Adderall salt

Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. The exact mode of therapeutic action in Attention Deficit Hyperactivity Disorder (ADHD) is not known. Amphetamines block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.1

The first amphetamine product (mixed amphetamine salts, or MAS, immediate-release) was approved for the treatment of ADHD in 1996. MAS have been used for the treatment of ADHD for over 20 years.2

MAS formulations differ in dosage, mechanism of release, pharmacokinetics, and duration of effect.
Three common formulations are presented below.1-4

MAS formulations differ in dosages, mechanism of release, pharmacokinetics, and duration of effect.

Tablet and capsules shown are not actual size.

*Definitive clinical trials comparing MAS IR, MAS ER (other), and Mydayis have not been performed. Duration of effect is not described in MAS IR and MAS ER (other) labels; estimates are from Jain and Katic, 2016.4
No estimates of onset for MAS IR and MAS ER (other) were provided in this publication.

To avoid substitution errors and overdosage, do not substitute for other amphetamine products on a milligram-per-milligram basis because of different amphetamine base compositions and differing pharmacokinetic profiles.

To avoid substitution errors and overdosage, do not substitute for other amphetamine products on a milligram-per-milligram basis  because of different amphetamine base compositions and differing PK profiles.

Tablet and capsules shown are not actual size.

References
  1. Mydayis [package insert]. Lexington, MA; Shire US Inc.
  2. Adderall XR [package insert]. Wayne, PA: Shire US Inc.
  3. Spencer TJ, Adler LA, Weisler RH, Youcha SH. Triple-bead mixed amphetamine salts (SPD465), a novel, enhanced extended-release amphetamine formulation for the treatment of adults with ADHD: a randomized, double-blind, multicenter, placebo-controlled study. J Clin Psychiatry. 2008;69(9):1437-1448.
  4. Jain R, Katic A. Current and investigational medication delivery systems for treating attention-deficit/hyperactivity disorder. Prim Care Companion CNS Disord. 2016;18(4):doi:10.4088/PCC.16r01979.

INDICATION AND LIMITATIONS OF USE

MYDAYIS® is indicated for the treatment of ADHD in patients ≥13 years. Patients ≤12 years experienced higher plasma exposure at the same dose and higher rates of adverse reactions, mainly insomnia and decreased appetite.

IMPORTANT SAFETY INFORMATION

WARNING: ABUSE AND DEPENDENCE

  • CNS stimulants, including Mydayis, other amphetamine-containing products, and methylphenidate, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing and monitor for signs of abuse and dependence while on therapy.
  • Contraindications
    • Known hypersensitivity to amphetamines or other ingredients of Mydayis. Angioedema and anaphylactic reactions have been reported with other amphetamines.
    • Use with monoamine oxidase inhibitors (MAOIs) or within 14 days of last MAOI dose, due to increased risk of hypertensive crisis.
  • Warnings and Precautions
    • Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia, coronary artery disease, and other serious heart problems. Sudden death, stroke and myocardial infarction have been reported in adults with CNS stimulants at recommended doses, as well as sudden death in pediatric patients with structural cardiac abnormalities and other serious heart problems while taking CNS stimulants at recommended doses. Further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during Mydayis treatment.
    • CNS stimulants cause increased blood pressure (mean increase ~2-4 mm Hg) and heart rate (mean increase ~3-6 bpm). Monitor for tachycardia and hypertension.
    • Exacerbation of Pre-existing Psychosis : May exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder. Induction of a Manic Episode in Patients with Bipolar Disorder : May induce a mixed/manic episode in patients with bipolar disorder. Prior to initiating treatment, screen for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms, or a family history of suicide, bipolar disorder, and depression). New Psychotic or Manic Symptoms : At recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients with no prior history of psychotic illness or mania. Discontinue if symptoms occur.
    • CNS stimulants are associated with weight loss and slowing of growth rate in pediatric patients (monitor weight and height). Treatment may need to be interrupted in patients not growing or gaining weight as expected. Mydayis is not approved in pediatric patients ≤12 years.
    • CNS stimulants are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; very rare sequelae include digital ulceration and/or soft tissue breakdown. Careful observation for digital changes is necessary during treatment with ADHD stimulants; further evaluation and referral may be required.
    • Mydayis may lower the convulsive threshold in patients with prior history of seizure, prior EEG abnormalities in the absence of seizures, and in patients without a history of seizures and no prior EEG evidence of seizures. Discontinue if a seizure occurs.
    • Increased risk of serotonin syndrome when co-administered with serotonergic agents (e.g., SSRIs, SNRIs, triptans), but also during overdosage situations. Discontinue Mydayis if it occurs and initiate supportive treatment.
    • To avoid substitution errors and overdosage, do not substitute for other amphetamines on a mg-per-mg basis because of different amphetamine base compositions and differing PK profiles.
  • Adverse Reactions
    Most common adverse reactions in patients with ADHD (incidence ≥5% and at a rate at least twice placebo) are:
    • Pediatrics (13 years and older) : insomnia, decreased appetite, decreased weight, irritability, and nausea.
    • Adults : insomnia, decreased appetite, decreased weight, dry mouth, increased heart rate, and anxiety.
  • Pregnancy and Lactation
    Mydayis may cause fetal harm. Breastfeeding is not recommended during Mydayis treatment.

Please click for Full Prescribing Information.

Takeda is committed to helping ensure the proper use of stimulant medication. Please see the Proper Use of Prescription Stimulant Medication for additional information.

MYDAYIS and the MYDAYIS logo are registered trademarks of Takeda Pharmaceuticals U.S.A., Inc. TAKEDA and the TAKEDA logo are registered trademarks of Takeda Pharmaceutical Company Limited. ©2021 Takeda Pharmaceuticals U.S.A., Inc. All rights reserved. 1-800-828-2088. Takeda Pharmaceuticals U.S.A., Inc., 95 Hayden Avenue, Lexington, Massachusetts 02421.

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US-MIX-0094v1.0 01/21

INDICATION AND LIMITATIONS OF USE

MYDAYIS® is indicated for the treatment of ADHD in patients ≥13 years. Patients ≤12 years experienced higher plasma exposure at the same dose and higher rates of adverse reactions, mainly insomnia and decreased appetite.

IMPORTANT SAFETY INFORMATION

WARNING: ABUSE AND DEPENDENCE

  • CNS stimulants, including Mydayis, other amphetamine-containing products, and methylphenidate, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing and monitor for signs of abuse and dependence while on therapy.
  • Contraindications
    • Known hypersensitivity to amphetamines or other ingredients of Mydayis. Angioedema and anaphylactic reactions have been reported with other amphetamines.
    • Use with monoamine oxidase inhibitors (MAOIs) or within 14 days of last MAOI dose, due to increased risk of hypertensive crisis.
  • Warnings and Precautions
    • Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia, coronary artery disease, and other serious heart problems. Sudden death, stroke and myocardial infarction have been reported in adults with CNS stimulants at recommended doses, as well as sudden death in pediatric patients with structural cardiac abnormalities and other serious heart problems while taking CNS stimulants at recommended doses. Further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during Mydayis treatment.
    • CNS stimulants cause increased blood pressure (mean increase ~2-4 mm Hg) and heart rate (mean increase ~3-6 bpm). Monitor for tachycardia and hypertension.
    • Exacerbation of Pre-existing Psychosis : May exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder. Induction of a Manic Episode in Patients with Bipolar Disorder : May induce a mixed/manic episode in patients with bipolar disorder. Prior to initiating treatment, screen for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms, or a family history of suicide, bipolar disorder, and depression). New Psychotic or Manic Symptoms : At recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients with no prior history of psychotic illness or mania. Discontinue if symptoms occur.
    • CNS stimulants are associated with weight loss and slowing of growth rate in pediatric patients (monitor weight and height). Treatment may need to be interrupted in patients not growing or gaining weight as expected. Mydayis is not approved in pediatric patients ≤12 years.
    • CNS stimulants are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; very rare sequelae include digital ulceration and/or soft tissue breakdown. Careful observation for digital changes is necessary during treatment with ADHD stimulants; further evaluation and referral may be required.
    • Mydayis may lower the convulsive threshold in patients with prior history of seizure, prior EEG abnormalities in the absence of seizures, and in patients without a history of seizures and no prior EEG evidence of seizures. Discontinue if a seizure occurs.
    • Increased risk of serotonin syndrome when co-administered with serotonergic agents (e.g., SSRIs, SNRIs, triptans), but also during overdosage situations. Discontinue Mydayis if it occurs and initiate supportive treatment.
    • To avoid substitution errors and overdosage, do not substitute for other amphetamines on a mg-per-mg basis because of different amphetamine base compositions and differing PK profiles.
  • Adverse Reactions
    Most common adverse reactions in patients with ADHD (incidence ≥5% and at a rate at least twice placebo) are:
    • Pediatrics (13 years and older) : insomnia, decreased appetite, decreased weight, irritability, and nausea.
    • Adults : insomnia, decreased appetite, decreased weight, dry mouth, increased heart rate, and anxiety.
  • Pregnancy and Lactation
    Mydayis may cause fetal harm. Breastfeeding is not recommended during Mydayis treatment.

Please click for Full Prescribing Information.

Takeda is committed to helping ensure the proper use of stimulant medication. Please see the Proper Use of Prescription Stimulant Medication for additional information.

