Dextroamphetamine

What it is

Dextroamphetamine is the dextro (right-handed) enantiomer of amphetamine, supplied as dextroamphetamine sulfate tablets and as other formulations including an extended-release capsule and a transdermal patch. The FDA label classes amphetamines as non-catecholamine sympathomimetic amines with central nervous system stimulant activity, and records peripheral effects on blood pressure and the airways. It is a controlled substance that the label states has a high potential for abuse and misuse. The same molecule is one of the four salts in mixed amphetamine salts products.

What the research says

The evidence for dextroamphetamine and the wider amphetamine class is strongest, and almost entirely confined to, short-term reduction in rating-scale symptoms of ADHD: a 133-trial network meta-analysis found amphetamines reduced clinician-rated core symptoms in children (SMD -1.02) and adults (SMD -0.79) at around 12 weeks, while a Cochrane review of 23 paediatric trials rated most of those outcomes low to very low quality and judged most trials to be at high risk of bias. The same reviews found amphetamines less well tolerated than placebo. Evidence about what happens over years rather than weeks is thin: in the MTA follow-up, extended stimulant use was associated with about 2.5 cm less adult height but not with lower symptom severity, and a 2024 Swedish case-control study found longer cumulative use associated with more cardiovascular disease, mainly hypertension. The drug carries an FDA boxed warning about abuse, misuse and addiction, and the label describes physical dependence with a withdrawal syndrome.

Evidence grade: Limited evidence.

How it works

Drug class: Central nervous system stimulant; non-catecholamine sympathomimetic amine (amphetamine class), Schedule II controlled substance

Dextroamphetamine is the right-handed (dextro) form of amphetamine. It is a sympathomimetic amine that stimulates the central nervous system and also acts outside the brain, raising blood pressure and acting weakly on the airways. The FDA label is explicit that how it produces its mental and behavioural effects in children is not established. (Source 1)

Boxed warning

Dextroamphetamine sulfate has a high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Misuse and abuse of CNS stimulants, including dextroamphetamine sulfate, can result in overdose and death (see OVERDOSAGE), and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.

(Source 2)

What it is used for

• Short-term reduction in rating-scale symptoms is reproduced across 23 randomised trials and a 133-trial network, with large effect sizes on clinician ratings. Cochrane rated most of those outcomes low to very low quality because most trials were at high risk of bias, nearly all ran under six months, and the drug was less well tolerated than placebo. Evidence: limited. (Source 3)
• The dextroamphetamine sulfate tablet label limits its ADHD indication to pediatric patients aged 3 to 16, so adult use of this product for ADHD is off-label even though adults are widely prescribed amphetamines. The current Cochrane review (2018, 19 studies, 2,521 participants, mean study length 5.3 weeks) finds short-term symptom reduction on clinician ratings (SMD -0.90) with no improvement in retention and 2.7 times the dropout for adverse events, and rates the evidence overall as low or very low quality with no included study at low overall risk of bias. Sixteen of the nineteen studies were industry-funded. Evidence: limited. (Source 4)
• Narcolepsy is an approved indication and the American Academy of Sleep Medicine suggests dextroamphetamine for narcolepsy in adults, but only as a conditional recommendation, while modafinil, pitolisant, sodium oxybate and solriamfetol carry strong recommendations. We found no modern randomised comparison of dextroamphetamine against those drugs. The same guideline's only paediatric narcolepsy recommendations, modafinil and sodium oxybate, are both conditional and neither names dextroamphetamine. Evidence: limited. (Source 4)
• This is the use that drives most non-medical stimulant taking and it is not an approved use. A meta-analysis in healthy adults found a small improvement in processing-speed accuracy (g = 0.282) and no detectable change in planning, decision-making or cognitive perseveration, with the authors noting few studies for those outcomes. Evidence: limited. (Source 5)

Interactions

• Monoamine oxidase inhibitors (including the MAOI antidepressants and a metabolite of furazolidone) (label): Monoamine oxidase inhibitors slow the breakdown of amphetamine, so its effect on noradrenaline release is amplified. The label describes headaches and other signs of hypertensive crisis, neurological toxicity and malignant hyperpyrexia, sometimes fatal. (Source 6)
• Ascorbic acid (vitamin C) supplements and other gastrointestinal acidifying agents (label): Acidifying the gut lowers how much amphetamine is absorbed, and acidifying the urine increases how much is excreted. The label says both effects lower blood levels and efficacy. Vitamin C is named in the label's own list. (Source 7)
• Fruit juices (label): Fruit juices appear in the label's list of gastrointestinal acidifying agents that lower amphetamine absorption; the label states that agents in this group lower blood levels and efficacy of amphetamines. No pharmacokinetic study is cited for the juice effect specifically. (Source 7)
• Sodium bicarbonate and other alkalinizing agents (including acetazolamide and some thiazides) (label): Alkalinizing the gut increases how much amphetamine is absorbed and alkalinizing the urine reduces how much is excreted, so blood levels rise and the drug's actions are potentiated. Sodium bicarbonate is sold as an over-the-counter antacid and supplement. (Source 8)
• Monoamine oxidase inhibitors, during or within 14 days of stopping them (label): The label makes amphetamine use during, or within 14 days after, a monoamine oxidase inhibitor an outright contraindication, because a hypertensive crisis may result. This is stated in the label’s Contraindications section rather than in its interactions text. (Source 9)

Stopping it

• The label states that dextroamphetamine may produce physical dependence, defined as physiological adaptation showing itself as withdrawal signs and symptoms after abrupt stopping or a significant dose reduction. (Source 10)
• The label also states the drug may produce tolerance, so a dose that once worked can stop working. (Source 11)
• For ADHD, the label itself asks prescribers to interrupt the drug from time to time to see whether symptoms come back enough to need continued treatment. (Source 12)
• The literature on managing amphetamine-type withdrawal is weak. A systematic review of methamphetamine withdrawal, the amphetamine-type stimulant with the largest withdrawal literature, reported symptoms of depression, agitation, cognitive impairment and fatigue lasting days to months, and found no medication standing out. (Source 13)
• In the MTA follow-up, the group that stayed on stimulants consistently was shorter in adulthood than the group that used them inconsistently, which is the only long-term signal we found that bears on continuing versus stopping; it is observational and cannot establish cause. (Source 14)

