ADHD

ADHD

• Is a brain-based disorder that affects how a person pays attention, controls impulses, and manages activity levels

• It can begin in preschool years and continue into adulthood

• Prevalence:

  • About 5.3% of children/adolescents have ADHD

  • Around 4.4% of adults (ages 19–45) have it

  • Rates drop to 1–2.8% in adults ≥50 years

• Main Symptoms:

  • Inattention: easily distracted, trouble focusing

  • Hyperactivity: fidgeting, difficulty sitting still

  • Impulsivity: acting without thinking

  • Some people show a mix of these symptoms

ADHD → Diagnosis

• > 6 symptoms of inattention or hyperactivity/impulsivity (5 for adults)

• > 6 months and are not appropriate for the person’s age

• Symptoms must occur in two or more places (e.g., home and school/work)

• Symptoms must start before age 12

• Symptoms can’t be explained by another condition or medication

• Symptoms must cause real problems in daily life, such as at school, work, home, or social situations

Risk Factors of ADHD

• Boys

• Socioeconomic Status

  • ADHD can be influenced by environmental and social factors

• Family History & Genetics

  • ADHD often runs in families

  • If a parent has ADHD, their child is more likely to have it too (strong genetic link)

• Prematurity

  • Babies born early (prematurely) have a higher chance of developing ADHD due to differences in early brain development

Executive Functioning

• Mental skills that help you plan, organize, and take action to complete tasks

• Key Roles:

  • Prioritizing: deciding what’s most important

  • Decision-making: choosing between options

  • Motor control: managing physical actions

  • Time & space awareness: understanding timing and surroundings

  • Filtering distractions: ignoring unimportant stimuli

  Brain Region Involved:

  • Controlled mainly by the prefrontal cortex

  • Individuals with ADHD → Issue with the prefrontal cortex 

In ADHD, to help the brain better manage focus, attention, and impulse control, must balance:

• Dopamine

• Norepinephrine

People with ADHD usually have high or low levels of Dopamine and Norepinephrine?

• Low levels 

ADHD → Drug Class

• Stimulants

• Atomoxetine and Viloxazine

• Alpha-2 Agonists

  • Guanfacine and Clonidine

Stimulants MOA

• Help increase dopamine (DA) and norepinephrine (NE) levels in the brain

• Mechanisms of Action:

  • Inhibit monoamine oxidase (MAO) 

    • Prevents breakdown of dopamine and norepinephrine

      • Amphetamines > Methylphenidate

  • Increase presynaptic release 

    • Causes nerve cells to release more dopamine and norepinephrine

      • Amphetamines only

  • Block reuptake of DA & NE 

    • Keeps dopamine and norepinephrine active longer in the brain

      • Both amphetamines and methylphenidate

Non-stimulants MOA

• Non-stimulant ADHD medications that help improve focus and attention without increasing dopamine directly

• Mechanism of Action:

  • They inhibit norepinephrine (NE) reuptake

  • This leads to higher NE levels, improving attention and reducing impulsivity

• They don’t directly target dopamine, but they can indirectly raise their levels as well 

Alpha-2 Agonists MOA

• Help calm brain activity by stimulating alpha-2A receptors in the prefrontal cortex

• Mechanism of Action:

  • They directly activate post-synaptic alpha-2A receptors (NE receptors)

  • This helps the brain strengthen communication between neurons in areas responsible for attention, planning, and impulse control

  • Overall effect → reduces hyperactivity, improves focus, and promotes calm behavior

Preschool (4–6 yrs) Treatment Guideliness

• First Line: 

  • Behavior Therapy

Children (6–12 yrs) Treatment Guideliness

• First Line: 

  • Behavior Therapy + Medication

Adolescents (12–18 yrs) Treatment Guideliness

• First Line: 

  • Medication 

  • Behaviour therapy is encouraged 

Methylphenidate can be utilized as a second-line agent for children aged…..