Sours: https://www.mydayis-pro.com/mechanism-of-delivery/mixed-amphetamine-salts

The mixed amphetamine salt extended release (Adderall XR, Max-XR) as an adjunctive to SSRIS or SNRIS in the treatment of adult ADHD patients with comorbid partially responsive generalized anxiety: an open-label study

To examine the changes in partially responsive anxiety symptoms utilizing adjunctive treatment with the mixed amphetamine salt extended release (Adderall XR, MAX-XR) in the treatment of adult ADHD patients, with comorbid refractory anxiety. Consenting adult patients (n = 32) with confirmed diagnosis of generalized anxiety (GA) and comorbid (ADHD) participated in this open-label study. All patients had significant comorbid anxiety symptoms (HAM-A > 7) and failed to respond to 8-week trials of Serotonin Reuptake Inhibitors (SSRIs) or Norepinephrine Reuptake inhibitors (SNRIs). All patients were treated with the "Mixed Amphetamine salts Extended Release Adderall XR, (MAS-XR), as adjunctive to SSRIs or to SNRIs and were followed for at least 12 weeks. The primary effectiveness measure was the Clinical Global Impression severity subscale (CGI-S). Other scales included the Hamilton Anxiety Scale (HAM-A), the adult ADHD Self-Report Scale (ASRS-v1.1) symptom checklist, and Sheehan's disability scale. Baseline measures prior to the treatment with MAS-XR were compared to those at 4, 8, and at 12 weeks of treatment. Monitoring for pulse, blood pressure, and weight changes was carried out at baseline and at end point. All patients completed this open-label trial. There was significant and robust resolution of symptoms of all effectiveness measures, including the symptoms of anxiety, as shown by changes from baseline in HAM-A, ASRS-v1.1, and CGI at 8 weeks. Also there was significant reduction in the disability score at 12 weeks. Patients tolerated the treatment, and there were no significant cardiovascular changes at 12 weeks. There was decrease in mean weight at 12 weeks by 2.2 kg (P < .001). Mixed amphetamine salts MAS-XR can be used in adult patients with ADHD and comorbid anxiety symptoms. Larger controlled studies are needed to support the effectiveness of mixed amphetamine salts in patients with comorbid anxiety symptoms. Treatments need to include the targeting of the ADHD symptoms effectively in order to achieve better resolution of anxiety symptoms.

Sours: https://pubmed.ncbi.nlm.nih.gov/21432593/
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Dexedrine vs. Adderall: Differences, similarities, and which is better for you

Drug overview & main differences | Conditions treated | Efficacy | Insurance coverage and cost comparison | Side effects | Drug interactions | Warnings | FAQ

Dexedrine and Adderall are two prescription medications classified as central nervous system (CNS) stimulants. Dexedrine and Adderall are brand-name medications, but they have generics available. These two CNS stimulants are used in the treatment of a condition known as attention deficit hyperactivity disorder (ADHD) as well as narcolepsy. These drugs affect neurotransmitters in the brain which affect how focused and alert a patient feels.

What are the main differences between Dexedrine and Adderall?

Dexedrine is a brand medication whose generic is dextroamphetamine sulfate. It is a CNS stimulant, and more specifically, it is a type of amphetamine. Amphetamines stimulate the release of norepinephrine, and the primary site of this activity is in the cerebral cortex of the brain. CNS stimulation by amphetamines leads to a decreased sense of fatigue, increased motor activity and alertness, and an overall better mood. Dexedrine (Dexedrine details) is FDA approved in the treatment of ADHD and narcolepsy. It is also used off-label, or without approval from the FDA, in the treatment of certain types of obesity-resistant to other interventions. Dexedrine is available in immediate-release tablets, spansules, and extended-release capsules are available as well.

Adderall is a combination of amphetamine salts, containing a 3 to 1 ratio of dextroamphetamine (d-amphetamine) and levoamphetamine (l-amphetamine). It contains the active ingredient of Dexedrine, combined with other amphetamines. It is a prescription drug used in the treatment of ADHD and narcolepsy and works in the same manner as Dexedrine. Adderall is available in a much wider range of strengths as compared to Dexedrine. Adderall (Adderall details) comes in immediate-release tablets. Adderall XR is an extended-release capsule formulation.

The Drug Enforcement Agency (DEA) deems Dexedrine and Adderall schedule II narcotic drugs. Due to the fact that they are habit-forming and have a high potential for abuse, there are restrictions and guidelines for obtaining these drugs, which vary by state.

Main differences between Dexedrine and Adderall
Drug classCentral nervous system stimulantCentral nervous system stimulant
Brand/generic statusBrand and generic availableBrand and generic available
What is the generic name?Dextroamphetamine sulfateAmphetamine salts (d-amphetamine and l-amphetamine)
What form(s) does the drug come in?Tablets, spansules, and extended-release capsulesTablets and extended-release capsules
What is the standard dosage?5 mg once or twice daily titrated up to 40 mg/day5 mg once or twice daily titrated up to 60 mg/day
How long is the typical treatment?Long-term (indefinite)Long-term (indefinite)
Who typically uses the medication?Children and adolescents 3 years of age and older; adultsChildren and adolescents 3 years of age and older; adults

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Conditions treated by Dexedrine and Adderall

Dexedrine and Adderall are indicated in the treatment of ADHD. ADHD is characterized by moderate to severe distractibility, short attention span, hyperactivity, and impulsivity. If left untreated, ADHD can affect academic and professional performance, as well as basic daily functions.

Dexedrine and Adderall are each indicated in the treatment of narcolepsy as well. Narcolepsy is excessive and uncontrollable daytime sleepiness. Like ADHD, untreated narcolepsy can have negative effects on day-to-day activities.

Dexedrine is used off-label in the short-term (few weeks duration) treatment of obesity that has not been responsive to other interventions such as diet, exercise, group programs, or other drugs.

Only your physician can determine what treatment is best for your condition.

Attention hyperactivity deficit disorder (ADHD)YesYes
NarcolepsyYesYes
Refractory obesityOff-labelNo

Is Dexedrine or Adderall more effective?

An analysis of 19 studies compares amphetamine-type treatments to placebo in the treatment of ADHD. In general, the analysis showed that amphetamine treatments reduced the severity of ADHD symptoms but were also linked with a higher number of patients who withdrew from the studies due to side effects. When comparing Dexedrine and Adderall directly, studies appeared to show that while Adderall showed an ability to decrease symptoms of ADHD overall, there was no evidence that Dexedrine reduced ADHD symptoms. Based on this information, Adderall may be preferred over Dexedrine.

Only your physician can decide which treatment is best for you.

Coverage and cost comparison of Dexedrine vs. Adderall

Dexedrine is a prescription medication that is typically covered by commercial insurance. Coverage by Medicare plans may vary or require special exceptions to be made. The out-of-pocket price for Dexedrine can cost more than $800. A coupon from SingleCare can bring the generic price to less about $91.

Get the SingleCare prescription discount card

Adderall is a prescription medication that is typically covered by commercial insurance. Coverage by Medicare plans may vary or require special exceptions to be made. The out-of-pocket price for Adderall can be more than $300. A coupon from SingleCare can bring the price of the generic to approximately $230 for 30, 20 mg tablets at select pharmacies.

Typically covered by insurance?YesYes
Typically covered by Medicare Part D?NoNo
Standard dosage30, 15 mg ER capsules60, 30 mg tablets
Typical Medicare copayn/an/a
SingleCare cost$91-$145$29-$50

Dexedrine and Adderall have a similar list of potential adverse effects. This is expected due to the similarities in ingredients. Dexedrine and Adderall have been linked to serious side effects such as elevated blood pressure, tachycardia, and palpitation. In some instances, myocardial infarction (heart attack) and sudden death have occurred. Caution should be used when prescribing stimulants in patients when pre-existing cardiac abnormalities.

Dexedrine and Adderall may lead to a sleep disorder known as insomnia, or an inability to fall and stay asleep. This can affect daily functioning and should be monitored. These drugs are also known to cause dry mouth and dizziness. You should discuss these adverse events with your healthcare provider if they occur and are bothersome.

The following is not intended to be an all-inclusive list of potential side effects. A complete list can be obtained from your healthcare professional.

Side effectApplicable?FrequencyApplicable?Frequency
High blood pressureYesNot definedYesNot defined
TachycardiaYesNot definedYesNot defined
PalpitationYesNot definedYesNot defined
InsomniaYesNot definedYesNot defined
Loss of appetiteYesNot definedYesNot defined
VomitingYesNot definedYesNot defined
Weight lossYesNot definedYesNot defined
Dry mouthYesNot definedYesNot defined
DizzinessYesNot definedYesNot defined

Source: Dexedrine (DailyMed)  Adderall (DailyMed).

Drug interactions of Dexedrine vs. Adderall

Dexedrine and Adderall, when used concurrently with serotonergic drugs, may increase the incidence of serotonin syndrome. This syndrome can result in the patient feeling agitated, dizzy, and having an increased heart rate. Common antidepressants such as selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors, as well as the pain medication Tramadol, may cause this interaction with Dexedrine or Adderall.

Dexedrine and Adderall should not be used in patients taking monoamine oxidase inhibitors (MAOIs). MAO inhibitors slow amphetamine metabolism, increasing the amphetamine’s effect on the release of norepinephrine and other monoamines from the nerve endings causing headaches and other signs of hypertensive crisis.

The following list is not intended to be a complete list of drug interactions. It is best to consult your doctor or pharmacist for a complete list.

Warnings of Dexedrine and Adderall

Dexedrine and Adderall have each been associated with strokes, myocardial infarction, and sudden death in children and adults. These may be more likely to occur in patients with pre-existing cardiac conditions. Prescribers should screen for these conditions and use extreme caution in prescribing these drugs for patients who may have cardiac abnormalities.

Dexedrine and Adderall, along with other CNS stimulants, have been associated with moderate increases in blood pressure and heart rate. These parameters should be monitored when patients take stimulants.

Some types of ADHD medication, such as Dexedrine and Adderall, can exacerbate behavior disturbances in patients with pre-existing psychiatric disorders. These patients should be monitored closely if CNS stimulants are necessary. Bipolar patients may experience mixed or manic episodes while on CNS stimulants.

Long-term use of stimulants in children and adolescents has been linked to growth suppression. Patients experiencing slow growth while on stimulants may be encouraged to temporarily pause treatment. Oftentimes, healthcare providers recommend taking breaks from treatment when children are not in school, such as on weekends, holidays, and summer breaks.

If you have experienced allergic reactions to other stimulants or amphetamine drugs, you should not take Dexedrine or Adderall.

Frequently asked questions about Dexedrine vs. Adderall

What is Dexedrine?

Dexedrine is a CNS stimulant used in the treatment of ADHD and narcolepsy. It is considered a schedule II narcotic by the DEA due to its abuse potential and is available by prescription only. Dexedrine is available in a variety of strengths in immediate-release tablets and spansules, as well as extended-release capsules.

What is Adderall?

Adderall is a CNS stimulant used in the treatment of ADHD and narcolepsy. It is also considered a schedule II narcotic by the DEA due to its abuse potential and is available by prescription only. Adderall is available in a variety of strengths in both immediate-release tablets and extended-release capsules.

Are Dexedrine and Adderall the same?

