What are non-stimulant alternatives to Adderall (amphetamine and dextroamphetamine) for treating Attention Deficit Hyperactivity Disorder (ADHD)?

Non-Stimulant Alternatives to Adderall for ADHD Treatment

The most effective non-stimulant alternatives to Adderall for treating ADHD are atomoxetine, extended-release guanfacine, and extended-release clonidine, with atomoxetine having the strongest evidence as the preferred first-line non-stimulant option. 1

Primary Non-Stimulant Options

Atomoxetine (Strattera)

• Works through norepinephrine reuptake inhibition, providing "around-the-clock" effects for 24-hour symptom control 1
• Recommended dosing starts at 40mg daily, with titration every 7-14 days up to 1.4mg/kg/day or 100mg daily maximum 1
• Takes 6-12 weeks to reach full therapeutic effect, unlike stimulants which work immediately 1
• Has fewer and less pronounced adverse effects compared to other non-stimulants 1
• Common side effects include decreased appetite, headache, stomach pain, and clinical worsening 1
• Particularly beneficial for patients with comorbid anxiety, autism spectrum disorder, substance use disorders, or tic disorders 1, 2

Alpha-2 Adrenergic Agonists

• Extended-release guanfacine:

  • Available in 1mg, 2mg, 3mg, and 4mg tablets with once-daily dosing (0.1mg/kg as a rule of thumb) 1
  • Takes 2-4 weeks to show therapeutic effects 1
  • Particularly useful for patients with comorbid sleep disorders or tics 1
  • Common side effects include somnolence, fatigue, hypotension, and irritability 1

• Extended-release clonidine:

  • Available in tablet form (0.1mg, 0.2mg) and transdermal patches 1
  • Recommended starting dose is 0.1mg at bedtime, with careful titration up to 0.4mg/day maximum 1
  • Requires twice-daily dosing for optimal effect 1
  • Similar side effect profile to guanfacine but may cause more sedation 1

Comparative Efficacy and Selection Considerations

• All non-stimulants have smaller effect sizes (medium range) compared to stimulants, which have large effect sizes 1, 2
• Among non-stimulants, evidence is strongest for atomoxetine, followed by extended-release guanfacine, then extended-release clonidine 1, 2
• Atomoxetine has been shown to improve functional impairment and quality of life in addition to core ADHD symptoms 1
• Non-stimulants offer advantages of not being controlled substances and providing continuous 24-hour coverage 1

Special Clinical Scenarios

• For patients with comorbid substance use disorders, non-stimulants are preferred first-line options due to lack of abuse potential 1, 3
• For patients with tic disorders or Tourette's syndrome, atomoxetine does not worsen tics, while guanfacine may potentially reduce them 1
• For patients with sleep disturbances, the sedating properties of guanfacine or clonidine may be beneficial when administered in the evening 1
• For patients with inadequate response to stimulants, guanfacine and clonidine are FDA-approved as adjunctive therapy to stimulants 1, 2

Monitoring and Management

• Monitor vital signs, particularly blood pressure and pulse, as non-stimulants can affect cardiovascular parameters 1
• For atomoxetine, monitor for suicidality, particularly during the first few weeks of treatment (carries FDA black box warning) 4
• For guanfacine and clonidine, monitor for hypotension, bradycardia, and somnolence 1
• Evening administration is generally preferable for guanfacine and clonidine due to sedative effects 1

Alternative Options

• Bupropion (Wellbutrin) may be considered as an off-label option for ADHD, particularly with comorbid depression 1, 4
• Available in SR (100-150mg BID) and XL (150-300mg daily) formulations with a maximum dose of 450mg daily 1
• Not FDA-approved specifically for ADHD but has shown efficacy in clinical practice 4

Remember that non-stimulant medications should be part of a comprehensive multimodal treatment approach that includes psychoeducation and psychosocial interventions 1.