Stimulants Stimulants are the most commonly prescribed medications for ADHD. The stimulant medications indicated to treat ADHD are
methylphenidate (Ritalin, Biphentin, Concerta),
dexmethylphenidate (Focalin, Focalin XR),
Serdexmethylphenidate/dexmethylphenidate (Azstarys),
mixed amphetamine salts (Adderall, Mydayis),
dextroamphetamine (Dexedrine),
lisdexamfetamine (Vyvanse), and in rare cases
dextromethamphetamine (Desoxyn).
Controlled-release pharmaceuticals may allow once daily administration of medication in the morning. This is especially helpful for children who do not like taking their medication in the middle of the school day. Several controlled-release methods are used. Stimulants used to treat ADHD raise the extracellular concentrations of the
neurotransmitters
dopamine and
norepinephrine, which increases cellular communication between
neurons that utilize these compounds. Stimulants increase the availability of synaptic dopamine, reduce the overactivity, impulsivity, and inattention characteristics of patients with ADHD, and improve associated behaviors, including on-task behavior, academic performance, and social functioning. The therapeutic benefits are due to
noradrenergic effects at the
locus coeruleus and the
prefrontal cortex and
dopaminergic effects at the
ventral tegmental area,
nucleus accumbens, and prefrontal cortex. This elevation of catecholamines, predominantly in the prefrontal cortex, preferentially activates dopamine D1 and norepinephrine α2 receptors, both of which are crucial for mediating cognitive processes including attention, inhibitory control, and working memory. Neuroimaging studies have shown that stimulants act to modulate activity in the right inferior frontal cortex and insula—regions implicated in attention and inhibition—and regulate fronto-striato-parietal networks, which are often dysregulated in ADHD. These effects are manifested in correlated clinical improvements in attention, reduced distractibility, and decreased hyperactivity and impulsivity. Stimulant medications are considered safe when used under medical supervision. as well as social and ethical issues regarding their use and dispensation. The U.S. FDA has added
black-box warnings to some ADHD medications, warning that abuse can lead to psychotic episodes, psychological dependence, and that severe depression may occur during withdrawal from abusive use. Studies consistently show that most students report using stimulant medications, legally or illegally to improve academic performance, specifically to increase concentration, organization, and the ability to stay up longer and study. The abuse of this drug has made prescribing it much more meticulous. Stimulants are some of the most effective medications available for the treatment of ADHD. Seven different formulations of stimulants have been approved by the U.S.
Food and Drug Administration (FDA) for the treatment of ADHD: four
amphetamine-based formulations, two
methylphenidate-based formulations, and
dextromethamphetamine hydrochloride. They have not been found to improve school performance and data is lacking on long-term effectiveness and the severity of side effects. Stimulants, however, may reduce the risk of unintentional injuries in children with ADHD. This class of medicines is generally regarded as one unit; however, they affect the brain differently. Some investigations are dedicated to finding the similarities of children who respond to a specific medicine. Stimulant medication is an effective treatment for
adult attention-deficit hyperactivity disorder although the response rate may be lower for adults than children. A 2025
meta-analytic systematic review of 113 randomized controlled trials demonstrated that stimulant medications significantly improved core ADHD symptoms in adults over a three-month period, with good acceptability compared to other pharmacological and non-pharmacological treatments. Some physicians may recommend antidepressant drugs as the first line treatment instead of stimulants although antidepressants have much lower treatment
effect sizes than stimulant medication.
Amphetamine Amphetamine is a
chiral compound which is composed of two
isomers: levoamphetamine and dextroamphetamine. Levoamphetamine and dextroamphetamine have the same chemical formula but are
mirror images of each other, the same way that a person's hands are the same but are mirror images of each other. Five different amphetamine-based pharmaceuticals are currently used in ADHD treatment:
racemic amphetamine,
dextroamphetamine,
lisdexamfetamine, and two mixed
enantiomer products (
Adderall and Dyanavel XR). Some children with ADHD have been reported to respond better to medications containing levoamphetamine.
Clinical research indicates that amphetamine's treatment efficacy for ADHD may vary depending on
menstrual cycle phase, possibly due to fluctuations in
female sex hormones. In
menstruating individuals with ADHD, subjective and behavioral responses to amphetamine appear to be heightened during the
follicular phase (i.e., when
estrogen levels are higher), and reduced during the
luteal phase (i.e., when
progesterone is elevated);
Methamphetamine Methamphetamine, prescribed as its
dextrorotatory enantiomer dextromethamphetamine under the brand name Desoxyn, is a second-line psychostimulant for ADHD in the United States. The body
metabolizes methamphetamine into amphetamine (in addition to less active
metabolites). A quarter of methamphetamine will ultimately become amphetamine. After comparing only the common ground between dextroamphetamine and dextromethamphetamine, the latter is said to be the stronger stimulant.