Dexedrine and Adderall are similar drugs but are not exactly the same. Dexedrine is composed of dextroamphetamine sulfate, while Adderall is made of mixed amphetamine salts, including dextroamphetamine. Both drugs are CNS stimulants and have similar side effects and drug interaction profiles.

Is Dexedrine or Adderall better?

Collective data across multiple studies comparing amphetamine treatments to placebo in the treatment of ADHD showed that Adderall may be preferred as it showed some improvement in ADHD symptoms, while Dexedrine did not. Amphetamine drugs overall cause side effects that may make it difficult for some patients to continue treatment long term.

Can I use Dexedrine or Adderall while pregnant?

Dexedrine and Adderall are pregnancy category C, meaning there are no adequate, controlled studies to establish safety. These drugs should only be used in pregnancy when the benefit clearly outweighs the risk.

Can I use Dexedrine or Adderall with alcohol?

Alcohol use could increase the serum blood concentrations of Dexedrine and Adderall, and therefore alcohol should be avoided when on these medications.

Sours: https://www.singlecare.com/blog/dexedrine-vs-adderall/

What to Know About Adderall XR

Adderall XR is a central nervous system (CNS) stimulant most commonly used to treat attention-deficit/hyperactivity disorder (ADHD). Taken as an oral capsule, this medication works by altering norepinephrine and dopamine in the brain. It can increase concentration, help people stay on task longer, and manage behavioral issues associated with ADHD.

Adderall XR is the extended-release version of Adderall. Half the dose takes effect immediately, and the other half takes effect in about four hours.

The generic version is called amphetamine salt combo XR, and is made up of a combination of amphetamine and dextroamphetamine salts.

Finding the Best Treatment for ADHD

Uses

Adderall XR is only FDA-approved to treat ADHD (notably, the immediate-release version of the medication is also approved to treat narcolepsy). It may be prescribed for use in children age 6 to 12, adolescents age 13 to 17, and adults.

Off-Label Uses

While Adderall XR is only approved to treat ADHD, some research indicates it may be useful in treating children who have ADHD and oppositional defiant disorder (ODD). Stimulants, in general, may be used as an adjunct for treatment-resistant depression, though the research is not clear on their efficacy.

Due to some of its side effects, like improved focus and weight loss, Adderall and Adderall XR have gained reputations as recreational drugs. It's important to note that these medications should not be taken without a doctor's supervision, as they can be habit-forming, and they carry their own set of risks and contraindications.

Before Taking

A prescription for Adderall XR will likely involve being evaluated for ADHD. If your child is 16 years old or younger and is being examined for the condition, their doctor will look for symptoms of inattention like:

  • Failing to listen when spoken to
  • Making careless mistakes or failing to pay attention to their schoolwork or other tasks
  • Frequently losing things they need
  • Struggling to keep their attention on tasks they're working on
  • Being distracted easily
  • Struggling to follow through on instructions
  • Failing to finish schoolwork or chores
  • Frequently forgetting things
  • Avoiding or feeling reluctant to do tasks that require sustained mental effort

Your child's doctor will check for symptoms of hyperactivity and impulsivity, which can include:

  • Failing to remain seated
  • Talking excessively
  • Fidgeting, squirming, or tapping hands or feet
  • Struggling to wait
  • Blurting out answers
  • Interrupting others
  • Running or climbing at inappropriate times
  • Struggling to remain quiet while playing
  • Acting as if they're always "on the go"

Before making a diagnosis of ADHD, a doctor will also need to determine if your child:

  • Shows six or more symptoms of inattention and hyperactivity-impulsivity
  • First experienced those symptoms before age 7
  • Has had these symptoms for at least six months
  • Notices their symptoms in two or more settings (like in school and at home)
  • Is having trouble functioning in social situations or at school
  • Has another mental condition that could explain their condition

These diagnostic criteria differ for adolescents age 17 and older and in adults. In those cases, five of these symptoms are enough to make a diagnosis, and some symptoms may look very different in an adult compared to a child. Hyperactivity in an adult, for example, may involve reckless driving and fidgeting during meetings, and adults with ADHD may find themselves drawn to active jobs that don't require long periods of sitting or being still.

There isn’t a single diagnostic test for ADHD. A diagnosis requires the use of medical, psychological, educational, and social resources, and it's made based on your doctor's evaluation and on your or your child's history.

Adderall XR isn't intended to act as the sole treatment for someone with ADHD. This medication is often coupled with psychological, social, and/or educational interventions intended to help someone learn how to cope with their ADHD symptoms. In fact, your doctor may recommend trying to implement those interventions first before prescribing Adderall XR.

Patients who are taking divided doses of immediate-release Adderall (such as twice daily) may be switched to Adderall XR at the same total daily dose taken once daily. Adderall XR is titrated at weekly intervals to ensure that it’s well-tolerated. Your doctor should regularly reevaluate your prescription to ensure its long-term usefulness for reducing your symptoms.

Talk to your doctor about all medications, supplements, and vitamins that you currently take. While some drugs pose minor interaction risks, others may outright contraindicate use or prompt careful consideration as to whether the pros of treatment outweigh the cons in your case.

Diagnosing ADHD requires a variety of resources and a comprehensive patient history and evaluation, and Adderall XR should be used as part of a total treatment plan. Other treatment measures may include psychological, educational, and social support.

Precautions and Contraindications

Non-drug interventions are often helpful for people with ADHD, and medication should only be used when those interventions fail to resolve symptoms. Your doctor's willingness to consider stimulant medication may depend on how chronic and severe your symptoms are. Amphetamines carry a risk of overdosage, so the smallest amount possible should always be prescribed.

Adderall XR should not be taken by people with:

  • Advanced arteriosclerosis
  • Glaucoma
  • History of agitated states
  • History of drug abuse
  • Hypersensitivity to stimulants (which can show up as serious skin rashes, anaphylaxis, or angioedema, which is rapid swelling under the skin)
  • Hyperthyroidism
  • Moderate to severe hypertension
  • Symptomatic cardiovascular disease

Adderall XR should also be avoided if you’ve taken monoamine oxidase inhibitors (MAOIs) within the last 14 days.

Stimulant medications can increase blood pressure and average heart rate. While some people may experience larger increases, on average, this amounts to a 2 to 4 mmHg increase in blood pressure and an increased heart rate of approximately three to six beats per minute. Alone, these increases aren't likely to lead to serious consequences, but people taking stimulants should be monitored for larger changes in blood pressure and heart rate.

Extra caution may be warranted for people with certain underlying cardiovascular conditions, like:

  • Heart failure
  • Pre-existing hypertension
  • Recent heart attack
  • Ventricular arrhythmia

Before starting Adderall XR, your doctor should complete an assessment to check for any family history of sudden death or ventricular arrhythmia and conduct a thorough physical exam to check for cardiac disease.

Anyone currently taking a stimulant should undergo an immediate cardiac evaluation if they experience symptoms like:

  • Chest pain as a result of exertion
  • Unexplained fainting (known as syncope)
  • Other symptoms that could suggest cardiac problems

Stimulants may also carry risks for people with pre-existing mental health conditions. These can include:

  • A history of psychosis or a psychotic disorder, as stimulants may exacerbate symptoms
  • Bipolar disorder, as these medications could induce a manic or "mixed" episode, which includes depressive and manic symptoms simultaneously

Before beginning any stimulant, it's important that you or your child are screened thoroughly for the presence of any existing psychiatric condition, particularly psychosis and bipolar disorder.

Stimulants also carry a low risk (about 0.1%) of causing psychotic or manic symptoms in children or adolescents without a prior history of those conditions. Symptoms may include:

  • Hallucinations
  • Delusions
  • Manic episodes

If symptoms occur, discontinuation of treatment may be appropriate.

Aggressive behavior is a common symptom seen in children with ADHD. Although there is no evidence that stimulants cause aggressive behavior or hostility, patients who are starting treatment for ADHD should be monitored for increased aggression or hostility.

Understanding Anger in Children With ADHD

Adderall XR carries other risks that you should be aware of. For instance:

  • Stimulant use may impact growth in children. If your child is taking Adderall XR and isn't growing or gaining weight, you may need to check with their doctor on interrupting their treatment.
  • These medications can be problematic for people with seizures.Stimulants may increase the likelihood of a seizure for people with a prior history of them, with established electroencephalogram (EEG) abnormalities, or, very rarely, for people without a history of this condition. If seizures are present, Adderall XR shouldn't be taken.
  • Stimulant treatment can disrupt vision. Blurred vision may occur with this type of medication.
  • Stimulants may cause blood circulation problems. These medications are associated with disrupted circulation to the extremities (called peripheral vasculopathy) and with Raynaud's phenomenon, which involves decreased blood flow to certain areas of the body, like the fingers or toes.
  • Tics may worsen with stimulant usage. If you or your child has Tourette's syndrome, Adderall XR could worsen motor and vocal tics.
  • Adderall XR could impair your ability to operate machinery or vehicles. You should use caution while operating vehicles and hazardous machinery, especially if you're just beginning to take this medication.

Other Stimulants

Together with the immediate-release version of Adderall, other common stimulants used to treat ADHD include:

  • Aptensio XR, Concerta, and Metadate ER (methylphenidate extended release)
  • Daytrana
  • Desoxyn (methamphetamine)
  • Dexedrine (dextroamphetamine)
  • Dyanavel XR (amphetamine)
  • Evekeo (amphetamine sulfate)
  • Focalin XR (dexmethylphenidate extended release)
  • Methylin (methylphenidate chewable tablets and solution)
  • ProCentra (dextroamphetamine sulfate oral solution)
  • Quillivant XR (methylphenidate extended release oral suspension)
  • Ritalin (methylphenidate) and Ritalin SR (methylphenidate SR) 
  • Vynase (lisdexamfetamine)

Dosage

Adderall XR is administered at the lowest effective dose, and dosages depend on the therapeutic needs and response of each individual.

All listed dosages are according to the manufacturer. Check your prescription, and talk to your doctor to make sure you are taking the right dose for you.

In children who are between the ages of 6 and 12, medication is often started at 10 milligrams (mg) once daily in the morning. The dosage may be adjusted in increments of 5 or 10 mg at weekly intervals. There may be times when a physician decides to start the dose at 5 mg once in the morning.

The maximum recommended dose for children 6 to 12 years of age is 30 mg per day. Doses greater than 30 mg per day have not been studied in children, and Adderall XR has not been studied in children under 6 years of age.