What goes wrong

Amphetamines were less well tolerated than placebo in both children and adults, measured as dropping out because of side-effects. (Source 3)

• Meta-analysis, Moderate certainty.
• Size: tolerability analysis based on 11 018 children and adolescents and 5362 adults.
• Who: children, adolescents and adults with ADHD.
• How long: timepoints closest to 12 weeks.
• Result: amphetamines vs placebo for dropout due to side-effects: children and adolescents OR 2.30, 95% CI 1.36-3.89; adults OR 3.26, 1.54-6.92.
• Funding: Stichting Eunethydis and the UK NIHR Oxford Health Biomedical Research Centre.

With respect to tolerability, amphetamines were inferior to placebo in both children and adolescents (odds ratio [OR] 2·30, 95% CI 1·36-3·89) and adults (3·26, 1·54-6·92); guanfacine was inferior to placebo in children and adolescents only (2·64, 1·20-5·81); and atomoxetine (2·33, 1·28-4·25), methylphenidate (2·39, 1·40-4·08), and modafinil (4·01, 1·42-11·33) were less well tolerated than placebo in adults only.

The same Cochrane review found amphetamines caused appetite loss, insomnia and abdominal pain more often than placebo, and more children had at least one adverse event. (Source 15)

• Systematic review, Low certainty.
• Size: up to 2467 children/adolescents across 11 trials for the commonest event.
• Who: children and adolescents under 18 with ADHD.
• How long: 14 days to 365 days.
• Result: decreased appetite RR 6.31 (95% CI 2.58 to 15.46, 11 studies); insomnia RR 3.80 (2.12 to 6.83, 10 studies); abdominal pain RR 1.44 (1.03 to 2.00, 10 studies); at least one adverse event RR 1.30 (1.18 to 1.44, 6 studies, low quality evidence)
• Funding: not stated for the review.

The most commonly reported adverse events included decreased appetite, insomnia/trouble sleeping, abdominal pain, nausea/vomiting, headaches, and anxiety. Amphetamines were associated with a higher proportion of participants experiencing decreased appetite (RR 6.31; 95% CI 2.58 to 15.46; 11 studies; 2467 children/adolescents), insomnia (RR 3.80; 95% CI 2.12 to 6.83; 10 studies; 2429 children/adolescents), and abdominal pain (RR 1.44; 95% CI 1.03 to 2.00; 10 studies; 2155 children/adolescents). In addition, the proportion of children who experienced at least one adverse event was higher in the amphetamine group (RR 1.30; 95% CI 1.18 to 1.44; 6 studies; 1742 children/adolescents; low quality evidence).

In the long-term follow-up of the MTA cohort, children who stayed on stimulants were shorter as adults than those who did not, and extended use was not associated with lower symptom severity. (Source 14)

• Cohort study, Low certainty.
• Size: 515 cases from the original 579 randomised children, plus 289 classmates as a local normative comparison group.
• Who: children diagnosed with ADHD-combined type at ages 7-10, followed to about age 25.
• How long: assessments 2-16 years after baseline.
• Result: ADHD group 1.29 +/- 0.55 cm shorter than comparison group (p < .01, d = .21); Consistent or Inconsistent medication subgroup 2.55 +/- 0.73 cm shorter than Negligible subgroup (p < .0005, d = .42); Consistent 2.36 +/- 1.13 cm shorter than Inconsistent (p < .04, d = .38); naturalistic subgroup comparisons for symptom severity were not significant.
• Funding: not stated in the abstract.

Limit of this finding: The MTA was randomised for its first 14 months and observational after that, and these medication subgroups were not randomised: children were grouped by the pattern of stimulant use they happened to have. The authors call the follow-up analyses hypothesis-generating. So the height difference is an association in children who stayed on medication, not proof that the medication caused it.

For adult height, the ADHD group was 1.29 ± 0.55 cm shorter than the LNCG (p < .01, d = .21), and the comparisons of the naturalistic subgroups were significant: the treated group with the Consistent or Inconsistent pattern was 2.55 ± 0.73 cm shorter than the subgroup with the Negligible pattern (p < .0005, d = .42), and within the treated group, the subgroup with the Consistent pattern was 2.36 ± 1.13 cm shorter than the subgroup with the Inconsistent pattern (p < .04, d = .38).

The MTA investigators state the association was with height suppression and not with symptom reduction, and the design is observational, so it cannot establish that the medication caused either result. (Source 14)

• Cohort study, Low certainty.
• Size: 515 ADHD cases and 258 classmates without ADHD.
• Who: the MTA cohort in early adulthood.
• How long: to 16 years after baseline.
• Result: no new numbers; the authors' summary of direction.
• Funding: not stated in the abstract.

Limit of this finding: The same caution applies: naturalistic, non-randomised subgroups inside a long-term follow-up that the authors themselves describe as hypothesis-generating.

Within naturalistic subgroups of ADHD cases, extended use of medication was associated with suppression of adult height but not with reduction of symptom severity.

In a Swedish nationwide case-control study, each additional year of ADHD medication use was associated with a higher rate of cardiovascular disease, driven mainly by hypertension and arterial disease. (Source 16)

• Case-control study, Low certainty.
• Size: 10 388 people with ADHD and incident cardiovascular disease matched to 51 672 controls, from 278 027 people with ADHD.
• Who: people in Sweden aged 6 to 64 with ADHD or an ADHD medication dispensation, 2007-2020.
• How long: median follow-up 4.1 years; cumulative medication exposure assessed up to 14 years.
• Result: versus non-use: 1 to <=2 years AOR 1.09 (95% CI 1.01-1.18); 3 to <=5 years AOR 1.27 (1.17-1.39); >5 years AOR 1.23 (1.12-1.36); hypertension at >5 years AOR 1.80 (1.55-2.08); arterial disease at >5 years AOR 1.49 (0.96-2.32); each 1-year increase AOR 1.04 (1.03-1.05)
• Funding: not stated in the abstract.

