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Research · Medication

ADHD stimulants

A network meta-analysis of 133 trials found amphetamines and methylphenidate reduced ADHD symptoms more than placebo in children and adults over about 12 weeks, with little data beyond that. In adults without ADHD, gains on memory and attention tests were small. Labels carry a boxed warning for abuse, misuse and addiction. Appetite loss, insomnia and a faster pulse were common.

Add to Bio HackChecked 2026-11-13
Status
Prescription drugs in the US and Schedule II controlled substances. Mixed amphetamine salts and methylphenidate are FDA-approved for ADHD and narcolepsy. Lisdexamfetamine is FDA-approved for ADHD and for moderate to severe binge eating disorder in adults. None is approved for weight loss or for use by people without these conditions.
Also called
mixed amphetamine salts, amphetamine, dextroamphetamine, Adderall, Adderall XR, methylphenidate, Ritalin, Concerta, lisdexamfetamine, Vyvanse, prescription stimulants, CNS stimulants, study drugs
Taken for
ADHD, attention, focus, studying, staying alert, binge eating, narcolepsy, weight loss, energy

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help8

Reported risks17

What people take it for, and what was found

Shown to help8

Strong

ADHD symptoms in children and adolescents

Shown to reduce ADHD symptoms more than placebo in children and adolescents over about 12 weeks, with moderate to large effects for amphetamines and methylphenidate.

The numbers and sources
Effect
In a network meta-analysis, clinician-rated ADHD symptoms closest to 12 weeks improved more than placebo with amphetamines (SMD -1.02, 95% CI -1.19 to -0.85) and methylphenidate (SMD -0.78, 95% CI -0.93 to -0.62). On teacher ratings, methylphenidate was better than placebo (SMD -0.82, 95% CI -1.16 to -0.48) [1]. A Cochrane review of methylphenidate found teacher-rated symptoms improved (SMD -0.74, 95% CI -0.88 to -0.61), equal to 10.58 points on a 72-point rating scale where 6.6 points is considered the smallest clinically relevant change [2]. A Cochrane review of amphetamines found improvement on parent ratings (SMD -0.57, 95% CI -0.86 to -0.27), teacher ratings (SMD -0.55, 95% CI -0.83 to -0.27) and clinician ratings (SMD -0.84, 95% CI -1.32 to -0.36), with more children rated as responders (RR 3.36, 95% CI 2.48 to 4.55) [3].
Population
10,068 children and adolescents in the efficacy analysis of 133 double-blind trials [1]; 16,302 participants aged 3 to 18 in 212 trials, mean treatment length 28.8 days [2]; 2,675 children aged 3 to 17 in 23 trials [3].
Sources
[1], [2], [3]
Caveats
Both Cochrane reviews rated the evidence low to very low certainty, and [2] judged every trial at high risk of bias once unblinding by side effects is counted. Of the methylphenidate trials, 41% had industry funding. Too few data existed for 26 or 52 weeks [1]. Methylphenidate did not change quality of life (SMD 0.40, 95% CI -0.03 to 0.83) [2].
Strong

ADHD symptoms in adults

Shown to reduce ADHD symptoms more than placebo in adults in short trials, with larger effects for amphetamines than for methylphenidate.

The numbers and sources
Effect
Clinician-rated symptoms improved more than placebo with amphetamines (SMD -0.79, 95% CI -0.99 to -0.58) and methylphenidate (SMD -0.49, 95% CI -0.64 to -0.35) [1]. A Cochrane review of amphetamines found reduced symptom severity rated by clinicians (SMD -0.90, 95% CI -1.04 to -0.75) and by patients (SMD -0.51, 95% CI -0.75 to -0.28). By drug, lisdexamfetamine (SMD -1.06, 95% CI -1.26 to -0.85) and mixed amphetamine salts (SMD -0.80, 95% CI -0.93 to -0.66) reduced symptoms, while one study of dexamphetamine found no evidence that it did (SMD -0.24, 95% CI -0.80 to 0.32) [4]. A Cochrane review of extended-release methylphenidate found a small to moderate improvement in self-rated symptoms (SMD -0.37, 95% CI -0.43 to -0.30) and investigator-rated symptoms (SMD -0.42, 95% CI -0.49 to -0.36), and no effect on days missed at work [5].
Population
8,131 adults in the efficacy analysis [1]; 2,521 adults in 19 studies with a mean length of 5.3 weeks [4]; 5,066 adults in 24 trials with a median length of 8 weeks [5].
Sources
[1], [4], [5]
Caveats
Certainty was rated low to very low in both Cochrane reviews. Amphetamines did not improve retention in treatment (RR 1.06, 95% CI 0.99 to 1.13) [4]. Trials often excluded people with depression or anxiety or enrolled only earlier responders, which may overstate benefit [5].
Moderate

Amphetamines compared with methylphenidate

Shown to reduce clinician-rated ADHD symptoms more with amphetamines than with methylphenidate in head-to-head comparisons, in children and in adults.

