From the Guidelines
Non-stimulant medications for ADHD, such as atomoxetine, guanfacine, and clonidine, are effective treatment options, particularly when stimulants are contraindicated or cause intolerable side effects, with atomoxetine being the most commonly recommended due to its relatively better efficacy and safety profile 1.
Key Considerations
- Non-stimulant medications have a medium effect size compared to placebo, which is smaller than that of stimulants, but they offer benefits such as 24-hour coverage and no abuse potential 1.
- Atomoxetine, guanfacine, and clonidine are the primary non-stimulant medications used, with atomoxetine being a selective norepinephrine reuptake inhibitor and guanfacine and clonidine being selective α-2 adrenergic agonists 1.
- The choice of medication depends on individual patient needs, including the presence of comorbidities such as anxiety, autism spectrum disorder, or substance use disorders, where non-stimulants may be preferred 1.
Dosage and Administration
- Atomoxetine is typically started at 40mg daily for adults and children over 70kg, with gradual increases to 80-100mg daily if needed, while for children under 70kg, dosing starts at 0.5mg/kg daily and may increase to 1.2mg/kg 1.
- Guanfacine is prescribed at 1-4mg once daily for children 6-17 years old, and clonidine is given at 0.1-0.4mg daily, often divided into smaller doses 1.
Efficacy and Safety
- Non-stimulant medications take 2-4 weeks to reach full effectiveness, and common side effects include initial drowsiness, dry mouth, and potential blood pressure changes that should be monitored, especially during dose adjustments 1.
- Atomoxetine has been shown to have a relatively better safety profile compared to guanfacine and clonidine, with fewer adverse effects and no significant difference in cardiovascular effects compared to stimulants 1.
From the FDA Drug Label
Atomoxetine capsules are indicated for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) The efficacy of atomoxetine capsules was established in seven clinical trials in outpatients with ADHD: four 6 to 9-week trials in pediatric patients (ages 6 to 18), two 10-week trial in adults, and one maintenance trial in pediatrics (ages 6 to 15)
Non-stimulant medication for ADHD:
- Atomoxetine is a non-stimulant medication approved for the treatment of ADHD in pediatric and adult patients 2.
- It is indicated as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, social) for patients with this syndrome.
- The decision to prescribe atomoxetine will depend upon the physician’s assessment of the chronicity and severity of the patient’s symptoms.
From the Research
Non-Stimulant Medications for ADHD
- Non-stimulant medications are used to treat ADHD in patients who do not respond to or cannot tolerate stimulant medications 3, 4, 5, 6, 7
- Atomoxetine is the only FDA-approved non-stimulant medication for ADHD and has been shown to be efficacious in treating ADHD symptoms in both children and adults 3, 5, 6, 7
- Other non-stimulant medications that have been used to treat ADHD include:
- Bupropion, which has been shown to decrease the severity of ADHD symptoms and increase the proportion of participants achieving clinical improvement 4
- Tricyclic antidepressants, which have been shown to be efficacious in treating ADHD but are limited by side effects 5, 6
- Alpha-2 adrenergic agonists, such as guanfacine and clonidine, which have been shown to be effective in treating ADHD 3, 6, 7
- Viloxazine, which is a norepinephrine reuptake inhibitor and has been shown to be effective in treating ADHD 6, 7
Mechanism of Action and Pharmacokinetics
- Atomoxetine works by selectively inhibiting the reuptake of norepinephrine, increasing the concentration of norepinephrine in the brain 5, 6, 7
- Bupropion works by inhibiting the reuptake of norepinephrine and dopamine, increasing the concentration of these neurotransmitters in the brain 4
- Tricyclic antidepressants work by inhibiting the reuptake of norepinephrine and serotonin, increasing the concentration of these neurotransmitters in the brain 5, 6
- Alpha-2 adrenergic agonists work by stimulating alpha-2 adrenergic receptors, decreasing the release of norepinephrine and increasing the concentration of norepinephrine in the brain 3, 6, 7
Efficacy and Safety
- Non-stimulant medications have been shown to be effective in treating ADHD symptoms in both children and adults 3, 4, 5, 6, 7
- Atomoxetine has been shown to be safe and well-tolerated in both children and adults 3, 5, 6, 7
- Bupropion has been shown to be safe and well-tolerated in adults, but may have a higher risk of side effects in children 4
- Tricyclic antidepressants have been shown to be effective in treating ADHD, but may have a higher risk of side effects due to their anticholinergic and antihistaminic properties 5, 6
- Alpha-2 adrenergic agonists have been shown to be safe and well-tolerated in both children and adults, but may have a higher risk of side effects such as hypotension and bradycardia 3, 6, 7