In adolescents with ADHD who are between the ages of 13 and 17, the recommended starting dose is 10 mg per day. The dose may be increased to 20 mg per day after one week if their ADHD symptoms are not adequately controlled.

In adults, the recommended dose is 20 mg per day.

Adderall XR comes in capsules with several dosage options, each with differentiating color combinations:

  • 5 mg capsules (clear and blue)
  • 10 mg capsules (blue and blue)
  • 15 mg capsules (blue and white)
  • 20 mg capsules (orange and orange)
  • 25 mg capsules (orange and white)
  • 30 mg capsules (natural and orange)

Capsules should be taken by mouth and swallowed whole. They should not be chewed or crushed, as this could release all the medication at once and increase the risk of side effects.

Modifications

The entire contents of a capsule may be sprinkled on a small amount of applesauce just before taking. The mixture should be swallowed immediately and should not be chewed. This may be particularly helpful for young children who are resistant to taking the medication.

How to Take and Store

Adderall XR can be taken with or without food as directed by your physician. It is usually taken once in the morning and should be taken the same way with every dose (such as with or without food). Drink a glass of liquid after each dose.

If you forget to take your medication, take it as soon as possible. Take caution when taking it in the afternoon, however, as it may interfere with sleep when it's taken too close to bedtime. You should also avoid doubling up on this medication—if it's almost time for your next dose, skip the one you missed and go back to your normal schedule.

Overdoses are possible with this medication, and they can be fatal. Symptoms include:

  • Abdominal cramps
  • Aggressiveness
  • Arrhythmias
  • Circulatory collapse
  • Confusion
  • Convulsions and coma
  • Diarrhea
  • Fatigue and depression after the stimulant wears off
  • Hallucinations
  • High fever over 106 F (known as hyperpyrexia)
  • Hypertension or hypotension
  • Nausea
  • Overactive reflexes (known as hyperreflexia)
  • Panic
  • Rapid breathing
  • Restlessness
  • Rhabdomyolysis, a condition where the muscles break down
  • Tremors
  • Vomiting

If you believe that you or a loved one has overdosed on Adderall XR, seek help immediately. In the United States, you can contact the Poison Control Center at 1-800-222-1222 or call 911 right away for help.

Store Adderall XR at room temperature (59 F to 86 F). This medication is a controlled substance and should be kept in a secure, safe place in a tightly closed container.

Since Adderall XR is a controlled substance, you should consider planning ahead if you need to travel. While Adderall XR is approved for use across the United States, you may need to comply with different drug labeling requirements while traveling from state to state. Your safest option may be to keep your medication in its original, prescribed container and ensure that you travel with roughly the amount you need—don't bring a large number of extra doses. If you plan to fly, you should keep your medication with you in a carry-on bag or purse, rather than checking it.

Traveling internationally with Adderall XR presents different problems, as this medication is not legal in certain countries. Check with the foreign embassy in your destination to determine if your medication is restricted in any way; if so, you'll likely need to comply with strict requirements for documentation. You should also speak with your doctor about what to do if you run out of medication while abroad.

Side Effects 

Adderall XR has a number of possible side effects, which can range from mild to severe. It is important to talk to your doctor about what to expect while taking Adderall XR, and you should always keep them informed about any new or unexpected reactions you experience.

Common

Side effects can vary depending on age. For children age 6 to 12, the most common are:

  • Abdominal pain
  • Emotional lability, or rapid mood changes
  • Fever
  • Insomnia
  • Loss of appetite
  • Nausea
  • Nervousness
  • Vomiting

In adolescents age 13 to 17, the most common side effects include:

  • Abdominal pain
  • Insomnia
  • Loss of appetite
  • Nervousness
  • Weight loss

Common side effects for adults are:

  • Agitation
  • Anxiety
  • Diarrhea
  • Dizziness
  • Dry mouth
  • Feeling weak
  • Headache
  • Insomnia
  • Loss of appetite
  • Nausea
  • Tachycardia (rapid heartbeat)
  • Urinary tract infection
  • Weight loss

Severe

Severe side effects of Adderall XR can include:

  • Allergic reactions 
  • Depression
  • Eyesight changes or blurred vision
  • Heart attack
  • Impotence
  • Increased blood pressure
  • Psychotic episodes
  • Seizures
  • Slowing of growth or height in children
  • Stroke
  • Sudden death due to existing heart problems
  • Trouble operating vehicles or machinery

If you are taking too high of a dosage of Adderall XR, you might experience symptoms like:

  • Hyperactivity
  • Irritability
  • Marked insomnia
  • Personality changes
  • Psychosis that's indistinguishable from schizophrenia
  • Severe skin issues, like lesions

Warnings and Interactions

Adderall XR is a Schedule II drug (meaning it has a high potential for abuse) and a controlled substance. It carries risks of abuse and dependence, and these risks may be higher if you’ve experienced a substance use disorder in the past. It's important that you follow your doctor's orders and do not increase the dose, take it more often, or use it for a longer period of time than is prescribed.

If you decide to stop taking Adderall XR, you should work closely with your doctor. Quitting cold turkey may lead to withdrawal symptoms (such as severe tiredness, sleep problems, or mental/mood changes like depression). Withdrawal symptoms are more likely if you have used this medication for a long time or in high doses. You should only decrease your dose or discontinue your medication under the supervision of your physician.

Adderall XR may interact with other medications and cause serious side effects, so it’s important to talk to your doctor about any prescription and non-prescription medicines, vitamins, and herbal supplements that you or your child take. Tell your doctor if you or your child takes:

  • Antidepressants
  • Antihistamines
  • Antipsychotics
  • Blood pressure medicines
  • Blood thinners
  • Lithium
  • MAOIs
  • Medication for seizures
  • Opioid pain medication
  • Stomach acid medicines

Adderall XR has not been evaluated for use in children under 6 years of age or in older adults.

If you are pregnant or are trying to become pregnant, discuss your options with your doctor. While it's not clear if Adderall XR is safe to take during pregnancy, data from animal testing show that there is a possible danger to the fetus, and there are well-established side effects for infants born to mothers with a dependency on amphetamines.

That said, Adderall XR may be used during pregnancy if the benefit to the mother outweighs those potential risks. Nursing mothers, however, should not breastfeed while taking this medication, as amphetamines can travel through the breastmilk.

It's important to remain under the care of a physician while taking Adderall XR. Your doctor can ensure you remain safe and free from serious side effects while evaluating your dosage and long-term treatment plan.

What to Know About Vyvanse and Adderall for ADHD

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Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

  1. FDA. Adderall XR label.

  2. Spencer TJ, Abikoff HB, Connor DF, et al. Efficacy and safety of mixed amphetamine salts extended release (Adderall xr) in the management of oppositional defiant disorder with or without comorbid attention-deficit/hyperactivity disorder in school-aged children and adolescents: A 4-week, multicenter, randomized, double-blind, parallel-group, placebo-controlled, forced-dose-escalation study. Clin Ther. 2006;28(3):402-418. doi:10.1016/j.clinthera.2006.03.006

  3. Malhi GS, Byrow Y, Bassett D, et al. Stimulants for depression: On the up and up? Aust N Z J Psychiatry. 2016;50(3):203-207. doi:10.1177/0004867416634208

  4. Vital Record, Texas A&M Health. You Asked: What does Adderall do to your body? 

  5. CDC. Symptoms and diagnosis of ADHD.

Sours: https://www.verywellmind.com/adderall-xr-4780485

Salt adderall

Amphetamine excretion profile following multidose administration of mixed salt amphetamine preparation

Interpretation of drug testing results requires detailed scientific information, particularly in those cases where the question of legitimate use versus illicit use arises. Amphetamine remains a widely abused drug throughout the world, although it is also used therapeutically for weight loss, narcolepsy, and attention-deficit disorder with hyperactivity (ADHD). Treatment of ADHD using stimulant drugs is much more common now than it was in even the recent past. Increasingly, older individuals are diagnosed and treated for ADHD, and treatment often continues into adulthood. Amphetamine is commonly used for the treatment of ADHD and is available by prescription as either the d-enantiomer or a mixture of enantiomers. Although used for many years, there are no data available to describe the excretion profile of amphetamine and its enantiomers following repeated use of the drug. As a result, medical review officers (MROs) and forensic toxicologists have no direct evidence to base their decisions on when it comes to evaluation of use of these drugs. The current study was designed to determine the concentration and enantiomer excretion profile following repeated daily administration of mixed enantiomers of amphetamine. Twenty milligrams of Adderall was administered daily to five healthy subjects with all subsequent ad lib urine samples collected for at least five days following administration of the five-dose regimen. Adderall is a 3:1 mixture of d- and l-enantiomers of amphetamine salts and represents the mixed enantiomer proportion of amphetamine available in the United States through pharmaceutical channels. Peak amphetamine concentrations ranged from 5739 to 19,172 ng/mL. Samples containing > or = 500 ng/mL amphetamine (the administrative cutoff for a positive result by gas chromatography-mass spectrometry) were seen up to 60:15 (h:min) following administration of the last dose. Enantiomer analysis showed the d-enantiomer to be in excess of the l-enantiomer for as long as the drug was administered. After administration of the last dose of drug, the proportion of l-enantiomer increased over time. Not all samples that contained > or = 500 ng/mL total amphetamine were positive when tested by immunoassay because of the differing cross-reactivity of the enantiomers. This study provides the first description of the excretion of amphetamine following repeated administration of Adderall. The presence of the l-enantiomer separates this drug from other formulations composed of only the d-enantiomer (i.e., Dexedrine and much illicit amphetamine), thus readily differentiating them from Adderall use. Some illicit and medicinal amphetamine is, however, a mixture of amphetamine enantiomers. Because the enantiomers are metabolized at different rates, their proportion offers the opportunity to describe excretion versus time. Coupling this data with drug concentration makes it possible for forensic toxicologists and MROs to come to an informed decision regarding the involvement of this drug in a positive drug test result.

Sours: https://pubmed.ncbi.nlm.nih.gov/15516315/

Concerta vs. Adderall: A Side-by-Side Comparison

Similar drugs

Concerta and Adderall are medications used to treat attention deficit hyperactivity disorder (ADHD). These drugs help activate the areas of your brain that are responsible for focusing and paying attention.

Concerta and Adderall are the brand names of generic medications. The generic form of Concerta is methylphenidate. Adderall is a mixture of four different “amphetamine” salts mixed together to create a 3 to 1 ratio of dextroamphetamine and levoamphetamine.