The numbers and sources
Effect
In head-to-head comparisons, amphetamines reduced clinician-rated symptoms more than modafinil, atomoxetine and methylphenidate, with SMDs from -0.46 to -0.24 in children and adolescents and from -0.94 to -0.29 in adults. Amphetamines were less well tolerated than placebo in children (OR 2.30, 95% CI 1.36 to 3.89) and adults (OR 3.26, 95% CI 1.54 to 6.92), and methylphenidate less well tolerated than placebo in adults only (OR 2.39, 95% CI 1.40 to 4.08). Weighing both, the authors' data favored methylphenidate in children and amphetamines in adults [1].
Population
133 double-blind trials, 81 in children and adolescents and 51 in adults [1].
Sources
[1]
Caveats
The SMD ranges cover three comparator drugs, and the abstract does not give the figure for methylphenidate alone. Confidence was low or very low for most indirect comparisons.
ModerateStudied in children

School work in children with ADHD

Shown to raise math output by 7.8% and math accuracy by 3.0% on methylphenidate in children with ADHD, gains the authors called small.

The numbers and sources
Effect
Across 34 studies, methylphenidate increased math productivity by 7.8%, math accuracy by 3.0% and reading speed (SMD 0.47), but not reading accuracy. Academic gains were small compared with symptom gains [6].
Population
Children with ADHD in 34 studies of methylphenidate [6].
Sources
[6]
Caveats
The evidence is for methylphenidate. The studies measured classroom tasks over short periods, not grades or long-term attainment.
ModerateVery common

Binge eating disorder

Shown to cut binge eating by about 1.4 to 1.7 more days a week than placebo on lisdexamfetamine in adults with moderate to severe binge eating disorder.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In two 12-week trials, lisdexamfetamine 50 or 70 mg a day reduced binge eating days per week more than placebo, by 1.35 days (95% CI 1.01 to 1.70) and 1.66 days (95% CI 1.28 to 2.04) [7]. In an earlier 11-week trial, four weeks free of binge eating was reached by 50.0% on 70 mg, 42.2% on 50 mg and 21.3% on placebo, and 30 mg did not differ from placebo [8]. Among people who had responded to open-label treatment, relapse over 6 months occurred in 3.7% who stayed on lisdexamfetamine and 32.1% switched to placebo (HR 0.09, 95% CI 0.04 to 0.23) [9].
Population
383 and 390 adults in two 12-week trials [7]; adults in an 11-week dose-ranging trial [8]; 275 responders randomized after open-label treatment, 87% women [9].
Sources
[7], [8], [9]
Caveats
The evidence is for lisdexamfetamine, the only stimulant approved for this use, and comes from manufacturer-run trials of 11 to 12 weeks plus one withdrawal trial. The withdrawal trial enrolled only people who had already responded.
Limited

Narcolepsy

One small trial found sleepiness scores improved 4.4 points on amphetamine-dextroamphetamine and 5.0 on modafinil, without showing the two were equivalent.

The numbers and sources
Effect
Methylphenidate and immediate-release mixed amphetamine salts carry narcolepsy as a labeled use [10][11]. In a 12-week blinded trial, Epworth sleepiness scores improved by 4.4 points on amphetamine-dextroamphetamine and 5.0 on modafinil. Noninferiority was not demonstrated on that primary outcome and was demonstrated on secondary measures of severity, sleepiness and sleep inertia. Dropouts for adverse events were 9.1% on amphetamine-dextroamphetamine and 31.8% on modafinil [12].
Population
44 adults with narcolepsy type 2 or idiopathic hypersomnia [12].
Sources
[10], [11], [12]
Caveats
One small trial with no placebo group, in narcolepsy type 2 and a related condition. The evidence is for amphetamine-dextroamphetamine. No recent placebo-controlled trial of a stimulant in narcolepsy was located.
Limited

Weight loss

One trial found adults with binge eating disorder lost 4.9 kg on lisdexamfetamine 50 or 70 mg over 11 weeks, against 0.1 kg on placebo.

The numbers and sources
Effect
In the 11-week binge eating trial, mean weight change was -0.1 kg on placebo, -3.1 kg on 30 mg, -4.9 kg on 50 mg and -4.9 kg on 70 mg [8]. In a 4-week ADHD trial, weight loss was reported as an adverse reaction by 10% of adults on extended-release mixed amphetamine salts and none on placebo [17]. The lisdexamfetamine label states that it is not indicated for weight loss, that other sympathomimetic drugs used for weight loss have been associated with serious cardiovascular adverse events, and that its safety and effectiveness for obesity have not been established [18].
Population
Adults with moderate to severe binge eating disorder in an 11-week trial [8]; 191 adults with ADHD on the drug and 64 on placebo [17].
Sources
[8], [17], [18]
Caveats
Weight was a secondary measure in a short trial of people with binge eating disorder, analyzed post hoc. No trial of these drugs for obesity was located. Not an approved use.
Limited

Death rates in people with ADHD

Linked to lower two-year mortality in people starting ADHD medication after diagnosis, 39.1 against 48.1 deaths per 10,000, in one Swedish cohort.

