest risk of abusing or diverting their stimulant prescriptions. Between 16 and 29 percent of students who are prescribed stimulants report diverting their prescriptions. Between 5 and 9 percent of grade/primary and high school children and between 5 and 35 percent of college students have used nonprescribed stimulants. Most often their motivation is to concentrate, improve alertness, "get high," or to experiment.
One review indicates that long-term use of methylphenidate has potential for abuse
Substance abuse
A substance-related disorder is an umbrella term used to describe several different conditions associated with several different substances .A substance related disorder is a condition in which an individual uses or abuses a...
and addiction
Substance dependence
The section about substance dependence in the Diagnostic and Statistical Manual of Mental Disorders does not use the word addiction at all. It explains:...
due to its similarity pharmacologically to cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
and amphetamines. However, other doctors argue that use of stimulant therapy for ADHD does not increase the risk of subsequent substance abuse and may be protective against it when treatment is started in childhood. However, when stimulant therapy is started during adolescence or adulthood, there is an increased risk of subsequent substance abuse.
One study found that children with ADHD actually need to move more to maintain the required level of alertness while performing tasks that challenge their working memory. Performing math problems mentally and remembering multi-step directions are examples of tasks that require working memory, which involves remembering and manipulating information for a short time. These findings may also explain why stimulant medications improve the behavior of most children with ADHD. Those medications improve the physiological arousal of children with ADHD, increasing their alertness. Previous studies have shown that stimulant medications temporarily improve working memory abilities.
Although "under medical supervision, stimulant medications are considered safe", the use of stimulant medications for the treatment of ADHD has generated controversy because of undesirable side effects, uncertain long term effects and social and ethical issues regarding their use and dispensation. The U.S. FDA has added black-box warnings to some ADHD medications, while the American Heart Association
American Heart Association
The American Heart Association is a non-profit organization in the United States that fosters appropriate cardiac care in an effort to reduce disability and deaths caused by cardiovascular disease and stroke. It is headquartered in Dallas, Texas...
and the American Academy of Pediatrics
American Academy of Pediatrics
The American Academy of Pediatrics is the major professional association of pediatricians in the United States. The AAP was founded in 1930 by 35 pediatricians to address pediatric healthcare standards. It currently has 60,000 members in primary care and sub-specialist areas...
feel that it is prudent to carefully assess children for heart conditions before treating them with stimulant medications.
A novel stimulant drug that has been used to treat ADHD is modafinil
Modafinil
Modafinil is an analeptic drug manufactured by Cephalon, and is approved by the U.S. Food and Drug Administration for the treatment of narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea...
. There have been double-blind randomized controlled trials that have demonstrated the efficacy and tolerability of modafinil, however there are risks of serious side effects such as skin reactions and modafinil is not recommended for use in children.
Stimulant
Stimulant
Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...
s are the most effective medications available for the treatment of ADHD. Five different formulations of stimulants have been approved by the U.S. Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) for the treatment of ADHD: three derived from amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
and two derived from methylphenidate
Methylphenidate
Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
. Atomoxetine is the only non-controlled, non-stimulant FDA-approved drug for the treatment of ADHD. There are no differences in effectiveness between medications used for ADHD.
Short term clinical trials have shown medications to be effective for treating ADHD, but the trials usually use exclusion criteria, meaning knowledge on medications for ADHD is based on a small subset of the typical patients seen in clinical practice. They have not been found to improve school performance and data is lacking on long term effectiveness and the severity of side effects. This class of medicines is generally regarded as one unit; however, they affect the brain differently. Some investigations are dedicated to finding the similarities of children who respond to a specific medicine. The behavioural response to stimulants in children is similar regardless of whether they have ADHD or not.
Stimulant medication is an effective treatment for Adult Attention-deficit hyperactivity disorder although the response rate may be lower for adults than children.
Some physicians may recommend antidepressant drugs as the first line treatment instead of stimulants although antidepressants have lower treatment effect size
Effect size
In statistics, an effect size is a measure of the strength of the relationship between two variables in a statistical population, or a sample-based estimate of that quantity...
s than stimulant medication.
A study shown that children taking stimulant medications tend to be lighter in weight and shorter than their peers.
Amphetamines
Three different medicines derived from amphetamine are used in ADHD treatment. Their trade names are AdderallAdderall
Adderall is a brand name of amphetamine salts–based medication used for attention-deficit hyperactivity disorder and narcolepsy. It is a brand-name psychostimulant medication composed of racemic amphetamine aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine saccharide, and...
(a mixture of 72% dextroamphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
and 28% levoamphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
), Dexedrine (pure dextroamphetamine), and Desoxyn (pure dextromethamphetamine). The differences in these three Amphetamine based medications' active compounds and mixture ratios results in each medications' slightly different activities.
Levoamphetamine and dextroamphetamine
Levoamphetamine and dextroamphetamine have the same chemical formula but are mirror images of each otherChirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....
, the same way that a person's hands are the same but are mirror images of each other. This mirror difference is enough to cause the two compounds to be metabolized differently. Adderall begins to work before dextroamphetamine because of levoamphetamine. Levoamphetamine also provides Adderall with a longer clinical effect than dextroamphetamine. However, the brain’s preference for dextroamphetamine over levoamphetamine shows that the clinical value of Adderall is, for the most part, due to dextroamphetamine. A few children with ADHD and comorbid disorders have helpful responses to levoamphetamine.
