Restart Atomoxetine at a Lower Dose After Missing Two Days
After missing two doses of atomoxetine 80 mg daily, restart at 40 mg daily for at least 7 days before re-escalating to 80 mg, rather than adding ondansetron to mask withdrawal and re-initiation symptoms. 1
Rationale for Dose Reduction
The nausea and vomiting you're experiencing represents a combination of discontinuation effects from the missed doses and re-initiation side effects when restarting at the full 80 mg dose. This is a well-recognized phenomenon with atomoxetine:
- Atomoxetine discontinuation can cause gastrointestinal symptoms including nausea and vomiting, similar to SSRI discontinuation syndrome. 1
- Nausea is one of the most common adverse events when initiating or re-initiating atomoxetine, occurring more frequently at higher doses. 2, 3
- Starting atomoxetine at subtherapeutic doses as a "test dose" is advisable to minimize initial adverse effects like nausea and agitation. 1
Recommended Re-Titration Strategy
Use a slow titration approach:
- Start at 40 mg daily for 7 days, then increase to 80 mg daily if tolerated. This mirrors the "slow titration" strategy validated in clinical trials. 4
- The slow titration approach (40 mg for 7 days before increasing to 80 mg) reduces discontinuation due to adverse events compared to on-label rapid titration (40 mg for 3 days then 80 mg). 4
- For patients who experience robust response to atomoxetine, maintenance doses as low as 0.5 mg/kg per day can retain therapeutic effect while reducing adverse events. 5
Why Ondansetron Is Not the Preferred Solution
Adding ondansetron treats the symptom but not the underlying problem:
- Ondansetron 4-8 mg IV/PO every 8 hours is appropriate for breakthrough nausea, but should be reserved for situations where the underlying cause cannot be modified. 6
- The National Comprehensive Cancer Network recommends addressing treatable causes of nausea (including medication-related factors) before adding antiemetics. 1, 6
- Simply masking atomoxetine-induced nausea with ondansetron may lead to continued intolerance and eventual treatment discontinuation, whereas dose adjustment addresses the root cause. 2, 3
If You Choose to Use Ondansetron Temporarily
If immediate symptom control is needed while re-titrating:
- Give ondansetron 4-8 mg orally every 8 hours as needed for the first 3-5 days of atomoxetine re-initiation at 40 mg. 6
- Switch to scheduled dosing (8 mg twice daily) if nausea persists beyond 48 hours, rather than continuing as-needed dosing. 6
- Taper ondansetron after 5-7 days once atomoxetine tolerance is re-established at the lower dose. 1
Common Pitfalls to Avoid
- Do not restart at 80 mg and rely solely on ondansetron—this increases the risk of treatment discontinuation and does not address the underlying dose-related adverse effect. 2, 4
- Do not use first-generation antihistamines like diphenhydramine for nausea, as they can worsen sedation and other side effects without effectively treating atomoxetine-induced nausea. 6
- Ensure adequate hydration and assess for constipation, as ondansetron can worsen constipation, which itself causes nausea. 1, 6
Monitoring During Re-Titration
- Monitor heart rate and blood pressure at each dose increase, as atomoxetine causes modest increases in both parameters that are dose-dependent. 2, 3
- Assess for return of ADHD symptoms during the lower-dose period; if symptoms are inadequately controlled at 40 mg, the full 80 mg dose will likely be needed once tolerance is re-established. 5
- Most nausea from atomoxetine is mild to moderate and resolves within the first week of treatment at a stable dose. 2, 3