The numbers and sources
Effect
Two-year mortality was 39.1 per 10,000 in people who started ADHD medication and 48.1 per 10,000 in those who did not (HR 0.79, 95% CI 0.70 to 0.88). Deaths from unnatural causes were lower (HR 0.75, 95% CI 0.66 to 0.86), and deaths from natural causes did not differ (HR 0.86, 95% CI 0.71 to 1.05) [20].
Population
148,578 people aged 6 to 64 with newly diagnosed ADHD in Sweden, 56.7% of whom started medication [20].
Sources
[20]
Caveats
Observational, and it covers all ADHD medications, not stimulants alone. People who start medication may differ from those who do not in ways the analysis could not measure.

Mixed results1

Moderate

Focus and studying in people without ADHD

Mixed results: healthy adults showed small gains on some memory and attention tests, no effect of d-amphetamine in one meta-analysis, and lower-quality effort on a complex task.

The numbers and sources
Effect
A meta-analysis of 48 studies found small but significant effects of methylphenidate and amphetamine on inhibitory control and short-term episodic memory, and medium effects on delayed episodic memory. The authors concluded the overall effect was probably modest after accounting for publication bias [13]. A second set of meta-analyses found an overall effect of methylphenidate (SMD 0.21), driven by recall (SMD 0.43), sustained attention (SMD 0.42) and inhibitory control (SMD 0.27), and no effects for d-amphetamine [14]. In a trial using a complex optimization task, methylphenidate and dextroamphetamine lowered the value of the solutions reached against placebo. Time and steps spent rose while the quality of effort fell [15]. A systematic review of nonmedical use found little evidence that it improves academic performance in people without ADHD [16].
Population
1,409 healthy participants in 48 studies [13]; healthy adults who were not sleep deprived in 24 methylphenidate studies and 10 d-amphetamine studies [14]; adults in one placebo-controlled experiment [15]; 111 studies of nonmedical use, mostly in college students [16].
Sources
[13], [14], [15], [16]
Caveats
Laboratory tests after single doses, which the authors of [14] said do not reflect how the drugs are used. Not an approved use. See the boxed warning and the misuse block below.

Not shown to help1

Moderate

Depression that has not responded to an antidepressant

Not shown to reduce depression scores when lisdexamfetamine was added to an antidepressant in two 8-week trials of adults with an inadequate response.

The numbers and sources
Effect
In two phase 3 trials, the difference from placebo in change in Montgomery-Asberg depression scores was 0.1 points (95% CI -1.7 to 2.0) in one and -0.5 points (95% CI -2.3 to 1.3) in the other. Dry mouth was the only adverse event reported by more than 5% at twice the placebo rate in both [19].
Population
Adults aged 18 to 65 with major depressive disorder and an inadequate response to 8 weeks of an antidepressant, in two trials [19].
Sources
[19]
Caveats
The evidence is for lisdexamfetamine. The trials excluded people with other psychiatric conditions. Not an approved use.

Doses studied

The labels give these daily doses for ADHD: extended-release mixed amphetamine salts 10 mg to start in children aged 6 to 12 with a ceiling of 30 mg, 10 to 20 mg in adolescents, and 20 mg in adults [17]. Lisdexamfetamine 30 mg to start and up to 70 mg, with 50 to 70 mg as the target for binge eating disorder [18]. Extended-release methylphenidate up to 54 mg in children aged 6 to 12 and 72 mg from age 13 to 65 [21]. Immediate-release methylphenidate averages 20 to 30 mg a day in adults in two or three doses, up to 60 mg [10].

Adult amphetamine trials in the Cochrane review used dexamphetamine 10.2 to 21.8 mg a day, lisdexamfetamine 30 to 70 mg a day and mixed amphetamine salts 12.5 to 80 mg a day [4]. The binge eating trials used lisdexamfetamine 30, 50 or 70 mg a day [8][7]. The narcolepsy trial titrated amphetamine-dextroamphetamine up to 20 mg twice a day [12].

Risks

Reported risks16

ModerateVery common

Misuse and use disorder in surveys

Linked to misuse by about 5 million of the 16 million US adults who used prescription stimulants in a year, with 0.4 million meeting criteria for a use disorder.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In a national survey, 6.6% of US adults used prescription stimulants in the past year: 4.5% used without misuse, 1.9% misused without a use disorder and 0.2% had a use disorder. That equals about 16.0 million users, 5.0 million who misused and 0.4 million with a use disorder. The most common reason for misuse was to stay alert or concentrate (56.3%), and the most common source was a friend or relative at no cost (56.9%) [22]. A systematic review of 111 studies found self-reported rates of nonmedical use from 2.1% to 58.7% across population samples. Most nonmedical use had no or minor medical effects, while adverse outcomes including death occurred in some people, particularly with non-oral routes [16].
Population
US adults in a national household survey [22]; 111 studies, most in college students [16].
Sources
[22], [16]
Caveats
Misuse in the survey includes taking pills prescribed to someone else, so the band above is misuse among everyone who used a stimulant, not among people prescribed one. Definitions of nonmedical use varied widely across studies [16].
StrongVery common

