Lisdexamfetamine, sold under the brand name Vyvanse among others, is a stimulant medication that is mainly used to treat

attention deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...

(ADHD) in people over the age of five as well as moderate-to-severe binge eating disorder in adults. Lisdexamfetamine is taken by mouth. Its effects generally begin within 2 hours and last for up to 14 hours. In the United Kingdom, it is usually less preferred than

methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser exten ...

for the treatment of children. Common side effects of lisdexamfetamine include

loss of appetite Anorexia is a medical term for a loss of appetite. While the term in non-scientific publications is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while others i ...

, anxiety, diarrhea, trouble sleeping,

irritability Irritability (also called as crankiness) is the excitatory ability that living organisms have to respond to changes in their environment. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessi ...

, and nausea. Rare but serious side effects include mania,

sudden cardiac death Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that, without immediate medical intervention, will result in sudden cardiac death within minutes. Cardiopulmonary resuscitation (CPR) and possib ...

in those with underlying heart problems, and psychosis. It has a high potential for substance abuse per the

Drug Enforcement Administration The Drug Enforcement Administration (DEA; ) is a Federal law enforcement in the United States, United States federal law enforcement agency under the U.S. Department of Justice tasked with combating drug trafficking and distribution within th ...

(DEA).

Serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain serotonergic medications or drugs. The degree of symptoms can range from mild to severe, including a potentiality of death. Symptoms in mild cases include high ...

may occur if used with certain other medications. Its use during

pregnancy Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...

may result in harm to the baby and use during

breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...

is not recommended by the manufacturer. Lisdexamfetamine is an inactive prodrug that works after being converted by the body into

dextroamphetamine Dextroamphetamine is a central nervous system (CNS) stimulant and an amphetamine enantiomer that is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance an ...

, a

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

(CNS) stimulant. Chemically, lisdexamfetamine is composed of the

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...

L-lysine, attached to dextroamphetamine. Lisdexamfetamine was approved for medical use in the United States in 2007. In 2020, it was the 85th most commonly prescribed medication in the United States, with more than 8million prescriptions. It is a Class B controlled substance in the United Kingdom and a

Schedule II controlled substance The Controlled Substances Act (CSA) is the statute establishing federal U.S. drug policy under which the manufacture, importation, possession, use, and distribution of certain substances is regulated. It was passed by the 91st United States ...

in the United States.

Uses

Medical

Lisdexamfetamine is used primarily as a treatment for

(ADHD) and binge eating disorder; it has similar uses as those of other pharmaceutical amphetamines. Individuals over the age of 65 were not commonly tested in clinical trials of lisdexamfetamine for ADHD.

Enhancing performance

Available forms

Lisdexamfetamine is available as the dimesylate salt in the form of both oral capsules and chewable tablets. The capsules are available in doses of 10, 20, 30, 40, 50, 60, and 70 mg, while the chewable tablets are available in doses of 10, 20, 30, 40, 50, and 60 mg. These amounts of lisdexamfetamine dimesylate are equivalent to 5.8, 11.6, 17.3, 23.1, 28.9, 34.7, and 40.5 mg lisdexamfetamine free-base, respectively. A dose of 50 mg of lisdexamfetamine dimesylate is approximately equimolar to a 20 mg dose of

dextroamphetamine sulfate Dextroamphetamine is a central nervous system (CNS) stimulant and an amphetamine enantiomer that is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance and c ...

or to 15 mg dextroamphetamine free-base in terms of the amount of

contained. Lisdexamfetamine capsules can be swallowed intact, or they can be opened and mixed into water, yogurt, or applesauce and consumed in that manner.

Contraindications

Pharmaceutical lisdexamfetamine is

contraindicated In medicine, a contraindication is a condition that serves as a reason not to take a certain medical treatment due to the harm that it would cause the patient. Contraindication is the opposite of indication, which is a reason to use a certain tre ...

in patients with

hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune ...

to amphetamine products or any of the formulation's inactive ingredients. It is also contraindicated in patients who have used a monoamine oxidase inhibitor (MAOI) within the last 14 days. Amphetamine products are contraindicated by the

United States Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...

(USFDA) in people with a history of drug abuse, heart disease, or severe agitation or anxiety, or in those currently experiencing arteriosclerosis, glaucoma, hyperthyroidism, or severe hypertension. However, a

Europe Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a subcontinent of Eurasia and it is located entirel ...

an consensus statement on adult ADHD noted that stimulants do not worsen substance misuse in adults with ADHD and comorbid substance use disorder and should not be avoided in these individuals. In any case, the statement noted that immediate-release stimulants should be avoided in those with both ADHD and substance use disorder and that slower-release stimulant formulations like

(Concerta) and lisdexamfetamine should be preferred due to their lower misuse potential. Prescribing information approved by the Australian

Therapeutic Goods Administration The Therapeutic Goods Administration (TGA) is the medicine and therapeutic regulatory agency of the Australian Government. As part of the Department of Health and Aged Care, the TGA regulates the quality, supply and advertising of medicines, p ...

further contraindicates

anorexia Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gre ...

