What are non-stimulant medications for Attention Deficit Disorder (ADD)?

From the Guidelines

Non-stimulant medications, such as atomoxetine, guanfacine, and clonidine, are effective treatment options for ADHD, particularly for patients who experience adverse effects from stimulants or have certain comorbidities, and should be considered as first-line treatment options in specific cases, as supported by recent evidence 1.

Key Considerations

• Atomoxetine is typically the first-line non-stimulant option, starting at 40mg daily and potentially increasing to 80-100mg daily based on response, with a medium effect size compared to placebo 1.
• Guanfacine and clonidine are alpha-2 adrenergic agonists that can help with hyperactivity and impulsivity, with guanfacine usually dosed at 1-4mg once daily, and clonidine typically 0.1-0.4mg daily, often divided into multiple doses 1.
• Non-stimulants are particularly useful for patients who experience adverse effects from stimulants, have concerns about stimulant abuse potential, or have conditions like anxiety, tics, or substance use disorders that might be worsened by stimulants, as they have been shown to improve functional impairment and quality of life 1.

Benefits and Limitations

• Non-stimulants have a slower onset of action compared to stimulants, with effects typically observed after 2-6 weeks of treatment 1.
• Atomoxetine has been shown to have similar cardiovascular effects to stimulants, but with lower effects on decreased appetite and growth/height problems 1.
• Guanfacine and clonidine have been approved as adjunctive therapy to stimulant medications, which can increase treatment effects and/or decrease adverse effects of stimulants, such as sleep disturbances and cardiovascular effects 1.

Clinical Applications

• Non-stimulants may be considered as first-line treatment options in disruptive behavior disorders, tic disorder, Tourette's syndrome, and substance use disorders, where stimulants may be regarded as an unviable treatment option due to their dopaminergic activity 1.
• When sleep disturbances are present, clonidine and guanfacine may be considered, and clinical trials have found that tics did not worsen under treatment with atomoxetine 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 for ADHD: Atomoxetine is a non-stimulant medication approved for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in pediatric and adult patients 2.

• Key points:
  • Indicated for the treatment of ADHD
  • Efficacy established in seven clinical trials
  • Approved for pediatric and adult patients
• Important consideration: Patients should be monitored closely for suicidality, clinical worsening, or unusual changes in behavior while on atomoxetine therapy.

From the Research

Non-Stimulant Medications for ADHD

• Atomoxetine is a non-stimulant medication approved by the FDA for the treatment of ADHD in children and adults 3, 4, 5, 6.
• Viloxazine extended-release is another non-stimulant medication approved by the FDA for the treatment of ADHD in children and adults 3, 5.
• Clonidine ER and guanfacine ER are non-stimulant medications approved by the FDA for the treatment of ADHD in children and adolescents in the US 3, 5.
• Other non-stimulant medications that have been used to treat ADHD include bupropion, alpha-2 agonists, and tricyclic antidepressants 4, 7.

Efficacy and Safety of Non-Stimulant Medications

• Atomoxetine has been found to be efficacious for the entire spectrum of ADHD symptoms in both children and adults 4, 6.
• The presence of comorbid disorders does not adversely impact the efficacy of atomoxetine in the treatment of ADHD symptoms 6.
• Non-stimulant medications may offer hope for patients who need medication alternatives, as more than 33% of children and 50% of adults discontinue treatment with stimulants during the first year 3.

Pipeline Non-Stimulant Medications

• Centanafadine, solriamfetol, and L-threonic acid magnesium salt are non-stimulant medications currently in Phase 3 trials for the treatment of ADHD 3.
• Modafinil is being studied for the treatment of pediatric ADHD, and there have been preliminary studies assessing the efficacy of cholinergic agents for ADHD 4.