Loss of appetite and weight loss

Shown to cause loss of appetite in 22% to 36% on extended-release mixed amphetamine salts against 2% to 3% on placebo, across children, adolescents and adults.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
On extended-release mixed amphetamine salts, loss of appetite was reported by 22% of children against 2% on placebo, 36% of adolescents against 2% and 33% of adults against 3%. Weight loss was reported by 4%, 9% and 10% against 0 on placebo in each group [17]. On extended-release methylphenidate in adults, decreased appetite was reported by 25% against 7% [21]. In children, amphetamines raised the rate of decreased appetite (RR 6.31, 95% CI 2.58 to 15.46) [3].
Population
374 children, 233 adolescents and 191 adults on the drug in placebo-controlled trials of 3 to 4 weeks [17]; 415 adults on methylphenidate and 212 on placebo in two trials [21]; 2,467 children and adolescents in 11 studies [3].
Sources
[17], [21], [3]
Caveats
Short trials. The label describes appetite loss as dose-related in adolescents [17].
StrongVery common

Trouble sleeping

Shown to cause insomnia in 12% to 27% on extended-release mixed amphetamine salts against 2% to 13% on placebo, and in 12% against 6% on methylphenidate.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
On extended-release mixed amphetamine salts, insomnia was reported by 17% of children against 2% on placebo, 12% of adolescents against 4% and 27% of adults against 13% [17]. On extended-release methylphenidate in adults it was 12% against 6% [21], and on lisdexamfetamine in adults with binge eating disorder 20% against 8% [18]. In children, amphetamines raised the rate of insomnia (RR 3.80, 95% CI 2.12 to 6.83) [3].
Population
374 children, 233 adolescents and 191 adults [17]; 415 adults [21]; 373 adults on lisdexamfetamine and 372 on placebo [18]; 2,429 children and adolescents in 10 studies [3].
Sources
[17], [21], [18], [3]
Caveats
Short trials of 3 to 12 weeks.
StrongVery common

Dry mouth, headache, stomach ache and anxiety

Shown to cause dry mouth in 35% of adults against 5% on placebo, with headache, stomach ache, nausea and anxiety also more frequent than placebo.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In adults on extended-release mixed amphetamine salts: dry mouth 35% vs 5% on placebo, headache 26% vs 13%, nausea 8% vs 3%, anxiety 8% vs 5% and dizziness 7% vs 0. In children: abdominal pain 14% vs 10%, emotional lability 9% vs 2% and vomiting 7% vs 4%. In the adult trial, 12.0% on the drug and 1.6% on placebo stopped because of adverse events [17]. In adults on extended-release methylphenidate: headache 22% vs 16%, dry mouth 14% vs 4%, nausea 13% vs 3% and anxiety 8% vs 2% [21]. On lisdexamfetamine in binge eating disorder, dry mouth was 36% vs 7% and feeling jittery 6% vs 1% [18]. Pooled across trials, any adverse event was more frequent on methylphenidate than placebo in children (RR 1.23, 95% CI 1.11 to 1.37) and adults (RR 1.27, 95% CI 1.19 to 1.37), and adults on amphetamines withdrew for adverse events more often (RR 2.69, 95% CI 1.63 to 4.45) [2][5][4].
Population
Children, adolescents and adults in label trials [17][21][18]; 5,342 children in 35 trials [2]; 4,214 adults in 14 trials [5]; 2,409 adults in 17 studies [4].
Sources
[17], [21], [18], [2], [5], [4]
Caveats
Serious adverse events did not differ from placebo in the pooled methylphenidate trials in children (RR 0.80, 95% CI 0.39 to 1.67) or adults (RR 1.43, 95% CI 0.85 to 2.43), with very low certainty [2][5].
StrongCommon

Raised blood pressure and heart rate

Shown to raise blood pressure by about 2 to 4 mm Hg and heart rate by about 3 to 6 beats a minute on average.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
The labels state that stimulants raise blood pressure by a mean of about 2 to 4 mm Hg and heart rate by about 3 to 6 beats a minute, and that some people have larger increases [17][18]. In a network meta-analysis of short trials, methylphenidate raised systolic pressure against placebo by 1.81 mm Hg in children and adolescents (95% CI 1.05 to 2.57) and 1.66 mm Hg in adults (95% CI 0.38 to 2.93), amphetamines raised it by 2.3 mm Hg in adults (95% CI 0.66 to 3.94), and methylphenidate raised adult pulse by 4.37 beats a minute (95% CI 3.16 to 5.59) [23]. In the binge eating trials, pulse rose 4.41 to 6.31 beats a minute on lisdexamfetamine [7]. Tachycardia was reported by 6% of adults on extended-release mixed amphetamine salts against 3% on placebo, by 5% against 0 on extended-release methylphenidate, and increased heart rate by 7% against 1% on lisdexamfetamine [17][21][18]. In a case-control study, 3 to 5 years of cumulative ADHD medication use was associated with hypertension (adjusted OR 1.72, 95% CI 1.51 to 1.97) [24].
Population
13,315 children and adolescents and 9,387 adults in 102 trials with a median follow-up of 7 weeks [23]; adults in label trials [17][21][18]; 278,027 people with ADHD aged 6 to 64 in Sweden [24].
Sources
[17], [18], [23], [7], [21], [24]
Caveats
The band above is the rate of reported tachycardia, since the average rises apply to everyone treated. Confidence in the adult estimates was rated very low [23]. Isolated blood pressure elevations in a 4-week adolescent trial were no more frequent on the drug than on placebo [17]. The hypertension finding is observational [24].
ModerateStudied in pregnancyCommon