Methylphenidate Like amphetamine,
methylphenidate (MPH) is a
chiral compound which is composed of two
isomers: d-threo-methylphenidate (also known as
dexmethylphenidate, d-methylphenidate, or d-MPH) and l-threo-methylphenidate (also known as l-methylphenidate or l-MPH). Both isomers have the same chemical formula but are
mirror images of each other, the same way that a person's hands are the same but are mirror images of each other. Unlike amphetamine, the difference in pharmacological properties between d-MPH and l-MPH is significant, as l-MPH is markedly inferior to d-MPH in its effects, which is due to a number of major differences between the isomers. The effectiveness of
methylphenidate is comparable to
atomoxetine but modestly lower than
amphetamines.
viloxazine,
guanfacine, and
clonidine are drugs approved for the treatment of ADHD that have been classified as "non-stimulant". Based on a recent systematic literature review of diverse ADHD treatment modalities, no differences were found between stimulants and non-stimulants in their effectiveness in treating ADHD symptoms in children and adolescents. ;
Atomoxetine : Atomoxetine is a
selective norepinephrine reuptake inhibitor. It has comparable efficacy, tolerability and response rate to methylphenidate in children and adolescents; efficacy and discontinuation rate is equivalent in adults. Controlled studies show increases in heart rate, decreases of body weight, decreased appetite and treatment-emergent nausea. ;
Viloxazine : Acts as a
selective norepinephrine reuptake inhibitor (NRI). However, it may also act as an
antagonist of the
serotonin 5-HT2B receptor and as an
agonist of the serotonin
5-HT2C receptors, actions which may be involved in its therapeutic effects. It was marketed for more than two decades as an
antidepressant in Europe before being repurposed as a treatment for ADHD and launched in the United States in April 2021. ;
Guanfacine : The extended release form has been approved by the FDA for the treatment of attention-deficit hyperactivity disorder (ADHD) in children as an alternative to stimulant medications. Its beneficial actions are likely due to its ability to strengthen prefrontal cortical regulation of attention and behavior. ;
Clonidine : An α2A adrenergic receptor agonist has also been approved in the US. Clonidine was initially developed as a treatment for high blood pressure. Low doses in evenings and/or afternoons are sometimes used in conjunction with stimulants to help with sleep and because clonidine sometimes helps moderate impulsive and oppositional behavior and may reduce
tics. It may be more useful for comorbid Tourette syndrome.
Other Some medications used to treat ADHD are prescribed
off-label, It inhibits the reuptake of norepinephrine, and to a lesser extent dopamine, in neuronal synapses, and has little or no effect on serotonergic reuptake. Bupropion is not a controlled substance. It is commonly prescribed as a timed release formulation to decrease the risk of side effects. ;
Modafinil : A
wakefulness-promoting agent that operates primarily as a selective, relatively weak, and atypical
dopamine reuptake inhibitor. Double-blind randomized controlled trials have demonstrated the efficacy and tolerability of modafinil in pediatric ADHD. There are risks of serious side effects such as
skin reactions, however these are rare and modafinil is not recommended for use in children. In the United States, it was originally pending marketing on-label as Sparlon, but approval was denied by the FDA due to major concerns over the occurrence of
Stevens–Johnson syndrome in clinical trials. ;
Selegiline : Selegiline acts as a
monoamine oxidase inhibitor, and increases levels of
monoamine neurotransmitters in the
brain. At doses under 20 mg/day, selegiline is a
selective and
irreversible inhibitor of
monoamine oxidase B (MAO-B), increasing levels of
dopamine in the brain. In clinical trials, Selegiline has been used in the treatment of
attention deficit hyperactivity disorder (ADHD). Selegiline may target specific symptoms of ADHD including: sustained attention, the learning of novel information, hyperactivity, and peer interactions. Selegiline has shown to be relatively effective in treating the inattention subtype of ADHD. Other medications which may be prescribed
off-label include certain
antidepressants such as
tricyclic antidepressants (TCAs),
SNRIs,
SSRIs, or
MAOIs. Canadian clinical practice guidelines only support the use of dopaminergic antipsychotics with selectivity for D2-type
dopamine receptors, particularly
risperidone, as a third-line treatment for both disorders following the failure of stimulant monotherapy and psychosocial interventions. Combined use of
D2-type receptor antagonists and ADHD stimulants for the treatment of ADHD with
comorbid behavioral disorders does not appear to have significantly worse adverse effects than ADHD stimulant or antipsychotic monotherapy. Research suggests, but has not yet confirmed, the treatment efficacy of antipsychotic and stimulant combination treatment for both disorders; Dopaminergic antipsychotics affect dopamine neurons by binding to postsynaptic
dopamine receptors, where they function as
receptor antagonists.