Adverse effects

Products containing lisdexamfetamine have a comparable

drug safety Term Given By Tushar Sharma (UPES Batch 2025) Pharmacovigilance (PV, or PhV), also known as drug safety, is the pharmaceutical science relating to the "collection, detection, assessment, monitoring, and prevention" of adverse effects with pha ...

profile to those containing amphetamine. The major

side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s of lisdexamfetamine in short-term clinical trials (≥5% incidence) have included decreased appetite,

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

dry mouth Xerostomia, also known as dry mouth, is dryness in the mouth, which may be associated with a change in the composition of saliva, or reduced salivary flow, or have no identifiable cause. This symptom is very common and is often seen as a side eff ...

, weight loss,

, upper abdominal pain, nausea, vomiting, diarrhea, constipation, increased heart rate, anxiety,

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical c ...

, and

feeling jittery Psychomotor agitation is a symptom in various disorders and health conditions. It is characterized by unintentional and purposeless motions and restlessness, often but not always accompanied by emotional distress. Typical manifestations include ...

. Rates of side effects may vary in adults, adolescents, and children. Rare but serious side effects of lisdexamfetamine may include mania,

in those with underlying heart problems, stimulant psychosis, and

serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain serotonergic medications or drugs. The degree of symptoms can range from mild to severe, including a potentiality of death. Symptoms in mild cases include high ...

Interactions

* Acidifying agents: Drugs that acidify the urine, such as ascorbic acid, increase urinary excretion of dextroamphetamine, thus decreasing the half-life of dextroamphetamine in the body. * Alkalinizing agents: Drugs that alkalinize the urine, such as sodium bicarbonate, decrease urinary excretion of dextroamphetamine, thus increasing the half-life of dextroamphetamine in the body. *

CYP2D6 inhibitor Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra. CYP2D ...

s: Hydroxylation via the

cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various co ...

enzyme

CYP2D6 Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra. CYP2D ...

is the major pathway of

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run c ...

of dextroamphetamine. Potent CYP2D6 inhibitors, such as paroxetine, fluoxetine, bupropion, and

duloxetine Duloxetine, sold under the brand name Cymbalta among others, is a medication used to treat major depressive disorder, generalized anxiety disorder, fibromyalgia, neuropathic pain and central sensitization. It is taken by mouth. It is a seroton ...

, among others, may inhibit the metabolism of dextroamphetamine and thereby increase exposure to it. Studies characterizing this potential interaction are currently lacking. Concomitant use of lisdexamfetamine with CYP2D6 inhibitors may increase the risk of

due to greater drug exposure according to the FDA label for lisdexamfetamine. * Monoamine oxidase inhibitors: Concomitant use of MAOIs and central nervous system stimulants such as lisdexamfetamine can cause a hypertensive crisis.

Pharmacology

Mechanism of action

Lisdexamfetamine is an inactive prodrug that is converted in the body to dextroamphetamine, a pharmacologically active compound which is responsible for the drug's activity. 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. The conversion of lisdexamfetamine to dextroamphetamine is not affected by gastrointestinal pH and is unlikely to be affected by alterations in normal gastrointestinal transit times. The optical isomers of amphetamine, i.e.,

and levoamphetamine, are TAAR1 agonists and vesicular monoamine transporter 2 inhibitors that can enter

monoamine Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin. All monoamines ar ...

neurons; this allows them to release monoamine neurotransmitters ( dopamine, norepinephrine, and serotonin, among others) from their storage sites in the

presynaptic neuron Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous sys ...

, as well as prevent the reuptake of these neurotransmitters from the

synaptic cleft Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous syste ...

. Lisdexamfetamine was developed with the goal of providing a long duration of effect that is consistent throughout the day, with reduced potential for abuse. The attachment of the amino acid lysine slows down the relative amount of dextroamphetamine available to the blood stream. Because no free dextroamphetamine is present in lisdexamfetamine capsules, dextroamphetamine does not become available through mechanical manipulation, such as crushing or simple extraction. A relatively sophisticated biochemical process is needed to produce dextroamphetamine from lisdexamfetamine. As opposed to

Adderall Adderall and Mydayis are trade names for a combination drug called mixed amphetamine salts containing four salts of amphetamine. The mixture is composed of equal parts racemic amphetamine and dextroamphetamine, which produces a (3:1) ratio ...

, which contains roughly equal parts of racemic amphetamine and dextroamphetamine salts, lisdexamfetamine is a single- enantiomer dextroamphetamine formula. Studies conducted show that lisdexamfetamine dimesylate may have less abuse potential than dextroamphetamine and an abuse profile similar to diethylpropion at dosages that are FDA-approved for treatment of ADHD, but still has a high abuse potential when this dosage is exceeded by over 100%.

Pharmacokinetics

Dextroamphetamine concentration-time curves after oral administration of equimolar doses of dextroamphetamine and lisdexamfetamine in adults

Chemistry

Lisdexamfetamine is a substituted amphetamine with an amide linkage formed by the condensation of

with the carboxylate group of the

essential amino acid An essential amino acid, or indispensable amino acid, is an amino acid that cannot be synthesized from scratch by the organism fast enough to supply its demand, and must therefore come from the diet. Of the 21 amino acids common to all life form ...