• 4-6 yrs old 

  • After behaviour therapy 

ADHD → Treatment (Comorbidities) 

• ADHD + Depression:

  • Use a stimulant + antidepressant (like bupropion)

• ADHD + Bipolar Disorder:

  • Use a stimulant + mood stabilizer

• ADHD + Psychosis:

  • Avoid Stimulants (they can worsen psychosis)

Stimulants → Drugs

• Amphetamine-based stimulants:

  • Amphetamine

  • Dextroamphetamine

  • Lisdexamfetamine

• Methylphenidate-based stimulants

  • Methylphenidate IR

  • Methylphenidate ER

  • Dexmethylphenidat

Non-Stimulants → Drugs 

• Atomoxetine

• Viloxazine

Alpha-2 Agonists → Drugs 

• Guanfacine ER 

• Clonidine ER

ADHD → Treatment (Stimulants not Contraindicated)

• First Line:

  • Short-acting amphetamine IR

• If not effective:

  • Switch to dextroamphetamine

• If patient prefers long-acting:

  • Switch to mixed amphetamine salts ER

    • If that fails → switch to lisdexamfetamine

• If too many side effects from amphetamines:

  • Switch to methylphenidate IR, then dexmethylphenidate

• If effective but needs longer coverage:

  • Switch to methylphenidate ER or dexmethylphenidate ER

Stimulants Contraindications

• History of heart attacks 

• History of arrhythmia

• Stimulant use disorder 

ADHD → Treatment (Stimulants Contraindicated)

• ADHD only:

  • Atomoxetine

• ADHD + Depression

  • Bupropion

• Insomnia, Nightmares, PTSD, Tic disorder, or Hyperactivity:

  • Guanfacine ER or Clonidine ER

Non-Pharm → Treatment

• Play or Sensory Therapy:

  • Used for young children but shows little benefit in preschoolers

• Cognitive Behavioral Therapy (CBT)

Methylphenidate

• Blocks dopamine (DAT) and norepinephrine (NET) reuptake transporters

• Extra: Also affects some serotonin receptors (5-HT₁A, 5-HT₂B)

• Enantiomers: d-MPH is twice as strong as l-MPH

• Metabolism: Broken down by carboxylesterase 1 (de-esterification)

• Duration:

  • 3–4 hrs (immediate-release)

  • 10–12 hrs (extended-release)

• Food: High-fat meals can delay absorption

Amphetamines

• Blocks DAT & NET, but adds an extra action, it pushes dopamine and norepinephrine out of presynaptic nerve

• Enantiomers:

  • d-AMP: stronger on dopamine (DAT)

  • l-AMP: stronger on norepinephrine (NET)

• Metabolism: By CYP2D6 (hydroxylation + oxidative deamination)

• Duration:

  • 4–6 hrs (immediate-release)

  • 8–12 hrs (extended-release)

  • ≈16 hrs (triple-beaded formulations)

• Food: High-fat meals can delay absorption

Methylphenidate vs. Amphetamines → Children/ Adolescents

• Methylphenidate is generally preferred as the first-line stimulant for kids and teens

Methylphenidate vs. Amphetamines → Adults

• Amphetamines > Methylphenidate per efficacy 

• But either AMP or MPH can be used, depends on individual response

Immediate & Short-Acting Stimulants

• Onset: 20–60 minutes

• Duration: 3–5 hours (up to 6–8 hours for some)

• Used when short coverage is needed (e.g., for school hours or dose flexibility)

Immediate / Short-Acting Stimulants Examples

• Methylphenidate (Metadate CD & Ritalin LA)

• Dexmethylphenidate

• Mixed Amphetamine salts

• Dextroamphetamine

Long-Acting Stimulants

• Onset: 20–60 minutes

• Duration: 10–12 hours

• Ideal for all-day symptom control, fewer doses, and better adherence

Long acting Stimulants Examples

• Methylphenidate (OROS formulation)

• Mixed amphetamine salts ER

• Methylphenidate (transdermal patch)

• Methylphenidate (extended-release orally disintegrating tablet)

• Methylphenidate (extended-release liquid)