Pregnancy

Linked to a small rise in heart malformations with methylphenidate in early pregnancy, 18.8 against 12.7 per 1,000 infants, and no rise with amphetamines.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In US data, cardiac malformations occurred in 18.8 per 1,000 infants exposed to methylphenidate, 15.4 per 1,000 exposed to amphetamines and 12.7 per 1,000 unexposed. After adjustment, the relative risk of cardiac malformations was 1.28 for methylphenidate (95% CI 0.94 to 1.74), and 1.28 (95% CI 1.00 to 1.64) when pooled with Nordic data. For amphetamines it was 0.96 (95% CI 0.78 to 1.19). Any malformation did not differ significantly for either drug [31]. The amphetamine label states that published studies have not identified a drug-associated risk of major birth defects or miscarriage, and that premature delivery and low birth weight have been seen in infants of mothers taking amphetamines [17]. The methylphenidate label describes the published findings as inconsistent [21].
Population
1,813,894 pregnancies in the US and 2,560,069 in the Nordic countries [31].
Sources
[31], [17], [21]
Caveats
Observational. The pooled confidence interval for methylphenidate reaches 1.00, and the unadjusted rates above differ more than the adjusted risks do.
ModerateUncommon

Psychosis and mania

Shown to cause psychotic or manic symptoms in about 0.1% against 0 on placebo in pooled short trials, with new psychosis more frequent on amphetamine than methylphenidate.

The numbers and sources
How common
Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect
The label reports that in a pooled analysis of short-term placebo-controlled trials, psychotic or manic symptoms such as hallucinations, delusional thinking or mania occurred in about 0.1% of people on stimulants and 0 on placebo, including people with no history of psychotic illness [17]. Among adolescents and young adults starting a stimulant for ADHD, new psychosis occurred in 0.21% on amphetamine and 0.10% on methylphenidate (HR 1.65, 95% CI 1.31 to 2.09), about 1 in 660 overall [28].
Population
Pooled short-term trials summarized in labeling [17]; 221,846 matched adolescents and young adults with 143,286 person-years of follow-up [28].
Sources
[17], [28]
Caveats
The cohort compared two stimulants with each other, not with no treatment [28]. The label also warns that stimulants may worsen an existing psychotic disorder or bring on a manic episode in people with bipolar disorder [17].
LimitedHow often is not known

FDA boxed warning: abuse, misuse and addiction

FDA states prescription stimulants have a high potential for abuse and misuse, which can lead to a substance use disorder including addiction, and to overdose and death.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The amphetamine, lisdexamfetamine and methylphenidate labels carry this boxed warning. It states that misuse and abuse of central nervous system stimulants can result in overdose and death, and that the risk rises with higher doses and with unapproved methods of administration such as snorting or injection. The labels state that the drugs can be diverted for non-medical use, and all are Schedule II controlled substances [17][18][21][10].
Population
Labeling statement for the class [17].
Sources
[17], [18], [21], [10]
Caveats
The label gives no rate. Survey figures are in the next block.
LimitedHow often is not known

Withdrawal and dependence

The label states stimulants may produce physical dependence and tolerance, with low mood, fatigue, vivid dreams, sleep changes and increased appetite after abrupt stopping. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label states that withdrawal signs after abrupt stopping or dose reduction following prolonged use include dysphoric mood, depression, fatigue, vivid and unpleasant dreams, insomnia or hypersomnia, increased appetite, and psychomotor slowing or agitation. It also states the drug may produce tolerance [17].
Population
Labeling statement for central nervous system stimulants [17].
Sources
[17]
Caveats
No rate and no trial of stopping after prescribed use is given in the label.
ModerateHow often is not known

Slower growth in children

Shown to slow growth in children, with about 2 cm less height and 2.7 kg less weight over 3 years of daily methylphenidate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The methylphenidate label reports that children aged 7 to 13 treated 7 days a week for 14 to 36 months grew on average about 2 cm less in height and 2.7 kg less in weight over 3 years, with no growth rebound during that period [21]. In the long-term follow-up of that trial, people with consistent or inconsistent stimulant use through childhood were 2.55 cm shorter as adults than those with negligible use [29]. In a 4-week trial in adolescents, mean weight change was -1.1 lb on 10 mg and -2.8 lb on 20 mg of extended-release mixed amphetamine salts [17].
Population
Children aged 7 to 13 followed for up to 3 years [21]; the same trial's participants followed to about age 25, with 289 classmates as a comparison group [29]; adolescents in a 4-week trial [17].
Sources
[21], [29], [17]
Caveats
The sources report average differences, not the share of children affected. The adult height comparison is between self-selected patterns of use, not randomized groups [29].
LimitedHow often is not known

Serotonin syndrome

The label warns that serotonin syndrome may occur when amphetamines are taken with other drugs acting on serotonin. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The amphetamine label names MAOIs, SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone and St. John's wort, and states that drugs blocking the liver enzyme CYP2D6 may raise amphetamine exposure and add to the risk [17]. The lisdexamfetamine label carries the same warning [18]. The methylphenidate label lists serotonin syndrome in combination with serotonergic drugs among postmarketing reports [21].
Population
Labeling statements [17][18][21].
Sources
[17], [18], [21]
Caveats
A label warning with no denominator.
LimitedHow often is not known