L-lysine. The reaction occurs with retention of stereochemistry, so the product lisdexamfetamine exists as a single

stereoisomer In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms in ...

. There are many possible names for lisdexamfetamine based on

IUPAC nomenclature A chemical nomenclature is a set of rules to generate systematic names for chemical compounds. The nomenclature used most frequently worldwide is the one created and developed by the International Union of Pure and Applied Chemistry (IUPAC). T ...

, but it is usually named as or . The condensation reaction occurs with loss of water: : (''S'')- + (''S'')- → (''S'',''S'')- +

Amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen Hydrogen is the chemical element wi ...

functional groups are vulnerable to oxidation in air and so pharmaceuticals containing them are usually formulated as

salts In chemistry, a salt is a chemical compound consisting of an ionic assembly of positively charged cations and negatively charged anions, which results in a compound with no net electric charge. A common example is table salt, with positively c ...

where this moiety has been

protonated In chemistry, protonation (or hydronation) is the adding of a proton (or hydron, or hydrogen cation), (H+) to an atom, molecule, or ion, forming a conjugate acid. (The complementary process, when a proton is removed from a Brønsted–Lowry acid, ...

. This increases stability, water solubility, and, by converting a molecular compound to an ionic compound, increases the melting point and thereby ensures a solid product. In the case of lisdexamfetamine, this is achieved by reacting with two equivalents of methanesulfonic acid to produce the di mesylate salt, a water-soluble (792 mg mL⁻¹) powder with a white to off-white color. : + 2 →

Comparison to other formulations

Lisdexamfetamine dimesylate is one marketed formulation delivering dextroamphetamine. The following table compares the drug to other amphetamine pharmaceuticals.

History

Lisdexamfetamine was developed by New River Pharmaceuticals, who were bought by Takeda Pharmaceuticals through its acquisition of Shire Pharmaceuticals, shortly before it began being marketed. It was developed with the intention of creating a longer-lasting and less-easily abused version of dextroamphetamine, as the requirement of conversion into dextroamphetamine via enzymes in the red blood cells delays its onset of action, regardless of the route of administration. On 23 April 2008, the FDA approved lisdexamfetamine for treatment of ADHD in adults. On 4 August 2009, Health Canada approved the marketing of 30 mg and 50 mg capsules of lisdexamfetamine for prescription use. In January 2015, lisdexamfetamine was approved by the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

for treatment of binge eating disorder in adults. The U.S. Food and Drug Administration gave tentative approval to generic formulations of lisdexamfetamine in 2015.https://web.archive.org/save/https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2015/202802Orig1s000TAltr.pdf The expiration date for patent protection of lisdexamfetamine in the U.S. is 24 February 2023. Final approval and availability of generic versions of the medication in the U.S. is anticipated after this date. Production quotas for 2016 in the United States were 29,750 kg.

Society and culture

Names

''Lisdexamfetamine'' is the International Nonproprietary Name (INN) and is a contraction of L-lysine-

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

Research

Depression

Some clinical trials that used lisdexamfetamine as an add-on therapy with a

selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracellul ...

(SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) for

treatment-resistant depression Treatment-resistant depression is a term used in psychiatry to describe people with major depressive disorder (MDD) who do not respond adequately to a course of appropriate antidepressant medication within a certain time. Definitions of treatment- ...

indicated that this is no more effective than the use of an SSRI or SNRI alone. Other studies indicated that psychostimulants potentiated antidepressants, and were under-prescribed for treatment resistant depression. In those studies, patients showed significant improvement in energy, mood, and psychomotor activity. Clinical guidelines advise caution in the use of stimulants for depression and advise them only as second- or third-line adjunctive agents. 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. A 2018

meta-analysis A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...

of randomized controlled trials of lisdexamfetamine for antidepressant augmentation in people with

major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Intro ...

—the first to be conducted—found that lisdexamfetamine was not significantly better than placebo in improving Montgomery–Åsberg Depression Rating Scale scores, response rates, or remission rates. However, there was indication of a small effect in improving depressive symptoms that approached trend-level significance. Lisdexamfetamine was well-tolerated in the meta-analysis. The quantity of evidence was limited, with only four trials included. In a subsequent 2022 network meta-analysis, lisdexamfetamine was significantly effective as an antidepressant augmentation for treatment-resistant depression. Although lisdexamfetamine has shown limited effectiveness in the treatment of depression in clinical trials, a phase II

clinical study Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

found that the addition of lisdexamfetamine to an antidepressant improved

executive dysfunction In psychology and neuroscience, executive dysfunction, or executive function deficit, is a disruption to the efficacy of the executive functions, which is a group of cognitive processes that regulate, control, and manage other cognitive processes ...

in people with mild major depressive disorder but persisting executive dysfunction. While development of lisdexamfetamine for major depressive disorder and

bipolar depression Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...

was discontinued, the drug remains in phase II clinical trials for treatment of " mood disorders" as of October 2021.

Explanatory notes

Reference notes

References

External links

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