Dextromethamphetamine
The body metabolizes dextromethamphetamine into dextroamphetamine (in addition to less important chemicals). A quarter of dextromethamphetamine will ultimately become dextroamphetamine. After comparing only the common ground between dextroamphetamine and dextromethamphetamine, the latter is said to be the stronger stimulant. In theory—and in practice—a larger dose of dextroamphetamine is needed to achieve dextromethamphetamine’s clinical potency. In fact, when dextroamphetamine and methylphenidate are unhelpful, some doctors may prescribe dextromethamphetamine. Although more rarely prescribed, anecdotal reports suggest dextromethamphetamine is very helpful in cases where the other two are ineffective, or cause limiting side effects.Methylphenidate based medications
Methylphenidate
Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
: Ritalin, which is half dextrothreomethylphenidate and half levothreomethylphenidate, and Focalin, which is pure dextrothreomethylphenidate. Dextrothreomethylphenidate has a higher pharmacological activity than its mirror levo-form or enantiomer
Enantiomer
In chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...
. Levothreomethylphenidate has much weaker activity than the dextro isomer, and so for instance if Daytrana
Daytrana
Daytrana is a medicinal patch marketed by Shire Pharmaceuticals and developed under contract by Noven Pharmaceuticals that was approved in June 2007. In the literature, Daytrana is most commonly referred to as Methylphenidate Transdermal System .Daytrana is approved by the U.S...
(Ritalin in transdermal patch
Transdermal patch
A transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream. Often, this promotes healing to an injured area of the body. An advantage of a transdermal drug delivery route over other types of...
form) is used, then the levothreomethylphenidate comprising half of the administered dose, accounts for only around one thirteenth of the total clinical effect. Methylphenidate
Methylphenidate
Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
has high potential for abuse
Substance abuse
A substance-related disorder is an umbrella term used to describe several different conditions associated with several different substances .A substance related disorder is a condition in which an individual uses or abuses a...
and addiction
Substance dependence
The section about substance dependence in the Diagnostic and Statistical Manual of Mental Disorders does not use the word addiction at all. It explains:...
due to its pharmacological similarity to cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
and amphetamines.
Formulations
Controlled release pharmaceutical 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.Non stimulants
Atomoxetine (Strattera) and guanfacineGuanfacine
Guanfacine is a sympatholytic. It is an agonist of the α2A subtype of norepinephrine receptors. These receptors are concentrated heavily in the prefrontal cortex and the locus coeruleus, with the potential to improve attention abilities via modulating post-synaptic α2A receptors in the prefrontal...
(Intuniv) are the only non-stimulant drugs approved for the treatment of ADHD. Other medications which may be prescribed off-label include α2A adrenergic receptor agonists such as clonidine
Clonidine
Clonidine is a sympatholytic medication used to treat medical conditions, such as high blood pressure, some pain conditions, ADHD and anxiety/panic disorder...
, certain antidepressants such as tricyclic antidepressants, SNRIs, SSRIs or MAOIs.
Atomoxetine (Strattera) is less effective than stimulants for ADHD, is associated with individual cases of liver damage, carries a U.S. FDA black box warning
Black box warning
In the United States, a black box warning is a type of warning that appears on the package insert for prescription drugs that may cause serious adverse effects...
regarding suicidal idealization, and 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.
Certain antidepressants such as tricyclic antidepressants, SNRIs or MAOIs are sometimes prescribed and are also effective in the treatment of ADHD.
Other
Some medications used to treat ADHD are prescribed off-labelOff-label use
Off-label use is the practice of prescribing pharmaceuticals for an unapproved indication or in an unapproved age group, unapproved dose or unapproved form of administration...
, outside the scope of their FDA-approved indications
Indication (medicine)
In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. The opposite of indication is contraindication.-Drugs:...
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.
- AmantadineAmantadineAmantadine is the organic compound known formally as 1-adamantylamine or 1-aminoadamantane. The molecule consists of adamantane backbone that has an amino group substituted at one of the four methyne positions. This pharmaceutical is sold under the name Symmetrel for use both as an antiviral and an...
(Symmetrel) — an antiviral drugAntiviral drugAntiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...
and dopamine agonistAgonistAn agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
. There have been reports of low-dose amantadine having been successfully used off-label to treat ADHD. - BupropionBupropionBupropion is an atypical antidepressant and smoking cessation aid. The drug is a non-tricyclic antidepressant and differs from most commonly prescribed antidepressants such as SSRIs, as its primary pharmacological action is thought to be norepinephrine-dopamine reuptake inhibition...
(Wellbutrin) is classified as an antidepressantAntidepressantAn antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
. It is the most common of off-label prescription for ADHD. It inhibits the reuptake of norepinephrine, and to a lesser extent, dopamine, in neuronal synapses, and has little or no effect on serotonergic re-uptake. Bupropion is not a controlled substance. It is commonly prescribed as a timed release formulation to decrease the risk of side effects. Bupropion is not particularly known for its stimulant properties because at high doses it tends to cause seizures in a large portion of the population. - ClonidineClonidineClonidine is a sympatholytic medication used to treat medical conditions, such as high blood pressure, some pain conditions, ADHD and anxiety/panic disorder...
— 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 ticTicA tic is a sudden, repetitive, nonrhythmic, stereotyped motor movement or vocalization involving discrete muscle groups. Tics can be invisible to the observer, such as abdominal tensing or toe crunching. Common motor and phonic tics are, respectively, eye blinking and throat clearing...
s. It may be more useful for comorbid Tourette syndrome. - MilnacipranMilnacipranMilnacipran is a serotonin–norepinephrine reuptake inhibitor used in the clinical treatment of fibromyalgia...
, an anti-depressant drug, is currently being investigated for potential to alleviate the symptoms of ADHD in adults. - ModafinilModafinilModafinil is an analeptic drug manufactured by Cephalon, and is approved by the U.S. Food and Drug Administration for the treatment of narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea...
