ADHD Medications

1. Medication

• Stimulants: The most commonly prescribed medications for ADHD are stimulants, such as methylphenidate (Ritalin, Concerta) and amphetamines (Adderall, Vyvanse). These can help increase focus and decrease impulsivity and hyperactivity.
• Non-stimulants: Medications like atomoxetine (Strattera), guanfacine (Intuniv), Clonidine (Kapvay), and Buproprion (Wellbutrin), are alternatives for those who do not respond well to stimulants. 
• Newer Non Stimulant ADHD medications include: Qelbree, ​Azstarys (Serdexmethylphenidate and Dexmethylphenidate), Xelstrym (Dextroamphetamine Transdermal System), and Onyda XR. 

Dr. Russell Barkley - ADHD medications description

Stimulant Medications

Stimulant medications for Attention Deficit Hyperactivity Disorder (ADHD) primarily work by increasing the levels of certain neurotransmitters, especially dopamine and norepinephrine, in the brain. These neurotransmitters are crucial for regulating attention, focus, and impulse control, areas where individuals with ADHD tend to have deficits. Here's a breakdown of how stimulant medications like amphetamines (e.g., Adderall) and methylphenidate (e.g., Ritalin) work:
1. Amphetamines (e.g., Adderall)

• Mechanism of Action: Amphetamines increase dopamine and norepinephrine levels by:
  • Promoting the release of these neurotransmitters from nerve endings.
  • Inhibiting their reuptake back into the nerve cells, which increases the amount of dopamine and norepinephrine available in the brain.
• Effect: The elevated levels of dopamine and norepinephrine enhance the brain’s ability to focus, maintain attention, and control impulses.

2. Methylphenidate (e.g., Ritalin, Concerta)

• Mechanism of Action: Methylphenidate works primarily by:
  • Blocking the reuptake of dopamine and norepinephrine into neurons.
  • This increases their availability in areas of the brain responsible for attention and behavioral control.
• Effect: Similar to amphetamines, the increase in neurotransmitter levels improves focus, attention, and self-control in individuals with ADHD.

Why Dopamine and Norepinephrine?

• Dopamine: Plays a key role in reward, motivation, and attention. In people with ADHD, dopamine signaling is often impaired, making it harder to sustain attention and resist distractions.
• Norepinephrine: Involved in arousal and alertness. It helps improve attention and the ability to stay focused on tasks.

Impact on ADHD Symptoms By increasing dopamine and norepinephrine levels in key areas of the brain (such as the prefrontal cortex), stimulants help improve:

• Attention and concentration.
• Impulse control and hyperactivity.
• Task completion and executive function.

These medications are generally fast-acting and can provide significant symptom relief within 30 minutes to an hour after taking them.
3. Focalin -  dexmethylphenidate
Focalin contains dexmethylphenidate, the pharmacologically active enantiomer of methylphenidate. Its mechanism of action includes:

1. Dopamine and Norepinephrine Reuptake Inhibition:
   • Blocks the dopamine transporter (DAT) and norepinephrine transporter (NET), increasing the levels of these neurotransmitters in the synaptic cleft.
   • This improves attention, impulse control, and focus by enhancing neurotransmission in the prefrontal cortex.
2. Selective Action:
   • As a single isomer, dexmethylphenidate has greater potency compared to racemic methylphenidate, allowing for effective symptom management at lower doses.

Non-Stimulant ADHD Medications

Non-stimulant medications for Attention Deficit Hyperactivity Disorder (ADHD) work differently from stimulants, but they still help improve attention, focus, and impulse control. These medications primarily target neurotransmitter systems in the brain, though they do so in a more gradual and less direct manner compared to stimulants. The three main non-stimulant medications used for ADHD are atomoxetine (Strattera), guanfacine (Intuniv), and clonidine (Kapvay).  Newer Non Stimulant ADHD medications include: Qelbree, ​Azstarys (Serdexmethylphenidate and Dexmethylphenidate), Xelstrym (Dextroamphetamine Transdermal System), and Onyda XR. 

​Here’s how they work:
1. Atomoxetine (Strattera)

• Mechanism of Action: Atomoxetine is a selective norepinephrine reuptake inhibitor (NRI).
  • It increases norepinephrine levels by preventing its reabsorption into the presynaptic neuron.
  • Norepinephrine plays a role in maintaining attention, alertness, and impulse control, especially in the prefrontal cortex, which is responsible for executive functions.
• Effect: By increasing norepinephrine in the brain, atomoxetine helps improve focus, reduce impulsivity, and regulate emotional responses. Unlike stimulants, atomoxetine does not directly increase dopamine levels, which is why it has a lower potential for abuse and addiction.
• Onset: Atomoxetine may take several weeks (2-4 weeks) to show its full effects.

