Can a Patient Take More Than One Nortriptyline Dose Per Day?
Yes, patients can and often should take nortriptyline in divided doses throughout the day, with the FDA-approved regimen being 25 mg 3-4 times daily, or alternatively as a single daily dose, with maximum dosing up to 150 mg per day. 1
FDA-Approved Dosing Regimens
The FDA label explicitly provides two acceptable dosing strategies for nortriptyline 1:
- Standard regimen: 25 mg 3-4 times daily (meaning 3-4 separate doses throughout the day)
- Alternative regimen: Total daily dose given once daily
- Maximum dose: 150 mg per day (doses above this are not recommended) 1
For elderly patients specifically, the FDA recommends 30-50 mg per day in divided doses 1.
Therapeutic Plasma Level Monitoring
When doses exceed 100 mg daily, plasma levels should be monitored and maintained in the optimum range of 50-150 ng/mL. 1 This therapeutic window is critical because:
- Optimal responses are associated with plasma concentrations of 50-150 ng/mL 1
- Higher concentrations may be associated with more adverse effects 1
- Elderly patients may develop higher plasma concentrations of the active metabolite 10-hydroxynortriptyline, which has been associated with cardiotoxicity even when nortriptyline levels appear therapeutic 1
Clinical Practice Guidelines for Neuropathic Pain
For neuropathic pain management, guidelines recommend 2:
- Starting dose: 25 mg at bedtime
- Titration: Increase by 25 mg/day every 3-7 days as tolerated
- Maximum dose: 150 mg/day
- Duration of adequate trial: 6-8 weeks with at least 2 weeks at maximum tolerated dose
The guideline notes that if blood concentration of active medication and its metabolite is <100 ng/mL, titration can continue with caution beyond standard dosing 2.
Divided Dosing vs. Single Daily Dosing
Divided dosing (multiple doses per day) is pharmacologically sound and may provide more stable plasma levels throughout the day. 3 The choice between divided and single daily dosing should consider:
- Divided dosing advantages: More stable plasma levels, potentially better tolerability 3
- Single daily dosing advantages: Improved adherence, convenience, can be timed for bedtime to leverage sedative effects 3
Research supports that nortriptyline can be administered either way without clinically significant differences in therapeutic effect 3.
Important Safety Considerations
Clinical findings should predominate over plasma concentrations as primary determinants of dosage changes. 1 Key monitoring parameters include:
- Orthostatic hypotension: The most significant cardiovascular concern, particularly in elderly patients 1, 4
- ECG changes: Monitor for cardiac conduction abnormalities 1
- Anticholinergic effects: Dry mouth, constipation, urinary retention 2
Common Pitfalls to Avoid
- Do not exceed 150 mg per day without compelling clinical justification and close plasma level monitoring 1
- Do not assume lower doses are always safer in elderly patients - the therapeutic window (50-150 ng/mL) still applies, and underdosing may lead to treatment failure 1, 5
- Do not ignore orthostatic hypotension - this is the primary dose-limiting side effect and requires monitoring, particularly when initiating therapy or increasing doses 4
- Do not make rapid dose adjustments - titration should occur every 3-7 days to allow assessment of tolerability and therapeutic response 2
Practical Dosing Algorithm
For initiating nortriptyline therapy:
- Start: 25 mg at bedtime (or 10-25 mg for elderly/frail patients) 2, 1
- Assess tolerability after 3-7 days, checking for orthostatic hypotension and anticholinergic effects 2
- Increase by 25 mg every 3-7 days as tolerated 2
- Consider divided dosing (3-4 times daily) if single daily dosing causes peak-related side effects 1
- Monitor plasma levels once dose exceeds 100 mg daily, targeting 50-150 ng/mL 1
- Maximum dose: 150 mg daily (or 100 mg daily in elderly patients) 2, 1
- Adequate trial duration: 6-8 weeks with at least 2 weeks at maximum tolerated dose 2