A side-by-side comparison of these two ADHD medications shows that they’re similar in many ways. However, there are some differences.

Drug features

Concerta and Adderall help reduce hyperactivity and impulsive actions in people with ADHD. They’re both central nervous system stimulant drugs. This type of drug helps control the constant activity in ADHD, such as fidgeting. It also helps control impulsive actions that are common in people with certain forms of ADHD.

The table below compares features of these two drugs.

Dosage

Concerta is only available as an extended-release tablet. Adderall is available as an immediate-release and extended-release drug. In the immediate-release form, the tablet releases the drug into your system right away. In the extended-release form, the capsule slowly releases small amounts of medication into your body throughout the day.

If your doctor prescribes Adderall, they may start you on the immediate-release form at first. If you take the immediate-release form, you’ll likely need more than one dose per day. Eventually, they may change you to the extended-release form.

If you take an extended-release drug, you may only need one dose per day to manage your symptoms.

The standard dosage of each drug starts at 10–20 mg per day. However, your dosage depends on certain factors. This includes your age, other health issues you have, and how you respond to the drug. Children often take a smaller dosage than adults.

Always take your dosage as prescribed. If you routinely take too much, you may need more of the drug for it to be effective. These drugs also carry the risk of addiction.

How to take the medications

Swallow either drug whole with water. You can take them with or without food. Some people prefer to take their medication with breakfast so it won’t upset their stomachs.

If you have trouble swallowing Adderall, you may open the capsule and mix the granules with food. Do not cut or crush Concerta, however.

What are their side effects?

Concerta and Adderall share many potential side effects. Some are serious. For instance, both drugs can slow growth in children. Your child’s doctor may watch your child’s height and weight during treatment. If your doctor sees negative effects, they may take your child off the drug for a period of time.

If you have side effects from one drug, call your doctor right away. Your doctor may change your medication or adjust your dosage. Common side effects of Concerta and Adderall include:

Serious side effects of both drugs can include:

Concerta may also cause painful erections that last several hours in men.

Who should avoid Concerta or Adderall?

Perhaps the biggest difference between the drugs is who should avoid each one. Concerta and Adderall aren’t right for everyone. There are many drugs and health conditions that can change the way the medications work. For this reason, you may not be able to take one or both of the drugs.

Do not take either Concerta or Adderall if you:

Do not take Concerta if you have:

Do not take Adderall if you have:

Both drugs can also affect your blood pressure and how your heart works. They may cause sudden death in people with undiagnosed heart problems. Your doctor may check your blood pressure and heart function during treatment with these drugs. Talk to your doctor to learn more.

Also, both medications are pregnancy category C drugs. This means that some animal studies have shown harm to a pregnancy, but the drugs haven’t been studied enough in humans to know if they’re harmful to a human pregnancy. If you’re pregnant, breastfeeding, or planning to become pregnant, talk to your doctor to see if you should avoid either of these drugs.

Cost, availability, and insurance

Concerta and Adderall are both brand-name drugs. Brand-name drugs tend to cost more than their generic versions. In general, Adderall extended-release is more expensive than Concerta, according to a review by . However, the generic form of Adderall is less expensive than the generic form of Concerta.

Drug prices depend on many factors, though. Insurance coverage, geographic location, dosage, and other factors can all affect the price you pay. You can check GoodRx.com for current prices from pharmacies near you.

Final comparison

Concerta and Adderall are very similar in treating ADHD. Some people may respond better to one drug than the other. It’s important to share your full health history with your doctor. Tell them about all medications, vitamins, or supplements you take. This will help your doctor prescribe the right drug for you.

Sours: https://www.healthline.com/health/adhd/concerta-adderall

Similar news:

Adderall

Drug mixture used mainly to treat ADHD and narcolepsy

This article is about a common mixture of amphetamine salts. For general information about the drug and its racemate, see Amphetamine.

Adderall and Mydayis[4] are trade names[note 2] for a combination drug containing four salts of amphetamine. The mixture is composed of equal parts racemic amphetamine and dextroamphetamine, which produces a (3:1) ratio between dextroamphetamine and levoamphetamine, the two enantiomers of amphetamine. Both enantiomers are stimulants, but differ enough to give Adderall an effects profile distinct from those of racemic amphetamine or dextroamphetamine,[1][2] which are marketed as Evekeo and Dexedrine/Zenzedi, respectively.[1][6][7] Adderall is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance enhancer, cognitive enhancer, appetite suppressant, and recreationally as an aphrodisiac and euphoriant. It is a central nervous system (CNS) stimulant of the phenethylamine class.[1]

Adderall is generally well tolerated and effective in treating the symptoms of ADHD and narcolepsy. At therapeutic doses, Adderall causes emotional and cognitive effects such as euphoria, change in sex drive, increased wakefulness, and improved cognitive control. At these doses, it induces physical effects such as a faster reaction time, fatigue resistance, and increased muscle strength. In contrast, much larger doses of Adderall can impair cognitive control, cause rapid muscle breakdown, provoke panic attacks, or induce a psychosis (e.g., paranoia, delusions, hallucinations). The side effects of Adderall vary widely among individuals, but most commonly include insomnia, dry mouth, loss of appetite, and weight loss. The risk of developing an addiction or dependence is insignificant when Adderall is used as prescribed at fairly low daily doses, such as those used for treating ADHD; however, the routine use of Adderall in larger daily doses poses a significant risk of addiction or dependence due to the pronounced reinforcing effects that are present at high doses. Recreational doses of amphetamine are generally much larger than prescribed therapeutic doses, and carry a far greater risk of serious adverse effects.[sources 1]

The two amphetamine enantiomers that compose Adderall (levoamphetamine and dextroamphetamine) alleviate the symptoms of ADHD and narcolepsy by increasing the activity of the neurotransmittersnorepinephrine and dopamine in the brain, which results in part from their interactions with human trace amine-associated receptor 1 (hTAAR1) and vesicular monoamine transporter 2 (VMAT2) in neurons. Dextroamphetamine is a more potent CNS stimulant than levoamphetamine, but levoamphetamine has slightly stronger cardiovascular and peripheral effects and a longer elimination half-life than dextroamphetamine. The levoamphetamine component of Adderall has been reported to improve the treatment response in some individuals relative to dextroamphetamine alone.[citation needed] Adderall's active ingredient, amphetamine, shares many chemical and pharmacological properties with the human trace amines, particularly phenethylamine and N-methylphenethylamine, the latter of which is a positional isomer of amphetamine.[sources 2] In 2019, Adderall was the 24th most commonly prescribed medication in the United States, with more than 24 million prescriptions.[27][28]

Uses[edit]

30 Adderall XR 10 mg capsules

30 capsules of 10 mg Adderall XR

Adderall 20 mg tablets

A group of 20 mg Adderall tablets, some broken in half, with a lengthwise-folded US dollar bill along the bottom (3.07 inches; 7.8 cm) for size comparison

Medical[edit]

Part of this section is transcluded from Amphetamine. (edit | history)

Adderall is used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy (a sleep disorder).[29][9] Long-term amphetamine exposure at sufficiently high doses in some animal species is known to produce abnormal dopamine system development or nerve damage,[30][31] but, in humans with ADHD, pharmaceutical amphetamines, at therapeutic dosages, appear to improve brain development and nerve growth.[32][33][34] Reviews of magnetic resonance imaging (MRI) studies suggest that long-term treatment with amphetamine decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function in several parts of the brain, such as the right caudate nucleus of the basal ganglia.[32][33][34]

Reviews of clinical stimulant research have established the safety and effectiveness of long-term continuous amphetamine use for the treatment of ADHD.[35][36][37]Randomized controlled trials of continuous stimulant therapy for the treatment of ADHD spanning 2 years have demonstrated treatment effectiveness and safety.[35][36] 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 3] 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.[35][37] One review highlighted a nine-month randomized controlled trial of amphetamine treatment for ADHD in children that found an average increase of 4.5 IQ points, continued increases in attention, and continued decreases in disruptive behaviors and hyperactivity.[36] 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.[35]

Current models of ADHD suggest that it is associated with functional impairments in some of the brain's neurotransmitter systems;[19] these functional impairments involve impaired dopamine neurotransmission in the mesocorticolimbic projection and norepinephrine neurotransmission in the noradrenergic projections from the locus coeruleus to the prefrontal cortex.[19] Psychostimulants like methylphenidate and amphetamine are effective in treating ADHD because they increase neurotransmitter activity in these systems.[10][19][38] Approximately 80% of those who use these stimulants see improvements in ADHD symptoms.[39] 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.[40][41] The Cochrane reviews[note 4] 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.[43][44] A Cochrane review on the treatment of ADHD in children with tic disorders such as Tourette syndrome indicated that stimulants in general do not make tics worse, but high doses of dextroamphetamine could exacerbate tics in some individuals.[45]

Available forms[edit]

Adderall is available as immediate-release (IR) tablets or two different extended-release (XR) formulations.[9][46] The extended-release capsules are generally used in the morning.[47] A shorter, 12-hour extended-release formulation is available under the brand Adderall XR and is designed to provide a therapeutic effect and plasma concentrations identical to taking two doses 4 hours apart.[46] The longer extended-release formulation, approved for 16 hours, is available under the brand Mydayis. In the United States, the immediate and extended release formulations of Adderall are both available as generic drugs,[48][49] while Mydayis is available only as a brand-name drug.[citation needed]

Enhancing performance[edit]

Part of this section is transcluded from Amphetamine. (edit | history)

Cognitive performance[edit]

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;[50][51] these cognition-enhancing effects of amphetamine are known to be partially mediated through the indirect activation of both dopamine receptor D1 and adrenoceptor α2 in the prefrontal cortex.[10][50] A systematic review from 2014 found that low doses of amphetamine also improve memory consolidation, in turn leading to improved recall of information.[52] Therapeutic doses of amphetamine also enhance cortical network efficiency, an effect which mediates improvements in working memory in all individuals.[10][53] Amphetamine and other ADHD stimulants also improve task saliency (motivation to perform a task) and increase arousal (wakefulness), in turn promoting goal-directed behavior.[10][54][55] Stimulants such as amphetamine can improve performance on difficult and boring tasks and are used by some students as a study and test-taking aid.[10][55][56] Based upon studies of self-reported illicit stimulant use, 5–35% of college students use diverted ADHD stimulants, which are primarily used for enhancement of academic performance rather than as recreational drugs.[57][58][59] However, high amphetamine doses that are above the therapeutic range can interfere with working memory and other aspects of cognitive control.[10][55]