Longer cumulative duration of ADHD medication use was associated with an increased risk of CVD compared with nonuse (0 to ≤1 year: AOR, 0.99 [95% CI, 0.93-1.06]; 1 to ≤2 years: AOR, 1.09 [95% CI, 1.01-1.18]; 2 to ≤3 years: AOR, 1.15 [95% CI, 1.05-1.25]; 3 to ≤5 years: AOR, 1.27 [95% CI, 1.17-1.39]; and >5 years: AOR, 1.23 [95% CI, 1.12-1.36]). Longer cumulative ADHD medication use was associated with an increased risk of hypertension (eg, 3 to ≤5 years: AOR, 1.72 [95% CI, 1.51-1.97] and >5 years: AOR, 1.80 [95% CI, 1.55-2.08]) and arterial disease (eg, 3 to ≤5 years: AOR, 1.65 [95% CI, 1.11-2.45] and >5 years: AOR, 1.49 [95% CI, 0.96-2.32]).

The label's own description of misuse and abuse lists the physical effects and includes anxiety, psychosis, hostility, aggression and suicidal or homicidal ideation. (Source 17)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: people misusing or abusing amphetamines.
• How long: including after a single non-therapeutic use.
• Result: no rates given.
• Funding: regulatory document.

Misuse and abuse of amphetamines may cause increased heart rate, respiratory rate, or blood pressure; sweating; dilated pupils; hyperactivity; restlessness; insomnia; decreased appetite; loss of coordination; tremors; flushed skin; vomiting; and/or abdominal pain. Anxiety, psychosis, hostility, aggression, and suicidal or homicidal ideation have also been observed with CNS stimulants abuse and/or misuse.

The FDA label carries a boxed warning that dextroamphetamine has a high potential for abuse and misuse and that misuse and abuse of stimulants can result in overdose and death. (Source 2)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: anyone prescribed dextroamphetamine sulfate.
• How long: throughout treatment.
• Result: no rate given in the warning.
• Funding: regulatory document.

Dextroamphetamine sulfate has a high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Misuse and abuse of CNS stimulants, including dextroamphetamine sulfate, can result in overdose and death (see OVERDOSAGE), and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.

The label states dextroamphetamine may produce physical dependence, and lists the withdrawal symptoms that follow abrupt stopping or a large dose cut. (Source 10)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: people taking dextroamphetamine over a prolonged period.
• How long: after prolonged use.
• Result: no rate given.
• Funding: regulatory document.

Withdrawal signs and symptoms after abrupt discontinuation or dose reduction following prolonged use of CNS stimulants including dextroamphetamine sulfate include dysphoric mood; depression; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.

The label records sudden death in people with structural cardiac abnormalities or other serious cardiac disease treated with stimulants at recommended ADHD doses. (Source 18)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: people with structural cardiac abnormalities or other serious cardiac disease.
• How long: at recommended ADHD dosages.
• Result: no rate given.
• Funding: regulatory document.

Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who are treated with CNS stimulants at the recommended ADHD dosages. Avoid dextroamphetamine sulfate use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease.

The label gives an average blood pressure and heart rate rise for stimulants as a class. (Source 19)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: all patients taking CNS stimulants.
• How long: not specified.
• Result: mean blood pressure increase about 2 to 4 mm Hg; mean heart rate increase about 3 to 6 bpm.
• Funding: regulatory document.

CNS stimulants cause an increase in blood pressure (mean increase about 2 to 4 mm Hg) and heart rate (mean increase about 3 to 6 bpm). Monitor all patients for potential tachycardia and hypertension.

The label's adverse reaction list includes rare psychotic episodes at recommended doses, isolated reports of cardiomyopathy with chronic use, and rhabdomyolysis. (Source 20)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: people taking dextroamphetamine.
• How long: including chronic use.
• Result: no rates given; the label lists reactions by body system without frequencies.
• Funding: regulatory document.

Palpitations, tachycardia, elevation of blood pressure. There have been isolated reports of cardiomyopathy associated with chronic amphetamine use. Central Nervous System Psychotic episodes at recommended doses (rare), overstimulation, restlessness, dizziness, insomnia, euphoria, dyskinesia, dysphoria, tremor, headache, exacerbation of motor and verbal tics and Tourette's syndrome.

Prescription stimulants and other diverted medicines reach non-medical users mainly through friends and family rather than through doctor shopping. (Source 21)

• Systematic review, Low certainty.
• Size: 54 cross-sectional studies meta-analysed, 95 more reviewed narratively.
• Who: people reporting non-medical use of pharmaceutical opioids, sedatives or stimulants.
• How long: studies published 1996 to 2017.
• Result: friends and family 57% (95% CI 53%-62%, I2 = 98.5, n = 30); doctor shopping 7% (6%-10%); dealers 32% (23%-41%)
• Funding: Research Support, Non-U.S. Gov't per the PubMed record.

Limit of this finding: The pooled percentages come from studies that disagree almost completely with one another: the heterogeneity statistic I² runs from 97.4 to 99.8 across these estimates, where anything above about 75 is usually called high. Read 57% and 7% as the broad direction of the literature, not as precise prevalences.

Pharmaceutical drugs are primarily sourced for NMU from friends and family (57%, 95% CI 53%-62%, I² = 98.5, n = 30) and despite perceptions of healthcare professionals to the contrary, illegitimate practices such as doctor shopping are uncommon (7%, 95% CI 6%-10%, I² = 97.4, n = 29).

