Has the patient tried non-stimulant medications, such as atomoxetine, for Attention Deficit Hyperactivity Disorder (ADHD) which did not help?

Understanding Non-Stimulant Treatment History for ADHD

This question asks whether the patient has previously tried non-stimulant medications for ADHD without success—this is a critical piece of information that directly determines the next treatment step in the ADHD medication algorithm.

Why This Question Matters

If the patient has already failed non-stimulant therapy (such as atomoxetine, guanfacine, or clonidine), this strongly supports moving to or optimizing stimulant medications as the next step. 1

Treatment Algorithm Based on Prior Non-Stimulant Response

• Stimulants are recommended as first-line therapy with effect sizes of approximately 1.0, demonstrating 70-80% response rates in treating core ADHD symptoms 1, 2

• Non-stimulants are generally second-line options with smaller effect sizes (approximately 0.7 for atomoxetine, guanfacine, and clonidine) and are typically reserved for specific circumstances 1

• If methylphenidate has been tried without adequate benefit, lisdexamfetamine should be the next option over additional non-stimulant trials 1

Specific Non-Stimulants to Ask About

When determining if non-stimulants "did not help," inquire specifically about:

Atomoxetine (Strattera)

• Target dose is 60-100 mg daily for adults, with maximum of 1.4 mg/kg/day or 100 mg/day 2
• Requires 6-12 weeks to achieve full therapeutic effect, unlike stimulants which work within days 1, 2
• Mean reductions in ADHD symptom scores were 28-30% versus 18-20% with placebo in controlled trials 3, 4
• Common adverse effects include dry mouth, insomnia, nausea, decreased appetite, constipation, and sexual dysfunction 3, 5

Alpha-2 Agonists (Guanfacine and Clonidine)

• Require 2-4 weeks until effects are observed 1, 2
• Effect sizes around 0.7, similar to atomoxetine 1
• Particularly useful for comorbid sleep disturbances or tics 1, 2
• Common adverse effects include somnolence and dry mouth 1

Critical Details to Clarify

Adequate Trial Parameters

To determine if a non-stimulant truly "did not help," verify:

• Atomoxetine was dosed at 60-100 mg daily for at least 6-12 weeks 1, 2
• Alpha-2 agonists were continued for at least 2-4 weeks at therapeutic doses 1
• Adherence was adequate (once-daily dosing should be confirmed) 1
• Response was assessed using validated rating scales (such as CAARS) rather than subjective impression alone 3, 4

Reasons for Discontinuation

Distinguish between:

• Lack of efficacy (no improvement in ADHD symptoms after adequate trial)
• Intolerable adverse effects (which specific ones—this guides future medication selection)
• Inadequate trial (insufficient dose, duration, or adherence)

Special Populations Where Non-Stimulant History Is Particularly Important

Substance Use History

• Non-stimulants, particularly atomoxetine, are preferred first-line options in patients with active substance abuse due to negligible abuse potential and non-controlled status 1, 3, 4
• If atomoxetine failed in this population, long-acting stimulant formulations with lower abuse potential (such as Concerta) become the next consideration 2

Comorbid Anxiety or Tics

• Alpha-2 agonists (guanfacine, clonidine) are particularly useful when these comorbidities are present 1, 2
• If these failed, stimulants can still be used with careful monitoring, as anxiety is not an absolute contraindication 6

Comorbid Depression

• Atomoxetine may have been chosen if depression was present, but no single antidepressant (including atomoxetine) is proven to effectively treat both ADHD and depression 2
• If atomoxetine failed, the algorithm suggests treating ADHD with stimulants and adding an SSRI if depressive symptoms persist 2

Common Pitfalls to Avoid

• Do not assume a brief trial (less than 4 weeks for atomoxetine) represents adequate non-stimulant exposure 1
• Do not overlook that atomoxetine requires dose adjustment when combined with CYP2D6 inhibitors (such as SSRIs like paroxetine or fluoxetine) 2, 7
• Do not forget that non-stimulants can be used as adjunctive therapy with stimulants if monotherapy with either class is insufficient—guanfacine and clonidine are FDA-approved for this indication 1, 2
• Do not continue non-stimulant trials indefinitely—if two adequate trials of different non-stimulant classes have failed, stimulants should be strongly considered unless contraindicated 1

Documentation Requirements

When documenting non-stimulant trial history, record:

• Specific medication name and formulation 1
• Maximum dose achieved and duration at that dose 1, 2
• Specific ADHD symptoms that did or did not improve (inattention vs. hyperactivity/impulsivity) 3, 4
• Adverse effects experienced 1
• Reason for discontinuation 7, 5
• Adherence assessment 1

This information directly determines whether to proceed with stimulant therapy, try an alternative non-stimulant class, or consider combination therapy 1.