Physical performance[edit]

Amphetamine is used by some athletes for its psychological and athletic performance-enhancing effects, such as increased endurance and alertness;[11][23] however, non-medical amphetamine use is prohibited at sporting events that are regulated by collegiate, national, and international anti-doping agencies.[60][61] 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.[11][62][63] Amphetamine improves endurance and reaction time primarily through reuptake inhibition and release of dopamine in the central nervous system.[62][63][64] Amphetamine and other dopaminergic drugs also increase power output at fixed levels of perceived exertion by overriding a "safety switch", allowing the core temperature limit to increase in order to access a reserve capacity that is normally off-limits.[63][65][66] At therapeutic doses, the adverse effects of amphetamine do not impede athletic performance;[11][62] however, at much higher doses, amphetamine can induce effects that severely impair performance, such as rapid muscle breakdown and elevated body temperature.[12][62]

Adderall has been banned in the National Football League (NFL), Major League Baseball (MLB), National Basketball Association (NBA), and the National Collegiate Athletics Association (NCAA).[67] In leagues such as the NFL, there is a very rigorous process required to obtain an exemption to this rule even when the athlete has been medically prescribed the drug by their physician.[67]

Recreational[edit]

See also: History and culture of substituted amphetamines

Adderall has high potential for misuse as a recreational drug.[68][69][70] Adderall tablets can either be swallowed, crushed and snorted, or dissolved in water and injected.[71] Injection into the bloodstream can be dangerous because insoluble fillers within the tablets can block small blood vessels.[71]

Many postsecondary students have reported using Adderall for study purposes in different parts of the developed world.[70] Among these students, some of the risk factors for misusing ADHD stimulants recreationally include: possessing deviant personality characteristics (i.e., exhibiting delinquent or deviant behavior), inadequate accommodation of special needs, basing one's self-worth on external validation, low self-efficacy, earning poor grades, and suffering from an untreated mental health disorder.[70]

Contraindications[edit]

This section is an excerpt from Amphetamine § Contraindications.[edit]

According to the International Programme on Chemical Safety (IPCS) and the United States Food and Drug Administration (USFDA),[note 5] amphetamine is contraindicated in people with a history of drug abuse,[note 6]cardiovascular disease, severe agitation, or severe anxiety.[74][75][76] It is also contraindicated in individuals with advanced arteriosclerosis (hardening of the arteries), glaucoma (increased eye pressure), hyperthyroidism (excessive production of thyroid hormone), or moderate to severe hypertension.[74][75][76] These agencies indicate that people who have experienced allergic reactions to other stimulants or who are taking monoamine oxidase inhibitors (MAOIs) should not take amphetamine,[74][75][76] although safe concurrent use of amphetamine and monoamine oxidase inhibitors has been documented.[77][78] These agencies also state that anyone with anorexia nervosa, bipolar disorder, depression, hypertension, liver or kidney problems, mania, psychosis, Raynaud's phenomenon, seizures, thyroid problems, tics, or Tourette syndrome should monitor their symptoms while taking amphetamine.[75][76] Evidence from human studies indicates that therapeutic amphetamine use does not cause developmental abnormalities in the fetus or newborns (i.e., it is not a human teratogen), but amphetamine abuse does pose risks to the fetus.[76] Amphetamine has also been shown to pass into breast milk, so the IPCS and the USFDA advise mothers to avoid breastfeeding when using it.[75][76] Due to the potential for reversible growth impairments,[note 7] the USFDA advises monitoring the height and weight of children and adolescents prescribed an amphetamine pharmaceutical.[75]

Adverse effects[edit]

Part of this section is transcluded from Amphetamine. (edit | history)

The adverse side effects of Adderall are many and varied, but the amount of substance consumed is the primary factor in determining the likelihood and severity of side effects.[12][23] Adderall is currently approved for long-term therapeutic use by the USFDA.[12]Recreational use of Adderall generally involves far larger doses and is therefore significantly more dangerous, involving a much greater risk of serious adverse drug effects than dosages used for therapeutic purposes.[23]

Physical[edit]

Cardiovascular side effects can include hypertension or hypotension from a vasovagal response, Raynaud's phenomenon (reduced blood flow to the hands and feet), and tachycardia (increased heart rate).[12][23][82] Sexual side effects in males may include erectile dysfunction, frequent erections, or prolonged erections.[12] Gastrointestinal side effects may include abdominal pain, constipation, diarrhea, and nausea.[3][12][83] Other potential physical side effects include appetite loss, blurred vision, dry mouth, excessive grinding of the teeth, nosebleed, profuse sweating, rhinitis medicamentosa (drug-induced nasal congestion), reduced seizure threshold, tics (a type of movement disorder), and weight loss.[sources 3] Dangerous physical side effects are rare at typical pharmaceutical doses.[23]

Amphetamine stimulates the medullary respiratory centers, producing faster and deeper breaths.[23] In a normal person at therapeutic doses, this effect is usually not noticeable, but when respiration is already compromised, it may be evident.[23] Amphetamine also induces contraction in the urinary bladder sphincter, the muscle which controls urination, which can result in difficulty urinating.[23] This effect can be useful in treating bed wetting and loss of bladder control.[23] The effects of amphetamine on the gastrointestinal tract are unpredictable.[23] If intestinal activity is high, amphetamine may reduce gastrointestinal motility (the rate at which content moves through the digestive system);[23] however, amphetamine may increase motility when the smooth muscle of the tract is relaxed.[23] Amphetamine also has a slight analgesic effect and can enhance the pain relieving effects of opioids.[3][23]

USFDA-commissioned studies from 2011 indicate that in children, young adults, and adults there is no association between serious adverse cardiovascular events (sudden death, heart attack, and stroke) and the medical use of amphetamine or other ADHD stimulants.[sources 4] However, amphetamine pharmaceuticals are contraindicated in individuals with cardiovascular disease.[sources 5]

Psychological[edit]

At normal therapeutic doses, the most common psychological side effects of amphetamine include increased alertness, apprehension, concentration, initiative, self-confidence and sociability, mood swings (elated mood followed by mildly depressed mood), insomnia or wakefulness, and decreased sense of fatigue.[12][23] Less common side effects include anxiety, change in libido, grandiosity, irritability, repetitive or obsessive behaviors, and restlessness;[sources 6] these effects depend on the user's personality and current mental state.[23]Amphetamine psychosis (e.g., delusions and paranoia) can occur in heavy users.[12][13][91] Although very rare, this psychosis can also occur at therapeutic doses during long-term therapy.[12][91][14] According to the USFDA, "there is no systematic evidence" that stimulants produce aggressive behavior or hostility.[12]

Amphetamine has also been shown to produce a conditioned place preference in humans taking therapeutic doses,[43][92] meaning that individuals acquire a preference for spending time in places where they have previously used amphetamine.[92][93]

Reinforcement disorders[edit]

Addiction[edit]

Addiction and dependence glossary[93][94][95][96]
  • addiction – a biopsychosocial disorder characterized by persistent use of drugs (including alcohol) despite substantial harm and adverse consequences
  • addictive drug – psychoactive substances that with repeated use are associated with significantly higher rates of substance use disorders, due in large part to the drug's effect on brain reward systems
  • dependence – an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake)
  • drug sensitization or reverse tolerance – the escalating effect of a drug resulting from repeated administration at a given dose
  • drug withdrawal – symptoms that occur upon cessation of repeated drug use
  • physical dependence – dependence that involves persistent physical–somatic withdrawal symptoms (e.g., fatigue and delirium tremens)
  • psychological dependence – dependence that involves emotional–motivational withdrawal symptoms (e.g., dysphoria and anhedonia)
  • reinforcing stimuli – stimuli that increase the probability of repeating behaviors paired with them
  • rewarding stimuli – stimuli that the brain interprets as intrinsically positive and desirable or as something to approach
  • sensitization – an amplified response to a stimulus resulting from repeated exposure to it
  • substance use disorder – a condition in which the use of substances leads to clinically and functionally significant impairment or distress
  • tolerance – the diminishing effect of a drug resulting from repeated administration at a given dose
Transcription factor glossary
  • gene expression – the process by which information from a gene is used in the synthesis of a functional gene product such as a protein
  • transcription – the process of making messenger RNA (mRNA) from a DNA template by RNA polymerase
  • transcription factor – a protein that binds to DNA and regulates gene expression by promoting or suppressing transcription
  • transcriptional regulationcontrolling the rate of gene transcription for example by helping or hindering RNA polymerase binding to DNA
  • upregulation, activation, or promotionincrease the rate of gene transcription
  • downregulation, repression, or suppressiondecrease the rate of gene transcription
  • coactivator – a protein (or a small molecule) that works with transcription factors to increase the rate of gene transcription
  • corepressor – a protein (or a small molecule) that works with transcription factors to decrease the rate of gene transcription
  • response element – a specific sequence of DNA that a transcription factor binds to
The image above contains clickable links
This diagram depicts the signaling events in the brain's reward centerthat are induced by chronic high-dose exposure to psychostimulants that increase the concentration of synaptic dopamine, like amphetamine, methamphetamine, and phenethylamine. Following presynaptic dopamineand glutamateco-releaseby such psychostimulants,[97][98]postsynaptic receptorsfor these neurotransmitterstrigger internal signaling events through a cAMP-dependent pathwayand a calcium-dependent pathwaythat ultimately result in increased CREBphosphorylation.[97][99][100]Phosphorylated CREB increases levels of ΔFosB, which in turn represses the c-Fosgene with the help of corepressors;[97][101][102]c-Fosrepressionacts as a molecular switch that enables the accumulation of ΔFosB in the neuron.[103]A highly stable (phosphorylated) form of ΔFosB, one that persists in neurons for 1–2 months, slowly accumulates following repeated high-dose exposure to stimulants through this process.[101][102]ΔFosB functions as "one of the master control proteins" that produces addiction-related structural changes in the brain, and upon sufficient accumulation, with the help of its downstream targets (e.g., nuclear factor kappa B), it induces an addictive state.[101][102]