Increasing use Outpatient treatment rates held steady in the U.S. from the late 1990s to early 2000s. Prior to this, outpatient treatment for ADHD in the U.S. grew from 0.9 children per 100 in 1987 to 3.4 per 100 in 1997. A survey conducted by the
Centers for Disease Control and Prevention in 2011–2012 found 11% of children between the ages of 4 and 17 were reported to have ever received a health care provider diagnosis of ADHD at some point (15% of boys and 7% of girls), a 16% increase since 2007 and a 41% increase over the last decade. The CDC notes that community samples suggest the incidence of ADHD in American children is higher than the five percent stated by the
American Psychiatric Association in
DSM-5, with 8.8% of U.S. children having a current diagnosis in the 2011 survey. However, only 6.1% of children in the 2011 survey were taking ADHD medication, suggesting as many as 17.5% of children with current ADHD were not receiving treatment. The use of stimulant medication has not been approved by the FDA for children under the age of six. A growing trend is the diagnosis of younger children with ADHD. Prescriptions for children under the age of 5 rose nearly 50 percent from 2000 to 2003. Research on this issue has indicated that stimulant medication can help younger children with "severe ADHD symptoms" but typically at a lower dose than older children. It was also found that children at this age are more sensitive to side effects and should be closely monitored. while medication only treats the symptoms of the disorder. "One of the primary reasons cited for the growing use of psychotropic interventions was that many physicians realize that psychological interventions are costly and difficult to sustain."
Side effects Gastrointestinal At therapeutic doses, amphetamine and methylphenidate may cause decreased appetite and abdominal pain, as well as constipation, indigestion, and nausea. Non-stimulant medications can also produce gastrointestinal side effects; atomoxetine has been associated with nausea and abdominal discomfort, while the alpha-2 adrenoreceptor agonists guanfacine and clonidine may cause constipation and abdominal pain.
Growth delay and weight loss There is some evidence of mild reductions in growth rate with prolonged stimulant treatment in children, but no causal relationship has been established and reductions do not appear to persist long-term. Weight loss almost always corresponds with loss of appetite, which may result from the medication. Severe weight loss is very uncommon though. Loss of appetite is very temporary and typically comes back as daily effects of stimulants wear off. Nausea, dizziness, and headaches, other side effect, can also indirectly affect appetite and result in weight loss.
Cardiovascular There is concern that
stimulants and
atomoxetine, which increase the heart rate and blood pressure, might cause serious cardiovascular problems. Recent extremely large-scale studies by the FDA indicate that, in children, young adults, and adults, there is no association between serious adverse cardiovascular events (
sudden death,
myocardial infarction, and
stroke) and the medical use of amphetamine, methylphenidate, or other ADHD stimulants.
Psychiatric Many of these drugs are associated with physical and psychological dependence. Sleep problems may occur. Methylphenidate can worsen
psychosis in psychotic patients, and in very rare cases it has been associated with the emergence of new psychotic symptoms. It should be used with extreme caution in patients with
bipolar disorder due to the potential induction of
mania or
hypomania. There have been very rare reports of
suicidal ideation, but evidence does not support a link. A 2009 FDA review of 49 clinical trials found that approximately 1.5% of children in clinical trials of medications for ADHD had experienced signs or symptoms of psychosis or mania. Postmarketing reports were also analyzed, with nearly half of them involving children under the age of eleven. Approximately 90% of cases had no reported previous history of similar psychiatric events. Hallucinations involving snakes, worms or insects were the most commonly reported symptoms.
Long-term use Long-term methylphenidate or amphetamine exposure in some species is known to produce abnormal
dopamine system development or nerve damage, but humans experience normal development and nerve growth.
Magnetic resonance imaging studies suggest that long-term treatment with amphetamine or methylphenidate decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function of the right
caudate nucleus. Controlled trials spanning two years have demonstrated continuous treatment effectiveness and safety. There is some evidence that ADHD itself may protect the brain against the natural aging process later in life, perhaps by exercising the brain, and helping maintain volume. It is unknown how long term medication treatment effects the trajectory of brain volume decline in the aging ADHD brain. and
rebound of symptoms may occur when the dose wears off. Rebound effects are often the result of the stimulant dosage being too high or the individual not being able to tolerate stimulant medication. Signs that the stimulant dose is too high include irritability, feeling stimulated or blunting of affect and personality. Stimulant
withdrawal or
rebound reactions can occur and can be minimised in intensity via a gradual tapering off of medication over a period of weeks or months. A small study of abrupt withdrawal of stimulants did suggest that withdrawal reactions are not typical, and may only occur in susceptible individuals.
Cancer Concerns about
chromosomal aberrations and possible cancer later in life was raised by a small-scale study on the use of methylphenidate, though a review by the
Food and Drug Administration (FDA) found significant methodological problems with the study. A follow-up study performed with improved methodology found no evidence that methylphenidate might cause cancer, stating "the concern regarding a potential increase in the risk of developing cancer later in life after long-term MPH treatment is not supported."
History The first reported evidence of stimulant medication used to treat children with concentration and hyperactivity problems came in 1937.
Charles Bradley in
Providence, Rhode Island, reported that a group of children with behavioral problems improved after being treated with the stimulant
Benzedrine. In 1954, the stimulant
methylphenidate (Ritalin, which was first produced in 1944) became available; it remains one of the most widely prescribed medications for ADHD. Initially the drug was used to treat
narcolepsy, chronic fatigue, depression, and to counter the sedating effects of other medications. The drug began to be used for ADHD in the 1960s and steadily rose in use. In 2007,
lisdexamfetamine (Vyvanse) became the first
prodrug for ADHD to receive FDA approval. In March 2019, a
Purdue Pharma subsidiary received approval from the FDA for
Adhansia XR, a methylphenidate medication to treat ADHD. == Cost-effectiveness ==