What the evidence supports

In a 133-trial network meta-analysis, amphetamines reduced clinician-rated ADHD core symptoms in children and adolescents at about 12 weeks, but the review states its confidence in the estimates ranged from high or moderate down to low or very low. (Source 3)

• Meta-analysis, Moderate certainty.
• Size: 133 double-blind randomised controlled trials; efficacy analysis closest to 12 weeks based on 10 068 children and adolescents and 8131 adults.
• Who: children, adolescents and adults with ADHD.
• How long: timepoints closest to 12 weeks; no sufficient data at 26 or 52 weeks.
• Result: amphetamines SMD -1.02, 95% CI -1.19 to -0.85 (clinicians' ratings, children and adolescents); methylphenidate -0.78, -0.93 to -0.62.
• Funding: Stichting Eunethydis and the UK National Institute for Health Research Oxford Health Biomedical Research Centre (independent of manufacturers)

The confidence of estimates varied from high or moderate (for some comparisons) to low or very low (for most indirect comparisons). For ADHD core symptoms rated by clinicians in children and adolescents closest to 12 weeks, all included drugs were superior to placebo (eg, SMD -1·02, 95% CI -1·19 to -0·85 for amphetamines, -0·78, -0·93 to -0·62 for methylphenidate, -0·56, -0·66 to -0·45 for atomoxetine).

In the same network meta-analysis, amphetamines reduced clinician-rated symptoms in adults. (Source 3)

• Meta-analysis, Moderate certainty.
• Size: 51 trials in adults within the 133-trial network; 8131 adults in the efficacy analysis.
• Who: adults with ADHD.
• How long: timepoints closest to 12 weeks.
• Result: amphetamines SMD -0.79, 95% CI -0.99 to -0.58; methylphenidate -0.49, -0.64 to -0.35; modafinil 0.16, -0.28 to 0.59 (not better than placebo)
• Funding: Stichting Eunethydis and the UK NIHR Oxford Health Biomedical Research Centre.

In adults (clinicians' ratings), amphetamines (SMD -0·79, 95% CI -0·99 to -0·58), methylphenidate (-0·49, -0·64 to -0·35), bupropion (-0·46, -0·85 to -0·07), and atomoxetine (-0·45, -0·58 to -0·32), but not modafinil (0·16, -0·28 to 0·59), were better than placebo.

A Cochrane review of amphetamines in children and adolescents found symptom reductions on parent, teacher and clinician ratings, but graded the evidence low to very low quality. (Source 15)

• Systematic review, Very low certainty.
• Size: 23 trials, 2675 children aged three to 17 years.
• Who: children and adolescents under 18 with ADHD.
• How long: 14 days to 365 days, the majority under six months.
• Result: parent ratings SMD -0.57 (95% CI -0.86 to -0.27, 7 studies, 1247 children, very low quality); teacher ratings SMD -0.55 (-0.83 to -0.27, 5 studies, low quality); clinician ratings SMD -0.84 (-1.32 to -0.36, 3 studies, very low quality); CGI-I responders RR 3.36 (2.48 to 4.55, 9 studies, very low quality)
• Funding: not stated for the review; subgroup analysis by funding source (industry versus non-industry) was performed.

Amphetamines improved total ADHD core symptom severity according to parent ratings (SMD -0.57; 95% confidence interval (CI) -0.86 to -0.27; 7 studies; 1247 children/adolescents; very low quality evidence), teacher ratings (SMD -0.55; 95% CI -0.83 to -0.27; 5 studies; 745 children/adolescents; low quality evidence), and clinician ratings (SMD -0.84; 95% CI -1.32 to -0.36; 3 studies; 813 children/adolescents; very low quality evidence). In addition, the proportion of responders as rated by the Clinical Global Impression - Improvement (CGI-I) scale was higher when children were taking amphetamines (RR 3.36; 95% CI 2.48 to 4.55; 9 studies; 2207 children/adolescents; very low quality evidence).

The FDA label's ADHD indication for dextroamphetamine sulfate tablets is written for pediatric patients aged 3 to 16 only, and only as part of a total treatment programme that includes non-drug measures. (Source 4)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: pediatric patients aged 3 to 16 years with the described behavioural syndrome; narcolepsy is listed without an age restriction.
• How long: not specified.
• Result: no effect size; a statement of scope.
• Funding: regulatory document.

Attention Deficit Disorder with Hyperactivity, as an integral part of a total treatment program which typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in pediatric patients (ages 3 to 16 years) with a behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: moderate to severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity.

A professional body recommends dextroamphetamine for narcolepsy in adults only conditionally, while four other drugs get a strong recommendation. (Source 22)

• Official position, Certainty not rated.
• Size: based on an accompanying systematic review of 144 included studies.
• Who: adults with narcolepsy.
• How long: not specified.
• Result: conditional recommendation, graded with GRADE; modafinil, pitolisant, sodium oxybate and solriamfetol are strong recommendations.
• Funding: American Academy of Sleep Medicine task force.

6: We suggest that clinicians use dextroamphetamine for the treatment of narcolepsy in adults. (CONDITIONAL).

What the evidence does not support

When the raters were teachers rather than clinicians, amphetamines were not among the drugs shown to beat placebo in children and adolescents. (Source 3)

• Meta-analysis, Low certainty.
• Size: the subset of the 133 trials with available teacher ratings.
• Who: children and adolescents with ADHD.
• How long: timepoints closest to 12 weeks.
• Result: only methylphenidate (SMD -0.82, 95% CI -1.16 to -0.48) and modafinil (-0.76, -1.15 to -0.37) were more efficacious than placebo on teachers' ratings.
• Funding: Stichting Eunethydis and the UK NIHR Oxford Health Biomedical Research Centre.

By contrast, for available comparisons based on teachers' ratings, only methylphenidate (SMD -0·82, 95% CI -1·16 to -0·48) and modafinil (-0·76, -1·15 to -0·37) were more efficacious than placebo.

The evidence base for managing amphetamine-type withdrawal is itself weak: a systematic review found only a small number of medications studied and none standing out. (Source 13)

• Systematic review, Very low certainty.
• Size: not stated in the abstract.
• Who: people withdrawing from methamphetamine (the amphetamine-type stimulant with the largest withdrawal literature)
• How long: symptoms described as lasting from a few days to a few months.
• Result: no pooled effect estimate reported.
• Funding: Research Support, Non-U.S. Gov't per the PubMed record.

