What non-stimulant can be added to Prozac (fluoxetine)?

Non-Stimulant Medications That Can Be Added to Prozac (Fluoxetine)

Atomoxetine (Strattera) is the preferred non-stimulant medication that can be added to Prozac (fluoxetine) due to its favorable side effect profile and lower potential for drug interactions compared to other non-stimulants. 1

Recommended Non-Stimulant Options

First-Line Option:

• Atomoxetine (Strattera)
  • Dosing: Start at 0.5 mg/kg/day and titrate to 1.2 mg/kg/day (maximum 1.4 mg/kg/day or 100 mg/day, whichever is lower)
  • Dose adjustments typically every 7-14 days
  • Has fewer and less pronounced adverse effects compared to other non-stimulants 2
  • Citalopram/escitalopram and atomoxetine have the least effect on CYP450 isoenzymes, reducing the risk of drug interactions with fluoxetine 2

Alternative Options:

• Guanfacine Extended-Release (Intuniv)

  • FDA-approved as adjunctive therapy to stimulant medications 2
  • Can help decrease adverse effects of stimulants, particularly sleep disturbances 2
  • Evening administration is generally preferable due to somnolence/fatigue as a common side effect 2
  • Requires monitoring of blood pressure and heart rate due to potential hypotension 1

• Clonidine Extended-Release (Kapvay)

  • Also FDA-approved as adjunctive therapy to stimulant medications 2
  • Similar to guanfacine in helping with sleep disturbances 2
  • Evening administration is generally preferable 2

Important Considerations

Safety Monitoring

1. For Atomoxetine:

   • Monitor for suicidal ideation, particularly during the first few months (FDA black box warning) 1
   • Assess for cardiovascular effects, though these are typically minimal 2

2. For Alpha-2 Agonists (Guanfacine/Clonidine):

   • Regular monitoring of blood pressure and heart rate is essential 1
   • Watch for excessive sedation, especially during initial titration 1

Drug Interaction Precautions

• Avoid combining fluoxetine with MAOIs due to risk of serotonin syndrome 2
• Be cautious when combining multiple serotonergic drugs; monitor for symptoms of serotonin syndrome, especially in first 24-48 hours after dosage changes 2
• Fluoxetine may interact with drugs metabolized by CYP2D6 2

Onset of Action

• Atomoxetine's treatment effects typically take 6-12 weeks to fully manifest 2
• Clonidine and guanfacine effects usually appear within 2-4 weeks 2
• This differs significantly from stimulants, which have more rapid onset 2

Special Populations

• For patients with comorbid anxiety, atomoxetine may be beneficial 2
• For patients with sleep disturbances, clonidine or guanfacine may be preferred 2
• For patients with tic disorders or Tourette's syndrome, atomoxetine is a good option as it doesn't worsen tics 2

Clinical Approach

1. Start with atomoxetine if adding a non-stimulant to fluoxetine
2. If atomoxetine is ineffective or poorly tolerated, consider guanfacine extended-release
3. Monitor closely for drug interactions and side effects, particularly during the initial weeks of combination therapy
4. Adjust dosing based on clinical response and tolerability

Remember that while buspirone has historically been used as an augmentation strategy with SSRIs like fluoxetine, more recent evidence suggests it may delay the onset of antidepressant efficacy 3, making atomoxetine the preferred choice when adding a non-stimulant to Prozac.