(Provigil/Alertec/Sparlon) — In the U.S., it is off-label pending decision by the FDA on August 22, 2006. It was originally pending marketing on-label as Alertec but denied for a reported incidence of Stevens-Johnson SyndromeStevens-Johnson syndromeStevens–Johnson syndrome and toxic epidermal necrolysis are two forms of a life-threatening skin condition, in which cell death causes the epidermis to separate from the dermis. The syndrome is thought to be a hypersensitivity complex that affects the skin and the mucous membranes...
. - ReboxetineReboxetineReboxetine is a drug marketed as an antidepressant for use in the treatment of clinical depression, panic disorder and ADD/ADHD, developed by Pharmacia . Its mesylate salt is sold under tradenames including Edronax, Norebox, Prolift, Solvex, Davedax or Vestra...
(Edronax) — is a selective norepinephrine reuptake inhibitorNorepinephrine reuptake inhibitorA norepinephrine reuptake inhibitor or adrenergic reuptake inhibitor , is a type of drug which acts as a reuptake inhibitor for the neurotransmitters norepinephrine and epinephrine by blocking the action of the norepinephrine transporter...
which is mainly used as an antidepressant. Studies outside the USA have found it to be an effective treatment for ADHD, and it is prescribed off-label for this purpose in Israel and some European countries, however reboxetine has never been approved by the FDA in the United States.
Antipsychotic medication
Atypical antipsychotic
The atypical antipsychotics are a group of antipsychotic tranquilizing drugs used to treat psychiatric conditions. Some atypical antipsychotics are FDA approved for use in the treatment of schizophrenia...
medication as an off-label treatment has been rising. Antipsychotics work by blocking dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
, whereas stimulants trigger its release. Atypical antipsychotics have been approved for use in children and teenagers with schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
spectrum disorders and autistic spectrum disorders by the U.S. FDA.
Non-ADHD children do not respond differently than ADHD children when prescribed antipsychotic drugs, which are also increasingly prescribed off-label for children with aggression or defiant behavior. Social pressure to control a child's difficult and disruptive behavior, both at home and at school, may inadvertently change focus from what is in the best interest of the child's wellbeing; to how to render the child more compliant and easier to manage.
Careful approach needs to be taken when blocking dopamine function, which is responsible for the psychological reward system
Reward system
In neuroscience, the reward system is a collection of brain structures which attempts to regulate and control behavior by inducing pleasurable effects...
. Excessive blocking of this neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
can causedysphoria
Dysphoria
Dysphoria is medically recognized as a mental and emotional condition in which a person experiences intense feelings of depression, discontent and indifference to the world around them.Mood disorders can induce dysphoria, often with a heightened risk of suicide, especially in...
. This may in turn cause suicidal ideation
Suicidal ideation
Suicidal ideation is a common medical term for thoughts about suicide, which may be as detailed as a formulated plan, without the suicidal act itself. Although most people who undergo suicidal ideation do not commit suicide, some go on to make suicide attempts...
, or lead some teenagers to compensate for their dopamine deficiency with illicit drugs or alcohol. Atypical antipsychotics are preferred for this reason, because they are less likely to cause movement disorders, dysphoria, and increased drug cravings that have been associated with older typical antipsychotics.Weight gain
Weight gain
Weight gain is an increase in body weight. This can be either an increase in muscle mass, fat deposits, or excess fluids such as water.-Description:...
, diabetes, lactation
Lactation
Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process occurs in all female mammals, however it predates mammals. In humans the process of feeding milk is called breastfeeding or nursing...
, gynecomastia
Gynecomastia
Gynecomastia or Gynaecomastia, , is the abnormal development of large mammary glands in males resulting in breast enlargement. The term comes from the Greek γυνή gyné meaning "woman" and μαστός mastós meaning "breast"...
, drooling
Drooling
Drooling is when saliva flows outside the mouth...
, dysphoria
Dysphoria
Dysphoria is medically recognized as a mental and emotional condition in which a person experiences intense feelings of depression, discontent and indifference to the world around them.Mood disorders can induce dysphoria, often with a heightened risk of suicide, especially in...
, anhedonia
Anhedonia
In psychology and psychiatry, anhedonia is defined as the inability to experience pleasure from activities usually found enjoyable, e.g. hobbies, exercise, social interaction or sexual activity....
(inability to experience pleasure), fatigue, sexual dysfunction
Sexual dysfunction
Sexual dysfunction or sexual malfunction refers to a difficulty experienced by an individual or a couple during any stage of a normal sexual activity, including desire, arousal or orgasm....
, heart rhythm
Heart Rhythm
Heart Rhythm is a peer-reviewed medical journal that covers the study and management of cardiac arrhythmia. It is the official journal of the Heart Rhythm Society and the Cardiac Electrophysiology Society...
problems and the possibility of tardive dyskinesia
Tardive dyskinesia
Tardive dyskinesia is a difficult-to-treat form of dyskinesia that can be tardive...
, an irreversible movement disorder, are among the adverse events associated with antipsychotic drugs.
Concerns regarding stimulants
The National Institute of Mental HealthNational Institute of Mental Health
The National Institute of Mental Health is one of 27 institutes and centers that make up the National Institutes of Health...
states that, "stimulant drugs, when used with medical supervision, are usually considered quite safe." Still, some parents and professionals have raised questions about the side effects of drugs and their long term use. A recent review states that ADHD studies "have major methodological deficiencies which are compounded by their restriction to school-age children, relatively short follow-up, and few data on adverse effects."
The American Heart Association
American Heart Association
The American Heart Association is a non-profit organization in the United States that fosters appropriate cardiac care in an effort to reduce disability and deaths caused by cardiovascular disease and stroke. It is headquartered in Dallas, Texas...
feel that it is prudent to carefully assess children for heart conditions before treating them with stimulant medications.
Several studies have found growth and weight suppression for stimulants. Compared to the behavior modification group at 8 years of the government-funded MTA study, the stimulant group had higher level of reported substance abuse.