Addiction is a serious risk with heavy recreational amphetamine use, but is unlikely to occur from long-term medical use at therapeutic doses;[35][15][16] in fact, lifetime stimulant therapy for ADHD that begins during childhood reduces the risk of developing substance use disorders as an adult.[35] Pathological overactivation of the mesolimbic pathway, a dopamine pathway that connects the ventral tegmental area to the nucleus accumbens, plays a central role in amphetamine addiction.[104][105] Individuals who frequently self-administer high doses of amphetamine have a high risk of developing an amphetamine addiction, since chronic use at high doses gradually increase the level of accumbalΔFosB, a "molecular switch" and "master control protein" for addiction.[94][106][107] Once nucleus accumbens ΔFosB is sufficiently overexpressed, it begins to increase the severity of addictive behavior (i.e., compulsive drug-seeking) with further increases in its expression.[106][108] While there are currently no effective drugs for treating amphetamine addiction, regularly engaging in sustained aerobic exercise appears to reduce the risk of developing such an addiction.[109][110] Sustained aerobic exercise on a regular basis also appears to be an effective treatment for amphetamine addiction;[sources 7] exercise therapy improves clinical treatment outcomes and may be used as an adjunct therapy with behavioral therapies for addiction.[109][111]

Biomolecular mechanisms[edit]

Chronic use of amphetamine at excessive doses causes alterations in gene expression in the mesocorticolimbic projection, which arise through transcriptional and epigenetic mechanisms.[107][112][113] The most important transcription factors[note 8] that produce these alterations are Delta FBJ murine osteosarcoma viral oncogene homolog B (ΔFosB), cAMP response element binding protein (CREB), and nuclear factor-kappa B (NF-κB).[107] ΔFosB is the most significant biomolecular mechanism in addiction because ΔFosB overexpression (i.e., an abnormally high level of gene expression which produces a pronounced gene-related phenotype) in the D1-typemedium spiny neurons in the nucleus accumbens is necessary and sufficient[note 9] for many of the neural adaptations and regulates multiple behavioral effects (e.g., reward sensitization and escalating drug self-administration) involved in addiction.[94][106][107] Once ΔFosB is sufficiently overexpressed, it induces an addictive state that becomes increasingly more severe with further increases in ΔFosB expression.[94][106] It has been implicated in addictions to alcohol, cannabinoids, cocaine, methylphenidate, nicotine, opioids, phencyclidine, propofol, and substituted amphetamines, among others.[sources 8]

ΔJunD, a transcription factor, and G9a, a histone methyltransferase enzyme, both oppose the function of ΔFosB and inhibit increases in its expression.[94][107][117] Sufficiently overexpressing ΔJunD in the nucleus accumbens with viral vectors can completely block many of the neural and behavioral alterations seen in chronic drug abuse (i.e., the alterations mediated by ΔFosB).[107] Similarly, accumbal G9a hyperexpression results in markedly increased histone 3 lysineresidue 9 dimethylation (H3K9me2) and blocks the induction of ΔFosB-mediated neural and behavioral plasticity by chronic drug use,[sources 9] which occurs via H3K9me2-mediated repression of transcription factors for ΔFosB and H3K9me2-mediated repression of various ΔFosB transcriptional targets (e.g., CDK5).[107][117][118] ΔFosB also plays an important role in regulating behavioral responses to natural rewards, such as palatable food, sex, and exercise.[108][107][121] Since both natural rewards and addictive drugs induce the expression of ΔFosB (i.e., they cause the brain to produce more of it), chronic acquisition of these rewards can result in a similar pathological state of addiction.[108][107] Consequently, ΔFosB is the most significant factor involved in both amphetamine addiction and amphetamine-induced sexual addictions, which are compulsive sexual behaviors that result from excessive sexual activity and amphetamine use.[108][122][123] These sexual addictions are associated with a dopamine dysregulation syndrome which occurs in some patients taking dopaminergic drugs.[108][121]

The effects of amphetamine on gene regulation are both dose- and route-dependent.[113] Most of the research on gene regulation and addiction is based upon animal studies with intravenous amphetamine administration at very high doses.[113] The few studies that have used equivalent (weight-adjusted) human therapeutic doses and oral administration show that these changes, if they occur, are relatively minor.[113] This suggests that medical use of amphetamine does not significantly affect gene regulation.[113]

Pharmacological treatments[edit]

Further information: Addiction § Research

As of December 2019,[update] there is no effective pharmacotherapy for amphetamine addiction.[124][125][126] Reviews from 2015 and 2016 indicated that TAAR1-selective agonists have significant therapeutic potential as a treatment for psychostimulant addictions;[127][128] however, as of February 2016,[update] the only compounds which are known to function as TAAR1-selective agonists are experimental drugs.[127][128] Amphetamine addiction is largely mediated through increased activation of dopamine receptors and co-localizedNMDA receptors[note 10] in the nucleus accumbens;[105]magnesium ions inhibit NMDA receptors by blocking the receptor calcium channel.[105][129] One review suggested that, based upon animal testing, pathological (addiction-inducing) psychostimulant use significantly reduces the level of intracellular magnesium throughout the brain.[105]Supplemental magnesium[note 11] treatment has been shown to reduce amphetamine self-administration (i.e., doses given to oneself) in humans, but it is not an effective monotherapy for amphetamine addiction.[105]

A systematic review and meta-analysis from 2019 assessed the efficacy of 17 different pharmacotherapies used in RCTs for amphetamine and methamphetamine addiction;[125] it found only low-strength evidence that methylphenidate might reduce amphetamine or methamphetamine self-administration.[125] There was low- to moderate-strength evidence of no benefit for most of the other medications used in RCTs, which included antidepressants (bupropion, mirtazapine, sertraline), antipsychotics (aripiprazole), anticonvulsants (topiramate, baclofen, gabapentin), naltrexone, varenicline, citicoline, ondansetron, prometa, riluzole, atomoxetine, dextroamphetamine, and modafinil.[125]

Behavioral treatments[edit]

A 2018 systematic review and network meta-analysis of 50 trials involving 12 different psychosocial interventions for amphetamine, methamphetamine, or cocaine addiction found that combination therapy with both contingency management and community reinforcement approach had the highest efficacy (i.e., abstinence rate) and acceptability (i.e., lowest dropout rate).[130] Other treatment modalities examined in the analysis included monotherapy with contingency management or community reinforcement approach, cognitive behavioral therapy, 12-step programs, non-contingent reward-based therapies, psychodynamic therapy, and other combination therapies involving these.[130]

Additionally, research on the neurobiological effects of physical exercise suggests that daily aerobic exercise, especially endurance exercise (e.g., marathon running), prevents the development of drug addiction and is an effective adjunct therapy (i.e., a supplemental treatment) for amphetamine addiction.[sources 7] Exercise leads to better treatment outcomes when used as an adjunct treatment, particularly for psychostimulant addictions.[109][111][131] In particular, aerobic exercise decreases psychostimulant self-administration, reduces the reinstatement (i.e., relapse) of drug-seeking, and induces increased dopamine receptor D2 (DRD2) density in the striatum.[108][131] This is the opposite of pathological stimulant use, which induces decreased striatal DRD2 density.[108] One review noted that exercise may also prevent the development of a drug addiction by altering ΔFosB or c-Fosimmunoreactivity in the striatum or other parts of the reward system.[110]

Dependence and withdrawal[edit]

Drug tolerance develops rapidly in amphetamine abuse (i.e., recreational amphetamine use), so periods of extended abuse require increasingly larger doses of the drug in order to achieve the same effect.[132][133] According to a Cochrane review on withdrawal in individuals who compulsively use amphetamine and methamphetamine, "when chronic heavy users abruptly discontinue amphetamine use, many report a time-limited withdrawal syndrome that occurs within 24 hours of their last dose."[134] This review noted that withdrawal symptoms in chronic, high-dose users are frequent, occurring in roughly 88% of cases, and persist for 3–4 weeks with a marked "crash" phase occurring during the first week.[134] Amphetamine withdrawal symptoms can include anxiety, drug craving, depressed mood, fatigue, increased appetite, increased movement or decreased movement, lack of motivation, sleeplessness or sleepiness, and lucid dreams.[134] The review indicated that the severity of withdrawal symptoms is positively correlated with the age of the individual and the extent of their dependence.[134] Mild withdrawal symptoms from the discontinuation of amphetamine treatment at therapeutic doses can be avoided by tapering the dose.[3]

Overdose[edit]

This section is an excerpt from Amphetamine § Overdose.[edit]

An amphetamine overdose can lead to many different symptoms, but is rarely fatal with appropriate care.[135][76][136] The severity of overdose symptoms increases with dosage and decreases with drug tolerance to amphetamine.[137][76] Tolerant individuals have been known to take as much as 5 grams of amphetamine in a day, which is roughly 100 times the maximum daily therapeutic dose.[76] Symptoms of a moderate and extremely large overdose are listed below; fatal amphetamine poisoning usually also involves convulsions and coma.[75][137] In 2013, overdose on amphetamine, methamphetamine, and other compounds implicated in an "amphetamine use disorder" resulted in an estimated 3,788 deaths worldwide (3,425–4,145 deaths, 95% confidence).[note 12][138]

Interactions[edit]

Pharmacology[edit]

Pharmacodynamics of amphetamine in a dopamine neuron
The image above contains clickable links
Amphetamine enters the presynaptic neuron across the neuronal membrane or through DAT.[20]Once inside, it binds to TAAR1or enters synaptic vesicles through VMAT2.[20][21]When amphetamine enters synaptic vesicles through VMAT2, it collapses the vesicular pH gradient, which in turn causes dopamine to be released into the cytosol(light tan-colored area) through VMAT2.[21][148]When amphetamine binds to TAAR1, it reduces the firing rateof the dopamine neuron via potassium channelsand activates protein kinase A(PKA) and protein kinase C(PKC), which subsequently phosphorylates DAT.[20][149][150]PKA-phosphorylationcauses DAT to withdraw into the presynaptic neuron (internalize) and cease transport.[20]PKC-phosphorylatedDAT may either operate in reverse or, like PKA-phosphorylatedDAT, internalize and cease transport.[20]Amphetamine is also known to increase intracellular calcium, an effect which is associated with DAT phosphorylation through a CAMKIIα-dependent pathway, in turn producing dopamine efflux.[151][152]

Mechanism of action[edit]

For a more complete and detailed description of amphetamine pharmacodynamics, see Amphetamine § Pharmacodynamics.

