Can Prozac (fluoxetine) and Strattera (atomoxetine) be prescribed together?

Co-administration of Prozac (Fluoxetine) and Strattera (Atomoxetine)

Yes, Prozac (fluoxetine) and Strattera (atomoxetine) can be prescribed together, but caution is required due to potential drug interactions through the CYP2D6 pathway that may increase atomoxetine levels and side effects.

Mechanism of Interaction

The primary concern when combining these medications is their pharmacokinetic interaction:

• Fluoxetine is a potent inhibitor of the CYP2D6 enzyme 1
• Atomoxetine is primarily metabolized by CYP2D6 2
• This combination can lead to increased atomoxetine blood levels, similar to what occurs in poor CYP2D6 metabolizers 2

Clinical Efficacy of Combination

Research supports the potential efficacy of this combination:

• A randomized controlled trial found that atomoxetine combined with fluoxetine was effective for treating ADHD with comorbid depression or anxiety symptoms 3
• The combination was well-tolerated in the study population, though with some notable cardiovascular effects 3

Safety Considerations

When prescribing this combination, monitor for:

1. Cardiovascular effects:

   • The combination group had greater increases in blood pressure and pulse than atomoxetine monotherapy 3
   • Both medications individually can affect cardiovascular parameters 2

2. Serotonin syndrome risk:

   • While not specifically documented with this combination, caution is advised when combining serotonergic agents like fluoxetine with other psychotropics 4
   • Monitor for symptoms such as agitation, tremor, hyperthermia, and autonomic instability

3. Hepatic effects:

   • Atomoxetine has been associated with rare cases of serious liver injury 2
   • Fluoxetine is also metabolized hepatically

Dosing Recommendations

When using this combination:

• Start with lower doses of atomoxetine (approximately 50% of standard starting dose) when adding to established fluoxetine therapy 1
• Titrate atomoxetine slowly with careful monitoring for side effects
• Standard atomoxetine dosing is typically 40mg daily initially, titrated to a maximum of 1.4mg/kg/day or 100mg daily 4
• Monitor for side effects that may indicate elevated atomoxetine levels

Monitoring Parameters

Regular monitoring should include:

• Blood pressure and pulse at each visit
• Liver function tests periodically
• Mental status assessment, particularly for anxiety, agitation, or suicidal ideation (atomoxetine carries a black box warning for suicidal ideation) 2
• Effectiveness for target symptoms
• Side effects including sleep disturbances, appetite changes, and GI symptoms

Clinical Pitfalls to Avoid

1. Avoid rapid titration of atomoxetine when used with fluoxetine
2. Don't ignore cardiovascular monitoring as both medications can affect heart rate and blood pressure
3. Be cautious in patients with hepatic impairment as both medications undergo hepatic metabolism
4. Don't overlook the potential for drug interactions with other medications metabolized by CYP2D6
5. Avoid abrupt discontinuation of either medication, particularly fluoxetine which has a long half-life

Conclusion

While Prozac and Strattera can be prescribed together for conditions like comorbid ADHD and depression/anxiety, the combination requires careful dosing adjustments, monitoring, and awareness of potential drug interactions. The clinical benefits may outweigh the risks in appropriately selected and monitored patients.