Increase in use
Outpatient treatment rates have held steady in the US recently. Prior to this, outpatient treatment for ADHD in the US grew from 0.9 children per 100 in 1987 to 3.4 per 100 in 1997. There is concern about the rising use of methylphenidateMethylphenidate
Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
(Ritalin), mainly to treat ADHD and similar disorders, in the UK. The incidence of ADHD is estimated at three to five percent of the population, while the number of children in the United States taking Ritalin is estimated at one to two percent. In a small study of four American communities, the reported incidence of ADHD varied from 1.6% to 9.4%. The study also found that only 12.5% of the children reportedly meeting the DSM-III-R ADHD criteria for ADHD had been treated with stimulants during the past year.
Stimulant misuse
There is non-medical prescription stimulant use. A 2003 study found that non prescription use by college students in the US was 6.9% with 4.1% using them within the last year. A 2006 study with teens in Grades 7 to Grade 12 found that 2% reported non-medical use of prescription stimulant medication in the past 12 months, with 2% also reporting non-medical use of prescribed sedatives/and or anxiety medications, 3% using sleeping medications, and 12% reporting non-medical use of prescribed pain medications.Medication in preschoolers
Parents of children with ADHD note that they usually display their symptoms at an early age. Dr. John Van Brakle has stated, "pediatricians have long questioned whether such children can accurately be identified, given the overlap with normal behaviors in young children." The use of stimulant medication has not been approved by the FDA for children under the age of six. A growing trend is the diagnosis of younger children with ADHD. Prescriptions for children under the age of 5 rose nearly 50 percent from 2000 to 2003. Research on this issue has indicated that stimulant medication can help younger children with "severe ADHD symptoms" but typically at a lower dose then older children. It was also found that children at this age are more sensitive to side effects and should be closely monitored. Manos states, "it is prudent for physicians to be cautious," with medications. Evidence suggests that careful assessment and highly individualized behavioural interventions significantly improve both social and academic skills while medication only treats the symptoms of the disorder. Manos suggests that, "one of the primary reasons cited for the growing use of psychotropic interventions was that many physicians realize that psychological interventions are costly and difficult to sustain."Adverse effects
A number of possible side effects are of concern with respect to ADHD medications.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." 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.In 2007 the FDA requires all ADHD drug manufacturers to notify patients about serious cardiovascular side effects. This was due to reports of sudden death
Sudden death
In a sport or game, sudden death is a form of competition where play ends as soon as one competitor is ahead of the others, with that competitor becoming the winner. Sudden death is typically used as a tiebreaker when a contest is tied at the end of the normal playing time or the completion of...
in children taking these medications who had underlying heart problems and of high risk adults who suffered heart attacks and strokes.
Studies indicated that, "the rate of sudden death of children taking ADHD medications do not appear to exceed the base rate of sudden death in the general population". Matthew Smith is purported to have died at age 14 after long-term use of Ritalin. The medical examiner determined that Smith died from Ritalin usage, but medical experts dispute this. The examiner also argued that it was likely that diabeticchildren were at higher risk for cardiac problems.
Psychiatric side effects
In 2006 the FDA examined the occurrence of psychiatric side effects in ADHD medication. They found increased rates of psychosisPsychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
and or mania
Mania
Mania, the presence of which is a criterion for certain psychiatric diagnoses, is a state of abnormally elevated or irritable mood, arousal, and/ or energy levels. In a sense, it is the opposite of depression...
with all drug treatments examined, including: Concerta, Ritalin LA, d-MPH, Atomoxetine, Adderall
Adderall
Adderall is a brand name of amphetamine salts–based medication used for attention-deficit hyperactivity disorder and narcolepsy. It is a brand-name psychostimulant medication composed of racemic amphetamine aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine saccharide, and...
XR, Modafinil
Modafinil
Modafinil is an analeptic drug manufactured by Cephalon, and is approved by the U.S. Food and Drug Administration for the treatment of narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea...
, MTS, and Metadate.
Sleep problems may occur.
Many of these drugs are associated with physical and psychological dependence.
Issues with long-term use of stimulant medication
The short term use of stimulant medication has been shown to be effective yet its long term effects are yet to be determined. The Multimodal Treatment Study of Children with ADHD study concluded that while drugs such as Ritalin and Concerta (a delayed release form of Ritalin) worked in the short term, there was no demonstrable improvement in children's behavior after three years of medication."While ADHD is associated with an increased risk of substance abuse
Substance abuse
A substance-related disorder is an umbrella term used to describe several different conditions associated with several different substances .A substance related disorder is a condition in which an individual uses or abuses a...
, stimulant medications have been shown to reduce the risk of subsequent development of substance abuse
Substance abuse
A substance-related disorder is an umbrella term used to describe several different conditions associated with several different substances .A substance related disorder is a condition in which an individual uses or abuses a...
.
Long term use and schizophrenia and drug induced psychosis
Although the safety profile of short-term methylphenidate therapy in clinical trials has been well established, repeated use of psychostimulants such as methylphenidate is less clear. The long term effects of methylphenidate in drug addiction, withdrawalWithdrawal
Withdrawal can refer to any sort of separation, but is most commonly used to describe the group of symptoms that occurs upon the abrupt discontinuation/separation or a decrease in dosage of the intake of medications, recreational drugs, and alcohol...
reactions, psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
, depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
, and pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
has received very little research and thus the long term effects of using stimulants for ADHD are largely unknown. There are no well defined withdrawal schedules for discontinuing long term use of stimulants. Short term clinical trials have shown an incidence of psychosis of 0.1%.Psychosis occurs more commonly as a result of chronic use effecting about 6% of children on long term methylphenidate. The long term effects on mental health disorders in later life of chronic use of methylphenidate is unknown.Concerns have been raised that long-term therapy might cause drug dependence, paranoia
Paranoia
Paranoia [] is a thought process believed to be heavily influenced by anxiety or fear, often to the point of irrationality and delusion. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy concerning a perceived threat towards oneself...
, schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
and behavioral sensitisation, similar to other stimulants.Psychotic symptoms from methylphenidate can include, hearing voices
Hearing Voices
Hearing Voices or Hearing voices may be:* Auditory hallucination* Hearing Voices , 2001 audio-recording collection by D. Mahler* Hearing Voices Movement, a different way of viewing people who hear voices...
, visual hallucinations, urges to harm oneself, severeanxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
, euphoria
Euphoria
Euphoria is an emotional and mental state defined as a sense of great elation and well being.Euphoria may also refer to:* Euphoria , a genus of scarab beetles* Euphoria, a genus name previously used for the longan and other trees...
, grandiosity
Grandiosity
Grandiosity is chiefly associated with narcissistic personality disorder, but also commonly features in manic or hypomanic episodes of bipolar disorder....
, paranoid delusions, confusion
ConFusion
ConFusion is an annual science fiction convention organized by the Stilyagi Air Corps and its parent organization, the Ann Arbor Science Fiction Association. Commonly, it is held the third weekend of January. It is the oldest science fiction convention in Michigan, a regional, general SF con...
, increased aggression
Aggression
In psychology, as well as other social and behavioral sciences, aggression refers to behavior between members of the same species that is intended to cause humiliation, pain, or harm. Ferguson and Beaver defined aggressive behavior as "Behavior which is intended to increase the social dominance of...
and irritability
Irritability
Irritability is an excessive response to stimuli. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimuli; It is usually used to refer to anger or frustration....
.Methylphenidate psychosis is unpredictable in who it will occur. Family history of mental illness does not predict the incidence of stimulant toxicosis in ADHD children. High rates of childhood stimulant use are found in ADHD patients who will eventually be diagnosed with comorbid schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
and bipolar
Bipolar disorder
Bipolar disorder or bipolar affective disorder, historically known as manic–depressive disorder, is a psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevated energy levels, cognition, and mood with or without one or...
disorder. Individuals with a diagnosis of bipolar or schizophrenia who were prescribed stimulants during childhood typically have a significantly earlier onset of the psychotic disorder and suffer a more severe clinical course of psychotic disorder.
Stimulant withdrawal and rebound effects
Stimulant withdrawalWithdrawal
Withdrawal can refer to any sort of separation, but is most commonly used to describe the group of symptoms that occurs upon the abrupt discontinuation/separation or a decrease in dosage of the intake of medications, recreational drugs, and alcohol...
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
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
, irritability
Irritability
Irritability is an excessive response to stimuli. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimuli; It is usually used to refer to anger or frustration....
and depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
and a return of ADHD symptoms in an exaggerated form. Methylphenidate
Methylphenidate
Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
may be worse for causing rebound and withdrawal effects due to its very short half life. Amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
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
Rebound effect
The rebound effect, or rebound phenomenon, is the tendency of some medications, when discontinued suddenly, to cause a return of the symptoms it relieved, and that, to a degree stronger than they were before treatment first began...
in ADHD symptoms when the methylphenidate dose wears off.
Cancer
Concerns about chromosomal aberrations and possible cancer later in life was raised by a small-scale study on the use of methylphenidate, though a review by the Food and Drug AdministrationFood and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) found significant methodological problems with the study. A follow-up study performed with improved methodology found no evidence that methylphenidate might cause cancer, stating "the concern regarding a potential increase in the risk of developing cancer later in life after long-term MPH treatment is not supported."
Cost effectiveness
Combined medical management and behavioral treatment is the most effective ADHD management strategy, followed by medication alone, and then behavioral treatment. In terms of cost-effectiveness, management with medication has been shown to be the most cost-effective, followed by behavioral treatment, and combined treatment. The individually most effective and cost efficient way is with stimulantStimulant
Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...
medication. Additionally, long-acting medications for ADHD, in comparison to short-acting varieties, generally seem to be cost effective.Comorbid
Comorbidity
In medicine, comorbidity is either the presence of one or more disorders in addition to a primary disease or disorder, or the effect of such additional disorders or diseases.- In medicine :...
(relating to two diseases that occur together, e.g. depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
and ADHD) disorders make finding the right treatment and diagnosis much more costly than when comorbid disorders are absent.
History
The first reported evidence of stimulant medication used to treat children with concentration and hyperactivity problems came in 1937. Dr. Charles Bradley in Providence, Rhode IslandProvidence, Rhode Island
Providence is the capital and most populous city of Rhode Island and was one of the first cities established in the United States. Located in Providence County, it is the third largest city in the New England region...
reported that a group of children with behavioral problems improved after being treated with the stimulantBenzedrine
Benzedrine
Benzedrine is the trade name of the racemic mixture of amphetamine . It was marketed under this brandname in the USA by Smith, Kline & French in the form of inhalers, starting in 1928...
. In 1957, the stimulant methylphenidate
Methylphenidate
Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
(Ritalin, which was first produced in 1950) became available under various names (including Focalin, Concerta, Metadate, and Methylin); it remains one of the most widely prescribed medications for ADHD. Initially the drug was used to treat narcolepsy
Narcolepsy
Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive sleepiness and sleep attacks at inappropriate times, such as while at work. People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia...
, 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
Pemoline was first synthesized in 1913 but it's activity was not discovered until the 1930s. Under the names it was used as a medication used to treat attention-deficit hyperactivity disorder and narcolepsy. Under the Convention on Psychotropic Substances, it is a Schedule IV drug...
(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
Prodrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
to receive FDA approval for ADHD.