Common methamphetamine withdrawal symptoms include symptoms relating to depression, agitation, cognitive impairment and fatigue. These symptoms may last anywhere from a few days to a few months. Methamphetamine withdrawal is most commonly undertaken in an outpatient setting, and psychosocial interventions remain the primary treatment approach in Australia. Two withdrawal scales (Amphetamine Withdrawal Questionnaire and Amphetamine Cessation Symptom Assessment) have been validated for the assessment of methamphetamine withdrawal. Only a small number of medications for methamphetamine withdrawal have been investigated, and to date no medications stand out over the others.

The authors of the methamphetamine withdrawal review state that current withdrawal recommendations rest on clinical opinion and vary between settings, and that the review exposed a lack of well-conducted research. (Source 13)

• Systematic review, Very low certainty.
• Size: a systematic review of the published literature; no pooled estimate.
• Who: people withdrawing from methamphetamine, largely in Australian services.
• How long: not applicable.
• Result: no effect estimate is reported; the finding is the absence of evidence.
• Funding: not stated in the abstract.

Limit of this finding: This is about methamphetamine, which is a different drug from prescribed dextroamphetamine, and the review describes Australian practice. It is included because it is the clearest statement in the literature that amphetamine-type withdrawal management is based on opinion rather than trials. The earlier description of withdrawal symptoms in this entry should be read in that light, not as settled practice.

Current recommendations for methamphetamine withdrawal tend to be based on clinical opinion and subsequently vary between settings. More research in the area is essential to ensure the development of more targeted, timely and effective withdrawal treatment interventions.

The same sleep-medicine guideline makes only two recommendations for children with narcolepsy, both conditional and neither for dextroamphetamine. (Source 22)

• Official position, Low certainty.
• Size: 22 recommendations in one guideline.
• Who: children and adults with central disorders of hypersomnolence.
• How long: not applicable.
• Result: recommendations 21 and 22, modafinil and sodium oxybate, are both CONDITIONAL, and no paediatric recommendation names dextroamphetamine.
• Funding: American Academy of Sleep Medicine.

Limit of this finding: A conditional recommendation is the guideline’s weaker category. The absence of dextroamphetamine from the paediatric recommendations is not a statement that it is unsafe in children; it means the task force did not find evidence to recommend it there. The FDA label’s narcolepsy dosing section does cover children.

21: We suggest that clinicians use modafinil for the treatment of narcolepsy in pediatric patients. (CONDITIONAL).

Where the evidence is mixed

Cochrane's own verdict on the paediatric amphetamine trials is that most were at high risk of bias, that the benefit shown is short term, and that longer trials are needed. (Source 23)

• Systematic review, Very low certainty.
• Size: 23 trials, 2675 children.
• Who: children and adolescents with ADHD.
• How long: most trials under six months.
• Result: no effect estimate; a judgement on the body of evidence.
• Funding: not stated.

Most of the included studies were at high risk of bias and the overall quality of the evidence ranged from low to very low on most outcomes. Although amphetamines seem efficacious at reducing the core symptoms of ADHD in the short term, they were associated with a number of adverse events.

In adults, a Cochrane review of seven short trials found amphetamines reduced symptom severity but caused three times as many withdrawals for adverse events, and the reviewers judged no trial to be at low risk of bias. (Source 24)

• Systematic review, Low certainty.
• Size: 7 studies, 1091 participants.
• Who: adults with ADHD.
• How long: mean study length 8.1 weeks.
• Result: symptom severity SMD -0.72 (95% CI -0.87 to -0.57); dropout due to adverse events RR 3.03 (95% CI 1.52 to 6.05); no dose-response difference detected.
• Funding: not stated for the review.

Limit of this finding: This is the 2011 version of the review and it has been superseded by the authors' own 2018 update (CD007813.pub3), which includes 19 studies and 2,521 participants rather than 7 and 1,091, and concludes that the evidence overall is of low or very low quality. Use the 2018 figures for anything current.

Amphetamines improved ADHD symptom severity (SMD = -0.72; 95% CI -0.87 to -0.57) but did not improve retention in treatment overall and were associated with increased dropout due to adverse events (RR 3.03; 95% CI 1.52 to 6.05). The three amphetamine derivatives investigated (dextroamphetamine, lisdexamphetamine and mixed amphetamine salts (MAS)) were all efficacious for reducing ADHD symptoms, but MAS also increased retention in treatment. Different doses did not appear associated with differences in efficacy. We investigated immediate and sustained drug release formulations but found no difference between them on any outcome. When amphetamines were compared to other drug interventions, no differences were found. We did not find any study to be at low risk of bias overall, mainly because amphetamines have powerful subjective effects that may reveal the assigned treatment.

The adult Cochrane reviewers warn that the risk of bias in the included trials was high enough that amphetamine efficacy may be overestimated. (Source 24)

• Systematic review, Low certainty.
• Size: 7 studies, 1091 participants.
• Who: adults with ADHD.
• How long: mean 8.1 weeks.
• Result: no effect estimate; a judgement on the body of evidence.
• Funding: not stated.

Limit of this finding: Same caution as above: this is the superseded 2011 review. The 2018 update repeats the warning and adds that none of its 19 included studies had an overall low risk of bias.

The short study length and the restrictive inclusion criteria limit the external validity of these findings. Furthermore, the possibility that the results of the included studies were biased was high, which could have led to an overestimation of amphetamine efficacy.

For the off-label use that drives most non-medical stimulant taking, cognitive enhancement in healthy adults, a meta-analysis found a small gain in processing-speed accuracy and no change in planning, decision-making or perseveration. (Source 5)

• Meta-analysis, Low certainty.
• Size: n = 345 for the processing-speed accuracy estimate; a small number of studies for the other outcomes.
• Who: healthy adults, many of them college students.
• How long: single-dose laboratory testing.
• Result: processing speed accuracy g = 0.282 (95% CI 0.077 to 0.488); no improvement or impairment detected for planning time, planning accuracy, advantageous decision-making or cognitive perseveration.
• Funding: not stated.

