[16] Common side effects of lisdexamfetamine include loss of appetite, anxiety, diarrhea, trouble sleeping, irritability, and nausea.

[32][33] Two reviews have indicated that long-term continuous stimulant therapy for ADHD is effective for reducing the core symptoms of ADHD (i.e., hyperactivity, inattention, and impulsivity), enhancing quality of life and academic achievement, and producing improvements in a large number of functional outcomes[note 1] across 9 categories of outcomes related to academics, antisocial behavior, driving, non-medicinal drug use, obesity, occupation, self-esteem, service use (i.e., academic, occupational, health, financial, and legal services), and social function.

[33] Another review indicated that, based upon the longest follow-up studies conducted to date, lifetime stimulant therapy that begins during childhood is continuously effective for controlling ADHD symptoms and reduces the risk of developing a substance use disorder as an adult.

[32] A 2025 meta-analytic systematic review of 113 randomized controlled trials demonstrated that stimulant medications significantly improved core ADHD symptoms in adults over a three-month period, with good acceptability compared to other pharmacological and non-pharmacological treatments.

[41] Children with ADHD who use stimulant medications generally have better relationships with peers and family members, perform better in school, are less distractible and impulsive, and have longer attention spans.

[42][43] The Cochrane reviews[note 2] on the treatment of ADHD in children, adolescents, and adults with pharmaceutical amphetamines stated that short-term studies have demonstrated that these drugs decrease the severity of symptoms, but they have higher discontinuation rates than non-stimulant medications due to their adverse side effects.

[49][50] Lisdexamfetamine's therapeutic effects for BED primarily involve direct action in the central nervous system after conversion to its pharmacologically active metabolite, dextroamphetamine.

[52] Centrally, dextroamphetamine increases neurotransmitter activity of dopamine and norepinephrine in prefrontal cortical regions that regulate cognitive control of behavior.

Peripherally, dextroamphetamine triggers lipolysis through noradrenergic signaling in adipose fat cells, leading to the release of triglycerides into blood plasma to be utilized as a fuel substrate.

[55][53] While lisdexamfetamine's anorexigenic effects contribute to its efficacy in BED, evidence indicates that the enhancement of cognitive control is necessary and sufficient for addressing the disorder's underlying psychopathology.

[49][57] This view is supported by the failure of anti-obesity medications and other appetite suppressants to significantly reduce BED symptom severity, despite their capacity to induce weight loss.

[57] Medical reviews of randomized controlled trials have demonstrated that lisdexamfetamine, at doses between 50–70 mg, is safe and effective for the treatment of moderate-to-severe BED in adults.

[51][55] Based on reviews of neuroimaging studies involving BED-diagnosed participants, therapeautic neuroplasticity in dopaminergic and noradrenergic pathways from long-term use of lisdexamfetamine may be implicated in lasting improvements in the regulation of eating behaviors that are observed.

[60] Lateral hypothalamic orexin neurons innervate every component of the ascending reticular activating system (ARAS), which includes noradrenergic, dopaminergic, histaminergic, and serotonergic nuclei that promote wakefulness.

[63][65] Dextroamphetamine, the more dopaminergic enantiomer of amphetamine, is particularly effective at promoting wakefulness because dopamine release has the greatest influence on cortical activation and cognitive arousal, relative to other monoamines.

[61][67][66] Amphetamine appears to be most effective at improving symptoms associated with hypersomnolence, with three reviews finding clinically significant reductions in daytime sleepiness in patients with narcolepsy.

[66] In 2015, a systematic review and a meta-analysis of high quality clinical trials found that, when used at low (therapeutic) doses, amphetamine produces modest yet unambiguous improvements in cognition, including working memory, long-term episodic memory, inhibitory control, and some aspects of attention, in normal healthy adults;[70][71] these cognition-enhancing effects of amphetamine are known to be partially mediated through the indirect activation of both dopamine D1 receptor and α2-adrenergic receptor in the prefrontal cortex.

[72] Therapeutic doses of amphetamine also enhance cortical network efficiency, an effect which mediates improvements in working memory in all individuals.

[82][83] In healthy people at oral therapeutic doses, amphetamine has been shown to increase muscle strength, acceleration, athletic performance in anaerobic conditions, and endurance (i.e., it delays the onset of fatigue), while improving reaction time.

[80][84][85] Amphetamine improves endurance and reaction time primarily through reuptake inhibition and release of dopamine in the central nervous system.

[20] The major side effects of lisdexamfetamine in short-term clinical trials (≥5% incidence) have included decreased appetite, insomnia, dry mouth, weight loss, irritability, upper abdominal pain, nausea, vomiting, diarrhea, constipation, increased heart rate, anxiety, dizziness, and feeling jittery.

[7] Rare but serious side effects of lisdexamfetamine may include mania, sudden cardiac death in those with underlying heart problems, stimulant psychosis, and serotonin syndrome.

[109] After oral ingestion, lisdexamfetamine is broken down by enzymes in red blood cells to form L-lysine, a naturally occurring essential amino acid, and dextroamphetamine.

[14][90] Because of its behavior as a prodrug and its pharmacokinetic differences, lisdexamfetamine has a longer duration of therapeutic effect than immediate-release dextroamphetamine and shows reduced misuse potential.

[14][90] CYP2D6, dopamine β-hydroxylase (DBH), flavin-containing monooxygenase 3 (FMO3), butyrate-CoA ligase (XM-ligase), and glycine N-acyltransferase (GLYAT) are the enzymes known to metabolize amphetamine or its metabolites in humans.

[131] The condensation reaction occurs with loss of water: Amine functional groups are vulnerable to oxidation in air and so pharmaceuticals containing them are usually formulated as salts where this moiety has been protonated.

[132] In the case of lisdexamfetamine, this is achieved by reacting with two equivalents of methanesulfonic acid to produce the dimesylate salt, a water-soluble (792 mg mL−1) powder with a white to off-white color.

[148] As of November 2020, lisdexamfetamine is sold under the following brand names: Aduvanz, Elvanse, Juneve, Samexid, Tyvense, Venvanse, and Vyvanse.

[150] In clinical studies in the 1970s and 1980s, psychostimulants, including amphetamine and methylphenidate, were found to transiently improve mood in a majority of people with depression and to increase psychomotor activation in almost all individuals.

[154] In February 2014, Shire announced that two late-stage clinical trials had found that Vyvanse was not an effective treatment for depression, and development for this indication was discontinued.