In 1999 the largest study of treatment for ADHD was published in the American Journal of Psychiatry
American Journal of Psychiatry
The American Journal of Psychiatry is a monthly peer-reviewed medical journal covering all aspects of psychiatry and the official journal of the American Psychiatric Association. The first volume was issued in 1844, at which time it was known as the American Journal of Insanity...
. Known as the Multimodal Treatment Study of ADHD (MTA Study), it involved more than 570 children with ADHD at 6 sites in the United States and Canada randomly assigned to 4 treatment groups
Treatment groups
In the design of experiments, treatments are applied to experimental units in the treatment group, while no treatments would be applied to members of a control group....
. All 4 treatment groups showed marked improvement from the time of baseline measurements to completion of the study 14 months later. Behavioral treatment was as effective as medication alone on 16 of 19 outcome measures. This was especially good for the behavior modification group, since the behavioral protocols were faded 3 months prior to the last evaluation and the stimulant group continued to receive medication right up to the last evaluation point.
Alternative medicine
Some people report short-term positive results using medical cannabis
Medical cannabis
Medical cannabis refers to the use of parts of the herb cannabis as a physician-recommended form of medicine or herbal therapy, or to synthetic forms of specific cannabinoids such as THC as a physician-recommended form of medicine...
for treating ADHD and doctor David Bearman supported this treatment. However, long-term effects of cannabis
Long-term effects of cannabis
Though the long-term effects of cannabis have been studied, there remains much to be concluded. Because use of cannabis ranges widely from users who try it once, to people using it frequently in a year, as well as users who use it daily, it is hard to measure the health effects it has on the human...
use can include substance dependence
Substance dependence
The section about substance dependence in the Diagnostic and Statistical Manual of Mental Disorders does not use the word addiction at all. It explains:...
, drug tolerance, increase risk for schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
, bipolar disorders, and major depression.
Biofeedback
EEG biofeedback is a treatment strategy used for children, adolescents and adults with ADHD. EEG biofeedback, also sometimes referred to as neurofeedback, is effective in treating attentionAttention
Attention is the cognitive process of paying attention to one aspect of the environment while ignoring others. Attention is one of the most intensely studied topics within psychology and cognitive neuroscience....
, impulsivity
Impulsivity
Impulsivity is a personality trait characterized by the inclination of an individual to initiate behavior without adequate forethought as to the consequences of their actions, acting on the spur of the moment. Eysenck and Eysenck related impulsivity to risk-taking, lack of planning, and making up...
and hyperactivity. There are no known side effects from biofeedback therapy although research into biofeedback has been limited and further research has been recommended.
One 2009 study concluded "that NF may be considered as a clinically effective module in the treatment of children with ADHD" The human brain emits electrical energy which is measured with electrodes on the brain. Biofeedback alerts the patient when beta waves are present. This theory believes that those with ADHD can train themselves to decrease ADHD symptoms. There is a distinct split in the scientific community about the effectiveness of the treatment. A number of studies indicate the scientific evidence has been increasing in recent years for the effectiveness of EEG biofeedback for the treatment of ADHD. According to a 2007 review, the effectiveness of the treatment was demonstrated to be equivalent to that of stimulant medication. The review noted that improvements are seen at the behavioral and neuropsychological level with the symptoms of inattention, hyperactivity and impulsivity, showing significant decreases after treatment. There are no known side effects from EEG biofeedback therapy. There are methodological limitations and weaknesses in study designs however. In a 2005 review, Loo and Barkley stated that problems including lack of blinding such as placebo control and randomization are significant limitations to the studies into EEG biofeedback and make definitive conclusions impossible to make. As a result more robust clinical studies have been strongly recommended. A German review in 2004 found that EEG biofeedback, also sometimes referred to as neurofeedback, is more effective than previously thought in treating attention
Attention
Attention is the cognitive process of paying attention to one aspect of the environment while ignoring others. Attention is one of the most intensely studied topics within psychology and cognitive neuroscience....
deficiency, impulsivity
Impulsivity
Impulsivity is a personality trait characterized by the inclination of an individual to initiate behavior without adequate forethought as to the consequences of their actions, acting on the spur of the moment. Eysenck and Eysenck related impulsivity to risk-taking, lack of planning, and making up...
and hyperactivity; short-term effects match those of stimulant treatment, and a persistent normalization of EEG parameters is found even after treatment--this is not found after treatment with stimulants. There are no known side effects from biofeedback therapy although research into biofeedback has been limited and further research has been recommended. An American review the following year also emphasized the benefits of this method. Similar findings were reported in a study by another German team in 2004.
Aerobic fitness
Aerobic fitness may improve cognitive functioning and neural organization related to executive control during pre-adolescent development, though more studies are needed in this area. One study suggests that athletic performance in boys with ADHD may increase peer acceptance when accompanied by fewer negative behaviors.Massage Therapy
For children and adolescents with ADHD, pediatric massage therapy has been found to improve mood and increase on-task behaviors, while reducing anxiety and hyperactivity.Art Therapy
Art is thought by some to be an effective therapy for some of the symptoms of ADHD. Other sources, including some psychologists who have written on the subject, feel that cutting down on time spent on television, video games, or violent media can help some children. One study indicated a correlation between excessive TV time as a child with higher rates of ADHD symptoms. Other therapies that have been effective for some have been ADHD coaching, positive changes in diet, such as low sugar, low additives, and no caffeine. Children who spend time outdoors in natural settings, such as parks, seem to display fewer symptoms of ADHD, which has been dubbed "Green Therapy".Dietary supplements
Dietary supplementDietary supplement
A dietary supplement, also known as food supplement or nutritional supplement, is a preparation intended to supplement the diet and provide nutrients, such as vitamins, minerals, fiber, fatty acids, or amino acids, that may be missing or may not be consumed in sufficient quantities in a person's diet...
