Starting Non-Stimulant ADHD Medication in an Adult on Prozac
Start with atomoxetine (Strattera) 40 mg once daily in the morning, titrating to a target dose of 80-100 mg daily over 2-4 weeks. This is the only FDA-approved non-stimulant specifically studied and approved for adult ADHD, and there are no significant drug interactions between atomoxetine and fluoxetine (Prozac) 1, 2, 3.
Why Atomoxetine is the Clear First Choice
- Atomoxetine is the primary second-line option recommended by the Canadian ADHD Resource Alliance (CADDRA) when stimulants are contraindicated, not tolerated, or ineffective 4
- It is the first and only non-stimulant approved by the FDA specifically for adult ADHD based on well-controlled adult trials 2, 3, 5
- In two large 10-week trials in adults, atomoxetine (60-120 mg/day) produced mean reductions in ADHD symptom scores of 28-30% versus 18-20% with placebo 2, 3
- The medication is not a controlled substance, carries negligible risk of abuse or diversion, and allows for convenient repeat prescriptions during long-term treatment 2, 3
Dosing Strategy
Start with 40 mg once daily in the morning for the first 3-7 days, then increase to the target dose of 80 mg daily 1. For patients weighing over 70 kg, the target is 80-100 mg/day 5. The dose can be split into two evenly divided doses (morning and evening) if needed to reduce adverse effects 2, 3.
Important Timing Consideration
Full therapeutic effect requires 2-4 weeks, unlike stimulants which work within days 4, 6. Set appropriate expectations with your patient that symptom improvement will be gradual, with maximum benefit typically seen at 6-12 weeks 7.
Critical Safety Monitoring
Monitor for suicidality, clinical worsening, and unusual behavioral changes, especially during the first few months or at dose changes 1. The FDA has issued a black box warning for atomoxetine due to increased risk of suicidal ideation in children and adolescents (0.4% vs 0% with placebo) 1, 6.
Additional monitoring parameters include:
- Blood pressure and pulse at baseline and regularly during treatment (modest increases are common but generally well tolerated) 2, 3
- Common adverse effects: dry mouth, insomnia, nausea, decreased appetite, constipation, dizziness, sweating, dysuria, and sexual problems 2, 3
- Discontinuation rates due to adverse events range from 7.8-9.3% versus 2.4-4.3% with placebo 2, 3
Drug Interaction Considerations with Prozac
Fluoxetine (Prozac) can elevate serum atomoxetine levels through CYP2D6 inhibition, potentially requiring dose adjustment 6. However, this interaction is manageable and does not contraindicate combination therapy. Start at the lower end of the dosing range and titrate more cautiously if needed.
Alternative Non-Stimulant Options (If Atomoxetine Fails)
If atomoxetine is ineffective or not tolerated after an adequate trial (8-12 weeks at target dose):
- Bupropion (Wellbutrin) 150 mg XL daily, titrating to 300 mg daily can be used as monotherapy or added to existing treatment, with a maximum dose of 450 mg per day 4, 6
- Guanfacine extended-release (1-4 mg daily) or clonidine are additional options, particularly useful if sleep disturbances are present, though these require 2-4 weeks until effects are observed 4, 6
Common Pitfall to Avoid
Do not assume bupropion alone will effectively treat both ADHD and any comorbid depression—no single antidepressant is proven for this dual purpose 6. If depression is severe or primary, address the mood disorder first before tackling ADHD symptoms 4.