Limit of this finding: One domain out of five moved. Processing-speed accuracy improved by g = 0.282, a small effect, in healthy adults; planning time, planning accuracy, decision-making and cognitive perseveration all showed nothing, and the authors say those null results rest on very few studies. This does not support stimulants as a general cognitive enhancer.

The meta-analysis results indicated a positive influence of prescription stimulant medication on processing speed accuracy, with an overall mean effect size of g = 0.282 (95% CI [0.077, 0.488]; n = 345). Neither improvements nor impairments were revealed for planning time, planning accuracy, advantageous decision-making, or cognitive perseveration; however, findings are limited by the small number of studies examining these outcomes.

The 2018 Cochrane update of the adult amphetamine review is more than twice the size of the 2011 version, with 19 studies and 2,521 participants, a mean study length of 5.3 weeks, and 16 of the 19 studies funded by the pharmaceutical industry. (Source 25)

• Systematic review, Low certainty.
• Size: 19 studies, 2,521 participants.
• Who: adults aged 18 and over with ADHD, mostly middle-aged men.
• How long: mean study length 5.3 weeks.
• Result: clinician-rated symptom severity SMD -0.90 (95% CI -1.04 to -0.75; 13 studies, 2,028 participants); patient-rated SMD -0.51 (-0.75 to -0.28; six studies, 120 participants); retention RR 1.06 (0.99 to 1.13); withdrawal for adverse events RR 2.69 (1.63 to 4.45)
• Funding: 16 of 19 included studies were funded by the pharmaceutical industry, one publicly funded, two not reported.

Limit of this finding: This replaces the 2011 review quoted elsewhere in this entry. Even with twice the data the trials are short - about five weeks on average - and almost all were paid for by the companies that make the drugs. Nothing here speaks to taking amphetamines for years.

We included 19 studies that investigated three types of amphetamines: dexamphetamine (10.2 mg/d to 21.8 mg/d), lisdexamfetamine (30 mg/d to 70 mg/d), and mixed amphetamine salts (MAS; 12.5 mg/d to 80 mg/d). These studies enrolled 2521 participants; most were middle-aged (35.3 years), Caucasian males (57.2%), with a combined type of ADHD (78.8%). Eighteen studies were conducted in the USA, and one study was conducted in both Canada and the USA. Ten were multi-site studies. All studies were placebo-controlled, and three also included an active comparator: guanfacine, modafinil, or paroxetine. Most studies had short-term follow-up and a mean study length of 5.3 weeks.

Cochrane's 2018 verdict on amphetamines in adults is that symptoms improve in the short term but retention does not, that more people stop because of side-effects, that no included study had an overall low risk of bias, and that the evidence overall is of low or very low quality. (Source 26)

• Systematic review, Very low certainty.
• Size: 19 studies, 2,521 participants.
• Who: adults with ADHD.
• How long: mean 5.3 weeks.
• Result: the reviewers give no pooled number in this section; their stated overall certainty is low or very low.
• Funding: Cochrane review; 16 of the 19 included studies were industry-funded.

Limit of this finding: "Low or very low quality" is Cochrane’s own GRADE rating and it means the true effect could be substantially different from the estimate. The reviewers name the reason: amphetamines have strong subjective effects, so people can often tell whether they got the drug, which undermines blinding.

The short duration of studies coupled with their restrictive inclusion criteria limits the external validity of these findings. Furthermore, none of the included studies had an overall low risk of bias. Overall, the evidence generated by this review is of low or very low quality.

Where the research disagrees

Whether dextroamphetamine suppresses growth in children

• FDA label, WARNINGS section (SPL published 12 January 2026), position: CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients, including dextroamphetamine sulfate. Closely monitor growth (weight and height) in dextroamphetamine sulfate -treated pediatric patients treated with CNS stimulants. (Source 27)
• FDA label, PRECAUTIONS / Pediatric Use section of the same document, position: Data are inadequate to determine whether chronic administration of amphetamines may be associated with growth inhibition; therefore, growth should be monitored during treatment. (Source 28)
• Swanson and colleagues, MTA long-term follow-up, cohort: For adult height, the ADHD group was 1.29 ± 0.55 cm shorter than the LNCG (p < .01, d = .21) (Source 14)

Whether the short-term trial evidence supports amphetamines as a first choice

• Cortese and colleagues, network meta-analysis, meta-analysis: Taking into account both efficacy and safety, evidence from this meta-analysis supports methylphenidate in children and adolescents, and amphetamines in adults, as preferred first-choice medications for the short-term treatment of ADHD. New research should be funded urgently to assess long-term effects of these drugs. (Source 29)
• Punja and colleagues, Cochrane review of children and adolescents, systematic-review: This review found no evidence that supports any one amphetamine derivative over another, and does not reveal any differences between long-acting and short-acting amphetamine preparations. Future trials should be longer in duration (i.e. more than 12 months), include more psychosocial outcomes (e.g. quality of life and parent stress), and be transparently reported. (Source 23)

How much

• Reference intake: Dosing is set by the prescriber. As a position, the FDA label for dextroamphetamine sulfate tablets gives a usual narcolepsy dose of 5 to 60 mg per day in divided doses, titrated to the individual, with different starting points for ages 6 to 12 and 12 and over. (Source 30)
• Upper limit: As a position, the FDA label states that for ADHD in pediatric patients 6 years of age and older, who start at 5 mg once or twice daily, only in rare cases will it be necessary to exceed a total of 40 mg per day. This ceiling is stated for that age band, not for everyone; the narcolepsy section of the same label runs to 60 mg per day. (Source 12)
• Studied: The Cochrane review of amphetamines in adults found that the different doses studied did not appear to differ in efficacy, and found no difference between immediate-release and sustained-release formulations. (Source 24)
• Studied: The paediatric Cochrane review covered 23 trials of 14 to 365 days, the majority under six months, comparing amphetamine derivatives against placebo in children aged three to 17. (Source 15)

A common belief, and what the research shows

The belief: If a stimulant helps a child's ADHD symptoms, staying on it for years keeps that benefit and the main question is side-effects.