s and specialized diets are sometimes used by people with ADHD with the intent to mitigate some or all of the symptoms. For example, Omega-3
Omega-3 fatty acid
N−3 fatty acids are essential unsaturated fatty acids with a double bond starting after the third carbon atom from the end of the carbon chain....
supplementation (seal, fish or krill oil) may reduce ADHD symptoms for a subgroup of children and adolescents with ADHD "characterized by inattention and associated neurodevelopmental disorders." Although vitamin or mineral supplements (micronutrients) may help children diagnosed with particular deficiencies, there is no evidence that they are helpful for all children with ADHD. Furthermore, megadoses of vitamins, which can be toxic, must be avoided. In the United States, no dietary supplement has been approved for the treatment for ADHD by the FDA. There is however a pilot study done which shows that phosphatidyl serine (PS)
Phosphatidylserine
Phosphatidylserine is a phospholipid component, usually kept on the inner-leaflet of cell membranes by an enzyme called flippase...
can help against ADHD.
Some popular supplements used to manage ADHD symptoms:
- ZincZincZinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
- Although the role of zinc in ADHD has not be elucidated, "numerous controlled studies report cross-sectional evidence of lower zinc tissue levels." - Omega-3 fatty acids - Some studies suggest that a lack of omega-3 fatty acids is associated with certain ADHD symptoms. and it has therefore been suggested that diet modification may play a role in the management of ADHD. People with ADHD were found to have significantly lower plasma phospholipids and erythrocytes omega-3 fatty acids. Their intake of saturated fatSaturated fatSaturated fat is fat that consists of triglycerides containing only saturated fatty acids. Saturated fatty acids have no double bonds between the individual carbon atoms of the fatty acid chain. That is, the chain of carbon atoms is fully "saturated" with hydrogen atoms...
was found to be 30% higher than in controls, while the intake of many other nutrients was not different. In support of the idea that it is not the intake of essential fatty acids that causes low tissue levels, a preliminary study showed that exhaled ethaneEthaneEthane is a chemical compound with chemical formula C2H6. It is the only two-carbon alkane that is an aliphatic hydrocarbon. At standard temperature and pressure, ethane is a colorless, odorless gas....
, a marker of omega-3 fatty acids peroxidation, was higher in children with ADHD relative to controls. Researchers from CSIRO, Australia's national science agency, showed polyunsaturated fatty acids to provide "medium to strong positive treatment effects" in ADHD. Another double blind study conducted by the University of Oxford, where children were given omega 3 fatty acids concluded that "significant improvements for active treatment versus placebo were found in reading, spelling, and behavior over 3 months of treatment in parallel groups." A 2008 study also concludes that Omega-3/Omega-6 supplementation reduces ADHD-symptoms for some. Thus it increasingly is documented in clinical studies that omega 3 fatty acids provide a safe way to treat hyperactivity. - MagnesiumMagnesiumMagnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...
and vitamin B6Vitamin B6Vitamin B6 is a water-soluble vitamin and is part of the vitamin B complex group. Several forms of the vitamin are known, but pyridoxal phosphate is the active form and is a cofactor in many reactions of amino acid metabolism, including transamination, deamination, and decarboxylation...
(pyridoxine) - In 2006, a study demonstrated that children with autism had significantly lower magnesium than controls, and that the correction of this deficit was therapeutic: Mousain-Bosc et al. showed that children with ADHD (n =46) had significantly lower red blood cellRed blood cellRed blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
magnesium levels than controls (n =30). Intervention with magnesium and vitamin B6 reduced hyperactivity, hyperemotivity/aggressiveness and improved school attention. - Iron supplements - In 2005, the official journal of the American Academy of PediatricsAmerican Academy of PediatricsThe American Academy of Pediatrics is the major professional association of pediatricians in the United States. The AAP was founded in 1930 by 35 pediatricians to address pediatric healthcare standards. It currently has 60,000 members in primary care and sub-specialist areas...
, PediatricsPediatrics (journal)Pediatrics is an official peer-reviewed journal of the American Academy of Pediatrics. In the inaugural January 1948 issue, the journal's first editor, Hugh McCulloch, articulated the journal's vision: "The content of the journal is... intended to encompass the needs of the whole child in his...
, published the case report of a child with ADHD with low ferritinFerritinFerritin is a ubiquitous intracellular protein that stores iron and releases it in a controlled fashion. The amount of ferritin stored reflects the amount of iron stored. The protein is produced by almost all living organisms, including bacteria, algae and higher plants, and animals...
who showed "considerable behavioral improvement" after his ferritin was normalized by iron supplementation. Based on earlier studies on iron deficiency and attentional function (notably the dopamine synthesis aspect), the screening of ferritin levels in children with ADHD was suggested. - PotassiumPotassiumPotassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
- In 2007, Harvard-associated researchers described a form of ADHDHypokalemic sensory overstimulationHypokalemic sensory overstimulation is a form of attention deficit hyperactivity disorder that has several similarities to disorders of ion channels, in particular to the muscle disorder hypokalemic periodic paralysis.-Characterization of the disorder:...
that was well treated with over-the-counter potassiumPotassiumPotassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
supplements. The molecular mechanism suggested by the authors was one producing sensory overstimulation, often triggered by ingesting carbohydrates, suggesting that people with ADHD who have sensitivity to sugar may be particularly likely to have this variant. - In the 1980s vitamin B6Vitamin B6Vitamin B6 is a water-soluble vitamin and is part of the vitamin B complex group. Several forms of the vitamin are known, but pyridoxal phosphate is the active form and is a cofactor in many reactions of amino acid metabolism, including transamination, deamination, and decarboxylation...