• Methylphenidate (extended-release chewable tablet)

• Lisdexamfetamine

• Amphetamine (extended-release liquid suspension)

• Mixed amphetamine salts (triple-bead extended-release)

Stimulants Acute Adverse Effects 

• Irritability (feeling moody or easily frustrated)

• Headache

• Insomnia

• Loss of appetite

• Abdominal pain

Stimulants Chronic Adverse Effects 

• Slight increase in heart rate and blood pressure

• Anorexia

• Decreased growth velocity 

  • May slightly slow growth in children (usually reversible when medication is stopped or paused)

Niche Stimulants (Unique ADHD Options)

• Methylphenidate OROS

• Lisdexamfetamine

• Daytrana Patch

• Mydayis (Mixed Amphetamine Salts)

• Adhansia XR

• The Liquids

• The ODTs (Orally Disintegrating Tablets)

Atomoxetine

• A selective norepinephrine reuptake inhibitor

• FDA-approved for ages 6 and up

• Dosed by body weight and slowly increased depending on how the person tolerates it and responds

• Not a stimulant → non-controlled substance with low abuse potential

• Takes time to work — effects are gradual (not immediate like stimulants)

  • 2 - 4 weeks to fully work

• Good choice for people who have substance misuse issues or don’t tolerate stimulants well

Atomoxetine BBW

• Hepatic Toxicity

• Increased suicidal thoughts 

Viloxazine

• A selective norepinephrine reuptake inhibitor

• Serotonin-norepinephrine modulating agent (SNMA)

  • Acts as a 5-HT2B antagonist and 5-HT2C agonist

• Extended-release formulation → once-daily dosing

• FDA approved for ADHD in children and adolescents (ages 6–17)

• Low abuse potential (non-controlled substance)

• Strong CYP1A2 inhibitor

CYP1A2 inhibitor Interaction w Viloxazine

• Duloxetine

• Tizanidine

• Ramelteon

• Tasimelteon

• Theophylline

Alpha-2 Agonists

• Calm brain activity by stimulating alpha-2A receptors (mainly in the prefrontal cortex)

• This improves attention and impulse control by helping neurons “fire” more steadily

• Extended-release forms (like guanfacine ER and clonidine ER) are approved for ADHD in children ages 6–17

• Limited studies on effectiveness in adults

• Main action: work on post-synaptic alpha-2 receptors but can also regulate nerve firing through autoreceptors

• Can lower blood pressure and cause sedation 

• Often preferred when ADHD occurs with tic disorders or autism spectrum disorder, since they can help reduce tics and calm irritability

Other Treatments 

• Bupropion (Wellbutrin)

  • Works by increasing dopamine and norepinephrine levels

    • Effective for adults with ADHD, especially if they also have depression

    • Non-stimulant and non-controlled option

• Caffeine

  • Acts as a mild stimulant that can increase alertness

    • However, not enough strong evidence to recommend it for ADHD treatment

• Modafinil (Provigil)

  • Promotes wakefulness and attention

  • Shows some benefit in ADHD, but not used in children due to serious rash risk (Stevens–Johnson syndrome)

• Immediate-release Alpha-2 Agonists (e.g., clonidine IR, guanfacine IR)

  • Can help reduce hyperactivity and impulsivity

  • Less tolerated than extended-release versions (more sedation, BP effects)

  • Used only when XR formulations are unavailable

Desipramine (TCAs)

• Blocks the reuptake of norepinephrine (NE) and dopamine (DA) to improve attention and focus

• “Messy pharmacology” 

  • Affects many receptors, not just NE/DA

• Has anticholinergic, antihistamine, and alpha-blocking effects

  • Causes side effects like dry mouth, sedation, and low BP

• Also blocks sodium channels, which can affect the heart

• Avoid in children under 12 due to cardiovascular risks

• Delayed onset (takes weeks to show benefits)

• Used only as a last-resort (“reserved”) treatment

• Who might use it:

  • Adults with ADHD + depression, but it’s rarely used because of tolerability and safety concerns