Use with MAOIs

The label lists MAOIs as a contraindication because the combination can cause a hypertensive crisis. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The amphetamine and methylphenidate labels state that taking a stimulant with a monoamine oxidase inhibitor, or within 14 days of stopping one, can cause hypertensive crisis, with possible outcomes including death, stroke, heart attack and aortic dissection. The amphetamine label counts the antibiotic linezolid and intravenous methylene blue among MAOIs [17][21].
Population
Labeling statements [17][21].
Sources
[17], [21]
Caveats
The labels give no rate or case counts.
LimitedHow often is not known

Other drug interactions

The label states that alkalinizing agents raise amphetamine blood levels, acidifying agents lower them, and tricyclic antidepressants can strengthen cardiovascular effects. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The amphetamine label states that gastrointestinal or urinary alkalinizing agents increase blood levels and potentiate the action of amphetamine, acidifying agents lower blood levels, CYP2D6 inhibitors may increase exposure, tricyclic antidepressants may potentiate cardiovascular effects, and proton pump inhibitors shorten the time to peak level [17]. The methylphenidate label lists blood pressure drugs as an interaction that calls for closer blood pressure monitoring and dose adjustment of the blood pressure drug, and states that the risk of movement side effects from risperidone may rise when either dose is changed [21].
Population
Labeling statements [17][21].
Sources
[17], [21]
Caveats
Changes in drug levels or effects, with no rate of harm.
LimitedHow often is not known

Cold, numb or discolored fingers and toes

The label warns stimulants are associated with peripheral vasculopathy, including Raynaud's phenomenon, usually intermittent and mild, with rare skin ulceration. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The labels state that effects were seen in postmarketing reports at therapeutic doses in all age groups and throughout treatment, that after-effects have included ulceration of the fingers or toes and soft tissue breakdown, and that signs generally improved after the dose was lowered or the drug stopped [17][21].
Population
Postmarketing reports summarized in labeling [17][21].
Sources
[17], [21]
Caveats
Reports with no denominator.
LimitedHow often is not known

Priapism with methylphenidate

The label warns of prolonged and painful erections, sometimes needing surgery, in men and boys taking methylphenidate. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The methylphenidate label states that priapism was not reported at the start of treatment but after some time, often following a dose increase, and also during drug holidays or after stopping [21].
Population
Reports in adult and pediatric male patients summarized in labeling [21].
Sources
[21]
Caveats
The evidence is for methylphenidate. Reports with no denominator.
LimitedHow often is not known

Seizures

The label states there is some clinical evidence that stimulants may lower the seizure threshold, mainly in people with earlier seizures or EEG abnormalities. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The amphetamine label states that stimulants may lower the convulsive threshold in people with a history of seizures, in people with earlier EEG abnormalities, and very rarely in people with neither [17]. The methylphenidate label lists convulsions among postmarketing reports [21].
Population
Labeling statements [17][21].
Sources
[17], [21]
Caveats
No rate or trial data are given.

Mixed results1

ModerateUncommon

Heart attack, stroke and sudden death

Mixed results: two large cohorts and a meta-analysis found no significant rise in serious cardiovascular events, while one study linked longer use to more cardiovascular disease.

The numbers and sources
How common
Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect
The labels state that sudden death has been reported in people with structural heart abnormalities or other serious heart disease treated with stimulants at ADHD doses [17]. In children and young adults, current users of ADHD drugs had no increase in serious cardiovascular events (adjusted HR 0.75, 95% CI 0.31 to 1.85), against a cohort rate of 3.1 per 100,000 person-years [25]. In adults aged 25 to 64, current users had 1.34 heart attacks, 0.30 sudden cardiac deaths and 0.56 strokes per 1,000 person-years, with no increase against non-use (adjusted RR 0.83, 95% CI 0.72 to 0.96) or against past use (RR 1.03, 95% CI 0.86 to 1.24) [26]. A meta-analysis of 19 observational studies found no significant association with cardiovascular disease in children and adolescents (RR 1.18, 95% CI 0.91 to 1.53), young or middle-aged adults (RR 1.04, 95% CI 0.43 to 2.48) or older adults (RR 1.59, 95% CI 0.62 to 4.05) [27]. In a later case-control study, each added year of ADHD medication use was associated with 4% higher odds of cardiovascular disease (adjusted OR 1.04, 95% CI 1.03 to 1.05), mainly hypertension and arterial disease [24].
Population
Children and young adults in a US cohort with 81 events [25]; adults with 806,182 person-years of follow-up [26]; 3,931,532 participants in 19 studies [27]; 10,388 people with ADHD and cardiovascular disease and 51,672 matched controls [24].
Sources
[17], [25], [26], [27], [24]
Caveats
Observational. The authors of [26] attributed the apparent protective association to healthy-user bias, and [25] could not rule out a doubling of risk. Heterogeneity was high in the meta-analysis [27]. The band above is the event rate in adult current users, which did not exceed the rate in non-users.