Amphetamine, the active ingredient of Adderall, works primarily by increasing the activity of the neurotransmittersdopamine and norepinephrine in the brain.[19][38] It also triggers the release of several other hormones (e.g., epinephrine) and neurotransmitters (e.g., serotonin and histamine) as well as the synthesis of certain neuropeptides (e.g., cocaine and amphetamine regulated transcript (CART) peptides).[21][153] Both active ingredients of Adderall, dextroamphetamine and levoamphetamine, bind to the same biological targets,[23][24] but their binding affinities (that is, potency) differ somewhat.[23][24] Dextroamphetamine and levoamphetamine are both potent full agonists (activating compounds) of trace amine-associated receptor 1 (TAAR1) and interact with vesicular monoamine transporter 2 (VMAT2), with dextroamphetamine being the more potent agonist of TAAR1.[24] Consequently, dextroamphetamine produces more CNS stimulation than levoamphetamine;[24][154] however, levoamphetamine has slightly greater cardiovascular and peripheral effects.[23] It has been reported that certain children have a better clinical response to levoamphetamine.[25][26]

In the absence of amphetamine, VMAT2 will normally move monoamines (e.g., dopamine, histamine, serotonin, norepinephrine, etc.) from the intracellular fluid of a monoamine neuron into its synaptic vesicles, which store neurotransmitters for later release (via exocytosis) into the synaptic cleft.[21] When amphetamine enters a neuron and interacts with VMAT2, the transporter reverses its direction of transport, thereby releasing stored monoamines inside synaptic vesicles back into the neuron's intracellular fluid.[21] Meanwhile, when amphetamine activates TAAR1, the receptor causes the neuron's cell membrane-bound monoamine transporters (i.e., the dopamine transporter, norepinephrine transporter, or serotonin transporter) to either stop transporting monoamines altogether (via transporter internalization) or transport monoamines out of the neuron;[20] in other words, the reversed membrane transporter will push dopamine, norepinephrine, and serotonin out of the neuron's intracellular fluid and into the synaptic cleft.[20] In summary, by interacting with both VMAT2 and TAAR1, amphetamine releases neurotransmitters from synaptic vesicles (the effect from VMAT2) into the intracellular fluid where they subsequently exit the neuron through the membrane-bound, reversed monoamine transporters (the effect from TAAR1).[20][21]

Pharmacokinetics[edit]

This section is transcluded from Amphetamine#Pharmacokinetics. (edit | history)

The oral bioavailability of amphetamine varies with gastrointestinal pH;[12] it is well absorbed from the gut, and bioavailability is typically over 75% for dextroamphetamine.[155] Amphetamine is a weak base with a pKa of 9.9;[156] consequently, when the pH is basic, more of the drug is in its lipid soluble free base form, and more is absorbed through the lipid-rich cell membranes of the gut epithelium.[156][12] Conversely, an acidic pH means the drug is predominantly in a water-soluble cationic (salt) form, and less is absorbed.[156] Approximately 20% of amphetamine circulating in the bloodstream is bound to plasma proteins.[157] Following absorption, amphetamine readily distributes into most tissues in the body, with high concentrations occurring in cerebrospinal fluid and brain tissue.[158]

The half-lives of amphetamine enantiomers differ and vary with urine pH.[156] At normal urine pH, the half-lives of dextroamphetamine and levoamphetamine are 9–11 hours and 11–14 hours, respectively.[156] Highly acidic urine will reduce the enantiomer half-lives to 7 hours;[158] highly alkaline urine will increase the half-lives up to 34 hours.[158] The immediate-release and extended release variants of salts of both isomers reach peak plasma concentrations at 3 hours and 7 hours post-dose respectively.[156] Amphetamine is eliminated via the kidneys, with 30–40% of the drug being excreted unchanged at normal urinary pH.[156] When the urinary pH is basic, amphetamine is in its free base form, so less is excreted.[156] When urine pH is abnormal, the urinary recovery of amphetamine may range from a low of 1% to a high of 75%, depending mostly upon whether urine is too basic or acidic, respectively.[156] Following oral administration, amphetamine appears in urine within 3 hours.[158] Roughly 90% of ingested amphetamine is eliminated 3 days after the last oral dose.[158]

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.[sources 11] Amphetamine has a variety of excreted metabolic products, including 4-hydroxyamphetamine, 4-hydroxynorephedrine, 4-hydroxyphenylacetone, benzoic acid, hippuric acid, norephedrine, and phenylacetone.[156][159] Among these metabolites, the active sympathomimetics are 4-hydroxyamphetamine,[160]4-hydroxynorephedrine,[161] and norephedrine.[162] The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-hydroxylation, N-oxidation, N-dealkylation, and deamination.[156][163] The known metabolic pathways, detectable metabolites, and metabolizing enzymes in humans include the following:

Pharmacomicrobiomics[edit]

This section is an excerpt from Amphetamine § Pharmacomicrobiomics.[edit]

The human metagenome (i.e., the genetic composition of an individual and all microorganisms that reside on or within the individual's body) varies considerably between individuals.[172][173] Since the total number of microbial and viral cells in the human body (over 100 trillion) greatly outnumbers human cells (tens of trillions),[note 15][172][174] there is considerable potential for interactions between drugs and an individual's microbiome, including: drugs altering the composition of the human microbiome, drug metabolism by microbial enzymes modifying the drug's pharmacokinetic profile, and microbial drug metabolism affecting a drug's clinical efficacy and toxicity profile.[172][173][175] The field that studies these interactions is known as pharmacomicrobiomics.[172]

Similar to most biomoleculesand other orally administeredxenobiotics(i.e., drugs), amphetamine is predicted to undergo promiscuous metabolism by human gastrointestinal microbiota(primarily bacteria) prior to absorption into the blood stream.[175]The first amphetamine-metabolizing microbial enzyme, tyramine oxidasefrom a strain of E. colicommonly found in the human gut, was identified in 2019.[175]This enzyme was found to metabolize amphetamine, tyramine, and phenethylamine with roughly the same binding affinity for all three compounds.[175]

Related endogenous compounds[edit]

This section is transcluded from Amphetamine#Related endogenous compounds. (edit | history)

Further information on related compounds: Trace amine

Amphetamine has a very similar structure and function to the endogenous trace amines, which are naturally occurring neuromodulator molecules produced in the human body and brain.[20][22][176] Among this group, the most closely related compounds are phenethylamine, the parent compound of amphetamine, and N-methylphenethylamine, an isomer of amphetamine (i.e., it has an identical molecular formula).[20][22][177] In humans, phenethylamine is produced directly from L-phenylalanine by the aromatic amino acid decarboxylase (AADC) enzyme, which converts L-DOPA into dopamine as well.[22][177] In turn, N-methylphenethylamine is metabolized from phenethylamine by phenylethanolamine N-methyltransferase, the same enzyme that metabolizes norepinephrine into epinephrine.[22][177] Like amphetamine, both phenethylamine and N-methylphenethylamine regulate monoamine neurotransmission via TAAR1;[20][176][177] unlike amphetamine, both of these substances are broken down by monoamine oxidase B, and therefore have a shorter half-life than amphetamine.[22][177]

History, society, and culture[edit]

Main article: History and culture of substituted amphetamines

History[edit]

The pharmaceutical company Rexar reformulated their popular weight loss drug Obetrol following its mandatory withdrawal from the market in 1973 under the Kefauver Harris Amendment to the Federal Food, Drug, and Cosmetic Act due to the results of the Drug Efficacy Study Implementation (DESI) program (which indicated a lack of efficacy). The new formulation simply replaced the two methamphetamine components with dextroamphetamine and amphetamine components of the same weight (the other two original dextroamphetamine and amphetamine components were preserved), preserved the Obetrol branding, and despite it utterly lacking FDA approval, it still made it onto the market and was marketed and sold by Rexar for many years.

In 1994 Richwood Pharmaceuticals acquired Rexar and began promoting Obetrol as a treatment for ADHD (and later narcolepsy as well), now marketed under the new brand name of Adderall, a contraction of the phrase "A.D.D. for All" intended to convey that "it was meant to be kind of an inclusive thing" for marketing purposes.[178] The FDA cited the company for numerous significant CGMP violations related to Obetrol discovered during routine inspections following the acquisition (including issuing a formal warning letter for the violations), then later issued a second formal warning letter to Richwood Pharmaceuticals specifically due to violations of "the new drug and misbranding provisions of the FD&C Act". Following extended discussions with Richwood Pharmaceuticals regarding the resolution of a large number of issues related to the company's numerous violations of FDA regulations, the FDA formally approved the first Obetrol labeling/sNDA revisions in 1996, including a name change to Adderall and a restoration of its status as an approved drug product.[179][180] In 1997 Richwood Pharmaceuticals was acquired by Shire Pharmaceuticals in a $186 million transaction.[178]

Richwood Pharmaceuticals, which later merged with Shire plc, introduced the current Adderall brand in 1996 as an instant-release tablet.[181] In 2006, Shire agreed to sell rights to the Adderall name for the instant-release form of the medication to Duramed Pharmaceuticals.[182] DuraMed Pharmaceuticals was acquired by Teva Pharmaceuticals in 2008 during their acquisition of Barr Pharmaceuticals, including Barr's Duramed division.[183]

The first generic version of Adderall IR was introduced to market in 2002.[5] Later on, Barr and Shire reached a settlement agreement permitting Barr to offer a generic form of the extended-release drug beginning in April 2009.[5][184]

Commercial formulation[edit]

Chemically, Adderall is a mixture of four amphetamine salts; specifically, it is composed of equal parts (by mass) of amphetamine aspartate monohydrate, amphetamine sulfate, dextroamphetamine sulfate, and dextroamphetamine saccharate.[46] This drug mixture has slightly stronger CNS effects than racemic amphetamine due to the higher proportion of dextroamphetamine.[20][23] Adderall is produced as both an immediate release (IR) and extended release (XR) formulation.[5][9][46] As of December 2013[update], ten different companies produced generic Adderall IR, while Teva Pharmaceutical Industries, Actavis, and Barr Pharmaceuticals manufactured generic Adderall XR.[5] As of 2013[update], Shire plc, the company that held the original patent for Adderall and Adderall XR, still manufactured brand name Adderall XR, but not Adderall IR.[5]

Sours: https://en.wikipedia.org/wiki/Adderall


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