What the research shows: The trial evidence is almost all short term. The 133-trial network meta-analysis reports that it did not find sufficient data for the 26-week and 52-week timepoints and calls for long-term research, writing: "New research should be funded urgently to assess long-term effects of these drugs." In the MTA observational follow-up, the subgroups defined by how consistently they took medication did not differ in adult symptom severity, while they did differ in adult height: "Within naturalistic subgroups of ADHD cases, extended use of medication was associated with suppression of adult height but not with reduction of symptom severity."

Questions and answers

What is it?

Dextroamphetamine is the right-handed form of the amphetamine molecule, given as dextroamphetamine sulfate tablets and in other formulations. Regulators class it as a non-catecholamine sympathomimetic amine with central nervous system stimulant activity. It is a Schedule II controlled substance. The same molecule is one of the salts in mixed amphetamine salts products. (Source 1)

What does it do in the body?

It stimulates the central nervous system and acts on the sympathetic nervous system outside the brain, raising systolic and diastolic blood pressure and acting weakly on the airways. How that produces its effects on attention and behaviour is not established: the FDA label says there is neither specific evidence establishing the mechanism nor conclusive evidence about how those effects relate to the state of the nervous system. Across stimulants as a class the label gives an average blood pressure rise of about 2 to 4 mm Hg and a heart rate rise of about 3 to 6 bpm. (Source 1)

Is it good or bad for you?

It depends entirely on the setting. In children with diagnosed ADHD it reduces rating-scale symptoms over weeks to a few months, with large effect sizes on clinician ratings, though Cochrane graded most of that evidence low to very low quality. The same reviews found it less well tolerated than placebo, and it carries an FDA boxed warning about abuse, misuse and addiction. Taken outside a diagnosis, for study or performance, the measured gain in healthy adults was small and confined to processing-speed accuracy. (Source 23)

How do you get more of it?

Dextroamphetamine is a prescription-only controlled medicine, so the only lawful route is a prescription, and the dose is set by the prescriber. There is no food or supplement source. The label does record two things that change how much reaches the blood: alkalinizing agents such as sodium bicarbonate increase absorption and raise blood levels, while acidifying agents including vitamin C and fruit juices lower absorption. Neither is a way to get more of the drug; both are interactions to be aware of. (Source 8)

If it is harmful, what reduces it?

The label describes the pharmacology of clearing it: acidifying the urine increases the amount excreted and lowers blood levels, and this is used in managing overdose. Stopping abruptly after prolonged use is not harmless, because the label describes a withdrawal syndrome of low mood, depression, fatigue, vivid unpleasant dreams, sleep change, increased appetite and psychomotor slowing or agitation. The literature on treating amphetamine-type withdrawal is weak, with no medication standing out. (Source 7)

Why might someone be low in it or missing it?

This is a manufactured medicine, not a nutrient, so no one is naturally low in it. The relevant questions are why someone taking it might get less effect than expected, or lose access. The label names gastrointestinal and urinary acidifying agents, including vitamin C and fruit juices, as lowering blood levels and efficacy. It also describes tolerance, a reduced response after repeated administration so that a higher dose is needed for the same effect. (Source 11)

Which whole foods contain it or feed it?

No whole food contains dextroamphetamine. The only food relationship documented in the label runs the other way: fruit juices are listed among the gastrointestinal acidifying agents that lower absorption of amphetamines, and the label states that agents in this group lower blood levels and efficacy. (Source 7)

What happens if you do not have it?

Not taking it has no deficiency consequence, because it is a drug and not a nutrient. For someone with ADHD who stops, the short-term trial evidence predicts a return of rating-scale symptoms, since the trials measured reduction against placebo over weeks. The long-term picture is less clear: in the MTA follow-up the naturalistic subgroups defined by how consistently they had taken medication did not differ in adult symptom severity. For someone who has been taking it for a long time, abrupt stopping can produce the withdrawal syndrome the label lists. (Source 14)

How can you test for it?

There is no blood test that tells you whether dextroamphetamine is working; the trials measured response with rating scales filled in by parents, teachers and clinicians, and those sources disagree with each other. In the network meta-analysis, amphetamines beat placebo on clinician ratings in children but were not among the drugs shown to beat placebo on teacher ratings. The MTA follow-up reported a statistically significant parent/self-report difference, which the authors called source discrepancy. Urine and blood assays for amphetamine exist for detection, not for judging benefit. (Source 14)