Checked, no increase found1

ModerateStudied in children

Tics

Not shown to raise the rate of new or worsening tics in children with ADHD: 5.7% on stimulants against 6.5% on placebo across 22 trials.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
New or worsening tics were reported by 5.7% on stimulants (95% CI 3.7 to 8.6) and 6.5% on placebo (95% CI 4.4 to 9.5), a risk ratio of 0.99 (95% CI 0.78 to 1.27). Type of stimulant, dose, treatment length and age did not change the result [30].
Population
2,385 children with ADHD in 22 placebo-controlled trials [30].
Sources
[30]
Caveats
The amphetamine label still carries a warning on motor and verbal tics and worsening of Tourette's syndrome [17].

Claims tested and not found

  1. That stimulants make healthy people better at complex problem solving. In a trial using an optimization task, methylphenidate and dextroamphetamine lowered the value of the solutions people reached against placebo, while time and steps spent went up [15]. A meta-analysis found no cognitive effects of d-amphetamine in healthy adults [14].
  2. That taking a friend's stimulant improves grades. A systematic review of 111 studies found little evidence that nonmedical use improves academic performance in people without ADHD [16].
  3. That stimulants cause tics. Across 22 placebo-controlled trials in children with ADHD, new or worsening tics occurred in 5.7% on stimulants and 6.5% on placebo [30].
  4. That ADHD drugs raise the rate of heart attack, stroke or sudden death in young people. In children and young adults, current use was not associated with serious cardiovascular events (adjusted HR 0.75, 95% CI 0.31 to 1.85) [25], nor was it in adults aged 25 to 64 [26].
  5. That lisdexamfetamine lifts depression that an antidepressant has not. In two phase 3 trials, change in depression scores did not differ from placebo [19].
  6. That medication through childhood lowers ADHD symptoms in adulthood. In the long-term follow-up of a large treatment trial, symptom severity at about age 25 did not differ between people with consistent, inconsistent or negligible stimulant use [29].