2. Guanfacine (Intuniv)

• Mechanism of Action: Guanfacine is an alpha-2A adrenergic receptor agonist.
  • It works by stimulating receptors in the prefrontal cortex that regulate attention and impulse control.
  • The activation of these receptors helps modulate the brain circuits responsible for focus and emotional regulation.
• Effect: Guanfacine helps improve working memory, attention, and impulse control while also having a calming effect. It is often used for children with ADHD who also have issues with aggression or hyperactivity. It may also reduce anxiety and hyperarousal.
• Onset: It usually takes about 1-2 weeks for guanfacine to show noticeable effects.

3. Clonidine (Kapvay)

• Mechanism of Action: Like guanfacine, clonidine is also an alpha-2 adrenergic receptor agonist.
  • It works by decreasing nerve signal transmission that may contribute to hyperactivity, impulsivity, and emotional dysregulation.
• Effect: Clonidine is often used when hyperactivity or impulsivity is the main concern. It also has sedative properties, which makes it particularly helpful for individuals with ADHD who struggle with sleep problems or anxiety.
• Onset: Clonidine can take 1-2 weeks to produce noticeable effects

4. Wellbutrin (Buproprion) Treatment of ADHD: For ADHD, Wellbutrin's effect on dopamine is especially important. ADHD has been associated with a deficiency of dopamine in areas of the brain that control attention, behavior, and executive function. By boosting dopamine levels, Wellbutrin can help improve symptoms like inattention, impulsivity, and hyperactivity. It is often used in cases where stimulant medications (like methylphenidate or amphetamines) are not well tolerated or are contraindicated.
​Mechanism of Action: Wellbutrin is a norepinephrine-dopamine reuptake inhibitor (NDRI), meaning that it increases the levels of two key neurotransmitters: dopamine and norepinephrine. It works by inhibiting the reuptake of these neurotransmitters in the brain, which enhances their effects in the central nervous system.

• Dopamine: Plays a crucial role in mood regulation, motivation, and reward. In ADHD, low dopamine activity is thought to contribute to symptoms like inattention and impulsivity. By increasing dopamine availability, Wellbutrin can improve focus and reduce these symptoms in individuals with ADHD.
• Norepinephrine: Is involved in alertness, focus, and arousal. It is also related to stress responses. Increasing norepinephrine levels may help with concentration, energy levels, and mood regulation, making Wellbutrin effective in treating both ADHD and depression.

Why Non-Stimulants?

• Lower Abuse Potential: Non-stimulant ADHD medications have a lower risk of abuse compared to stimulants like amphetamines or methylphenidate because they don't directly increase dopamine levels.
• Gradual Action: They often have a slower onset of action and can be beneficial for individuals who experience side effects from stimulants or for whom stimulants are ineffective.
• Sleep and Emotional Regulation: Some non-stimulants, particularly guanfacine and clonidine, can help with sleep disturbances and emotional dysregulation, which may accompany ADHD.

Impact on ADHD Symptoms Non-stimulant medications can be particularly helpful for individuals who:

• Do not tolerate stimulant medications due to side effects.
• Have a history of substance use disorder.
• Need additional help with anxiety, sleep, or emotional regulation, which may be worsened by stimulants.

Though non-stimulants can be effective, they typically take longer to work compared to stimulant medications and may be less effective for improving symptoms of inattention and hyperactivity in some individuals.

Newer Medications for the Treatment of ADHD

​Qelbree (Viloxazine Extended-Release)
A non-stimulant medication approved by the FDA in 2021 for the treatment of ADHD in children aged 6 to 17, and later for adults. Qelbree offers an alternative for those who may not respond well to stimulant medications.

​Azstarys (Serdexmethylphenidate and Dexmethylphenidate)
A stimulant medication approved by the FDA in 2021 for patients aged 6 years and older. Azstarys combines a prodrug of dexmethylphenidate with immediate-release dexmethylphenidate, providing both immediate and extended symptom control. 

Xelstrym (Dextroamphetamine Transdermal System)
Approved by the FDA in 2022, Xelstrym is the first transdermal (skin patch) delivery system for dextroamphetamine, offering an alternative administration route for individuals with ADHD.

​Onyda XR (Clonidine Hydrochloride Extended-Release Oral Suspension)
Approved by the FDA in 2024, Onyda XR is the first liquid non-stimulant medication for ADHD. It can be used alone or as an adjunctive therapy to stimulant medications in pediatric patients aged 6 years and older.