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 such as caffeineCaffeineCaffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
, theobromineTheobromineTheobromine , also known as xantheose, is a bitter alkaloid of the cacao plant, with the chemical formula C7H8N4O2. It is found in chocolate, as well as in a number of other foods, including the leaves of the tea plant, and the kola nut...
, and nicotineNicotineNicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves...
may improve the function of some children suffering from ADHD.
Diets
Perhaps the best known of the dietary alternatives is the Feingold dietFeingold diet
The Feingold diet is a food elimination program developed by Ben F. Feingold, MD to treat hyperactivity. It eliminates a number of artificial colors and artificial flavors, aspartame, three petroleum-based preservatives, and certain salicylates. There has been much debate about the efficacy of...
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
Feingold diet
The Feingold diet is a food elimination program developed by Ben F. Feingold, MD to treat hyperactivity. It eliminates a number of artificial colors and artificial flavors, aspartame, three petroleum-based preservatives, and certain salicylates. There has been much debate about the efficacy of...
on the behavior of children with ADHD.
A meta-analysis has found that dietary elimination of artificial food coloring and preservatives provides a statistically significant benefit in children with ADHD. Other more recent studies agree with these conclusions. The UK Food Standards Agency (FSA) has called for a ban on the use of six artificial food colorings and the European Union (EU) has ruled that some food dyes must be labeled with the relevant E number as well as this warning: "may have an adverse effect on activity and attention in children."
Comorbid disorders
Because ADHD comorbidities are diverse and the rate of comorbidity is high, special care must dedicated to certain comorbidities. The FDA is not set up to address this issue, and does not approve medications for comorbidities, nonetheless certain such topics have been extensively researched.Tic disorders
Patients with Tourette syndromeTourette syndrome
Tourette syndrome is an inherited neuropsychiatric disorder with onset in childhood, characterized by multiple physical tics and at least one vocal tic; these tics characteristically wax and wane...
who are referred to specialty clinics have a high rate of comorbid ADHD. Patients who have ADHD along with tic
Tic
A tic is a sudden, repetitive, nonrhythmic, stereotyped motor movement or vocalization involving discrete muscle groups. Tics can be invisible to the observer, such as abdominal tensing or toe crunching. Common motor and phonic tics are, respectively, eye blinking and throat clearing...
s or tic disorder
Tic disorder
Tic disorders are defined in the Diagnostic and Statistical Manual of Mental Disorders based on type and duration of tics...
s 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
Physicians' Desk Reference
The Physicians' Desk Reference is a commercially published compilation of manufacturers' prescribing information on prescription drugs, updated annually...
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
Methylphenidate
Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
(brand names Ritalin, Metadate, Concerta), dextroamphetamine
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....
(Dexedrine), and mixed amphetamine salts (Adderall
Adderall
Adderall is a brand name of amphetamine salts–based medication used for attention-deficit hyperactivity disorder and narcolepsy. It is a brand-name psychostimulant medication composed of racemic amphetamine aspartate monohydrate, racemic amphetamine sulfate, dextroamphetamine saccharide, and...
). Other medications can be used when stimulants are not an option. These include the alpha-2 agonists (clonidine
Clonidine
Clonidine is a sympatholytic medication used to treat medical conditions, such as high blood pressure, some pain conditions, ADHD and anxiety/panic disorder...
and guanfacine
Guanfacine
Guanfacine is a sympatholytic. It is an agonist of the α2A subtype of norepinephrine receptors. These receptors are concentrated heavily in the prefrontal cortex and the locus coeruleus, with the potential to improve attention abilities via modulating post-synaptic α2A receptors in the prefrontal...
), tricyclic antidepressant
Tricyclic antidepressant
Tricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...
s (desipramine
Desipramine
Desipramine is a tricyclic antidepressant . It inhibits the reuptake of norepinephrine and to a lesser extent serotonin. It is used to treat depression, but not considered a first line treatment since the introduction of SSRI antidepressants...
and nortriptyline
Nortriptyline
Nortriptyline is a second-generation tricyclic antidepressant marketed as the hydrochloride salt under the trade names Sensoval, Aventyl, Pamelor, Norpress, Allegron, Noritren and Nortrilen. It is used in the treatment of major depression and childhood nocturnal enuresis...
), and newer antidepressants (bupropion
Bupropion
Bupropion is an atypical antidepressant and smoking cessation aid. The drug is a non-tricyclic antidepressant and differs from most commonly prescribed antidepressants such as SSRIs, as its primary pharmacological action is thought to be norepinephrine-dopamine reuptake inhibition...
and venlafaxine
Venlafaxine
Venlafaxine is an antidepressant of the serotonin-norepinephrine reuptake inhibitor class. First introduced by Wyeth in 1993, now marketed by Pfizer, it is licensed for the treatment of major depressive disorder , as a treatment for generalized anxiety disorder, and comorbid indications in...
. There have been case reports of tics worsening with bupropion
Bupropion
Bupropion is an atypical antidepressant and smoking cessation aid. The drug is a non-tricyclic antidepressant and differs from most commonly prescribed antidepressants such as SSRIs, as its primary pharmacological action is thought to be norepinephrine-dopamine reuptake inhibition...
(brand name Wellbutrin). There is good empirical evidence for short-term safety and efficacy for the use of desipramine
Desipramine
Desipramine is a tricyclic antidepressant . It inhibits the reuptake of norepinephrine and to a lesser extent serotonin. It is used to treat depression, but not considered a first line treatment since the introduction of SSRI antidepressants...
, bupropion
Bupropion
Bupropion is an atypical antidepressant and smoking cessation aid. The drug is a non-tricyclic antidepressant and differs from most commonly prescribed antidepressants such as SSRIs, as its primary pharmacological action is thought to be norepinephrine-dopamine reuptake inhibition...
and atomoxetine (Strattera).