Sources

  1. Cortese S, Adamo N, Del Giovane C, et al. Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. The Lancet Psychiatry. 2018. https://doi.org/10.1016/S2215-0366(18)30269-4
  2. Storebø OJ, Storm MRO, Pereira Ribeiro J, et al. Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD). Cochrane Database of Systematic Reviews. 2025. https://doi.org/10.1002/14651858.CD009885.pub4
  3. Punja S, Shamseer L, Hartling L, et al. Amphetamines for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database of Systematic Reviews. 2016. https://doi.org/10.1002/14651858.CD009996.pub2
  4. Castells X, Blanco-Silvente L, Cunill R. Amphetamines for attention deficit hyperactivity disorder (ADHD) in adults. Cochrane Database of Systematic Reviews. 2018. https://doi.org/10.1002/14651858.CD007813.pub3
  5. Boesen K, Paludan-Müller AS, Gøtzsche PC, Jørgensen KJ. Extended-release methylphenidate for attention deficit hyperactivity disorder (ADHD) in adults. Cochrane Database of Systematic Reviews. 2022. https://doi.org/10.1002/14651858.CD012857.pub2
  6. Kortekaas-Rijlaarsdam AF, Luman M, Sonuga-Barke E, Oosterlaan J. Does methylphenidate improve academic performance? A systematic review and meta-analysis. European Child & Adolescent Psychiatry. 2019. https://doi.org/10.1007/s00787-018-1106-3
  7. McElroy SL, Hudson J, Ferreira-Cornwell MC, et al. Lisdexamfetamine Dimesylate for Adults with Moderate to Severe Binge Eating Disorder: Results of Two Pivotal Phase 3 Randomized Controlled Trials. Neuropsychopharmacology. 2016. https://doi.org/10.1038/npp.2015.275
  8. McElroy SL, Hudson JI, Mitchell JE, et al. Efficacy and safety of lisdexamfetamine for treatment of adults with moderate to severe binge-eating disorder: a randomized clinical trial. JAMA Psychiatry. 2015. https://doi.org/10.1001/jamapsychiatry.2014.2162
  9. Hudson JI, McElroy SL, Ferreira-Cornwell MC, et al. Efficacy of Lisdexamfetamine in Adults With Moderate to Severe Binge-Eating Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2017. https://doi.org/10.1001/jamapsychiatry.2017.1889
  10. U.S. Food and Drug Administration. Ritalin (methylphenidate hydrochloride) tablets, prescribing information (Sandoz). 2025. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d6fb2750-cdab-4749-ba0d-7534840a5892
  11. U.S. Food and Drug Administration. Adderall (mixed salts of a single entity amphetamine product) tablets, prescribing information (Teva Pharmaceuticals USA). 2024. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f22635fe-821d-4cde-aa12-419f8b53db81
  12. Trotti LM, Blake T, Hoque R, et al. Modafinil Versus Amphetamine-Dextroamphetamine For Idiopathic Hypersomnia and Narcolepsy Type 2: A Randomized, Blinded, Non-inferiority Trial. CNS Drugs. 2024. https://doi.org/10.1007/s40263-024-01122-y
  13. Ilieva IP, Hook CJ, Farah MJ. Prescription Stimulants' Effects on Healthy Inhibitory Control, Working Memory, and Episodic Memory: A Meta-analysis. Journal of Cognitive Neuroscience. 2015. https://doi.org/10.1162/jocn_a_00776
  14. Roberts CA, Jones A, Sumnall H, et al. How effective are pharmaceuticals for cognitive enhancement in healthy adults? A series of meta-analyses of cognitive performance during acute administration of modafinil, methylphenidate and D-amphetamine. European Neuropsychopharmacology. 2020. https://doi.org/10.1016/j.euroneuro.2020.07.002
  15. Bowman E, Coghill D, Murawski C, Bossaerts P. Not so smart? "Smart" drugs increase the level but decrease the quality of cognitive effort. Science Advances. 2023. https://doi.org/10.1126/sciadv.add4165
  16. Faraone SV, Rostain AL, Montano CB, et al. Systematic Review: Nonmedical Use of Prescription Stimulants: Risk Factors, Outcomes, and Risk Reduction Strategies. Journal of the American Academy of Child & Adolescent Psychiatry. 2020. https://doi.org/10.1016/j.jaac.2019.06.012
  17. U.S. Food and Drug Administration. Adderall XR (mixed salts of a single entity amphetamine product) extended-release capsules, prescribing information (Takeda Pharmaceuticals America). 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aff45863-ffe1-4d4f-8acf-c7081512a6c0
  18. U.S. Food and Drug Administration. Vyvanse (lisdexamfetamine dimesylate) capsules and chewable tablets, prescribing information (Takeda Pharmaceuticals America). 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=704e4378-ca83-445c-8b45-3cfa51c1ecad
  19. Richards C, McIntyre RS, Weisler R, et al. Lisdexamfetamine dimesylate augmentation for adults with major depressive disorder and inadequate response to antidepressant monotherapy: Results from 2 phase 3, multicenter, randomized, double-blind, placebo-controlled studies. Journal of Affective Disorders. 2016. https://doi.org/10.1016/j.jad.2016.07.006
  20. Li L, Zhu N, Zhang L, et al. ADHD Pharmacotherapy and Mortality in Individuals With ADHD. JAMA. 2024. https://doi.org/10.1001/jama.2024.0851
  21. U.S. Food and Drug Administration. Concerta (methylphenidate hydrochloride) extended-release tablets, prescribing information (Janssen Pharmaceuticals). 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1a88218c-5b18-4220-8f56-526de1a276cd
  22. Compton WM, Han B, Blanco C, et al. Prevalence and Correlates of Prescription Stimulant Use, Misuse, Use Disorders, and Motivations for Misuse Among Adults in the United States. American Journal of Psychiatry. 2018. https://doi.org/10.1176/appi.ajp.2018.17091048
  23. Farhat LC, Lannes A, Del Giovane C, et al. Comparative cardiovascular safety of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. The Lancet Psychiatry. 2025. https://doi.org/10.1016/S2215-0366(25)00062-8
  24. Zhang L, Li L, Andell P, et al. Attention-Deficit/Hyperactivity Disorder Medications and Long-Term Risk of Cardiovascular Diseases. JAMA Psychiatry. 2024. https://doi.org/10.1001/jamapsychiatry.2023.4294
  25. Cooper WO, Habel LA, Sox CM, et al. ADHD drugs and serious cardiovascular events in children and young adults. New England Journal of Medicine. 2011. https://doi.org/10.1056/NEJMoa1110212
  26. Habel LA, Cooper WO, Sox CM, et al. ADHD medications and risk of serious cardiovascular events in young and middle-aged adults. JAMA. 2011. https://doi.org/10.1001/jama.2011.1830
  27. Zhang L, Yao H, Li L, et al. Risk of Cardiovascular Diseases Associated With Medications Used in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-analysis. JAMA Network Open. 2022. https://doi.org/10.1001/jamanetworkopen.2022.43597
  28. Moran LV, Ongur D, Hsu J, et al. Psychosis with Methylphenidate or Amphetamine in Patients with ADHD. New England Journal of Medicine. 2019. https://doi.org/10.1056/NEJMoa1813751
  29. Swanson JM, Arnold LE, Molina BSG, et al. Young adult outcomes in the follow-up of the multimodal treatment study of attention-deficit/hyperactivity disorder: symptom persistence, source discrepancy, and height suppression. Journal of Child Psychology and Psychiatry. 2017. https://doi.org/10.1111/jcpp.12684
  30. Cohen SC, Mulqueen JM, Ferracioli-Oda E, et al. Meta-Analysis: Risk of Tics Associated With Psychostimulant Use in Randomized, Placebo-Controlled Trials. Journal of the American Academy of Child & Adolescent Psychiatry. 2015. https://doi.org/10.1016/j.jaac.2015.06.011
  31. Huybrechts KF, Bröms G, Christensen LB, et al. Association Between Methylphenidate and Amphetamine Use in Pregnancy and Risk of Congenital Malformations: A Cohort Study From the International Pregnancy Safety Study Consortium. JAMA Psychiatry. 2018. https://doi.org/10.1001/jamapsychiatry.2017.3644

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