What is the dosing of Strattera (atomoxetine) for a patient on Buspar (buspirone), Lexapro (escitalopram), and Trazodone?

Strattera (Atomoxetine) Dosing in Patients on Buspar, Lexapro, and Trazodone

Start atomoxetine at 40 mg daily and increase to a target dose of 80 mg daily after a minimum of 3 days, but only increase to 80 mg after 4 weeks if symptoms fail to improve and the initial dose is well tolerated, because escitalopram (Lexapro) is a strong CYP2D6 inhibitor that significantly increases atomoxetine levels. 1

Initial Dosing Strategy

• Begin with 40 mg once daily (either morning or split between morning and late afternoon/early evening) 1
• Wait a minimum of 3 days before any dose adjustment 1
• The usual target dose would be 80 mg daily, but this requires careful titration due to the drug interaction 1

Critical Drug Interaction: Escitalopram (Lexapro)

• Escitalopram inhibits CYP2D6, the primary enzyme metabolizing atomoxetine 1
• When atomoxetine is combined with strong CYP2D6 inhibitors like escitalopram, initial doses should be maintained at 40 mg/day 1
• Only increase to 80 mg after 4 weeks if symptoms fail to improve AND the initial 40 mg dose is well tolerated 1
• This conservative approach prevents excessive atomoxetine accumulation and reduces risk of adverse effects 1

Maximum Dosing Parameters

• The maximum recommended total daily dose is 100 mg for adults 1
• However, given the CYP2D6 inhibition from escitalopram, reaching maximum doses should be approached cautiously 1
• Doses above 80 mg should only be considered after 2-4 additional weeks if optimal response has not been achieved 1

Additional Considerations with Concurrent Medications

Buspirone (Buspar)

• No significant pharmacokinetic interaction with atomoxetine 2
• One study showed atomoxetine plus buspirone was well-tolerated with discontinuation rates of 15.5% due to adverse effects 2
• Common side effects when combined include insomnia, nausea, dry mouth, headache, and dizziness 2

Trazodone

• No direct pharmacokinetic interaction with atomoxetine reported in the evidence
• Trazodone is commonly used for sleep at doses of 25-400 mg daily 3
• Both medications can cause sedation, so monitor for additive CNS effects 4

Serotonin Syndrome Risk

• Monitor carefully for serotonin syndrome when combining multiple serotonergic agents (escitalopram, trazodone, and potentially buspirone) 5
• Watch for diaphoresis, tremor, diarrhea, mydriasis, and mental status changes 5
• While atomoxetine primarily affects norepinephrine, the combination of escitalopram and trazodone already increases serotonin syndrome risk 5

Practical Dosing Algorithm

1. Week 1-4: Atomoxetine 40 mg daily (single morning dose or divided doses)
2. Week 4 assessment: If inadequate response AND good tolerability → increase to 80 mg daily
3. Week 6-8 assessment: If still inadequate response AND good tolerability → may increase to 100 mg daily maximum
4. Maintenance: Continue effective dose; can be discontinued without tapering 1

Monitoring Requirements

• Assess ADHD symptoms using standardized rating scales at each dose adjustment 1
• Monitor blood pressure and heart rate as atomoxetine can increase both 1
• Screen for mood changes, particularly increased anxiety or agitation, given the activating nature of atomoxetine 2
• Watch for serotonergic symptoms given the polypharmacy with multiple serotonergic agents 5
• Evaluate sleep patterns as the combination may affect sedation levels differently than individual agents 4

Common Pitfalls to Avoid

• Do not use standard adult dosing (rapid escalation to 80 mg after 3 days) due to the CYP2D6 inhibition from escitalopram 1
• Do not open atomoxetine capsules; they must be swallowed whole 1
• Do not exceed 100 mg total daily dose regardless of response 1
• Do not ignore the 4-week waiting period before increasing from 40 mg to 80 mg when on CYP2D6 inhibitors 1