References

1. DailyMed / Azurity Pharmaceuticals (SPL published 12 January 2026). ZENZEDI (dextroamphetamine sulfate) tablet - FDA label, CLINICAL PHARMACOLOGY, parent narrative only (the nested Pharmacokinetics subsection, n = 12 healthy subjects, is not in this block). 2026. Read the source
2. DailyMed / Azurity Pharmaceuticals (SPL published 12 January 2026). ZENZEDI (dextroamphetamine sulfate) tablet - FDA label, boxed warning section (LOINC 34066-1). 2026. Read the source
3. The lancet. Psychiatry. Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis.. 2018. PMID 30097390, DOI 10.1016/S2215-0366(18)30269-4. Read the source
4. DailyMed / Azurity Pharmaceuticals (SPL published 12 January 2026). ZENZEDI (dextroamphetamine sulfate) tablet - FDA label, INDICATIONS AND USAGE. 2026. Read the source
5. Experimental and clinical psychopharmacology. Neurocognitive enhancement or impairment? A systematic meta-analysis of prescription stimulant effects on processing speed, decision-making, planning, and cognitive perseveration.. 2016. PMID 27454675, DOI 10.1037/pha0000079. Read the source
6. DailyMed / Azurity Pharmaceuticals (SPL published 12 January 2026). ZENZEDI (dextroamphetamine sulfate) tablet - FDA label, Drug Interactions: MAO Inhibitors. 2026. Read the source
7. DailyMed / Azurity Pharmaceuticals (SPL published 12 January 2026). ZENZEDI (dextroamphetamine sulfate) tablet - FDA label, Drug Interactions: Acidifying Agents. 2026. Read the source
8. DailyMed / Azurity Pharmaceuticals (SPL published 12 January 2026). ZENZEDI (dextroamphetamine sulfate) tablet - FDA label, Drug Interactions: Alkalinizing Agent. 2026. Read the source
9. DailyMed / Azurity Pharmaceuticals, Inc.. ZENZEDI (dextroamphetamine sulfate) tablet - FDA label, CONTRAINDICATIONS. 2026. Read the source
10. DailyMed / Azurity Pharmaceuticals (SPL published 12 January 2026). ZENZEDI (dextroamphetamine sulfate) tablet - FDA label, DRUG ABUSE AND DEPENDENCE: Physical Dependence. 2026. Read the source
11. DailyMed / Azurity Pharmaceuticals (SPL published 12 January 2026). ZENZEDI (dextroamphetamine sulfate) tablet - FDA label, DRUG ABUSE AND DEPENDENCE: Tolerance. 2026. Read the source
12. DailyMed / Azurity Pharmaceuticals (SPL published 12 January 2026). ZENZEDI (dextroamphetamine sulfate) tablet - FDA label, DOSAGE AND ADMINISTRATION: Attention Deficit Disorder with Hyperactivity. 2026. Read the source
13. Drug and alcohol review. Putting the call out for more research: the poor evidence base for treating methamphetamine withdrawal.. 2011. PMID 21355922, DOI 10.1111/j.1465-3362.2010.00240.x. Read the source
14. Journal of child psychology and psychiatry, and allied disciplines. Young adult outcomes in the follow-up of the multimodal treatment study of attention-deficit/hyperactivity disorder: symptom persistence, source discrepancy, and height suppression.. 2017. PMID 28295312, DOI 10.1111/jcpp.12684. Read the source
15. The Cochrane database of systematic reviews. Amphetamines for attention deficit hyperactivity disorder (ADHD) in children and adolescents.. 2016. PMID 26844979, DOI 10.1002/14651858.CD009996.pub2. Read the source
16. JAMA psychiatry. Attention-Deficit/Hyperactivity Disorder Medications and Long-Term Risk of Cardiovascular Diseases.. 2024. PMID 37991787, DOI 10.1001/jamapsychiatry.2023.4294. Read the source
17. DailyMed / Azurity Pharmaceuticals (SPL published 12 January 2026). ZENZEDI (dextroamphetamine sulfate) tablet - FDA label, DRUG ABUSE AND DEPENDENCE: Abuse. 2026. Read the source
18. DailyMed / Azurity Pharmaceuticals (SPL published 12 January 2026). ZENZEDI (dextroamphetamine sulfate) tablet - FDA label, WARNINGS: Risks to Patients with Serious Cardiac Disease. 2026. Read the source
19. DailyMed / Azurity Pharmaceuticals (SPL published 12 January 2026). ZENZEDI (dextroamphetamine sulfate) tablet - FDA label, WARNINGS: Increased Blood Pressure and Heart Rate. 2026. Read the source
20. DailyMed / Azurity Pharmaceuticals (SPL published 12 January 2026). ZENZEDI (dextroamphetamine sulfate) tablet - FDA label, ADVERSE REACTIONS (with its subsections, in document order). 2026. Read the source
21. Drug and alcohol dependence. The source and diversion of pharmaceutical drugs for non-medical use: A systematic review and meta-analysis.. 2018. PMID 29626777, DOI 10.1016/j.drugalcdep.2018.02.010. Read the source
22. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline.. 2021. PMID 34743789, DOI 10.5664/jcsm.9328. Read the source
23. The Cochrane database of systematic reviews. Amphetamines for attention deficit hyperactivity disorder (ADHD) in children and adolescents.. 2016. PMID 26844979, DOI 10.1002/14651858.CD009996.pub2. Read the source
24. The Cochrane database of systematic reviews. Amphetamines for Attention Deficit Hyperactivity Disorder (ADHD) in adults [CD007813.pub2 - SUPERSEDED by the 2018 update CD007813.pub3, PMID 30091808]. 2011. PMID 21678370, DOI 10.1002/14651858.CD007813.pub2. Read the source
25. Cochrane Database of Systematic Reviews (CD007813.pub3). Amphetamines for attention deficit hyperactivity disorder (ADHD) in adults.. 2018. PMID 30091808, DOI 10.1002/14651858.CD007813.pub3. Read the source
26. Cochrane Database of Systematic Reviews (CD007813.pub3). Amphetamines for attention deficit hyperactivity disorder (ADHD) in adults - AUTHORS' CONCLUSIONS.. 2018. PMID 30091808, DOI 10.1002/14651858.CD007813.pub3. Read the source
27. DailyMed / Azurity Pharmaceuticals (SPL published 12 January 2026). ZENZEDI (dextroamphetamine sulfate) tablet - FDA label, WARNINGS: Long-Term Suppression of Growth in Pediatric Patients. 2026. Read the source
28. DailyMed / Azurity Pharmaceuticals (SPL published 12 January 2026). ZENZEDI (dextroamphetamine sulfate) tablet - FDA label, PRECAUTIONS: Pediatric Use. 2026. Read the source
29. The lancet. Psychiatry. Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis.. 2018. PMID 30097390, DOI 10.1016/S2215-0366(18)30269-4. Read the source
30. DailyMed / Azurity Pharmaceuticals (SPL published 12 January 2026). ZENZEDI (dextroamphetamine sulfate) tablet - FDA label, DOSAGE AND ADMINISTRATION: Narcolepsy. 2026. Read the source